Specification
1
DESCRIPTION
TITLE OF INVENTION:
OXIME-SUBSTITUTED AMIDE COMPOUND AND PEST CONTROL AGENT
5 TECHNICAL FIELD
The present invention relates to a novel oxime-substituted amide compound or its
salt, and a pesticidal composition containing the compound as an active ingredient.
BACKGROUND ART
10 Heretofore, with respect to oxime-substituted amide compounds, N-[2-
(methoxyimino)-2-phenylethyl]-4-(trifluoromethyl)nicotinamide and 3-iodo-N2-[2-
(methoxyimino)-2-phenylethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-
(trifluoromethyl)ethyl]phenyl]phthalic acid diamide are known to have insecticidal activity
(for example, Patent Documents 1 and 2).
15 Further, 2-chloro-N-[2-(4-chlorophenyl)-2-(methoxyimino)ethyl]benzamide, N-[2-
(4-chlorophenyl)-2-(methoxyimino)ethyl]-2,4-dichlorobenzamide and the like are known
to alter the lifespan of eukaryotic organisms (Patent Document 3).
Further, certain pyrazole-4-carboxamide derivatives are known to have fungicidal
activity (for example, Patent Documents 4 to 7).
20 However, the oxime-substituted amide compound of the present invention is not
disclosed at all, and its usefulness as a pesticide has not been known.
PRIOR ART DOCUMENTS
PATENT DOCUMENTS
25 Patent Document 1: JP-A-2004-035439
Patent Document 2: WO2001/021576
Patent Document 3: U.S. Patent Application Publication No. 2009/0163545
Patent Document 4: WO2001 -055136
Patent Document 5: WO2009-127722
30 Patent Document 6: WO2011 -151369
Patent Document 7: WO2011 -151370
DISCLOSURE OF INVENTION
TECHNICAL PROBLEM
35 Infection or parasitism of pests such as pathogens and parasites causes, in a
case where the hosts are plants such as grain, fruits, vegetables or ornamental plants, a
decrease in the quality of agricultural crops and a remarkable decrease in the yield, and
in some cases, serious damages such as death of the plants, and inflicts heavy
economic losses not only on the producers but also on the consumers. Thus, to
40 effectively control such pests is a very important object to achieve efficient and stable
production of agricultural crops. Further, in a case where the hosts are animals such
as companion creatures/pets or livestock/poultry, to effectively control such pests is an
important object also for the purpose of maintaining health of the target animals and
further, in a case where the target animals are livestock or poultry, for the purpose of
45 stably producing safe food or high quality general merchandise such as wool, feathers
or leathers. From such a viewpoint, heretofore, development of pesticides targeted at
pathogens or parasites has advanced, and various effective pesticides have been put
into practical use.
2
However, recently, control of pests with conventional pesticides has become
difficult in more and more cases, as pathogens or parasites acquire resistance to them
over many years of their use. Problems of the high toxicity of some conventional
pesticides and of the disturbance of the ecosystem by some conventional pesticides
5 which remain in the environment for a long period are becoming apparent. Under
these circumstances, development of novel pesticides not only having excellent
pesticidal activity on pathogens and parasites but also having high pesticidal properties
such as low toxicity and low persistence and of an effective controlling method is always
expected.
10
SOLUTION TO PROBLEM
The present inventors have conducted extensive studies to achieve the above
object and as a result, found that a novel oxime-substituted amide compound
represented by the following formula (I) is a very useful compound which is excellent in
15 pesticidal activities, especially in antifungal and nematicidal activities, and has little
harmful effect on non-target organisms such as plants, mammals, fishes, useful insects
and natural enemies, and accomplished the present invention.
That is, the present invention relates to an oxime-substituted amide compound
represented by the formula (I), or its N-oxide or salt:
W R2R3 / -X
V_y R4 N^
9
R1
20 wherein G1 is a structure represented by any one of G1-1 to G1-51:
G2 is a structure represented by any one of G2-1 to G2-19:
W is an oxygen atom or a sulfur atom,
X1 is a halogen atom, cyano, nitro, -SFs, C1-C6 alkyl, (Ci-Ce)alkyl optionally
substituted with R6, C3-C8 cycloalkyi, C3-C8 halocycloalkyl, C2-C6 alkenyl, C2-C6
haloalkenyl, C2-Ce alkynyl, C2-C6 haloalkynyl, -OR7, -S(0)rR7, -N(R9)R8, -C(0)NH2, -
C(S)NH2, tri(Ci-Ce alkyl)silyl, phenyl, phenyl substituted with (Z)m or D-3,
each of X2, X3, X4 and X5 is independently a hydrogen atom, a halogen atom,
cyano, nitro, C1-C6 alkyl, (Ci-Ce)alkyl optionally substituted with R6, C3-C8 cycloalkyi, C3-
C8 halocycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, -
OH, -OR7, -SH, -S(0)rR7, -N(R9)R8, Ci-Ce alkylcarbonyl, Ci-Ce alkoxycarbonyl, -
C(0)NH2, -C(S)NH2, phenyl, phenyl substituted with (Z)m, D-2 or D-32,
provided that when G1 is a structure represented by G1-27 and X1 is dihalomethyl,
X2 is a hydrogen atom,
each of Y1 and Y3 is independently a hydrogen atom, a halogen atom, cyano,
nitro, -SCN, -SF5, Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R6, C3-C10
cycloalkyi, (C3-Cio)cycloalkyl optionally substituted with R6, E-1 to E-22, C2-C6 alkenyl,
(C2-C6)alkenyl optionally substituted with R6, C5-C10 cycloalkenyl, C5-C10
halocycloalkenyl, C2-C6 alkynyl, (C2-C6)alkynyl optionally substituted with R6, -OH, -OR7,
-OS(0)2R7, -SH, -S(0)rR7, -N(R9)R8, -N=C(R9a)R8a, -C(0)R10, -C(R10)=NOH, -
6
C(R10)=NOR11, M-3, M-13, M-30, -C(0)OH, -C(0)OR11, -C(0)SR11, -C(0)N(R13)R12, M-
7, M-17, M-23, M-26, -C(S)OR11, -C(S)SR11, -C(S)N(R13)R12, M-9, M-19, M-23, M-24,
M-28, M-25, M-29, -S(0)2OR11, -S(0)2N(R13)R12, -Si(R14a)(R14b)R14, phenyl, phenyl
substituted with (Z)m, or D-1 to D-38,
5 each of Y2, Y4 and Y5 is independently a hydrogen atom, a halogen atom, cyano,
nitro, -SCN, -SF5, Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R6, Ca-Cs
cycloalkyl, Ca-Cs halocycloalkyl, -OH, -OR7, -SH, -S(0)rR7, -NH2) Ci-Ce alkylamino,
di(Ci-Ce alkyl)amino, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl,
Ci-Ce alkoxycarbonyl, -C(0)NH2 or -C(S)NH2,
10 or, Y1, Y2, Y3 and Y4 represent that Y1 or Y3 and Y2, or Y3 and Y4, together form -
CH2CH2CH2-, -CH2CH2O-, -CH2OCH2-, -OCH2O-, -CH2CH2CH2CH2-, -CH2CH2S-, -
CH2SCH2-, -SCH2S-, -CH2CH2N(R5)-, -CH2N(R5)CH2-, -CH2CH2CH2CH2-, -
CH2CH2CH2O-, -CH2CH2OCH2-, -CH2OCH2O-, -OCH2CH2O-, -OCH2CH2S-, -
SCH2CH2S-, -CH2CH=CH-, -N(R5)N=CH-, -OCH2CH=CH-, -CH=CHCH=CH-, -
15 CH=CHCH=N-, -CH=CHN=CH-, -CH=NCH=N- or -N=CHCH=N- to form a 5-membered
ring or a 6-membered ring together with the carbon atoms attached to Y1, Y2, Y3 and Y4,
wherein hydrogen atoms on the respective ring-constituting carbon atoms may
optionally be substituted with a halogen atom, cyano, nitro, C1-C4 alkyl or C1-C4
haloalkyl,
20 and further, when G1 is a structure represented by G1-1, G1-9, G1-10, G1-12, G1-
13, G1-16 to G1-20, G1-22 to G1-24, G1-26, G1-27, G1-30, G1-32, G1-35, G1-38, G1-40 or
G1-42 to G1-50, Y1 and Y2, Y2 and Y3, or Y3 and Y4, together may form -OCH=CH-, -
SCH=CH-, -N(R5)CH=CH-, -OCH=N-, -SCH=N- or -N(R5)CH=N- to form a 5-membered
ring together with the carbon atoms attached to Y1, Y2, Y3 and Y4, wherein hydrogen
25 atoms on the respective ring-constituting carbon atoms may optionally be substituted
with a halogen atom, cyano, nitro, C1-C4 alkyl or C1-C4 haloalkyl,
D-1 to D-38 are aromatic heterocyclic rings represented by the following structural
formulae, respectively:
E-1 to E-22 are saturated heterocyclic rings represented by the following structural
formulae, respectively:
Z is a halogen atom, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy(Ci-
C4)alkyl, C1-C4 haloalkoxy(Ci-C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, C1-C4
haloalkylthio(Ci-C4)alkyl, C1-C4 alkylsulfinyl(Ci-C4)alkyl, C1-C4 haloalkylsulfinyl(Ci-
C4)alkyl, C1-C4 alkylsulfonyl(Ci-C4)alkyl, C1-C4 haloalkylsulfonyl(Ci-C4)alkyl, Ca-Ce
5 cycloalkyl, C3-C6 halocycloalkyl, -OH, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4
alkylsulfonyloxy, C1-C4 haloalkylsulfonyloxy, C1-C4 alkylthio, C1-C4 haloalkylthio, C1-C4
alkylsulfinyl, C1-C4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, -NH2,
C1-C4 alkylamino, di(Ci-C4 alkyl)amino, C1-C4 alkoxycarbonyl, C1-C4
haloalkoxycarbonyl, -C(0)NH2, C1-C4 alkylaminocarbonyl, di(Ci-C4 alkyl)aminocarbonyl,
10 -C(S)NH2, -S(0)2NH2 or phenyl,
when m or n is an integer of at least 2, the respective Z's may be identical with or
10
different from one another, and when there are two neighboring Z's, the two neighboring
Z's may form -CH2CH2CH2-, -CH2CH2O-, -CH2OCH2-, -OCH2O-, -CH2CH2S-, -
CH2SCH2-, -CH2CH2CH2CH2-, -CH2CH2CH2O-, -CH2CH2OCH2-, -CH2OCH2O-, -
OCH2CH2O-, -CH2CH2CH2S-, -OCH2CH2S- or -CH=CH-CH=CH- to form a 5-membered
5 ring or a 6-membered ring together with the carbon atoms attached to the two Z's,
wherein hydrogen atoms on the respective ring-constituting carbon atoms may
optionally be substituted with a halogen atom, a cyano group, a nitro group, a methyl
group, a trifluoromethyl group, a methoxy group or a methylthio group,
Ft1 is Ci-Ce alkyl, (Ci-C8)alkyl optionally substituted with Ft18, C3-C10 cycloalkyi, C3-
10 C10 halocycloalkyi, E-2 to E-8, E-14 to E-18, E-21, Cs-Ce alkenyl, Cs-Ce haloalkenyl, C5-
C10 cycloalkenyl, C5-C10 halocycloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, phenyl(C3-
C6)alkynyl, phenyl or phenyl substituted with (Z)m,
R2 is a hydrogen atom, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C4 alkoxy(Ci-
C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 alkylsulfinyl(Ci-C4)alkyl, C1-C4
15 alkylsulfonyl(Ci-C4)alkyl, C3-C6 cycloalkyi or phenyl, or may form the after-mentioned
ring together with R3,
provided that when G1 is a structure represented by G1-1, X1 is a chlorine atom,
X2, X3 and X5 are hydrogen atoms, X4 is a hydrogen atom or a chlorine atom, G2 is a
structure represented by G2-1, Y3 is a chlorine atom, and Y1, Y2, Y4 and Y5 are hydrogen
20 atoms, R2 is cyano, Ci-Ce alkyl, Ci-Ce haloalkyl, C1-C4 alkoxy(Ci-C4)alkyl, C1-C4
alkylthio(Ci-C4)alkyl, C1-C4 alkylsulfinyl(Ci-C4)alkyl, C1-C4 alkylsulfonyl(Ci-C4)alkyl, C3-
C6 cycloalkyi or phenyl,
R3 is a hydrogen atom or C1-C6 alkyl,
or R3 may form, together with R2, a C2-C5 alkylene chain to form a 3- to 6-
25 membered ring together with the carbon atom attached to R2 and R3, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a C1-C4 alkyl group, a -CHO group, a C1-C4 alkylcarbonyl
group, a C1-C4 alkoxycarbonyl group, a C1-C4 alkylaminocarbonyl group, a C1-C4
haloalkylaminocarbonyl group, a di(Ci-C4 alkyl)aminocarbonyl group or a phenyl group,
30 R4 is a hydrogen atom, cyano, nitro, C1-C6 alkyl, (Ci-C6)alkyl optionally substituted
with R19, C3-C8 cycloalkyi, C3-C6 alkenyl, C3-C6 haloalkenyl, C5-C10 cycloalkenyl, C5-C10
halocycloalkenyl, C3-C6 alkynyl, Cs-Ce haloalkynyl, -C(0)R20, -C(0)OR21, -C(0)SR21, -
C(0)N(R23)R22, -C(0)C(0)OR21, -C(S)OR21, -C(S)SR21, -C(S)N(R23)R22, -OH, -OR21, -
SR21, -N(R25)R24, -N=C(R25a)R24a, -S(0)2R21, -S(0)2N(R23)R22 or-SN(R27)R26,
35 R5 is a hydrogen atom, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl(Ci-C4)alkyl,
C3-C6 cycloalkyi, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl or C2-C6 haloalkynyl,
R6 is a halogen atom, cyano, nitro, C3-C8 cycloalkyi, C3-C8 halocycloalkyi,
hydroxy(C3-C8)cycloalkyl, C1-C6 alkoxy(C3-C8)cycloalkyl, C3-C6 alkenyl, C3-C8
cycloalkenyl, E-1 to E-22, -OH, -OR7, -SH, -S(0)rR7, -N(R9)R8, -C(R10)=NOH, -
40 C(R10)=NOR11, -C(0)OR11, -C(0)N(R13)R12, -Si(R14a)(R14b)R14, phenyl, phenyl
substituted with (Z)m or D-1 to D-38,
R7 is Ci-Ce alkyl, (Ci-Ce) alkyl optionally substituted with R28, C3-C8 cycloalkyi,
(C3-Ca)cycloalkyl optionally substituted with R28, E-2 to E-8, E-14 to E-18, E-21, C2-C6
alkenyl, (C2-C6)alkenyl optionally substituted with R28, C5-C10 cycloalkenyl, C5-C10
45 halocycloalkenyl, C3-C6 alkynyl, (C3-C6)alkynyl optionally substituted with R28, C1-C6
alkylcarbonyl, C1-C6 alkoxycarbonyl, phenyl, phenyl substituted with (Z)m, D-1, D-2, D-4
to D-6, D-8 to D-10, D-12 to D-19, D-21, D-23, D-25, D-27 or D-30 to D-38,
R8 is a hydrogen atom, C1-C6 alkyl, (Ci-Ce)alkyl optionally substituted with R28, C3-
11
Cs cycloalkyi, C3-C8 halocycloalkyi, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-
Ce haloalkynyl, -C(0)R10, -C(0)C(0)R11, -C(0)OR11, -C(0)C(0)OR11, -C(0)SR11, -
C(0)N(R13)R12, -C(S)OR11, -C(S)SR11, -C(S)N(R13)R12, -OH, -S(0)2R11 or-
S(0)2N(R13)R12, or may form the after-mentioned ring together with R9,
5 R9 is a hydrogen atom, Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R28, C3-
Cs cycloalkyi, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, -CHO,
C1-C6 alkylcarbonyl, C1-C6 haloalkylcarbonyl or C1-C6 alkoxycarbonyl,
or R9 may form, together with R8, a C2-C6 alkylene chain to form a 3- to 7-
membered ring together with the nitrogen atom attached to R8 and R9, wherein the
10 alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl
group, an oxo group or a thioxo group,
R8a is Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C3-C6 alkenyloxy, phenoxy or
phenoxy substituted with (Z)m, or may form the after-mentioned ring together with R9a,
15 R9a is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 alkenyl, phenyl or
phenyl substituted with (Z)m,
or R9a may form, together with R8a, a C4-C6 alkylene chain to form a 5- to 7-
membered ring together with the carbon atom attached to R8a and R9a, wherein the
alkylene chain may contain an oxygen atom or sulfur atom,
20 R10 is a hydrogen atom, Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R28,
C3-C8 cycloalkyi, C3-C8 halocycloalkyi, C2-C6 alkenyl, C2-C6 haloalkenyl, C5-C10
cycloalkenyl, C5-C10 halocycloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, phenyl, phenyl
substituted with (Z)m, or D-1 to D-38,
R11 is Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R28, C3-C8 cycloalkyi, C3-
25 Ce halocycloalkyi, C3-C6 alkenyl, C3-C6 haloalkenyl, C5-C10 cycloalkenyl, C5-C10
halocycloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, phenyl, phenyl substituted with (Z)m,
D-1, D-2, D-4 to D-6, D-8 to D-10, D-12 to D-19, D-21, D-23, D-25, D-27 or D-30 to D-
38,
R12 is a hydrogen atom, Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R28,
30 C3-C8 cycloalkyi, C3-C8 halocycloalkyi, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl,
C3-C6 haloalkynyl, Ci-Ce alkylcarbonyl, Ci-Ce haloalkylcarbonyl, phenylcarbonyl, Ci-Ce
alkoxycarbonyl, phenyl, phenyl substituted with (Z)m, D-1 to D-25 or D-27 to D-38, or
may form the after-mentioned ring together with R13,
R13 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl(Ci-C4)alkyl,
35 C1-C4 alkoxy(Ci-C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 alkylsulfonyl(Ci-C4)alkyl,
cyano(Ci-C4)alkyl, C3-C6 alkenyl or C3-C6 alkynyl,
or R13 may form, together with R12, a C2-C6 alkylene chain to form a 3- to 7-
membered ring together with the nitrogen atom attached to R12 and R13, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
40 optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy
group, a -CHO group, a C1-C4 alkylcarbonyl group or a C1-C4 alkoxycarbonyl group,
R14 is Ci-Ce alkyl, C1-C6 haloalkyl, Ci-Ce alkoxy, phenyl or phenyl substituted with
(Z)m,
each of R14a and R14b is independently Ci-Ce alkyl, Ci-Ce haloalkyl or Ci-Ce
45 alkoxy,
R15 is a hydrogen atom, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl(Ci-
C4)alkyl, hydroxy(Ci-C4)alkyl, C1-C4 alkoxy(Ci-C4)alkyl, C1-C4 haloalkoxy(Ci-C4)alkyl,
C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 haloalkylthio(Ci-C4)alkyl, C1-C4 alkylamino(Ci12
C4)alkyl, di(Ci-C4 alkyl)amino(Ci-C4)alkyl, cyano(Ci-C4)alkyl, C1-C4 alkoxycarbonyl(Ci-
C4)alkyl, C1-C4 haloalkoxycarbonyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl
substituted with (Z)m, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl,
C2-C6 haloalkynyl, C1-C6 alkylcarbonyl, phenylcarbonyl, phenylcarbonyl substituted with
5 (Z)m, C1-C6 alkoxycarbonyl, C1-C6 haloalkoxycarbonyl, di(Ci-C6 alkyl)aminocarbonyl, Ci-
Ce alkylsulfonyl, phenylsulfonyl, phenylsulfonyl substituted with (Z)m, di(Ci-Ce
alkyl)aminosulfonyl, phenyl, phenyl substituted with (Z)m, or C1-C6 alkoxy,
and further, when R15 and Z are neighboring, the neighboring R15 and Z may form
-CH2CH2CH2CH2-, -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-
10 N=CH- or -CH=CH-CH=N- to form a 6-membered ring together with the atoms
respectively attached to R15 and Z, wherein hydrogen atoms on the respective ringconstituting
carbon atoms may optionally be substituted with a halogen atom, a methyl
group or a trifluoromethyl group,
R16 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl, C3-C6
15 halocycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, -
C(0)R10, -C(0)C(0)R11, -C(0)OR11, -C(0)C(0)OR11, -C(0)SR11, -C(0)N(R13)R12, -
C(S)OR11, -C(S)SR11, -C(S)N(R13)R12, -S(0)2R11, -S(0)2N(R13)R12, phenyl, phenyl
substituted with (Z)m or D-3,
R16a is a hydrogen atom, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6
20 alkylcarbonyl, C1-C6 haloalkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 haloalkoxycarbonyl,
C1-C6 alkylsulfonyl or C1-C6 haloalkylsulfonyl,
R17 is a halogen atom, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl, hydroxy(Ci-C4)alkyl,
C1-C4 alkoxy(Ci-C4) alkyl, C1-C4 alkoxycarbonyl(Ci-C4)alkyl, C1-C6 alkoxy, C1-C6
alkylthio, C1-C6 alkylamino, di(Ci-C6 alkyl)amino, C1-C6 alkoxycarbonyl, phenyl or
25 phenyl substituted with (Z)m,
when p is an integer of at least 2, the respective R17's may be identical with or
different from one another, and further, when two R17's are on the same carbon atom,
the two R17's together may form C1-C4 alkylidene, oxo, thioxo, imino, C1-C4 alkylimino or
C1-C4 alkoxyimino,
30 R18 is a halogen atom, cyano, nitro, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, E-1 to
E-22, C5-C10 cycloalkenyl, C5-C10 halocycloalkenyl, -OR29, -N(R30)R29, -SH, -S(0)rR31, -
S(0)t(R31)=NR16a, -C(0)R32, -C(R32)=NOH, -C(R32)=NOR33, -C(0)OH, -C(0)OR33, -
C(0)SR33, -C^NCR^R3 4 , -C(0)C(0)OR33, -C(S)OR33, -C(S)SR33, -C(S)N(R35)R34, -
S(0)2OH, -S(0)2OR33, -S(0)2N(R35)R34, -Si(R14a)(R14b)R14, M-1 to M-30, phenyl, phenyl
35 substituted with (Z)m or D-1 to D-38,
M-1 to M-30 are partial saturated heterocyclic rings represented by the following
structural formulae, respectively:
R19 is a halogen atom, cyano, nitro, C3-C8 cycloalkyi, E-5, E-6, E-14, E-15, C5-C10
cycloalkenyl, -OR36, -S(0)rR37, -C(R32)=NOH, -C(R32)=NOR33, M-3, -C(0)OR33, -
C(0)SR33, -C(0)NH2, M-7, M-17, -C(0)C(0)OR33, -C(S)OR33, -C(S)SR33, -C(S)NH2, M14
9, M-19, -S(0)2N(R35)R34 or-Si(R14a)(R14b)R14,
R20 is a hydrogen atom, C1-C6 alkyl, (Ci-Ce)alkyl optionally substituted with R28,
C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C5-C10
cycloalkenyl, C5-C10 halocycloalkenyl, C2-C6 alkynyl or C2-C6 haloalkynyl,
5 R21 is Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R28, Cs-Cs cycloalkyl, C3-
Cs halocycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C5-C10 cycloalkenyl, C5-C10
halocycloalkenyl, C3-C6 alkynyl or C3-C6 haloalkynyl,
R22 is a hydrogen atom, C1-C6 alkyl, (Ci-C6)alkyl optionally substituted with R28,
C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl,
10 C3-C6 haloalkynyl, C1-C6 alkylcarbonyl, C1-C6 haloalkylcarbonyl, phenylcarbonyl, C1-C6
alkoxycarbonyl, phenyl, phenyl substituted with (Z)m, D-1 to D-25 or D-27 to D-38, or
may form the after-mentioned ring together with R23,
R23 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl(Ci-C4)alkyl,
C1-C4 alkoxy(Ci-C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 alkylsulfonyl(Ci-C4)alkyl,
15 cyano(Ci-C4)alkyl, C3-C6 alkenyl or C3-C6 alkynyl,
or R23 may form, together with R22, a C2-C6 alkylene chain to form a 3- to 7-
membered ring together with the nitrogen atom attached to R22 and R23, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy
20 group, a -CHO group, a C1-C4 alkylcarbonyl group or a C1-C4 alkoxycarbonyl group,
R24 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C8 cycloalkyl, C3-C8
halocycloalkyl, C3-C8 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, -
S(0)2R33 or -S(0)2N(R35)R34, or may form the after-mentioned ring together with R25,
R25 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 alkenyl, C3-C6
25 haloalkenyl, C3-C6 alkynyl or C3-C6 haloalkynyl,
or R25 may form, together with R24, a C4-C5 alkylene chain to form a 5- to 6-
membered ring together with the nitrogen atom attached to R24 and R25, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl
30 group, a C1-C4 alkoxy group, a -CHO group, a C1-C4 alkylcarbonyl group, a C1-C4
alkoxycarbonyl group, an oxo group or a thioxo group,
R24a is a hydrogen atom, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, phenyl or
phenyl substituted with (Z)m, or may form the after-mentioned ring together with R25a,
R25a is a hydrogen atom, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio or di(Ci-C6
35 alkyl)amino,
or R25a may form, together with R24a, a C3-C5 alkylene chain to form a 4- to 6-
membered ring together with the carbon atom attached to R24a and R25a, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl
40 group, a -CHO group, a C1-C4 alkylcarbonyl group or a C1-C4 alkoxycarbonyl group,
R26 is C1-C12 alkyl, C1-C12 haloalkyl, C1-C12 alkoxy(Ci-Ci2)alkyl, cyano(Ci-
Ci2)alkyl, C1-C12 alkoxycarbonyl(Ci-Ci2)alkyl, phenyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl
substituted with (Z)m, C3-C12 alkenyl, C3-C12 haloalkenyl, C3-C12 alkynyl, C3-C12
haloalkynyl, C1-C12 alkylcarbonyl, C1-C12 alkoxycarbonyl, -C(0)ON=C(CH3)SCH3, -
45 C(0)ON=C(SCH3)C(0)N(CH3)2, phenyl or phenyl substituted with (Z)m, or may form the
after-mentioned ring together with R27,
R27 is C1-C12 alkyl, C1-C12 haloalkyl, C1-C12 alkoxy(Ci-Ci2 alkyl), cyano(Ci-Ci2)
alkyl, C1-C12 alkoxycarbonyl(Ci-Ci2)alkyl, phenyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl
15
substituted with (Z)m, C3-C12 alkenyl, C3-C12 haloalkenyl, C3-C12 alkynyl, C3-C12
haloalkynyl, phenyl or phenyl substituted with (Z)m,
or R27 may form, together with R26, a C4-C7 alkylene chain to form a 5- to 8-
membered ring together with the nitrogen atom attached to R26 and R27, wherein the
5 alkylene chain may contain an oxygen atom or sulfur atom, and may optionally be
substituted with a C1-C4 alkyl group or a C1-C4 alkoxy group,
R28 is a halogen atom, cyano, nitro, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C1-C6
alkoxy, Ci-Ce haloalkoxy, Ci-Ce alkylthio, Ci-Ce haloalkylthio, Ci-Ce alkylsulfinyl, Ci-Ce
haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, di(Ci-C6
10 alkyl)amino, C1-C6 alkoxycarbonyl, C1-C6 haloalkoxycarbonyl, -C(0)NH2, C1-C6
alkylaminocarbonyl, di(Ci-C6 alkyl)aminocarbonyl, -C(S)NH2, phenyl, phenyl substituted
with (Z)m, or D-1 to D-38,
R29 is a hydrogen atom, C-i-Cs alkyl, (Ci-Cs)alkyl optionally substituted with R38,
C3-C8 cycloalkyl, (Cs-Csjcycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14
15 to E-21, C3-C8 alkenyl, (C3-Cs)alkenyl optionally substituted with R38, C3-C8 alkynyl, (C3-
Cs)alkynyl optionally substituted with R38, -C(0)R39, -C(0)C(0)R40, -C(0)OR4°, -
C(0)C(0)OR4°, -C(0)SR40, -C(0)N(R42)R41, -C(S)R39, -C(S)OR40, -C(S)SR4°, -
C(S)N(R42)R41, -S(0)2R4°, -S(0)2N(R42)R41, -Si(R14a)(R14b)R14, -P(0)(OR43)2, -
P(S)(OR43)2, phenyl, phenyl substituted with (Z)m, D-1, D-2, D-4 to D-6, D-8 to D-10, D-
20 12 to D-19, D-21, D-23, D-25, D-27 or D-30 to D-38, or may form the after-mentioned
ring together with R30,
R30 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C4 cycloalkyl(Ci-C4)alkyl,
C1-C4 alkoxy(Ci-C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, cyano(Ci-C4)alkyl, Cs-Ce
cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, Ci-Ce haloalkylcarbonyl, Ci-Ce alkoxycarbonyl,
25 C1-C6 alkoxy, C1-C6 alkylsulfonyl, phenyl or phenyl substituted with (Z)m,
or R30 may form, together with R29, a C2-C6 alkylene chain to form a 3- to 7-
membered ring together with the nitrogen atom attached to R29 and R30, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl
30 group, a C1-C4 alkoxy group, a -CHO group, a C1-C4 alkylcarbonyl group, a C1-C4
alkoxycarbonyl group, a phenyl group, a phenyl group substituted with (Z)m, an oxo
group or a thioxo group,
R31 is Ci-Ce alkyl, (Ci-Cs)alkyl optionally substituted with R38, Cs-Cs cycloalkyl,
(C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14 to E-21, C3-C8
35 alkenyl, (C3-Cs)alkenyl optionally substituted with R38, C3-C8 alkynyl, (C3-Cs)alkynyl
optionally substituted with R38, -C(0)R39, -C(0)C(0)R40, -C(0)OR4°, -C(0)C(0)OR4°, -
C(0)SR40, -C(0)N(R42)R41, -C(S)R39, -C(S)OR40, -C(S)SR40, -C(S)N(R42)R41, -SH, Ci-Ce
alkylthio, Ci-Ce haloalkylthio, phenylthio, phenylthio substituted with (Z)m, -P(0)(OR43)2,
-P(S)(OR43)2, phenyl, phenyl substituted with (Z)m, D-9, D-10, D-12, D-14 to D-17, D-30
40 or D-32 to D-35,
R32 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl(Ci-C4)alkyl,
Ci-Ce alkoxy(Ci-C4)alkyl, Ci-Ce haloalkoxy(Ci-C4)alkyl, Ci-Ce alkylthio(Ci-C4)alkyl, Ci-
Ce haloalkylthio(Ci-C4)alkyl, Ci-Ce alkylsulfonyl(Ci-C4)alkyl, Ci-Ce haloalkylsulfonyl(Ci-
C4)alkyl, phenyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl substituted with (Z)m, C3-C6 cycloalkyl,
45 phenyl or phenyl substituted with (Z)m,
R33 is Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R38, Cs-Cs cycloalkyl,
(C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14 to E-21, C2-C6
alkenyl, (C2-Ce)alkenyl optionally substituted with R38, C3-C6 alkynyl, (C3-Ce)alkynyl
16
optionally substituted with R38, phenyl, phenyl substituted with (Z)m, D-1, D-2, D-4 to D-
6, D-8toD-10, D-12toD-19, D-21, D-23, D-25, D-27 or D-30 to D-38,
R34 is a hydrogen atom, C1-C6 alkyl, (Ci-Ce)alkyl optionally substituted with R38,
Cs-Cs cycloalkyi, (Cs-Csjcycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14
5 to E-21, C2-C6 alkenyl, (C2-Ce)alkenyl optionally substituted with R38, C3-C8 alkynyl, (C3-
C6)alkynyl optionally substituted with R38, phenyl, phenyl substituted with (Z)m, D-1 to
D25 or D-27 to D-38, or may form the after-mentioned ring together with R35,
R35 is a hydrogen atom, Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R38,
C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, phenyl or phenyl
10 substituted with (Z)m,
or R35 may form, together with R34, a C2-C5 alkylene chain to form a 3- to 6-
membered ring together with the nitrogen atom attached to R34 and R35, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy
15 group, a -CHO group, a C1-C4 alkylcarbonyl group, a C1-C4 alkoxycarbonyl group, a
phenyl group, a phenyl group substituted with (Z)m or an oxo group,
R36 is a hydrogen atom, Ci-Cs alkyl, (Ci-Cs)alkyl optionally substituted with R38,
Cs-Cs cycloalkyi, (C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14
to E-21, C3-C8 alkenyl, (C3-Cs)alkenyl optionally substituted with R38, C3-C8 alkynyl, (C3-
20 Cs)alkynyl optionally substituted with R38, -C(0)R39, -C(0)C(0)R40, -C(0)OR40, -
C(0)C(0)OR4°, -C(0)SR40, -C(0)N(R42)R41, -C(S)R39, -C(S)OR40, -C(S)SR4°, -
C(S)N(R42)R41, -S(0)2R4°, -S(0)2N(R42)R41, -Si(R14a)(R14b)R14, -P(0)(OR43)2 or-
P(S)(OR43)2,
R37 is Ci-Cs alkyl, (Ci-Cs)alkyl optionally substituted with R38, Cs-Cs cycloalkyi,
25 (C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14 to E-21, Cs-Cs
alkenyl, (C3-Cs)alkenyl optionally substituted with R38, C3-C8 alkynyl, (C3-Cs)alkynyl
optionally substituted with R38, -C(0)R39, -C(0)C(0)R40, -C(0)OR40, -C(0)C(0)OR40, -
C(0)SR40, -C(0)N(R42)R41, -C(S)R39, -C(S)OR40, -C(S)SR40, -C(S)N(R42)R41, -SH, Ci-Ce
alkylthio, Ci-Ce haloalkylthio, phenylthio, phenylthio substituted with (Z)m, -P(0)(OR43)2
30 or -P(S)(OR43)2,
R38 is a halogen atom, cyano, nitro, C3-C8 cycloalkyi, C3-C8 halocycloalkyl, E-5, E-
6, E-9, E-10, E-12, E-14, E-15, E-18, E-19, E-21, -OH, -OR40, -OC(0)R39, -OC(0)OR40,
-OC(0)N(R42)R41, -OC(S)N(R42)R41, -SH, -S(0)rR4°, -SC(0)R39, -SC(0)OR40, -
SC(0)N(R42)R41, -SC(S)N(R42)R41, -N(R42)R41, -N(R42)C(0)R39, -N(R42)C(0)OR40, -
35 N(R42)C(0)SR40, -N(R42)C(0)N(R42)R41, -N(R42)C(S)N(R42)R41, -N(R42)S(0)2R4°, -
C(0)R39, -C(0)OH, -C(0)OR40, -C(0)SR40, -C(0)N(R42)R41, -C(0)C(0)OR40, -C(S)SR40,
-C(S)N(R42)R41, -Si(R14a)(R14b)R14, -P(0)(OR43)2, -P(S)(OR43)2, -P(phenyl)2, -
P(0)(phenyl)2, phenyl, phenyl substituted with (Z)m, or D-1 to D-38,
R39 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, (Ci-C4)alkyl optionally
40 substituted with R44, C3-C6 cycloalkyi, C3-C6 halocycloalkyl, E-5, E-6, E-14, E-15, C2-C8
alkenyl, C2-C8 haloalkenyl, C5-C10 cycloalkenyl, C5-C10 halocycloalkenyl, C2-C8 alkynyl,
C2-C8 haloalkynyl, phenyl, phenyl substituted with (Z)m, or D-1 to D-38,
R40 is Ci-Ce alkyl, Ci-Ce haloalkyl, (Ci-C4)alkyl optionally substituted with R44, C3-
Ce cycloalkyi, E-5, E-6, C2-C8 alkenyl, C2-C8 haloalkenyl, C3-C8 alkynyl or phenyl,
45 R41 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, (Ci-C4)alkyl optionally
substituted with R44, C3-C6 cycloalkyi, E-5, E-6, E-14, C2-C8 alkenyl, C2-C8 haloalkenyl,
C3-C8 alkynyl, phenyl, phenyl substituted with (Z)m, D-1 to D-25 or D-27 to D-38, or may
form the after-mentioned ring together with R42,
17
R42 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C8 cycloalkyl, C3-C6
alkenyl or C3-C6 alkynyl,
or R42 may form, together with R41, a C2-C5 alkylene chain to form a 3- to 6-
membered ring together with the nitrogen atom attached to R41 and R42, wherein the
5 alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy
group, a -CHO group, a C1-C4 alkylcarbonyl group, a C1-C4 alkoxycarbonyl group, a
phenyl group or a phenyl group substituted with (Z)m,
R43 is Ci-Ce alkyl or Ci-Ce haloalkyl,
10 R44 is cyano, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, E-5, E-6, E-14, E-15, C1-C4
alkoxy, C1-C4 haloalkoxy, phenoxy, phenoxy substituted with (Z)m, C1-C4 alkylthio, C1-C4
haloalkylthio, phenylthio, phenylthio substituted with (Z)m, C1-C4 alkylsulfonyl, C1-C4
haloalkylsulfonyl, phenylsulfonyl, phenylsulfonyl substituted with (Z)m, -N(R46)R45, C1-C4
alkylcarbonyl, C1-C4 haloalkylcarbonyl, C1-C4 alkoxycarbonyl, C1-C4 alkylaminocarbonyl,
15 di(Ci-C4 alkyl)aminocarbonyl, tri(Ci-C4 alkyl)silyl, phenyl, phenyl substituted with (Z)m,
or D-1 to D-38,
R45 is a hydrogen atom, C1-C4 alkyl, C1-C4 alkylcarbonyl, C1-C4 haloalkylcarbonyl,
C1-C4 alkoxycarbonyl, phenylcarbonyl or phenylcarbonyl substituted with (Z)m,
R46 is a hydrogen atom or C1-C4 alkyl,
20 m is an integer of 1, 2, 3, 4 or 5,
n is an integer of 0, 1, 2, 3 or 4,
p is an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9,
r is an integer of 0, 1 or 2, and
t is an integer of 0 or 1.
25 Further, the present invention relates to all stereoisomers thereof, its intermediate,
and a pesticide containing it as an active ingredient.
ADVANTAGEOUS EFFECTS OF INVENTION
The compound of the present invention represented by the formula (I) and the
30 pesticide containing the compound as an active ingredient have excellent controlling
effect on pests, especially fungi and nematodes in agricultural fields or
zootechnical/hygienic fields, and have sufficient controlling effect on pests which have
acquired resistance to conventional pesticides. Further, they have little harmful effect
on non-target organisms such as plants, mammals, fishes, useful insects and natural
35 enemies, show low persistence and are environmentally friendly.
Thus, the present invention can provide useful novel pesticides.
DESCRIPTION OF EMBODIMENT(S)
The oxime-substituted amide compounds of the present invention represented by
40 the formula (I) can have geometrical isomers such as E-isomers and Z-isomers, and the
present invention covers both E-isomers and Z-isomers and mixtures containing them in
any ratios. The compounds of the present invention can have optically active isomers
due to the presence of one or more asymmetric carbon atoms depending on the types
of substituents in them, and the present invention covers any optically active isomers
45 and any racemates.
As a halogen atom herein, a fluorine atom, a chlorine atom, a bromine atom or an
iodine atom may be mentioned. Herein, the expression "halo" also means such a
halogen atom.
18
In the specific description of the substituents herein, the expression "n-" denotes
"normal", V "iso", "s-" "secondary", "tert-" "tertiary", and "Ph" "phenyl".
The expression "Ca-Cb alkyl" herein means a linear or branched hydrocarbon
group containing from a to b carbon atoms such as a methyl group, an ethyl group, a n-
5 propyl group, an i-propyl group, a n-butyl group, an i-butyl group, a s-butyl group, a tertbutyl
group, a pentyl group, a 1 -ethylpropyl group, a 2,2-dimethylpropyl group or a hexyl
group, and those within the designated carbon number range are selected.
The expression "Ca-Cb haloalkyl" herein means a linear or branched hydrocarbon
group containing from a to b carbon atoms in which hydrogen atom(s) on carbon
10 atom(s) are optionally substituted with halogen atom(s) which may be identical with or
different from one another if two or more halogen atoms are present, such as a
fluoromethyl group, a chloromethyl group, a bromomethyl group, an iodomethyl group, a
difluoromethyl group, a dichloromethyl group, a trifluoromethyl group, a
chlorodifluoromethyl group, a trichloromethyl group, a bromodifluoromethyl group, a 1-
15 fluoroethyl group, a 2-fluoroethyl group, a 2-chloroethyl group, a 2-bromoethyl group, a
2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 2-chloro-2,2-difluoroethyl group, a
2,2,2-trichloroethyl group, a 2-bromo-2,2-difluoroethyl group, a 1,1,2,2-tetrafluoroethyl
group, a 2-chloro-1,1,2-trifluoroethyl group, a pentafluoroethyl group, a 2,2-
difluoropropyl group, a 3,3,3-trifluoropropyl group, a 3-bromo-3,3-difluoropropyl group, a
20 2,2,3,3-tetrafluoropropyl group, a 2,2,3,3,3-pentafluoropropyl group, a 1,1,2,3,3,3-
hexafluoropropyl group, a heptafluoropropyl group, a 2,2,2-trifluoro-1-(methyl)ethyl
group, a2,2,2-trifluoro-1-(trifluoromethyl)ethyl group, a 1,2,2,2-tetrafluoro-1-
(trifluoromethyl)ethyl group, a 2,2,3,4,4,4-hexafluorobutyl group, a 2,2,3,3,4,4,4-
heptafluorobutyl group or a nonafluorobutyl group, and those within the designated
25 carbon number range are selected.
The expression "Ca-Cb cycloalkyl" herein means a cyclic hydrocarbon group
containing from a to b carbon atoms in the form of a 3- to 10-membered monocyclic or
polycyclic ring which may optionally be substituted with an alkyl group as long as the
number of carbon atoms does not exceed the designated carbon number range, such
30 as a cyclopropyl group, a 1 -methylcyclopropyl group, a 2-methylcyclopropyl group, a
2,2-dimethylcyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl
group, and those within the designated carbon number range are selected.
The expression "Ca-Cb halocycloalkyl" herein means a cyclic hydrocarbon group
containing from a to b carbon atoms in the form of a 3- to 10-membered monocyclic or
35 polycyclic ring which may optionally be substituted with an alkyl group as long as the
number of carbon atoms does not exceed the designated carbon number range, in
which hydrogen atom(s) on carbon atom(s) in a ring moiety and/or in a side chain are
optionally substituted with halogen atom(s) which may be identical with or different from
one another if two or more halogen atoms are present, such as a 2,2-difluorocyclopropyl
40 group, a 2,2-dichlorocyclopropyl group, a 2,2-dibromocyclopropyl group, a 2,2-difluoro-
1-methylcyclopropyl group, a 2,2-dichloro-1-methylcyclopropyl group, a 2,2-dibromo-1-
methylcyclopropyl group or a 2,2,3,3-tetrafluorocyclobutyl group, and those within the
designated carbon atom range are selected.
The expression "Ca-Cb alkenyl" herein means a linear or branched unsaturated
45 hydrocarbon group containing from a to b carbon atoms and having one or more double
bonds in the molecule such as a vinyl group, a 1-propenyl group, a 2-propenyl group, a
1-methylethenyl group, a 1-butenyl group, a 2-butenyl group, a 1-methyl-1-propenyl
group, a 2-methyl-1-propenyl group, a 2-methyl-2-propenyl group or a 3-methyl-2-
19
butenyl group, and those within the designated carbon atom range are selected.
The expression "Ca-Cb haloalkenyl" herein means a linear or branched
unsaturated hydrocarbon group containing from a to b carbon atoms and having one or
more double bonds in the molecule, in which hydrogen atom(s) on carbon atom(s) are
5 optionally substituted with halogen atom(s) which may be identical with or different from
one another if two or more halogen atoms are present, such as a 2-fluorovinyl group, a
2-chlorovinyl group, a 1,2-dichlorovinyl group, a 2,2-dichlorovinyl group, a 2-fluoro-2-
propenyl group, a 2-chloro-2-propenyl group, a 3-chloro-2-propenyl group, a 3,3-
difluoro-2-propenyl group, a 2,3-dichloro-2-propenyl group, a 3,3-dichloro-2-propenyl
10 group, a 2,3,3-trifluoro-2-propenyl group, a 2,3,3-trichloro-2-propenyl group, a 1-
(trifluoromethyl)ethenyl group, a 4,4-difluoro-3-butenyl group, a 3,4,4-trifluoro-3-butenyl
group, a 2,4,4,4-tetrafluoro-2-butenyl group or a 3-chloro-4,4,4-trifluoro-2-butenyl group,
and those within the designated carbon atom range are selected.
The expression "Ca-Cb cycloalkenyl" herein means a cyclic unsaturated
15 hydrocarbon group containing from a to b carbon atoms and containing one or more
endo- or exo-double bonds in the form of a 3- to 10-membered monocyclic or polycyclic
ring which may optionally be substituted with an alkyl group as long as the number of
carbon atoms does not exceed the designated carbon number range, such as a 1-
cyclopentenyl group, a 2-cyclopentenyl group, a 1-cyclohexenyl group, a 2-cyclohexenyl
20 group or a bicyclo[2.2.1 ]-5-hepten-2-yl group, and those within the designated carbon
atom range are selected.
The expression "Ca-Cb halocycloalkenyl" herein means a cyclic unsaturated
hydrocarbon group containing from a to b carbon atoms and containing one or more
endo- or exo-double bonds in the form of a 3- to 10-membered monocyclic or polycyclic
25 ring which may optionally be substituted with an alkyl group as long as the number of
carbon atoms does not exceed the designated carbon number range, in which hydrogen
atom(s) on carbon atom(s) in the ring moiety and/or in the side chain are optionally
substituted with halogen atom(s) which may be identical with or different from one
another if two or more halogen atoms are present, such as a 2-fluoro-1-cyclopentenyl
30 group, a 2-chloro-1-cyclopentenyl group, a 3-chloro-2-cyclopentenyl group or a 2-fluoro-
1-cyclohexenyl group, and those within the designated carbon atom range are selected.
The expression "Ca-Cb alkylidene" herein means a linear or branched hydrocarbon
group containing from a to b carbon atoms which attaches by a double bond, such as a
methylidene group, an ethylidene group, a propylidene group or a 1-methylethylidene
35 group, and those within the designated carbon number range are selected.
The expression "Ca-Cb alkynyl" herein means a linear or branched unsaturated
hydrocarbon group containing from a to b carbon atoms and having one or more triple
bonds in the molecule such as an ethynyl group, a 1-propynyl group, a 2-propynyl group,
a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, a 1-methyl-2-propynyl group, a
40 2-pentynyl group or a 3-hexynyl group, and those within the designated carbon atom
range are selected.
The expression "Ca-Cb haloalkynyl" herein means a linear or branched
unsaturated hydrocarbon group containing from a to b carbon atoms and having one or
more triple bonds in the molecule, in which hydrogen atom(s) on carbon atom(s) are
45 optionally substituted with halogen atom(s) which may be identical with or different from
one another if two or more halogen atoms are present, such as a 2-chloroethynyl group,
a 2-bromoethynyl group, a 2-iodoethynyl group, a 3-chloro-2-propynyl group or a 3-
bromo-2-propynyl group or a 3-iodo-2-propynyl group, and those within the designated
20
carbon number range are selected.
The expression "Ca-Cb alkoxy" herein means an alkyl-O- group in which the alkyl
is a previously mentioned alkyl group containing from a to b carbon atoms, such as a
methoxy group, an ethoxy group, a n-propyloxy group, an i-propyloxy group, a n-
5 butyloxy group, an i-butyloxy group, a s-butyloxy group, a tert-butyloxy group, a
pentyloxy group or a hexyloxy group, and those within the designated carbon atom
range are selected.
The expression "Ca-Cb haloalkoxy" herein means a haloalkyl-O- group in which the
haloalkyl is a previously mentioned haloalkyl group containing from a to b carbon atoms,
10 such as a difluoromethoxy group, a trifluoromethoxy group, a chlorodifluoromethoxy
group, a bromodifluoromethoxy group, a 2-fluoroethoxy group, a 2-chloroethoxy group,
a 2,2,2-trifluoroethoxy group, a 1,1,2,2,-tetrafluoroethoxy group, a 2-chloro-1,1,2-
trifluoroethoxy group or a 1,1,2,3,3,3-hexafluoropropyloxy group, and those within the
designated carbon atom range are selected.
15 The expression "Ca-Cb alkenyloxy" herein means an alkenyl-O- group in which the
alkenyl is a previously mentioned alkenyl group containing from a to b carbon atoms,
such as a 2-propenyloxy group, a 2-butenyloxy group, a 2-methyl-2-propenyloxy group
or a 3-methyl-2-butenyloxy group, and those within the designated carbon atom range
are selected.
20 The expression "Ca-Cb alkylthio" herein means an alkyl-S- group in which the alkyl
is a previously mentioned alkyl group containing from a to b carbon atoms, such as a
methylthio group, an ethylthio group, a n-propylthio group, an i-propylthio group, a nbutylthio
group, an i-butylthio group, a s-butylthio group or a tert-butylthio group, and
those within the designated carbon atom range are selected.
25 The expression "Ca-Cb haloalkylthio" herein means a haloalkyl-S- group in which
the haloalkyl is a previously mentioned haloalkyl group containing from a to b carbon
atoms, such as a difluoromethylthio group, a trifluoromethylthio group, a
chlorodifluoromethylthio group, a bromodifluoromethylthio group, a 2,2,2-
trifluoroethylthio group, a 1,1,2,2-tetrafluoroethylthio group, a 2-chloro-1,1,2-
30 trifluoroethylthio group, a pentafluoroethylthio group, a 1,1,2,3,3,3-hexafluoropropylthio
group, a heptafluoropropylthio group, a 1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethylthio
group or a nonafluorobutylthio group, and those within the designated carbon atom
range are selected.
The expression "Ca-Cb alkylsulfinyl" herein means an alkyl-S(O)- group in which
35 the alkyl is a previously mentioned alkyl group containing from a to b carbon atoms,
such as a methylsulfinyl group, an ethylsulfinyl group, a n-propylsulfinyl group, an ipropylsulfinyl
group, a n-butylsulfinyl group, an i-butylsulfinyl group, a s-butylsulfinyl
group or a tert-butylsulfinyl group, and those within the designated carbon atom range
are selected.
40 The expression "Ca-Cb haloalkylsulfinyl" herein means a haloalkyl-S(O)- group in
which the haloalkyl is a previously mentioned haloalkyl group containing from a to b
carbon atoms, such as a difluoromethylsulfinyl group, a trifluoromethylsulfinyl group, a
chlorodifluoromethylsulfinyl group, a bromodifluoromethylsulfinyl group, a 2,2,2-
trifluoroethylsulfinyl group or a nonafluorobutylsulfinyl group, and those within the
45 designated carbon atom range are selected.
The expression "Ca-Cb alkylsulfonyl" herein means an alkyl-S(0)2- group in which
the alkyl is a previously mentioned alkyl group containing from a to b carbon atoms,
such as a methylsulfonyl group, an ethylsulfonyl group, a n-propylsulfonyl group, an i21
propylsulfonyl group, a n-butylsulfonyl group, an i-butylsulfonyl group, a s-butylsulfonyl
group or a tert-butylsulfonyl group, and those within the designated carbon atom range
are selected.
The expression "Ca-Cb haloalkylsulfonyl" herein means a haloalkyl-S(0)2- group in
5 which the haloalkyl is a previously mentioned haloalkyl group containing from a to b
carbon atoms, such as a difluoromethylsulfonyl group, a trifluoromethylsulfonyl group, a
chlorodifluoromethylsulfonyl group, a bromodifluoromethylsulfonyl group, a 2,2,2-
trifluoroethylsulfonyl group, a 1,1,2,2-tetrafluoroethylsulfonyl group or a 2-chloro-1,1,2-
trifluoroethylsulfonyl group, and those within the designated carbon atom range are
10 selected.
The expression "Ca-Cb alkylamino" herein means an amino group in which either
hydrogen atom is replaced by a previously mentioned alkyl group containing from a to b
carbon atoms, such as a methylamino group, an ethylamino group, a n-propylamino
group, an i-propylamino group, a n-butylamino group, an i-butylamino group or a tert-
15 butylamino group, and those within the designated carbon atom range are selected.
The expression "di(Ca-Cb alkyl)amino" herein means an amino group in which both
hydrogen atoms are replaced by previously mentioned alkyl groups containing from a to
b carbon atoms which may be identical with or different from each other, such as a
dimethylamino group, an ethyl(methyl)amino group, a diethylamino group, a di(n-
20 propyl)amino group or a di(n-butyl)amino group, and those within the designated carbon
atom range are selected.
The expression "Ca-Cb alkylimino" herein means an alkyl-N= group in which the
alkyl is a previously mentioned alkyl group containing from a to b carbon atoms, such as
a methylimino group, an ethylimino group, a n-propylimino group, an i-propylimino group,
25 a n-butylimino group, an i-butylimino group or a s-butylimino group, and those within the
designated carbon atom range are selected.
The expression "Ca-Cb alkoxyimino" herein means an alkoxy-N= group in which
the alkoxy is a previously mentioned alkoxy group containing from a to b carbon atoms,
such as a methoxyimino group, an ethoxyimino group, a n-propyloxyimino group, an i-
30 propyloxyimino group or a n-butyloxyimino group, and those within the designated
carbon atom range are selected.
The expression "Ca-Cb alkylcarbonyl" herein means an alkyl-C(O)- group in which
the alkyl is a previously mentioned alkyl group containing from a to b carbon atoms,
such as an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a
35 valeryl group, an isovaleryl group, a 2-methylbutanoyl group or a pivaloyl group, and
those within the designated carbon atom range are selected.
The expression "Ca-Cb haloalkylcarbonyl" herein means a haloalkyl-C(O)- group in
which the haloalkyl is a previously mentioned haloalkyl group containing from a to b
carbon atoms, such as a fluoroacetyl group, a chloroacetyl group, a difluoroacetyl group,
40 a dichloroacetyl group, a trifluoroacetyl group, a chlorodifluoroacetyl group, a
bromodifluoroacetyl group, a trichloroacetyl group, a pentafluoropropionyl group, a
heptafluorobutanoyl group or a 3-chloro-2,2-dimethylpropanoyl group, and those within
the designated carbon atom range are selected.
The expression "Ca-Cb cycloalkylcarbonyl" herein means a cycloalkyl-C(O)- group
45 in which the cycloalkyi is a previously mentioned cycloalkyi group containing from a to b
carbon atoms, such as a cyclopropylcarbonyl group, a cyclobutylcarbonyl group, a
cyclopentylcarbonyl group, a 2,2-dimethylcyclopropylcarbonyl group or a
cyclohexylcarbonyl group, and those within the designated carbon atom range are
22
selected.
The expression "Ca-Cb alkoxycarbonyl" herein means an alkyl-O-C(O)- group in
which the alkyl is a previously mentioned alkyl group containing from a to b carbon
atoms, such as a methoxycarbonyl group, an ethoxycarbonyl group, a n-
5 propyloxycarbonyl group, an i-propyloxycarbonyl group, a n-butoxycarbonyl group, an ibutoxycarbonyl
group or a tert-butoxycarbonyl group, and those within the designated
carbon atom range are selected.
The expression "Ca-Cb haloalkoxycarbonyl" herein means a haloalkyl-O-C(O)-
group in which the haloalkyl is a previously mentioned haloalkyl group containing from a
10 to b carbon atoms, such as a chloromethoxycarbonyl group, a 2-chloroethoxycarbonyl
group, a 2,2-difluoroethoxycarbonyl group, a 2,2,2-trifluoroethoxycarbonyl group or a
2,2,2-trichloroethoxycarbonyl group, and those within the designated carbon atom range
are selected.
The expression "Ca-Cb alkylaminocarbonyl" herein means a carbamoyl group in
15 which either hydrogen atom is replaced by a previously mentioned alkyl group
containing from a to b carbon atoms, such as a methylcarbamoyl group, an
ethylcarbamoyl group, a n-propylcarbamoyl group, an i-propylcarbamoyl group, a nbutylcarbamoyl
group, an i-butylcarbamoyl group, a s-butylcarbamoyl group or a tertbutylcarbamoyl
group, and those within the designated carbon atom range are selected.
20 The expression "Ca-Cb haloalkylaminocarbonyl" herein means a carbamoyl group
in which either hydrogen atom is replaced by a previously mentioned haloalkyl group
containing from a to b carbon atoms, such as a 2-fluoroethylcarbamoyl group, a 2-
chloroethylcarbamoyl group, a 2,2-difluoroethylcarbamoyl group or a 2,2,2-
trifluoroethylcarbamoyl group, and those within the designated carbon atom range are
25 selected.
The expression "di(Ca-Cb alkyl)aminocarbonyl" herein means a carbamoyl group in
which both hydrogen atoms are replaced by previously mentioned alkyl groups
containing from a to b carbon atoms which may be identical with or different from each
other, such as an N,N-dimethylcarbamoyl group, an N-ethyl-N-methylcarbamoyl group,
30 an N,N-diethylcarbamoyl group, an N,N-di(n-propyl)carbamoyl group or an N,N-di(nbutyl)
carbamoyl group, and those within the designated carbon atom range are selected.
The expression "di(Ca-Cb alkyl)aminosulfonyl" herein means a sulfamoyl group in
which both hydrogen atoms are replaced by previously mentioned alkyl groups
containing from a to b carbon atoms which may be identical with or different from each
35 other, such as an N,N-dimethylsulfamoyl group, an N-ethyl-N-methylsulfamoyl group, an
N,N-diethylsulfamoyl group, an N,N-di(n-propyl)sulfamoyl group or an N,N-di(nbutyl)
sulfamoyl group, and those within the designated carbon atom range are selected.
The expression "tri(Ca-Cb alkyl)silyl" herein means a silyl group replaced by
previously mentioned alkyl groups containing from a to b carbon atoms which may be
40 identical with or different from one another, such as a trimethylsilyl group, a triethylsilyl
group, a tri(n-propyl)silyl group, an ethyldimethylsilyl group, a n-propyldimethylsilyl
group, a n-butyldimethylsilyl group, an i-butyldimethylsilyl group or a tertbutyldimethylsilyl
group, and those within the designated carbon atom range are
selected.
45 The expression "Ca-Cb alkylsulfonyloxy" herein means an alkylsulfonyl-O- group in
which the alkylsulfonyl is a previously mentioned alkylsulfonyl group containing from a
to b carbon atoms, such as a methylsulfonyloxy group, an ethylsulfonyloxy group, a npropylsulfonyloxy
group or an i-propylsulfonyloxy group, and those within the
23
designated carbon atom range are selected.
The expression "Ca-Cb haloalkylsulfonyloxy" herein means a haloalkylsulfonyl-Ogroup
in which the haloalkylsulfonyl is a previously mentioned haloalkylsulfonyl group
containing from a to b carbon atoms, such as a difluoromethylsulfonyloxy group, a
5 trifluoromethylsulfonyloxy group, a chlorodifluoromethylsulfonyloxy group or a
bromodifluoromethylsulfonyloxy group, and those within the designated carbon atom
range are selected.
The expression such as "Ca-Cb cycloalkyl(Cd-Ce)alkyl", "hydroxy(Cd-Ce)alkyl", "Ca-
Cb alkoxy(Cd-Ce)alkyl", "Ca-Cb haloalkoxy(Cd-Ce)alkyl", "Ca-Cb alkylthio(Cd-Ce)alkyl", "Ca-
1 o Cb haloalkylthio(Cd-Ce)alkyl", "Ca-Cb alkylsulfinyl(Cd-Ce)alkyl", "Ca-Cb
haloalkylsulfinyl(Cd-Ce)alkyl", "Ca-Cb alkylsulfonyl(Cd-Ce)alkyl", "Ca-Cb
haloalkylsulfonyl(Cd-Ce)alkyl", "Ca-Cb alkylamino(Cd-Ce)alkyl", "di(Ca-Cb alkyl)amino(Cd-
Ce)alkyl", "cyano(Cd-Ce)alkyl", "Ca-Cb alkoxycarbonyl(Cd-Ce)alkyl", "Ca-Cb
haloalkoxycarbonyl(Cd-Ce)alkyl", "phenyl(Cd-Ce)alkyl" or "phenyl(Cd-Ce)alkyl substituted
15 with (Z)m" herein means a previously mentioned alkyl group containing from d to e
carbon atoms in which hydrogen atom(s) on carbon atom(s) are optionally substituted
with previously mentioned optional Ca-Cb cycloalkyl group, Ca-Cb alkoxy group, Ca-Cb
haloalkoxy group, Ca-Cb alkylthio group, Ca-Cb haloalkylthio group, Ca-Cb alkylsulfinyl
group, Ca-Cb haloalkylsulfinyl group, Ca-Cb alkylsulfonyl group, Ca-Cb haloalkylsulfonyl
20 group, Ca-Cb alkylamino group, di(Ca-Cb alkyl)amino group, Ca-Cb alkoxycarbonyl group,
Ca-Cb haloalkoxycarbonyl group, hydroxy group, cyano group, phenyl group or phenyl
group substituted with (Z)m, and those within the designated carbon atom range are
selected.
The expression such as "hydroxy(Cd-Ce)cycloalkyl" or "Ca-Cb alkoxy(Cd-
25 Ce)cycloalkyl" herein means a previously mentioned cycloalkyl group containing from d
to e carbon atoms in which hydrogen atom(s) on carbon atom(s) are optionally
substituted with previously mentioned optional Ca-Cb alkoxy group(s) or hydroxy
group(s), and those within the designated carbon atom range are selected.
The expression "phenyl(Ca-Cb)alkynyl" herein means a previously mentioned
30 alkynyl group containing from a to b carbon atoms in which hydrogen atom(s) on carbon
atom(s) are optionally substituted with phenyl group(s), and those within the designated
carbon atom range are selected.
The expression such as "(Ca-Cb) alkyl optionally substituted with R6", "(Ca-Cb) alkyl
optionally substituted with R18", "(Ca-Cb) alkyl optionally substituted with R19", "(Ca-Cb)
35 alkyl optionally substituted with R28", "(Ca-Cb) alkyl optionally substituted with R38" or
"(Ca-Cb) alkyl optionally substituted with R44" herein means a previously mentioned alkyl
group containing from a to b carbon atoms in which hydrogen atom(s) on carbon
atom(s) are optionally substituted with optional R6, R18, R19, R28, R38 or R44, and those
within the designated carbon atom range are selected. When there are two or more
40 R6's, R18's, R19's, R28's, R38's or R^'s on a (Ca-Cb) alkyl group, each R6, R18, R19, R28,
R38 or R44 may be identical with or different from one another.
The expression such as "(Ca-Cb) cycloalkyl optionally substituted with R6", "(Ca-Cb)
cycloalkyl optionally substituted with R28" or "(Ca-Cb) cycloalkyl optionally substituted
with R38" herein means a previously mentioned cycloalkyl group containing from a to b
45 carbon atoms in which hydrogen atom(s) on carbon atom(s) in the ring moiety and/or in
the side chain are optionally substituted with optional R6, R28 or R38, and those within
the designated carbon atom range are selected. When there are two or more R6's,
R28's or R38's on a (Ca-Cb) cycloalkyl group, each R6, R28 or R38 may be identical with or
24
different from one another.
The expression such as "(Ca-Cb) alkenyl optionally substituted with R6", "(Ca-Cb)
alkenyl optionally substituted with R28" or "(Ca-Cb) alkenyl optionally substituted with R38"
herein means a previously mentioned alkenyl group containing from a to b carbon
5 atoms in which hydrogen atom(s) on carbon atom(s) are optionally substituted with
optional R6, R28 or R38, and those within the designated carbon atom range are selected.
When there are two or more R6's, R28's or R38's on a (Ca-Cb) alkenyl group, each R6, R28
or R38 may be identical with or different from one another.
The expression such as "(Ca-Cb) alkynyl optionally substituted with R6", "(Ca-Cb)
10 alkynyl optionally substituted with R28" or "(Ca-Cb) alkynyl optionally substituted with R38"
herein means a previously mentioned alkynyl group containing from a to b carbon
atoms in which hydrogen atom(s) on carbon atom(s) are optionally substituted with
optional R6, R28 or R38, and those within the designated carbon atom range are selected.
When there are two or more R6's, R28's or R38's on a (Ca-Cb) alkynyl group, each R6, R28
15 or R38 may be identical with or different from one another.
The expression "R3 may form, together with R2, a C2-C5 alkylene chain to form a
3- to 6-membered ring together with the carbon atom attached to R2 and R3, wherein
the alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom" is
specifically exemplified by a cyclopropane ring, a cyclobutane ring, a cyclopentane ring,
20 a tetrahydrofuran ring, a tetrahydrothiophene ring, a pyrrolidine ring, a cyclohexane ring,
a tetrahydropyran ring, a tetrahydrothiopyran ring, a piperidine ring, a cycloheptane ring,
an oxepane ring, a thiepane ring, an azepane ring or the like, and those within the
designated carbon atom range are selected.
The expression such as "R9 may form, together with R8, a C2-C6 alkylene chain to
25 form a 3- to 7-membered ring together with the nitrogen atom attached to R8 and R9,
wherein the alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom,
and may optionally be substituted with an oxo group or a thioxo group", "R25 and R24
together may form a C4-C5 alkylene chain to form a 5- to 6-membered ring together with
the nitrogen atom attached to R24 and R25, wherein the alkylene chain may contain an
30 oxygen atom, sulfur atom or nitrogen atom, and may optionally be substituted with an
oxo group or a thioxo group", "R30 may form, together with R29, a C2-C6 alkylene chain
to form a 3- to 7-membered ring together with the nitrogen atom attached to R29 and R30,
wherein the alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom,
and may optionally be substituted with an oxo group or a thioxo group" or "R35 may form,
35 together with R34, a C2-C5 alkylene chain to form a 3- to 6-membered ring together with
the nitrogen atom attached to R34 and R35, wherein the alkylene chain may contain an
oxygen atom, sulfur atom or nitrogen atom, and may optionally be substituted with an
oxo group" is specifically exemplified by aziridine, azetidine, azetidin-2-one, pyrrolidine,
pyrrolidin-2-one, oxazolidine, oxazolidin-2-one, oxazolidine-2-thione, thiazolidine,
40 thiazolidin-2-one, thiazolidine-2-thione, imidazolidine, imidazolidin-2-one, imidazolidine-
2-thione, piperidine, piperidin-2-one, piperidine-2-thione, 2H-3,4,5,6-tetrahydro-1,3-
oxazin-2-one, 2H-3,4,5,6-tetrahydro-1,3-oxazine-2-thione, morpholine, 2H-3,4,5,6-
tetrahydro-1,3-thiazin-2-one, 2H-3,4,5,6-tetrahydro-1,3-thiazine-2-thione, thiomorpholine,
thiomorpholine-1 -oxide, thiomorpholine-1,1-dioxide, perhydropyrimidin-2-one,
45 piperazine, homopiperidine, homopiperidin-2-one, heptamethyleneimine or the like, and
those within the designated carbon atom range are selected.
The expression such as "R13 may form, together with R12, a C2-C6 alkylene chain
to form a 3- to 7-membered ring together with the nitrogen atom attached to R12 and R13,
25
wherein the alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom",
"R23 may form, together with R22, a C2-C6 alkylene chain to form a 3- to 7-membered
ring together with the nitrogen atom attached to R22 and R23, wherein the alkylene chain
may contain an oxygen atom, sulfur atom or nitrogen atom", "R27 may form, together
5 with R26, a C4-C7 alkylene chain to form a 5- to 8-membered ring together with the
nitrogen atom attached to R26 and R27, wherein the alkylene chain may contain an
oxygen atom or sulfur atom" or "R42 may form, together with R41, a C2-C5 alkylene chain
to form a 3- to 6-membered ring together with the nitrogen atom attached to R41 and R42,
wherein the alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom"
10 is specifically exemplified by aziridine, azetidine, pyrrolidine, oxazolidine, thiazolidine,
imidazolidine, piperidine, morpholine, thiomorpholine, thiomorpholine-1 -oxide,
thiomorpholine-1,1 -dioxide, piperazine, homopiperidine, heptamethyleneimine or the
like, and those within the designated carbon atom range are selected.
The expression such as "R9a may form, together with R8a, a C4-C6 alkylene chain
15 to form a 5- to 7-membered ring together with the carbon atom attached to R8a and R9a,
wherein the alkylene chain may contain an oxygen atom or sulfur atom" or "R25a may
form, together with R24a, a C3-C5 alkylene chain to form a 4- to 6-membered ring
together with the carbon atom attached to R24a and R25a, wherein the alkylene chain
may contain an oxygen atom, sulfur atom or nitrogen atom" is specifically exemplified by
20 cyclopentylidene, tetrahydrofuran-3-ylidene, tetrahydrothiophen-3-ylidene,
cyclohexylidene, tetrahydropyran-3-ylidene, tetrahydropyran-4-ylidene,
tetrahydrothiopyran-3-ylidene, tetrahydrothiopyran-4-ylidene or the like, and those within
the designated carbon atom range are selected.
As the preferred range of the substituent represented by G1 in the compounds
25 which fall within the present invention, the following sets may, for example, be
mentioned.
G1-l: G1-1 [wherein X1 is a bromine atom, an iodine atom, methyl, difluoromethyl
or trifluoromethyl, and X2, X3, X4 and X5 are hydrogen atoms].
G1-ll: G1-1 [wherein X1 is a chlorine atom, and X2, X3, X4 and X5 are hydrogen
30 atoms].
G1-lll: G1-2 [wherein X1 is a halogen atom, methyl or trifluoromethyl, and X3, X4
and X5 are hydrogen atoms].
G1-IV: G1-3 [wherein X1 is a halogen atom or trifluoromethyl, and X2, X3 and X4
are hydrogen atoms].
35 G1-V: G1-7 [wherein X1 is trifluoromethyl, and X3 and X4 are hydrogen atoms].
G1-VI: G1-11 [wherein X1 is a halogen atom, methyl or trifluoromethyl, and X3
and X4 are hydrogen atoms].
G1-VII: G1-12 [wherein X1 is a halogen atom or trifluoromethyl, and X2 and X3 are
hydrogen atoms].
40 G1-VIII: G1-16 [wherein X1 is trifluoromethyl, X2 and X4 are hydrogen atoms, and
R5 is methyl].
G1-IX: G1-27 [wherein X1 is difluoromethyl or trifluoromethyl, X2 is a hydrogen
atom, and R5 is methyl].
G1-X: G1-33 [wherein X1 is difluoromethyl or trifluoromethyl, and X3 is methyl],
45 G1-XI: G1-1 [wherein X1 is nitro, and X2, X3, X4 and X5 are hydrogen atoms].
G1-XII: G1-1 [wherein X1 is trifluoromethyl, X2 and X3 are hydrogen atoms, X4 is a
halogen atom, and X5 is a hydrogen atom].
G1-XIII: G1-9 [wherein X1 is methyl or trifluoromethyl, X2 is a hydrogen atom, and
26
X3 is methyl].
G1-XIV: G1-27 [wherein X1 is a halogen atom or trifluoromethyl, X2 is a halogen
atom, and R5 is methyl].
G1-XV: G1-32 [wherein X1 and X3 are methyl].
5 G1-XVI: G1-50 [wherein X1 is trifluoromethyl, and r is 0].
G1-XVII: G1-1 [wherein X1 is a fluorine atom, cyano, C1-C4 alkoxy, C1-C4
haloalkoxy, C1-C4 alkylthio or phenyl, and X2, X3, X4 and X5 are hydrogen atoms].
G1-XVIII: G1-1 [wherein X1 is a halogen atom, methyl or trifluoromethyl, X2 is a
hydrogen atom or a halogen atom, X3 and X4 are hydrogen atoms, and X5 is a hydrogen
10 atom or a halogen atom].
G1-XIX: G1-2 [wherein X1 is a halogen atom, X3 is a hydrogen atom, X4 is
trifluoromethyl, and X5 is a hydrogen atom].
G1-XX: G1-4 [wherein X1 is trifluoromethyl, and X2, X3 and X5 are hydrogen
atoms].
15 G1-XXI: G1-8 [wherein X1 is a halogen atom or methyl, and X3 and X4 are
hydrogen atoms].
G1-XXII: G1-9 [wherein X1 is trifluoromethyl, X2 is a hydrogen atom, and X3 is
phenyl].
G1-XXIII: G1-13 [wherein X1 is a halogen atom, and X2 and X4 are hydrogen
20 atoms].
G1-XXIV: G1-20 [wherein X1 is trifluoromethyl, and X2 is a hydrogen atom].
G1-XXV: G1-30 [wherein X1 is trifluoromethyl, and X3 is methyl].
G1-XXVI: G1-33 [wherein X1 and X3 are trifluoromethyl].
G1-XXVII: G1-44 [wherein X1 is trifluoromethyl, and R5 is C1-C4 alkyl].
25 G1-XXVIII: G1-1 [wherein X1 is C1-C4 alkyl, C1-C4 haloalkyl, Ca-Ce cycloalkyl, C1-
C4 haloalkylthio, -NH2 or D-3, X2, X3, X4 and X5 are hydrogen atoms, and n is 0].
G1-XXIX: G1-2 [wherein X1 is difluoromethyl, and X3, X4 and X5 are hydrogen
atoms].
G1-XXX: G1-3 [wherein X1 is methyl, and X2, X3 and X4 are hydrogen atoms].
30 G1-XXXI: G1-5 [wherein X1 is trifluoromethyl, and X4 and X5 are hydrogen
atoms].
G1-XXXII: G1-7 [wherein X1 is a halogen atom or methyl, and X3 and X4 are
hydrogen atoms].
G1-XXXIII: G1-8 [wherein X1 is trifluoromethyl, and X3 and X4 are hydrogen
35 atoms].
G1-XXXIV: G1-9 and G1-12 [wherein X1 is difluoromethyl, and X2 and X3 are
hydrogen atoms].
G1-XXXV: G1-10 and G1-13 [wherein X1 is difluoromethyl or trifluoromethyl, and
X2 and X4 are hydrogen atoms].
40 G1-XXXVI: G1-11 [wherein X1 is difluoromethyl, and X3 and X4 are hydrogen
atoms].
G1-XXXVII: G1-16 [wherein X1 is difluoromethyl or trifluoromethyl, X2 and X4 are
hydrogen atoms, and R5 is C1-C4 alkyl].
G1-XXXVIII: G1-19 and G1-23 [wherein X1 is difluoromethyl or trifluoromethyl,
45 and X2 is a hydrogen atom].
G1-XXXIX: G1-27 [wherein X1 is a halogen atom, C1-C4 alkyl, C2-C4 haloalkyl or
C1-C4 alkoxy, X2 is a hydrogen atom, a fluorine atom or a chlorine atom, and R5 is C1-C4
alkyl].
27
G1-XL: G1-27 [wherein X1 is C1-C4 alkyl or C1-C4 haloalkyi, X2 is a hydrogen
atom, and R5 is C1-C4 alkyl, C1-C4 haloalkyi or C3-C6 cycloalkyl].
G1-XLI: G1-31 [wherein X1 is trifluoromethyl, and X3 is a halogen atom or methyl].
G1-XLII: G1-32 [wherein X1 is a halogen atom, difluoromethyl or trifluoromethyl,
5 and X3 is a hydrogen atom or methyl].
G1-XLIII: G1-33 [wherein X1 is a halogen atom, methyl, difluoromethyl or
trifluoromethyl, and X3 is a hydrogen atom, a halogen atom, C1-C4 alkyl, C1-C4 haloalkyi,
C3-C6 cycloalkyl, C1-C4 alkoxy or -NH2].
G1-XLIV: G1-41 and G1-43 [wherein X1 is trifluoromethyl].
10 G1-XLV: G1-45, G1-46, G1-49 and G1-51 [wherein X1 is methyl or trifluoromethyl].
G1-XLVI: G1-50 [wherein X1 is methyl or trifluoromethyl, and r is an integer of
from 0 to 2].
Among them, as the scope of the substituent represented by G\ more preferred
are G1-l to G1-XVI, G1-XXIX, G1-XXX, G1-XXXII to G1-XXXVII and G1-XLII, particularly
15 preferred are G1-l to G1-X.
As the preferred range of the substituent represented by G2 in the compounds
which fall within the present invention, the following sets may, for example, be
mentioned.
G2-l: G2-1 [wherein Y1 is a halogen atom, Y2 is a hydrogen atom, Y3 is a halogen
20 atom or methyl, and Y4 and Y5 are hydrogen atoms].
G2-ll: G2-2 [wherein Y1 is a halogen atom, Y2 is a hydrogen atom or a halogen
atom, Y3 is a halogen atom, cyano, trifluoromethyl, C1-C4 haloalkoxy, -C(R10)=NOR11,
C2-C6 alkynyl, cyclopropylethynyl, trimethylsilylethynyl or phenylethynyl, Y4 is a
hydrogen atom or a halogen atom, R10 is methyl, and R11 is methyl or ethyl].
25 G2-lll: G2-1 [wherein Y1 and Y2 are hydrogen atoms, Y3 is a halogen atom or
methyl, and Y4 and Y5 are hydrogen atoms].
G2-IV: G2-1 [wherein Y1 is a hydrogen atom, Y2 and Y3 together may form
-CH=CHCH=CH- to form a 6-membered ring together with the carbon atoms attached to
Y2 and Y3, and Y4 and Y5 are hydrogen atoms].
30 G2-V: G2-1 [wherein Y1 is a halogen atom, methyl, trifluoromethyl or methoxy, Y2
is a hydrogen atom or a halogen atom, Y3 is a hydrogen atom, a halogen atom, methyl,
trifluoromethyl, C1-C4 alkoxy, -C(R10)=NOR11, C2-C4 alkenyl, phenyl or D-7, Y4 is a
hydrogen atom or a halogen atom, Y5 is a hydrogen atom or a halogen atom, Z is
trifluoromethyl, R10 is methyl, R11 is methyl or ethyl, and n is 1].
35 G2-VI: G2-2 [wherein Y1 is a halogen atom, Y2 is a hydrogen atom, Y3 is methyl,
C1-C4 alkoxy, C2-C4 alkenyl, (C2-Ce)alkynyl substituted with R6, D-3 or D-7, Y4 is a
hydrogen atom, R6 is a halogen atom, C3-C6 cycloalkyl, -OH, trimethylsilyl or phenyl,
and n is 0].
G2-VII: G2-2 [wherein Y1 is a halogen atom, Y2 is cyano, Y3 is a halogen atom,
40 and Y4 is a hydrogen atom].
G2-VIII: G2-6 [wherein Y1 and Y3 are halogen atoms, and Y4 is a hydrogen atom].
G2-IX: G2-9 [wherein Y1 is a halogen atom, Y2 is a hydrogen atom or a halogen
atom, and Y3 is a halogen atom].
G2-X: G2-10 [wherein Y1 is a halogen atom, Y3 is a hydrogen atom or a halogen
45 atom, and Y4 is a hydrogen atom].
G2-XI: G2-1 [wherein Y1 and Y2 are hydrogen atoms, Y3 is C2-C4 alkyl, C1-C4
haloalkyi, C1-C4 haloalkoxy, phenoxy or phenyl, and Y4 and Y5 are hydrogen atoms].
G2-XII: G2-1 [wherein Y1 is a hydrogen atom, Y2 is a halogen atom or C1-C4
28
alkoxy, Y3 is a hydrogen atom or a halogen atom, Y4 is a hydrogen atom, a halogen
atom or trifluoromethyl, and Y5 is a hydrogen atom].
G2-XIII: G2-1 [wherein Y1 is a halogen atom, E-9 or -C(R10)=NOR11, Y2 is a
hydrogen atom, or Y2 may form, together with Y1, -CH=CHCH=CH- to form a 6-
5 membered ring together with the carbon atoms attached to Y1 and Y2, Y3 is a hydrogen
atom, a halogen atom, cyano, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, -
C(0)R10, M-7, phenyl substituted with (Z)m, D-3 or D-7, Y4 is a hydrogen atom or
trifluoromethyl, Y5 is a hydrogen atom, Z is trifluoromethoxy, R10 is a hydrogen atom or
C1-C4 alkyl, R11 is C1-C4 alkyl, R17 is methyl, m is 1, n is 0, and p is an integer of from 0
10 to 2.
G2-XIV: G2-2 [wherein Y1 is a hydrogen atom, a halogen atom, trifluoromethyl or
methoxy, Y2 is a hydrogen atom, Y3 is a halogen atom, C1-C4 haloalkyl, C1-C4
alkoxymethyl, -OR7 or D-22, Y4 is a hydrogen atom or methoxy, R7 is phenyl or phenyl
substituted with (Z)m, Z is a halogen atom, m is 1, and n is 0].
15 G2-XV: G2-3 [wherein Y1 is a halogen atom, each of Y3 and Y4 is independently a
hydrogen atom or a halogen atom, and Y5 is a hydrogen atom].
G2-XVI: G2-11 [wherein Y1 is a halogen atom, Y2 is C1-C4 alkoxy, and R5 is
methyl].
G2-XVII: G2-12 [wherein Y1 is trifluoromethyl, Y4 is a hydrogen atom, and R5 is
20 methyl].
G2-XVIII: G2-17 [wherein Y1 and Y3 are halogen atoms].
G2-XIX: G2-1 [wherein Y1 is a hydrogen atom, Y2 is a hydrogen atom, a halogen
atom, methyl, trifluoromethyl, C1-C4 alkoxy, C1-C4 haloalkoxy or phenoxy, Y3 is a
hydrogen atom, a halogen atom, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C3-C6
25 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy or C1-C4 haloalkylthio, or Y3 may form,
together with Y2, -OCH2O-, -OCH2CH2O- or -CH=CHCH=CH- to form a 5-membered
ring or a 6-membered ring together with the carbon atoms attached to Y2 and Y3,
wherein hydrogen atoms on the respective ring-constituting carbon atoms may
optionally be substituted with a halogen atom or methyl, Y4 is a hydrogen atom, a
30 halogen atom, methyl or trifluoromethyl, and Y5 is a hydrogen atom].
G2-XX: G2-1 [wherein Y1 is a halogen atom, methyl or trifluoromethyl, Y2 is a
hydrogen atom, Y3 is cyano, nitro, -OR7, -S(0)rR7, -C(R10)=NOR11, -C(0)NH2, -
C(S)NH2, C2-C6 alkynyl or (C2-Ce)alkynyl substituted with R6, Y4 and Y5 are hydrogen
atoms, R6 is a halogen atom, C3-C6 cycloalkyl, -OH, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3
35 alkylsulfinyl, C1-C3 alkylsulfonyl or -Si(R14a)(R14b)R14, R7 is C1-C4 haloalkyl, C2-C4
haloalkenyl, C3-C4 haloalkynyl, phenyl or phenyl substituted with (Z)m, R10 is a hydrogen
atom or C1-C4 alkyl, R11 is C1-C4 alkyl, R14 is C1-C4 alkyl or phenyl, each of R14a and
R14b is independently C1-C4 alkyl, Z is a halogen atom, m is 1, and r is an integer of from
0 to 2].
40 G2-XXI: G2-1 [wherein Y1 is a halogen atom, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4
alkoxymethyl, C1-C4 alkoxy, C1-C4 haloalkoxy, phenoxy or C1-C4 alkylthio, Y2 is a
hydrogen atom, methyl or methoxy, or Y2 may form, together with Y1, -OCH2O- or
-OCH2CH2O-, to form a 5-membered ring or a 6-membered ring together with the
carbon atoms attached to Y1 and Y2, wherein hydrogen atoms on the respective ring-
45 constituting carbon atoms may optionally be substituted with a halogen atom or methyl,
Y3 is a hydrogen atom, a halogen atom, cyano, nitro, methyl or trifluoromethyl, or Y3
may form, together with Y2, -OCH2O- or -OCH2CH2O- to form a 5-membered ring or a 6-
membered ring together with the carbon atoms attached to Y2 and Y3, wherein
29
hydrogen atoms on the respective ring-constituting carbon atoms may optionally be
substituted with a halogen atom or methyl, and Y4 and Y5 are hydrogen atoms].
G2-XXII: G2-1 [wherein Y1 is a halogen atom, methyl or methoxy, Y2 is a
hydrogen atom, Y3 is a hydrogen atom, a halogen atom, methyl or trifluoromethyl, Y4 is
5 a halogen atom, methyl or methoxy, or Y4 may form, together with Y3, -OCH2O- or -
OCH2CH2O-, to form a 5-membered ring or a 6-membered ring together with the carbon
atoms attached to Y3 and Y4, wherein hydrogen atoms on the respective ringconstituting
carbon atoms may optionally be substituted with a halogen atom or methyl,
and Y5 is a hydrogen atom].
10 G2-XXIII: G2-1 [wherein Y1 is a halogen atom, methyl or trifluoromethyl, Y2 is a
hydrogen atom or a halogen atom, Y3 is a hydrogen atom, a halogen atom, C1-C4 alkyl,
trifluoromethyl or methoxy, Y4 is a hydrogen atom, and Y5 is a halogen atom or methyl].
G2-XXIV: G2-2 [wherein Y1 is cyano, nitro, difluoromethoxy, trifluoromethoxy or
methylthio, Y2 is a hydrogen atom, Y3 is a halogen atom, C1-C4 alkyl or trifluoromethyl,
15 and Y4 is a hydrogen atom].
G2-XXV: G2-2 [wherein Y1 is a halogen atom, methyl or trifluoromethyl, Y2 is
cyano, methyl, C1-C4 alkoxy, C1-C4 haloalkoxy or C1-C4 alkylthio, Y3 is a halogen atom,
methyl or trifluoromethyl, and Y4 is a hydrogen atom].
G2-XXVI: G2-2 [wherein Y1 is a halogen atom, methyl or trifluoromethyl, Y2 is a
20 hydrogen atom, Y3 is a halogen atom, cyano, nitro, methyl, difluoromethyl,
trifluoromethyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, -N(R9)R8,
-C(R10)=NOR11, M-3, -C(0)NH2, -C(S)NH2, -S02N(CH3)2, C2-C6 alkynyl, (C2-C6)alkynyl
substituted with R6, D-11, D-28 or D-29, Y4 is a hydrogen atom, R6 is a halogen atom,
C3-C6 cycloalkyl, hydroxy(C3-C6)cycloalkyl, C3-C4 alkenyl, C5-C6 cycloalkenyl, -OH, C1-
25 C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, -
Si(R14a)(R14b)R14, phenyl, phenyl substituted with (Z)m, D-1, D-2, D-4, D-12 or D-32, R8
and R9 together may form a C4-C5 alkylene chain to form a 5- to 6-membered ring
together with the nitrogen atom attached to R8 and R9, wherein the alkylene chain may
contain an oxygen atom or sulfur atom, R10 is a hydrogen atom or C1-C4 alkyl, R11 is C1-
30 C4 alkyl, R14 is C1-C4 alkyl or phenyl, each of R14a and R14b is independently a C1-C4
alkyl, R17 is C1-C4 alkyl, Z is a halogen atom or C1-C4 alkyl, m is an integer of 1 or 2, n is
0, and p is an integer of from 0 to 2].
G2-XXVII: G2-3 [wherein Y1 is a halogen atom or methyl, Y3 is a halogen atom,
methyl, trifluoromethyl or methoxy, Y4 is a halogen atom or cyano, and Y5 is a hydrogen
35 atom].
G2-XXVIII: G2-4 [wherein Y1 is a halogen atom or methyl, Y2 is a hydrogen atom,
Y3 is a halogen atom or methoxy, and Y5 is a hydrogen atom].
G2-XXIX: G2-5 [wherein Y1 is a halogen atom, methyl, difluoromethyl or
trifluoromethyl, Y2 is a hydrogen atom, and Y3 is a halogen atom, methyl, trifluoromethyl
40 or methoxy].
G2-XXX: G2-6 [wherein each of Y1 and Y3 is independently a halogen atom or
methyl, and Y4 is a hydrogen atom or methyl].
G2-XXXI: G2-7 [wherein Y1, Y2 and Y3 are halogen atoms].
G2-XXXII: G2-9 [wherein Y1 is a halogen atom or methyl, Y2 is a hydrogen atom,
45 a halogen atom or methyl, Y3 is a halogen atom, or Y3 may form, together with Y2,
-CH=CHCH=CH- to form a 6-membered ring together with the carbon atoms attached to
Y2 and Y3, wherein hydrogen atoms on the respective ring-constituting carbon atoms
may optionally be substituted with a halogen atom].
30
G2-XXXI11: G2-10 [wherein Y1 is methyl, Y3 is a hydrogen atom, a halogen atom
or methyl, and Y4 is a hydrogen atom].
G2-XXXIV: G2-10 [wherein Y1 is a hydrogen atom or a halogen atom, Y3 is a
halogen atom, Y4 is a halogen atom, or Y4 may form, together with Y3,
5 -CH2CH2CH2CH2- or -CH=CHCH=CH- to form a 6-membered ring together with the
carbon atoms attached to Y3 and Y4, wherein hydrogen atoms on the respective ringconstituting
carbon atoms may optionally be substituted with a halogen atom].
G2-XXXV: G2-14 [wherein Y1 is methyl, and Y3 is trifluoromethyl].
G2-XXXVI: G2-16 and G2-17 [wherein Y1 is methyl, and Y3 is a halogen atom or
10 trifluoromethyl].
Among them, as the scope of the substituent represented by G2, more preferred
are G2-l to G2-X, G2-XX, G2-XXVIII, G2-XXIX and G2-XXX, particularly preferred are G2-l
and G2-ll.
In the compounds which fall within the present invention, the substituent
15 represented by W may be an oxygen atom or a sulfur atom, and W is preferably an
oxygen atom.
As the preferred range of the substituent represented by R1 in the compounds
which fall within the present invention, the following sets may, for example, be
mentioned.
20 R1-l: Ci-Ce alkyl, (Ci-C4)alkyl substituted with R18 [wherein R18 is Cs-Ce
cycloalkyl or trimethylsilyl], C3-C6 cycloalkyl, C3-C6 alkenyl and C3-C6 alkynyl.
R1-ll: C1-C4 haloalkyl, (Ci-C4)alkyl substituted with R18 [wherein R18 is phenyl,
phenyl substituted with (Z)m or D-32, Z is a halogen atom, cyano, nitro, methyl,
trifluoromethyl or trifluoromethoxy, when m is an integer of at least 2, the respective Z's
25 may be identical with or different from one another, m is an integer of from 1 to 3, and n
is 1], and C3-C4 haloalkenyl.
R1-lll: (Ci-C4)alkyl substituted with R18 [wherein R18 is cyano, E-5, C1-C4 alkoxy,
C1-C4 alkylthio, -C(R32)=NOR33, D-5 or D-10, R32 is methyl, R33 is methyl or ethyl, Z is a
halogen atom or methyl, n is an integer of 0 or 1, and p is 0], and phenyl.
30 R1-IV: (Ci-C4)alkyl substituted with R18 [wherein R18 is phenyl substituted with
(Z)m or D-32, Z is a halogen atom, C1-C4 alkyl, methoxy, trifluoromethylthio or phenyl,
when m and n are 2, the two Z's may be identical with or different from each other, and
when there are two neighboring Z's, the two neighboring Z's may form -CH=CHCH=
CH- to form a 6-membered ring together with the carbon atoms attached to the Z's,
35 m is an integer of 1 or 2, and n is an integer of from 0 to 2].
R1-V: (Ci-C4)alkyl substituted with R18 [wherein R18 is E-9, -C(R32)=NOR33, M-4,
C1-C4 alkoxycarbonyl, C1-C4 haloalkylaminocarbonyl or D-1, R32 is a hydrogen atom or
C1-C4 alkyl, R33 is C1-C4 alkyl, Z is methyl or trifluoromethyl, n is 1, and p is 0], E-2
[wherein p is 0] and E-14 [wherein p is 0].
40 R1-VI: C3-C6 halocycloalkyl and C3-C4 haloalkynyl.
R1-VII: E-3 [wherein p is 0, and r is an integer of from 0 to 2], E-4 [wherein R16 is
-C(0)R10 or -C(0)OR11, R10 is a hydrogen atom, C1-C4 alkyl or cyclopropyl, R11 is C1-C4
alkyl or C1-C4 haloalkyl, and p is 0], E-5 [wherein p is 0], E-6 [wherein p is 0, and r is an
integer of from 0 to 2], E-8 [wherein R16 is -C(0)R10 or -C(0)OR11, R10 is a hydrogen
45 atom, C1-C4 alkyl or cyclopropyl, R11 is C1-C4 alkyl or C1-C4 haloalkyl, and p is 0], E-15
[wherein p is 0, and r is an integer of from 0 to 2], and E-17 [wherein R16 is -C(0)R10 or -
C(0)OR11, R10 is a hydrogen atom, C1-C4 alkyl or cyclopropyl, R11 is C1-C4 alkyl or C1-
C4 haloalkyl, and p is 0].
31
R1-VIII: (Ci-C4)alkyl optionally substituted with R18 [wherein R18 is a halogen
atom, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy or C1-C4 alkylthio].
R1-IX: (Ci-C4)alkyl optionally substituted with R18 [wherein R18 is a halogen
atom, E-2 to E-4, E-6, E-8, M-3, -C(R32)=NOR33, -C(0)NH2 or -C(S)NH2, R16 is -C(0)R10
5 or -C(0)OR11, R10 is a hydrogen atom, C1-C4 alkyl or cyclopropyl, R11 is C1-C4 alkyl or
C1-C4 haloalkyl, R17 is C1-C4 alkyl, R32 is a hydrogen atom or methyl, R33 is C1-C4 alkyl
or C1-C4 haloalkyl, p is an integer of from 0 to 2, and r is an integer of from 0 to 2].
R1-X: (Ci-C4)alkyl optionally substituted with R18 [wherein R18 is a halogen atom,
phenyl substituted with (Z)m, D-2, D-4, D-6, D-8, D-9, D-12, D-14, D-15 or D-17, R15 is
10 methyl, Z is a halogen atom, methyl, ethyl, trifluoromethyl, difluoromethoxy, methylthio,
methylsulfinyl, methylsulfonyl, trifluoromethylsulfinyl or trifluoromethylsulfony, when m
and n are 2, the respective Z's may be identical with or different from each other, m is
an integer of 1 or 2, and n is an integer of from 0 to 2].
Among them, as the scope of the substituent represented by R1, more preferred
15 are R1-l to R1-IV, particularly preferred are R1-l and R1-ll.
As the preferred range of the substituent represented by R2 in the compounds
which fall within the present invention, the following sets may, for example, be
mentioned.
R2-l: A hydrogen atom.
20 R2-ll: Methyl
R2-lll Ethyl.
R2-IV: C3-C4 alkyl and phenyl.
R2-V: Fluoromethyl and trifluoromethyl.
R2-VI: Methoxymethyl, methylthiomethyl, methylsulfinylmethyl and
25 methylsulfonylmethyl.
R2-VII: Cyclopropyl and cyclobutyl.
Among them, as the scope of the substituted represented by R2, more preferred
are R2-l to R2-lll and R2-V, particularly preferred are R2-l and R2-ll.
As the scope of the substituent represented by R3 in the compounds which fall
30 within the present invention, the following sets may, for example, be mentioned.
R3-1: A hydrogen atom.
R3-ll: Methyl.
R3-III: R3 forms a cyclopropyl ring together with R2.
R3-IV: R3 forms, together with R2, a C3-C5 alkylene chain to form a 4- to 6-
35 membered ring together with the carbon atom attached to R2 and R3.
R3-V: C2-C4 alkyl.
R3-VI: R3 form, together with R2, a C2-C5 alkylene chain to form a 3- to 6-
membered ring together with the carbon atom attached to R2 and R3, wherein the
alkylene chain contains an oxygen atom or sulfur atom.
40 Among them, as the scope of the substituent represented by R3, more preferred
are R3-l to R3-III, and particularly preferred is R3-l.
As the scope of the substituent represented by R4 in the compounds which fall
within the present invention, the following sets may, for example, be mentioned.
R4-l: A hydrogen atom.
45 R4-ll: C1-C4 alkylcarbonyl.
R4-lll: C1-C4 alkoxycarbonyl.
R4-IV: C1-C4 haloalkylthio.
R4-V: C1-C4 alkyl, (Ci-C2)alkyl substituted with R19 [wherein R19 is cyano or C1-
32
C4 alkoxy], cyclopropyl, allyl and propargyl.
R4-VI: Ca-Ce cycloalkyl, C2-C4 alkenyl and C2-C4 alkynyl.
R4-VII: (Ci-C2)alkyl substituted with R19 [wherein R19 is -OR36, -C(0)NH2 or
-C(S)NH2, R36 is C2-C4 haloalkyi, C1-C4 alkylcarbonyl, Ca-Ce cycloalkylcarbonyl or C1-C4
5 alkoxycarbonyl].
R4-VIII: -C(0)R20 [wherein R20 is C1-C4 alkoxymethyl, C1-C4 alkylthiomethyl, C1-
C4 alkylsulfonylmethyl, C3-C4 cycloalkyl or C2-C4 alkenyl].
R4-IX: -C(0)OR21 [wherein R21 is C1-C4 haloalkyi, C1-C4 alkoxy(Ci-C2)alkyl, allyl
or propargyl].
10 R4-X: C1-C4 alkoxy.
Among them, as the scope of the substituent represented by R4, more preferred
are R4-l to R4-IV, particularly preferred is R4-l.
The sets indicating the preferred range of each substituent in the compounds
which fall within the present invention may be combined arbitrarily to indicate the
15 preferred range of the compounds of the present invention.
The preferred range of G\ G2, R1 and R2 of the compound represented by the
formula (I) may be combined, for example, as shown in Table 1. The combinations
shown in Table 1 merely exemplify the present invention, and the compound of the
present invention represented by the formula (I) is by no means restricted thereto.
Some of the compounds of the present invention represented by the formula (I)
5 can be converted, by ordinary methods, to acid addition salts with hydrogen halides
such as hydrofluoric acid, hydrochloric acid, hydrobromic acid and hydroiodic acid, with
inorganic acids such as nitric acid, sulfuric acid, phosphoric acid, chloric acid and
perchloric acid, with sulfonic acids such as methanesulfonic acid, ethanesulfonic acid,
trifluoromethanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid, with
10 carboxylic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid,
fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid, benzoic
acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid and citric acid, with amino
acids such as glutamic acid and aspartic acid.
Some of the compounds of the present invention represented by the formula (I)
15 can be converted, by ordinary methods, to metal salts with alkali metals such as lithium,
sodium and potassium, with alkaline earth metals such as calcium, barium and
magnesium, with metals such as aluminum.
The pesticides herein mean fungicides and parasiticides for controlling harmful
pathogens and parasites which infect/parasitize plants or animals.
20 Plants herein mean grain, fruits and vegetables, cultivated as food for human,
feed crop for livestock and poultry, ornamental plants of which appearances are
enjoyed, or Tracheophyta such as planting of parks, streets and the like, and
specifically, the following plants may, for example, be mentioned, but the present
invention is not restricted thereto.
25 Plants of the order Pinales belonging to the family Pinaceae such as Japanese
Red Pine (Pinus densiflora), Scots Pine (Pinus sylvestris), Japanese Black Pine (Pinus
thunberqii), etc.
Plants of the group Magnoliids belonging to the family Piperaceae such as pepper
(Piper nigrum), etc., the family Lauraceae such as Avocado (Persea americana), etc.
30 Plants of the group monocots belonging to the family Araceae such as Konjac
(Amorphophallus konjac), Eddoe (Colocasia esculenta), etc., the family Dioscoreaceae
such as Chinese yam (Dioscorea batatas), Japanese yam (Dioscorea iaponica), etc.,
37
the family Alliaceae such as Leek (Allium ampeloprasum var. porrum), Onion (Allium
cega), Rakkyo (Allium chinense), Welsh onion (Allium fistulosum), Garlic (Allium
sativum), Chives (Allium schoenoprasum). Chive (Allium schoenoprasum var. foliosum),
Oriental garlic (Allium tuberosum), Scallion (Allium x wakegi), etc., the family
5 Asparagaceae such as Asparagus (Asparagus officinalis), etc., the family Arecaceae
subfamily Arecoideae such as Coconut palm (Cocos nucifera), Oil palm (Elaeis
quineensis), etc., the family Arecaceae the subfamily Coryphoideae such as Date palm
(Phoenix dactyl if era), etc., the family Bromeliaceae such as Pineapple (Ananas
comosus), etc., the family Poaceae subfamily Ehrhartoideae such as Rice (Oryza
10 sativa), etc., the family Poaceae subfamily Pooideae such as Bent grass (Aqrostis spp.),
Blue grass (Poa spp.), Barley (Hordeum vulqare), Wheat (Triticum aestivum, T. durum),
Rye (Secale cereale), etc., the family Poaceae subfamily Chloridoideae such as
Bermuda grass (Cvnodon dactvlon), Grass (Zovsia spp.), etc., the family Poaceae
subfamily Panicoideae such as Sugarcane (Saccharum officinarum), Sorgum (Sorghum
15 bicolor), Corn (Zea mays), etc., the family Musaceae such as Banana (Musa spp.), etc.,
the family Zingiberaceae such as Myoga (Zingiber mioqa), Ginger (Zingiber officinale),
etc.
Plants of the group eudicots belonging to the family Nelumbonaceae such as
Lotus root (Nelumbo nucifera), etc., the family Fabaceae such as Peanut (Arachis
20 hypogaea). Chickpea (Cicer arietinum). Lentil (Lens culinaris). Pea (Pisum sativum),
Broad bean (Vicia faba). Soybean (Glycine max). Common bean (Phaseolus vulgaris),
Adzuki bean (Vigna angularis), Cowpea (Vigna unguiculata), etc., the family
Cannabaceae such as Hop (Humulus lupulus), etc., the family Moraceae such as Fig
Tree (Ficus carica), Mulberry (Moms spp.), etc., the family Rhamnaceae such as
25 Common jujube (Ziziphus jujuba), etc., the family Rosaceae subfamily Rosoideae such
as Strawberry (Fragaria), Rose (Rosa spp.), etc.,the family Rosaceae subfamily
Maloideae such as Japanese loquat (Eriobotrya iaponica), Apple (Malus pumila),
European Pear (Pyrus communis), Nashi Pear (Pyrus pvrifolia var. culta), etc., the
family Rosaceae subfamily Prunoideae such as Peach (Amygdalus persica), Apricot
30 (Prunus armeniaca), Cherry (Prunus avium), Prune (Prunus domestica), Almond
(Prunus dulcis), Japanese Apricot (Prunus mume), Japanese Plum (Prunus salicina),
Cerasus speciosa, Cerasus x yedoensis 'Somei-yoshino', etc., the family Cucurbitaceae
such as Winter melon (Benincasa hispida), Watermelon (Citrullus lanatus). Bottle gourd
(Lagenaria siceraria var. hispida), Luffa (Luffa cvlindrica), Pumpkin (Cucurbita spp.),
35 Zucchini (Cucurbita pepo), Bitter melon (Momordica charantia var. pavel), Muskmelon
(Cucumis melo), Oriental pickling melon (Cucumis melo var. conomon), Oriental melon
(Cucumis melo var. makuwa), Cucumber (Cucumis sativus), etc., the family Fagaceae
such as Japanese Chestnut (Castanea crenata), etc., the family Juglandaceae such as
Walnut (Juglans spp.), etc., the family Anacardiaceae such as Cashew (Anacardium
40 occidentale). Mango (Mangifera indica), Pistachio (Pistacia vera), etc., the family
Rutaceae subfamily Rutoideae such as Japanese pepper (Zanthoxvlum piperitum), etc.,
the family Rutaceae subfamily Aurantioideae such as Bitter orange (Citrus aurantium),
Lime (Citrus aurantifolia), Hassaku orange (Citrus hassaku), Yuzu (Citrus junos), Lemon
(Citrus limon), Natsumikan (Citrus natsudaidai). Grapefruit (Citrus x paradisi). Orange
45 (Citrus sinensis), Kabosu (Citrus sphaerocarpa), Sudachi (Citrus sudachi), Mandarin
Orange (Citrus tangerina), Satsuma (Citrus unshiu), Kumquat (Fortunella spp.), etc.,
the family Brassicaceae such as Horseradish (Armoracia rusticana), Mustard
(Brassica juncea), Takana (Brassica juncea var. integrifolia), Rapeseed (Brassica
38
napus), Cauliflower (Brassica oleracea var. botrvtis), Cabbage (Brassica oleracea var.
capjtata), Brussels sprout (Brassica oleracea var. gemmifera), Broccoli (Brassica
oleracea var. italica), Green pak choi (Brassica rapa var. chinensis), Nozawana
(Brassica rapa var. hakabura), Napa cabbage (Brassica rapa var. nippo-oleifera),
5 Potherb Mustard (Brassica rapa var. nipposinica), Napa cabbage (Brassica rapa var.
pekinensis), Turnip leaf (Brassica rapa var. perviridis), Turnip (Brassica rapa var. rapa),
Garden rocket (Eruca vesicaria), Daikon (Raphanus sativus var. lonqipinnatus), Wasabi
(Wasabia japonica), etc., the family Caricaceae such as Papaya (Carica papaya), etc.,
the family Malvaceae such as Okra (Abelmoschus esculentus), Cotton plant
10 (Gossvpium spp.), Cacao (Theobroma cacao), etc., the family Vitaceae such as Grape
(Vitis spp.), etc., the family Amaranthaceae such as Sugar beet (Beta vulgaris ssp.
vulgaris var. altissima). Table beet (Beta vulgaris ssp. vulgaris var. vulgaris), Spinach
(Spinacia oleracea), etc., the family Polygonaceae such as Buckwheat (Fagopyrum
esculentum), etc., the family Ebenaceae such as Kaki Persimmon (Diospyros kaki), etc.,
15 the family Theaceae scuh as Tea plant (Camellia sinensis), etc., the family Actinidiaceae
such as Kiwifruit (Actinidia deliciosa, A. chinensis), etc., the family Ericaceae such as
Blueberry (Vaccinium spp.), Cranberry (Vaccinium spp.), etc., the family Rubiaceae
such as Coffee plants (Coffea spp.), etc., the family Lamiaceae such as Lemon balm
(Melissa officinalis). Mint (Mentha spp.), Basil (Qcimum basilicum), Shiso (Perilla
20 frutescens var. crispa), Perilla frutescens var. frutescens, Common Sage (Salvia
officinalis). Thyme (Thymus spp.), etc., the family Pedaliaceae such as Sesame
(Sesamum indicum), etc., the family Oleaceae such as Olive (Qlea europaea), etc. the
family Convolvulaceae such as Sweet potato (Ipomoea batatas), etc.,
the family Solanaceae such as Tomato (Solanum Ivcopersicum), Eggplant (Solanum
25 melongena). Potato (Solanum tuberosum), Chili pepper (Capsicum annuum), Bell
pepper (Capsicum annuum var. 'grossum'). Tobacco (Nicotiana tabacum), etc., the
family Apiaceae such as Celery (Apium graveolens var. dulce), Coriander (Coriandrum
sativum), Japanese honeywort (Crvptotaenia Canadensis subsp. japonica), Carrot
(Daucus carota subsp. sativus), Parsley (Petroselium crispum), Italian parsley
30 (Petroselinum neapolitanum), etc., the family Araliaceae such as Udo (Aralia cordata),
Aralia elata, etc., the family Asteraceae subfamily Carduoideae such as Artichoke
(Cvnara scolvmus), etc., the family Asteraceae subfamily Asteraceae such as Chicory
(Cichorium intvbus). Lettuce (Lactuca sativa), etc., the family Asteraceae subfamily
Asteraceae such as Florists' daisy (Dendranthema grandiflorum), Crown daisy
35 . (Glebionis coronaria), Sunflower (Helianthus annuus), Fuki (Petasites iaponicus),
Burdock (Arctium lappa), etc.
Animals herein mean human, companion creatures/pets, livestock/poultry, and
vertebrate such as research/laboratory animals, and specifically, the following animals
may, for example, be mentioned, but the present invention is not restricted thereto.
40 Animals of the class Mammalia belonging to the family Cebidae such as Tufted
capuchin (Cebus apella), etc., the family Cercopithecidae such as Crab-eating macaque
(Macaca fascicularis). Rhesus macaque (Macaca mulatta), etc., the family Hominidae
such as Chimpanzee (Pan troglodytes). Human (Homo sapiens), etc., the family
Leporidae such as European rabbit (Qrvctolagus cuniculus), etc., the family
45 Chinchillidae such as Long-tailed chinchilla (Chinchilla lanigera), etc., the family
Caviidae such as Guinea pig (Cavia porcellus), etc., the family Cricetidae such as
Golden hamster (Mesocricetus auratus), Djungarian hamster (Phodopus sungorus),
Chinese hamster (Cricetulus griseus), etc., the family Muridae such as Mongolian gerbil
39
(Meriones unguiculatus), House mouse (Mus musculus), Black rat (Rattus rattus), etc.,
the family Sciuridae such as Chipmunk (Tamias sibiricus), etc., the family Camelidae
such as Dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus),
Alpaca (Vicugna pacos), Llama (Lama glama), etc., the family Suidae such as Pig (Sus
5 scrofa domesticus), etc., the family Cervidae such as Reindeer (Rangifer tarandus),
Red deer (Cervus elaphus), etc., the family Bovidae such as Yak (Bos grunniens),
Cattle (Bos taurus), Water buffalo (Bubalus arnee), Goat (Capra hi reus), Sheep (Ovis
arjes), etc., the family Felidae such as Cat (Felis silvestris catus), etc., the family
Canidae such as Dog (Canis lupus familiaris), Red fox (Vulpes vulpes), etc., the family
10 Mustelidae such as European mink (Mustela lutreola), American mink (Mustela yison),
Ferret (Mustela putorius furo). etc., the family Equidae such as Donkey (Eguus asinus),
Horse (Eguus caballus), etc., the family Macropodidae such as Red kangaroo
(Macropus rufus), etc.
Animals of the class Aves belonging to the
15 family Struthionidae such as Ostrich (Struthio camelus), etc., the family Rheidae such as
American rhea (Rhea americana), etc., the family Dromaiidae such as Emu (Dromaius
novaehollandiae), etc., the family Phasianidae such as Ptarmigan (Lagopus muta), Wild
turkey (Meleagris gallopavo), Japanese quail (Cotumix japonica), Chicken (Gallus
gallus domesticus), Common pheasant (Phasianus colchicus), Golden pheasant
20 (Chrvsolophus pictus), Indian peafowl (Pavo cristatus), etc., the family Numididae such
as Helmeted guineafowl (Numida meleagris), etc., the family Anatidae such as Mallard
(Anas platyrhynchos), Domesticated duck (Anas platyrhynchos var.domesticus), Spotbilled
duck (Anas poecilorhyncha), Greylag goose (Anser anser), Swan goose (Anser
cygnoides), Whooper swan (Cygnus cygnus). Mute swan (Cygnus olor), etc., the family
25 Columbidae such as Rock dove (Columba livia), Oriental turtle dove (Streptopelia
orientalis), European turtle dove (Streptopelia turtur), etc., the family Cacatuidae such
as Sulphur-crested cockatoo (Cacatua galerita), Galah (Eolophus roseicapilla),
Cockatiel (Nymphicus hollandicus), etc., the family Psittacidae such as Rosy-faced
lovebird (Agapornis roseicollis), Blue-and-yellow macaw (Ara ararauna), Scarlet Macaw
30 (Ara macao), Budgerigar (Melopsittacus undulatus), African grey parrot (Psittacus
erithacus), etc., the family Stumidae such as Common hill myna (Gracula religiosa), etc.,
the family Estrildidae such as Red avadavat (Amandava amandava), Zebra finch
(Taeniopygia guttata), Bengalese finch (Lonchura striata var. domestica), Java sparrow
(Padda oryzivora), etc., the family Fringillidae such as Domestic canary (Serinus
35 canaria domestica), European goldfinch (Carduelis carduelis), etc.
Animals of the class Reptilia belonging to the family Chamaeleonidae such as
Veiled chameleon (Chamaeleo calyptratus), etc., the family Iguanidae such as Green
iguana (Iguana iguana), Carolina anole (Anolis carolinensis), etc., the family Varanidae
such as Nile monitor (Varanus niloticus), Water monitor (Varanus salvator), etc., the
40 family Scincidae such as Solomon islands skink (Corucia zebrata), etc., the family
Colubridae such as Beauty rat snake (Elaphetaeniura), etc., the family Boidae such as
Boa constrictor (Boa constrictor), etc., the family Pythonidae such as Indian python
(Python molurus). Reticulated python (Python reticulatus), etc., the family Chelydridae
such as Common snapping turtle (Chelvdra serpentina), etc., the family Emydidae such
45 as Diamondback terrapin (Malaclemys terrapin), Pond slider (Trachemys scripta), etc.,
the family Geoemydidae such as Japanese pond turtle (Mauremys japonica), etc., the
family Testudinidae such as Central Asian tortoise (Agrionemys horsfieldii), etc., the
family Trionychidae such as Soft-shelled turtle (Pelodiscus sinensis), etc., the family
40
Alligatoridae such as American alligator (Alligator mississippiensis), Black caiman
(Melanosuchus niger), etc., the family Crocodylidae such as Siamese crocodile
(Crocodylus siamensis), etc.
Animals of the class Actinopterygii belonging to the family Cyprinidae such as
5 Carp (Cyprinus carpjo), Goldfish (Carassius auratus auratus), Zebrafish (Danio re ho),
etc., the family Cobitidae such as Kuhli loach (Panqio kuhjii), etc., the family Characidae
such as Red piranha (Pygocentrus nattereri), Neon tetra (Paracheirodon innesi), etc.,
the family Salmonidae such as Maraena whitefish (Coregonus lavaretus maraena),
Coho salmon (Oncorhynchus kisutsh), Rainbow trout (Oncorhynchus mykiss), Chinook
10 salmon (Oncorhynchus tshawvtscha), Atlantic salmon (Salmo salar), Brown trout
(Salmo trutta), etc., the family Percichthyidae such as Spotted sea bass (Lateolabrax
maculatus), etc., the family Serranidae such as Sea goldie (Pseudanthias squamipinnis),
Longtooth grouper (Epinephelus bruneus), Convict grouper (Epinephelus
septemfasciatus), etc., the family Centrarchidae such as Bluegill (Lepomis macrochirus),
15 etc., the family Carangidae such as White trevally (Pseudocaranx dentex), Greater
amberjack (Seriola dumerili), Japanese amberjack (Seriola quinqueradiata), etc., the
family Sparidae such as Red sea bream (Pagrus major), etc., the family Cichlidae such
as Nile tilapia (Oreochromis niloticus), Angelfish (Pterophvllum scalare), etc., the family
Scombridae such as Pacific bluefin tuna (Thunnus orientalis), etc., the family
20 Tetraodontidae such as Japanese pufferfish (Takifugu rubripes), etc.
Pathogens herein mean microorganisms which cause plant diseases and animal
infections, and specifically, the following microorganisms may, for example, be
mentioned, but the present invention is not restricted thereto.
Fungi of the phylum Ascomycota, such as Taphrina spp. (e.g. Taphrina deformans.
25 T. pruni, etc.), Pneumocystis spp., Geotrichum spp., Candida spp.(e.g. Candida
albicans, C. sorbosa, etc.), Pichia spp.(e.g. Pichia kluyveri, etc.), Geotrichum spp.,
Capnodium spp., Fumago spp., Hypocapnodium spp., Cercospora spp.(e.g. Cercospora
apii. C. asparaoi. C. beticola. C. capsici. C. carotae, C. kaki, C. kikuchii, C. zonata. etc.),
Cercosporidium spp., Cladosporium spp.(e.g. Cladosporium colocasiae, C.
30 cucumerinum. C. variabile, etc.), Davidiella spp., Didymosporium spp., Heterosporium
spp.(e.g. Heterosporium allii, etc.), Mvcosphaerella spp.(e.g. Mycosphaerella arachidis,
M. berkeleyi. M. cerasella, M. fijiensis, M. fraqariae, M. qraminicola, M. nawae, M.
pinodes, M. pomi. M. zinqiberis. etc.), Mvcovellosiella spp.(e.g. Mvcovellosiella fulva, M.
nattrassii, etc.), Paracercospora spp.(e.g. Paracercospora eqenula, etc.),
35 Phaeoisariopsis spp., Phaeoramularia spp., Pseudocercospora spp.(e.g.
Pseudocercospora abelmoschi. P. fuliqena, £. vitis, etc.), Pseudocercosporella spp.(e.g.
Pseudocercosporella capsellae, etc.), Ramichloridium spp., Ramularia spp.,
Septoqloeum spp., Septoria spp.(e.g. Septoria albopunctata, S. apiicola, S.
chrysanthemella. S. helianthi, S. obesa, etc.), Sphaerulina spp., Aureobasidium spp.,
40 Kabatiella spp., Plowrightia spp., Stigmina spp., Elsinoe spp.(e.g. Elsinoe ampelina. E.
araliae, E. fawcettii. etc.), Sphaceloma spp.(e.g. Sphaceloma caricae, etc.), Ascochyta
spp.(e.g. Ascochyta pisi, etc.), Corvnespora spp.(e.g. Corvnespora cassiicola, etc.),
Leptosphaeria spp.(e.g. Leptosphaeria coniothvrium, L maculans, etc.), Saccharicola
spp., Phaeosphaeria spp., Qphiosphaerella spp., Setophoma spp., Helminthosporium
45 spp., Altemaria spp.(e.g. Altemaria altemata. A. brassicae, A. brassicicola. A. citri. A.
dauci, A. helianthi. A. iaponica. A. kikuchiana. A. mali. A. panax, A. porri. A. radicina. A.
solani, etc.), Bipolaris spp.(e.g. Bipolaris sorghicola, etc.), Cochliobolus spp.(e.g.
Cochliobolus heterostrophus. C. lunatus, C. miyabeanus, etc.), Curvularia spp.(e.g.
41
Curvularia geniculata, C. verruculosa, etc.), Drechslera spp., Pleospora spp.(e.g.
Pleospora herbarum. etc.), Pyrenophora spp. (e.g. Pyrenophora graminea, P. teres,
etc.), Setosphaeria spp. (e.g. Setosphaeria turcica, etc.), Stemphvlium spp.(e.g.
Stemphylium botrvosum, S. lycopersici, S. solani, S. vesicarium, etc.), Fusicladium spp.,
5 Venturia spp.(e.g. Venturia carpophila, V. Inaegualis, V. nashicola, V. pirina, etc.),
Didymella spp.(e.g. Didymella bryoniae, D. fabae, etc.), Hendersonia spp., Phoma
spp.(e.g. Phoma erratica var. mikan, P. exigua var. exigua, P. wasabiae, etc.),
Pyrenochaeta spp.(e.g. Pyrenochaeta lycopersici. etc.), Stagonospora spp.(e.g.
Stagonospora sacchari, etc.), Botryosphaeria spp.(e.g. Botrvosphaeria berengeriana f.
10 sp. piricola, B. dothidea, etc.), Dothiorella spp., Fusicoccum spp., Guignardia spp.,
Lasiodiplodia spp.(e.g. Lasiodiplodia theobromae. etc.), Macrophoma spp.,
Macrophomina spp., Neofusicoccum spp., Phyllosticta spp. (e.g. Phyllosticta zingiberis,
etc.), Schizothvrium spp.(e.g. Schizothvrium pomi, etc.),
Acrospermum spp., Leptosphaerulina spp., Aspergillus spp., Penicillium spp.(e.g.
15 Penicillium digitatum, P. italicum, P. sclerotigenum, etc.), Microsporum spp.,
Trichophyton spp.(e.g. Trichophyton mentagrophvtes, T. rubrum, etc.), Histoplasma
spp., Blumeria spp.(e.g. Blumeria graminis f. sp. hordei, B. g. f. sp. tritici, etc.), Erysiphe
spp.(e.g. Erysiphe betae, E. cichoracearum, E. c. var. cichoracearum, E. heraclei, E.
pisi, etc.), Golovinomvces spp.(e.g. Golovinomvces cichoracearum var. latisporus, etc.),
20 Leveillula spp.(e.g. Leveillula taurica, etc.), Microsphaera spp., Oidium spp.(e.g. Oidium
neolvcopersici, etc.), Phyllactinia spp.(e.g. Phvllactinia kakicola, P. mali, P. moricola,
etc.), Podosphaera spp.(e.g. Podosphaera fusca, P. leucotricha, P. pannosa, P.
tridactyla var. tridactyla, P. xanthii, etc.), Sphaerotheca spp.(e.g. Sphaerotheca aphanis
var. aphanis, S. fuliginea, etc.), Uncinula spp.(e.g. Uncinula necator, LJ. n. var. necator,
25 etc.), Uncinuliella spp.(e.g. Uncinuliella simulans var. simulans, U. s. var. tandae, etc.),
Blumeriella spp.(e.g. Blumeriella jaapii, etc.), Cvlindrosporium spp., Diplocarpon
spp.(e.g. Diplocarpon mali, D. mespili, D. rosae, etc.), Gloeosporium spp.(e.g.
Gloeosporium minus, etc.), Marssonina spp., Tapesia spp.(e.g. Tapesia acuformis, T.
yallundae, etc.), Lachnum spp., Scleromitrula spp., Botryotinia spp.(e.g. Botrvotinia
30 fuckeliana, etc.), Botrvtis spp.(e.g. Botrvtis allii, B. bvssoidea, B. cinerea, B. elliptica, B.
fabae, B. sguamosa, etc.), Ciborinia spp., Grovesinia spp., Monilia mumecola, Monilinia
spp.(e.g. Monilinia fructicola, M- fructigena, M. laxa, M. mali, M. vaccinii-corvmbosi, etc.),
Sclerotinia spp.(e.g. Sclerotinia borealis, S. homoeocarpa, S. minor, S. sclerotiorum,
etc.), Valdensia spp.(e.g. Valdensia heterodoxa, etc.),
35 Claviceps spp.(e.g. Claviceps sorghi, C. sorghicola, etc.), Epichloe spp., Ephelis
iaponica. Villosiclava virens, Hypomyces spp.(e.g. Hypomyces solani f. sp. rnori, H. s. f.
sp. pisi. etc.), Trichoderma spp.(e.g. Trichoderma viride, etc.), Calonectria spp.(e.g.
Calonectria ilicicola, etc.), Candelospora spp., Cylindrocarpon spp., Cvlindrocladium
spp., Fusarium spp.(e.g. Fusarium arthrosporioides, F. crookwellense, F. culmorum, F.
40 cuneirostrum, F. oxysporum, F. o. f. sp. adzukicola, F. o. f. sp. allii. F. o. f. sp. asparagi,
F. o. f. sp. batatas, F. o. f. sp. cepae, F. o. f. sp. colocasiae, F. o. f. sp. conglutinans, F.
o. f. sp. cubense, F. o. f. sp. cucumerinum, F. o. f. sp. fabae, F. o. f. sp. fragariae, F. o. f.
sp. lactucae, F. o. f. sp. lagenariae, F. o. f. sp. lycopersici, F. o. f. sp. melongenae, F. o.
f. sp. melonis, F. o. f. sp. nelumbinicola, F. o. f. sp. niveum, F. o. f. sp. radicis-lvcopersici,
45 F. o. f. sp. raphani, F. o. f. sp. spinaciae, F. sporotrichioides, F. solani, F. s. f. sp.
cucurbitae, F. s. f. sp. eumartii, F. s. f. sp. pisi, F. s. f. sp. radicicola, etc.), Gibberella
spp.(e.g. Gibberella avenacea, G. baccata, G. fuiikuroi, G. zeae, etc.), Haematonectria
spp., Nectria spp., Ophionectria spp., Caldariomvces spp., Myrothecium spp.,
42
Trichothecium spp., Verticillium spp.(e.g. Verticillium albo-atrum, V. dahliae, V.
longisporum, etc.), Ceratocystis spp.(e.g. Ceratocystis ficicola, C. fimbriata, etc.),
Thielaviopsis spp.(e.g. Thielaviopsis basicola. etc.), Adisciso spp., Monochaetia spp.,
Pestalotia spp.(e.g. Pestalotia eriobotrifolia, etc.), Pestalotiopsis spp.(e.g. Pestalotiopsis
5 funerea. P. lonqiseta. P. neqlecta. P. theae, etc.), Phvsalospora spp., Nemania spp.,
Nodulisporium spp., Rosellinia spp.(e.g. Rosellinia necatrix, etc.), Monographella
spp.(e.g. Monographella nivalis, etc.), Ophiostoma spp., Cryphonectria spp.(e.g.
Cryphonectria parasitica, etc.), Diaporthe spp.(e.g. Diaporthe citri, D. kvushuensis, D.
nomurai, D. tanakae, etc.), Diaporthopsis spp., Phomopsis spp.(e.g. Phomopsis
10 asparagi, P. fukushii, P. obscurans, P. vexans, etc.),
Cryptosporella spp., Discula spp.(e.g. Discula theae-sinensis, etc.), Gnomonia spp.,
Coniella spp., Coryneum spp., Greeneria spp., Melanconis spp., Cvtospora spp.,
Leucostoma spp., Valsa spp.(e.g. Valsa ceratosperma, etc.), Tubakia spp.,
Monosporascus spp., Clasterosporium spp., Gaeumannomyces spp.(e.g.
15 Gaeumannomyces graminis, etc.). Magnaporthe spp.fe.g. Magnaporthe grisea, etc.),
Pyricularia spp.(e.g. Pyricularia zingiberis, etc.), Monilochaetes infuscans,
Colletotrichum spp.(e.g. Colletotrichum acutatum, C. capsici, C. cereale, C.
destructivum, C. fragariae, C. lindemuthianum, C. nigrum, C. orbiculare, C. spinaciae,
etc.), Glomerella spp.(e.g. Glomerella cingulata, etc.), Khuskia oryzae, Phvllachora
20 spp.(e.g. Phvllachora pomigena. etc.), Ellisembia spp., Briosia spp., Cephalosporium
spp.(e.g. Cephalosporium gramineum. etc.), Epicoccum spp., Gloeocercospora sorghi,
Mycocentrospora spp., Peltaster spp.(e.g. Peltaster fructicola, etc.), Phaeocvtostroma
spp., Phialophora spp.(e.g. Phialophora gregata, etc.), Pseudophloeosporella
dioscoreae, Pseudoseptoria spp., Rhvnchosporium spp.(e.g. Rhvnchosporium secalis,
25 etc.), Sarocladium spp., Coleophoma spp., Helicoceras oryzae, etc.
Fungi of the phylum Basidiomycota, such as Septobasidium spp.(e.g. Septobasidium
bogoriense, S. tanakae, etc.), Helicobasidium spp.(e.g. Helicobasidium longisporum,
etc.), Coleosporium spp.(e.g. Coleosporium plectranthi. etc.), Cronartium spp.,
Phakopsora spp.(e.g. Phakopsora artemisiae, P. nishidana, P. pachyrhizi, etc.),
30 Physopella spp.(e.g. Physopella ampelopsidis, etc.), Kuehneola spp.(e.g. Kuehneola
iaponica, etc.), Phragmidium spp.(e.g. Phragmidium fusiforme, P. mucronatum, P.
rosae-multiflorae, etc.), Gymnosporangium spp.(e.g. Gvmnosporangium asiaticum, G.
vamadae, etc.), Puccinia spp.(e.g. Puccinia allii, P. brachypodii var. poae-nemoralis, P.
coronata, P. c. var. coronata, P. cvnodontis. P. graminis. P. g. subsp. graminicola, P.
35 hordei. P. horiana. P. kuehnii. P. melanocephala. P. recondita, P. striiformis var.
striiformis, P. tanaceti var. tanaceti, P. tokyensis, P. zoysiae, etc.), Uromyces spp.(e.g.
Uromvces phaseoli var. azukicola. U. p_. var. phaseoli, Uromyces viciae-fabae var.
viciae-fabae, etc.), Naohidemyces vaccinii, Nvssopsora spp., Leucotelium spp.,
Tranzschelia spp.(e.g. Tranzschelia discolor, etc.), Aecidium spp., Blastospora spp.(e.g.
40 Blastospora smilacis, etc.), Uredo spp., Sphacelotheca spp., Urocvstis spp.,
Sporisorium spp.(e.g. Sporisorium scitamineum, etc.), Ustilago spp.(e.g. Ustilago
mavdis, LJ. nuda. etc.), Entyloma spp., Exobasidium spp.(e.g. Exobasidium reticulatum,
E. vexans, etc.), Microstroma spp., Tilletia spp.(e.g. Tilletia caries, T. controversa, T.
laevis, etc.), Itersonilia spp.(e.g. Itersonilia perplexans, etc.), Crvptococcus spp., Bovista
45 spp.(e.g. Bovista dermoxantha, etc.), Lycoperdon spp.(e.g. Lycoperdon curtisii, L
perlatum, etc.), Conocvbe spp.(e.g. Conocvbe apala. etc.), Marasmius spp.(e.g.
Marasmius oreades, etc.), Armillaria spp., Helotium spp., Lepista spp.(e.g. Lepista
subnuda, etc.), Sclerotium spp.(e.g. Sclerotium cepivorum, etc.), Typhula spp.(e.g.
43
Typhula incarnata. T. ishikariensis var. ishikariensis, etc.), Athelia spp.(e.g. Athelia rolfsii,
etc.), Ceratobasidium spp.(e.g. Ceratobasidium corniqerum, etc.), Ceratorhiza spp.,
Rhizoctonia spp.(e.g. Rhizoctonia solani, etc.), Thanatephorus spp.(e.g. Thanatephorus
cucumeris. etc.), Laetisaria spp., Waitea spp., Fomitiporia spp., Ganoderma spp.,
5 Chondrostereum purpureum. Phanerochaete spp., etc.
Fungi of the phylum Chitridiomycota such as Olpidium spp., etc.
Fungi of the phylum Blastocladiomycota such as Physoderma spp., etc.
Fungi of the phylum Mucoromycotina such as Choanephora spp.,
Choanephoroidea cucurbitae, Mucor spp. (e.g. Mucor fragilis, etc.), Rhizopus spp. (e.g.
10 Rhizopus arrhizus. R. chinensis, R. oryzae. R. stolonifer var. stolonifer, etc.), etc.
Protists of the phylum Cercozoa such as Plasmodiophora spp. (e.g.
Plasmodiophora brassicae, etc.), Sponqospora subterranea f. sp. subterranea, etc.
Microorganisms of the phylum Heterokontophyta class Oomycetes such as
Aphanomvces spp. (e.g. Aphanomvces cochlioides, A. raphani, etc.), Albugo spp. (e.g.
15 Albugo macrospora, A. wasabiae, etc.), Bremia spp. (e.g. Bremia lactucae, etc.),
Hvaloperonospora spp., Peronosclerospora spp., Peronospora spp. (e.g. Peronospora
alliariae-wasabi. P. chrvsanthemi-coronarii, P. destructor, P. farinosa f. sp. spinaciae, P.
manshurica, P. parasitica, P. sparsa, etc.), Plasmopara spp. (e.g. Plasmopara halstedii,
P. nivea, P. viticola, etc.), Pseudoperonospora spp. (e.g. Pseudoperonospora cubensis.
20 etc.), Sclerophthora spp., Phvtophthora spp. (e.g. Phvtophthora cactorum, P. capsici, P.
citricola, P. citrophthora, P. cryptogea, P. fragariae, P. infestans, P. melonis, P.
nicotianae, P. palmivora, P. porri, P. spjae, P. svrinqae, P. vignae f. sp. adzukicola, etc.),
Pythium spp. (e.g. Pvthium afertile, P. aphanidermatum, P. apleroticum, P.
aristosporum, P. arrhenomanes, P. buismaniae, P. debarvanum, P. qraminicola, P.
25 horinouchiense, P. irregulare, P. iwavamai, P. myriotylum, P. okanoganense, P.
paddicum, P. paroecandrum, P. periplocum, P. spinosum, P. sulcatum, P. svlvaticum, P.
ultimum var. ultimum, P. vanterpoolii, P. vexans, P. volutum, etc.), etc.
Gram-positive bacteria of the phylum Actinobacteria such as Clavibacter spp. (e.g.
Clavibacter michiganensis subsp. michiganensis, etc.), Curtobacterium spp., Leifsonia
30 spp. (e.g. Leifsonia xvli subsp. xyj], etc.), Streptomyces spp. (e.g. Streptomyces
ipomoeae, etc.), etc.
Gram-positive bacteria of the phylum Firmicutes such as Clostridium sp., etc.
Gram-positive bacteria of the phylum Tenericutes such as Phvtoplasma, etc.
Gram-negative bacteria of the phylum Proteobacteria such as Rhizobium spp.(e.g.
35 Rhizobium radiobacter, etc.), Acetobacterspp., Burkholderia spp. (e.g. Burkholderia
andropogonis, B. cepacia, B. gladioli, B. glumae, B. plantarii, etc.), Acidovorax spp. (e.g.
Acidovorax avenae subsp. avenae, A. a. subsp. citrulli, A. konjaci, etc.), Herbaspirillum
spp., Ralstonia spp. (e.g. Ralstonia solanacearum, etc.), Xanthomonas spp. (e.g.
Xanthomonas albilineans, X. arboricola p_y. pruni, X. axonopodis p_y. vitians, X.
40 campestris p_y. campestris, X. c. JDV. cucurbitae, X. c. p_y. glycines, X. c. p_y.
mangiferaeindicae, X. c. p_y. nigromaculans, X. c. p_y. vesicatoria, X. citri subsp. cjtri, X.
oryzae p_y. oryzae, etc.), Pseudomonas spp. (e.g. Pseudomonas cichorii, P. fluorescens,
P. marginalis, P. m. gy. marginalis, P. savastanoi gy. glvcinea, P. svringae, P. s. gy.
actinidiae, P. s. p_y. eriobotrvae, P. s. p_y. helianthi, P. s. p_y. lachrymans, P. s. p_y.
45 maculicola, P. s. JDV. mori, P. s. p_y. morsprunorum, P. s. p_y. spinaciae, P. s. QV. svringae,
P. s. py. theae, P. viridiflava, etc.), Rhizobacter spp., Brenneria spp. (e.g. Brenneria
nigrifluens, etc.), Dickeva spp.(e.g. Dickeva dianthicola, D. zeae, etc.), Erwinia spp. (e.g.
Erwinia amylovora, E. rhapontici, etc.), Pantoea spp., Pectobacterium spp. (e.g.
44
Pectobacterium atrosepticum. P. carotovorum. P. wasabiae. etc.), etc.
As specific examples the plant diseases and animal infections caused by
infection/proliferation of such pathogens, the following plant diseases and animal
infections may, for example, be mentioned, but the present invention is not restricted
5 thereto.
Plant diseases:
Leaf curl (Taphrina deformans). Plum pockets (Taphrina pruni). Leaf spot
(Cercospora asparaqi). Cercospora leaf spot (Cercospora beticola). Frogeye leaf spot
(Cercospora capsici). Angular leaf spot (Cercospora kaki), Purple stain (Cercospora
10 kikuchii). Brown Leaf spot (Mvcosphaerella arachidis). Cylindrosporium leaf spot
(Mvcosphaerella cerasella. Blumeriella iaapii). Speckled leaf blotch (Mvcosphaerella
graminicola). Circular leaf spot (Mvcosphaerella nawae), Mycosphaerella blight
(Mvcosphaerella pinodes), Leaf spot (Mvcosphaerella zinpjberis), Leaf mold
(Mvcovellosiella fulva). Leaf mold (Mvcovellosiella nattrassii), Cercospora leaf mold
15 (Pseudocercospora fuliqena). Isariopsis leaf spot (Pseudocercospora vitis), Leaf spot
(Pseudocercosporella capsellae). Leaf spot (Septoria chrvsanthemella). Leaf blight
(Septoria obesa). Anthracnose (Elsinoe ampelina), Spot anthracnose (Elsinoe araliae).
Scab (Elsinoe fawcettii). Leaf spot (Ascochvta pisi). Corynespora leaf spot
(Corynespora cassiicola). Stem canker (Leptosphaeria coniothvrium), Leaf spot
20 (Alternaria alternata). Leaf blight (Alternaria dauci). Black spot (Alternaria kikuchiana).
Alternaria blotch (Alternaria mali). Alternaria leaf spot (Alternaria porri). Target spot
(Bipolaris sorqhicola). Southern leaf blight (Cochliobolus heterostrophus).
Brown spot (Cochliobolus mivabeanus). Tip blight (Pleospora herbarum). Stripe
(Pvrenophora qraminea). Net blotch (Pvrenophora teres). Leaf blight (Setosphaeria
25 turcica). Northern leaf blight (Setosphaeria turcica). Leaf spot (Stemphvlium botrvosum).
Scab (Venturia carpophila). Scab (Venturia Inaequalis). Scab (Venturia nashicola).
Gummy stem blight (Didymella brvoniae). Leaf spot (Phoma exiqua var. exiqua). Streak
(Phoma wasabiae), Ring rot (Botrvosphaeria berenqeriana f. sp. piricola). Soft rot
(Botrvosphaeria dothidea. Lasiodiplodia theobromae. Diaporthe sp.), Common green
30 mold (Penicillium diqitatum). Blue mold (Penicillium italicum). Powdery mildew
(Blumeria qraminis f. sp. hordei). Powdery mildew (Blumeria qraminis f. sp. tritici),
Powdery mildew (Ervsiphe betae, Leveillula taurica. Oidium sp., Podosohaera xanthii).
Powdery mildew (Ervsiphe cichoracearum. Leveillula taurica. Sphaerotheca fuliqinea).
Powdery mildew (Ervsiphe heraclei), Powdery mildew (Ervsiphe pisi). Powdery mildew
35 (Leveillula taurica. Oidium neolvcopersici. Oidium sp.), Powdery mildew (Leveillula
taurica). Powdery mildew (Oidium sp., Podosohaera xanthii). Powdery mildew (Oidium
sp.), Powdery mildew (Phvllactinia kakicola). Powdery mildew (Podosohaera fusca).
Powdery mildew (Podosohaera leucotricha). Powdery mildew (Podosohaera pannosa.
Uncinuliella simulans var. simulans. U. s. var. tandae), Powdery mildew (Podosohaera
40 xanthii). Powdery mildew (Sphaerotheca aphanis var. aphanis). Powdery mildew
(Sphaerotheca fuliqinea). Powdery mildew (Uncinula necator. U. n. var. necator),
Blotch (Diplocarpon mali). Black spot (Diplocarpon rosae). Gray mold neck rot (Botrvtis
allii). Gray mold, Botrytis blight (Botrvtis cinerea). Leaf blight (Botrvtis cinerea. B.
bvssoidea. B. squamosa), Chocolate spot (Botrvtis cinerea. B. elliptica. B. fabae),
45 Brown rot (Monilinia fructicola. M. fructigena. M. laxa). Blossom blight (Monilinia mali).
Dollar spot (Sclerotinia homoeocarpa). Cottony rot, Sclerotinia rot, Stem rot (Sclerotinia
sclerotiorum). False smut (Villosiclava virens). Root necrosis (Calonectria ilicicola).
Fusarium blight (Fusarium crookwellense. F. culmorum, Gibberella avenacea. G. zeae.
45
Monoqraphella nivalis), Fusarium blight (Fusarium culmorum, Gibberella avenacea, G.
zeae), Dry rot (Fusarium oxysporum, F. solani f. sp. radicicola), Brown rot (Fusarium
oxysporum, F. solani f. sp. pisi, F. s. f. sp. radicicola), Fusarium wilt (Fusarium
oxysporum f. sp. adzukicola), Fusarium basal rot (Fusarium oxysporum f. sp. allii. F.
5 solani f. sp. radicicola), Stem rot (Fusarium oxysporum f. sp. batatas, F. solani), Dry rot
(Fusarium oxysporum f. sp. colocasiae), Yellows (Fusarium oxysporum f. sp.
conqlutinans), Panama disease (Fusarium oxysporum f. sp. cubense), Fusarium wilt
(Fusarium oxysporum f. sp. fraqariae), Root rot (Fusarium oxysporum f. sp. lactucae),
Fusarium wilt (Fusarium oxysporum f. sp. laqenariae, F. o. f. sp. niveum), Fusarium wilt
10 (Fusarium oxysporum f. sp. lycopersici), Fusarium wilt (Fusarium oxysporum f. sp.
melonis), Yellows (Fusarium oxysporum f. sp. raphani), Fusarium wilt (Fusarium
oxysporum f. sp. spinaciae),
"Bakanae" disease (Gibberella fuiikuroi). Verticillium black spot (Verticillium albo-atrum,
V. dahliae), Verticillium wilt (Verticillium dahliae), Ceratocystis canker (Ceratocvstis
15 ficicola), Black rot (Ceratocvstis fimbriata), Gray blight (Pestalotiopsis lonqiseta, P.
theae), Endothia canker (Cryphonectria parasitica), Melanose (Diaporthe citri), Stem
blight (Phomopsis asparaqi), Phomopsis canker (Phomopsis fukushii), Brown spot
(Phomopsis vexans), Anthracnose (Discula theae-sinensis), Valsa canker (Valsa
ceratosperma). Blast (Maqnaporthe qrisea), Crown rot (Colletotrichum acutatum, C.
20 fraqariae, Glomerella cinqulata), Bitter rot (Colletotrichum acutatum, Glomerella
cinqulata), Anthracnose (Colletotrichum acutatum, Glomerella cinqulata), Anthracnose
(Colletotrichum acutatum), Ripe rot (Colletotrichum acutatum, Glomerella cinqulata),
Anthracnose (Colletotrichum acutatum), Anthracnose (Colletotrichum lindemuthianum),
Anthracnose (Colletotrichum orbiculare), Anthracnose (Glomerella cinqulata),
25 Anthracnose (Glomerella cinqulata), Anthracnose (Glomerella cinqulata), Brown stem
rot (Phialophora qreqata), Leaf spot (Pseudophloeosporella dioscoreae), Scald
(Rhynchosporium secalis),
Rust (Phakopsora nishidana), Rust (Phakopsora pachyrhizi). Rust (Kuehneola iaponica,
Phraqmidium fusiforme, P. mucronatum, P. rosae-multiflorae), Rust (Gymnosporangium
30 asiaticum). Rust (Gymnosporangium vamadae), Rust (Puccinia allii), Rust (Puccinia
horiana), Brown rust (Puccinia recondita), Rust (Puccinia tanaceti var. tanaceti), Rust
(Uromvces viciae-fabae var. viciae-fabae), Smut (Sporisorium scitamineum), Smut
(Ustilago maydis), Loose smut (Ustilago nuda), Net blister blight (Exobasidium
reticulatum), Blister blight (Exobasidium vexans), Stem rot, Southern blight (Athelia
35 rolfsii), Root and stem rot (Ceratobasidium comiqerum, Rhizoctonia solani),
(Rhizoctonia solani), Damping-off (Rhizoctonia solani), Damping-off (Rhizoctonia solani),
Bottom rot (Rhizoctonia solani), Brown patch, Large patch (Rhizoctonia solani), Sheath
blight (Thanatephorus cucumeris). Root rot/Leaf blight (Thanatephorus cucumeris),
Rhizopus rot (Rhizopus stolonifer var. stolonifer), Clubroot (Plasmodiophora brassicae),
40 Aphanomyces root rot (Aphanomyces cochlioides), White rust (Albugo macrospora),
Downy mildew (Bremia lactucae), Downy mildew (Peronospora chrvsanthemi-coronarii).
Downy mildew (Peronospora destructor), Downy mildew (Peronospora farinosa f. sp.
spinaciae). Downy mildew (Peronospora manshurica), Downy mildew (Peronospora
parasitica), Downy mildew (Peronospora sparsa), Downy mildew (Plasmopara halstedii),
45 Downy mildew (Plasmopara nivea), Downy mildew (Plasmopara viticola), Downy
mildew (Pseudoperonospora cubensis), Phytophthora root rot (Phvtophthora cactorum),
Brown rot (Phvtophthora capsici), Phytophthora rot (Phvtophthora capsici),
Phytophthora blight (Phvtophthora capsici), Phytophthora rot (Phvtophthora cryptoqea).
46
Late blight (Phvtophthora infestans), White powdery rot (Phvtophthora palmivora), Leaf
blight (Phvtophthora porri), Phytophthora root and stem rot (Phvtophthora soiae),
Phytophthora stem rot (Phvtophthora viqnae f. sp. adzukicola), Damping-off (Pvthium
aphanidermatum, P. myriotvlum, P. paroecandrum, P. ultimum var. ultimum), Root rot
5 (Pvthium aristosporum), Browning root rot (Pvthium arrhenomanes, P. qraminicola),
Damping-off (Pvthium buismaniae, P. myriotvlum), Root rot (Pvthium myriotvlum), Root
rot (Pvthium myriotvlum, P. ultimum var. ultimum), Brown blotted root rot (Pvthium
sulcatum), Bacterial canker (Clavibacter michiqanensis subsp. michiqanensis), Scab
(Streptomvces spp.),
10 Crown gall (Rhizobium radiobacter), Bacterial stripe (Burkholderia andropogonis), Soft
rot (Burkholderia cepacia, Pseudomonas marqinalis p_v. marqinalis, Erwinia rhapontici).
Bacterial grain rot (Burkholderia gladioli, B. qlumae). Bacterial fruit blotch (Acidovorax
avenae subsp. citrulli). Bacterial leaf blight (Acidovorax koniaci), Bacterial wilt (Ralstonia
solanacearum). Bacterial shot hole (Xanthomonas arboricola pv. pruni, Pseudomonas
15 syrinqae p_v. syrinqae, Brenneria niqrifluens), Bacterial leaf spot (Xanthomonas
arboricola pv. pruni), Bacterial spot (Xanthomonas axonopodis pv. vitians), Black rot
(Xanthomonas campestris p_v. campestris), Bacterial pustule (Xanthomonas campestris
p_v. glycines), Bacterial spot (Xanthomonas campestris pv. niqromaculans), Bacterial
spot (Xanthomonas campestris p_v. vesicatoria). Citrus canker (Xanthomonas citri subsp.
20 citri), (Pseudomonas cichorii, P. marqinalis p_y_. marqinalis, Erwinia sp.), Bacterial rot
(Pseudomonas cichorii, P. marqinalis p_y_. marqinalis, P. viridiflava), Bacterial blossom
blight (Pseudomonas marqinalis p_v. marqinalis, P. syrinqae p_y_. syrinqae, P. viridiflava),
Bacterial canker (Pseudomonas syrinqae p_y_. actinidiae), Canker (Pseudomonas
syrinqae p_v. eriobotryae), Bacterial spot (Pseudomonas syrinqae p_v. lachrvmans),
25 Bacterial black spot (Pseudomonas syrinqae p_y_. maculicola). Bacterial canker
(Pseudomonas syrinqae p_v. morsprunorum, Erwinia sp.), Bacterial shoot blight
(Pseudomonas syrinqae p_v. theae). Bacterial soft rot (Dickeva sp., Pectobacterium
carotovorum), Fire blight (Erwinia amylovora), Soft rot (Pectobacterium carotovorum),
Bacterial soft rot (Pectobacterium carotovorum).
30 Animal diseases:
Pneumocystis pneumonia (Pneumocystis iirovecii). Candidiasis (Candida albicans),
Aspergillosis (Aspergillus fumigatus), Trichophytosis (Microsporum canis, M. gypseum,
Trichophyton mentagrophytes, T. rubrum, T. tonsurans, T. verrucosum), Histoplasmosis
(Histoplasma capsulatum). Cryptococcosis (Cryptococcus neoformans).
35 Parasites herein mean plant-parasitic nematodes parasitizing plants, animalparasitic
nematodes parasitizing animals, Acanthocephala, Platyhelminthes, Protozoa
and the like, and specifically, the following parasites may, for example, be mentioned,
but the present invention is not restricted thereto.
Nematodes of the order Enoplida such as Giant kidney worm (Dioctophvma
40 renale), Thread worms (Capillaria annulata), Cropworm (Capillaria contorta), Capillary
liver worm (Capillaria hepatica), Capillaria perforans, Capillaria philippinensis, Capillaria
suis, Whipworm (Trichuris discolor). Whipworm (Trichuris ovis), Pig whipworm (Trichuris
suis), Human whipworm (Trichuris trichiura), Dog whipworm (Trichuris vulpis), Pork
worm (Trichinella spiralis), etc.
45 Nematodes of the order Rhabditida such as Intestinal threadworm (Strongyloides
papillosus), Strongyloides planiceps, Pig threadworm (Strongyloides ransomi),
Threadworm (Strongyloides stercoralis), Micronema spp., etc.
Nematodes of the order Strongylida such as Hookworm (Ancvlostoma braziliense),
47
Dog hookworm (Ancvlostoma caninum), Old World hookworm (Ancylostoma duodenale),
Cat hookworm (Ancvlostoma tubaeforme), The Northern hookworm of dogs (Uncinaria
stenocephala), Cattle hookworm (Bunostomum phlebotomum), Small ruminant
hookworm (Bunostomum triqonocephalum), New World hookworm (Necator
5 americanus), Cvathostomum spp., Cvlicocyclus spp.. Cvlicodontophorus spp.,
Cylicostephanus spp., Stronqylus asini, Stronqylus edentatus, Blood worm (Stronqylus
eguinus), Blood worm (Stronqylus vulgaris), Large-mouthed bowel worm (Chabertia
ovina), Nodular worm (Oesophaqostomum brevicaudatum), Nodule worm
(Oesophaqostomum columbianum), Nodule worm (Oesophaqostomum dentatum),
10 Nodular worm (Oesophaqostomum qeorqianum), Nodular worm (Oesophaqostomum
mapjestonei), Nodular worm (Oesophaqostomum quadrispinulatum), Nodular worm
(Oesophaqostomum radiatum), Nodular worm (Oesophaqostomum venulosum),
Svnqamus skriabinomorpha, Gapeworm (Synqamus trachea), Swine kidney worm
(Stephanurus dentatus). Cattle bankrupt worm (Cooperia oncophora), Red stomach
15 worm (Hvostrongylus rubidus), Stomach hair worm (Trichostronqylus axei),
Trichostrongylus colubriformis, Oriental trichostrongylus (Trichostronqylus orientalis),
Red stomach worm (Haemonchus contortus). Cattle stomach worm (Mecistocirrus
digjtatus), Brown stomach worm (Ostertaqia ostertagi), Common lungworm
(Dictvocaulus filaria). Bovine lungworm (Dictvocaulus viviparus), Thin-necked intestinal
20 worm (Nematodirus filicollis), Swine lungworm (Metastronqylus elonqatus), Lungworm
(Filaroides hirthi), Lungworm (Crenosoma aerophila), Fox lungworm (Crenosoma vulpis),
Rat lung worm (Anqiostronqylus cantonensis), French heartworm (Anqiostronqylus
vasorum), Protostronqylus spp., etc.
Nematodes of the order Aphelenchida such as Rice white tip nematode
25 (Aphelenchoides besseyi), Strawberry foliar nematode (Aphelenchoides fraqariae),
Chrysanthemum foliar nematode (Aphelenchoides ritzemabosi), Pine wood nematode
(Bursaphelenchus xylophilus), etc.
Nematodes of the order Tylenchida such as White potato cyst nematode
(Globodera pallida). Potato cyst nematode (Globodera rostochiensis). Cereal cyst
30 nematode (Heterodera avenae). Soybean cyst nematode (Heterodera glycines),
Sugarbeet cyst nematode (Heterodera schachtii). Clover cyst nematode (Heterodera
trifolii). Peanut root-knot nematode (Meloidogyne arenaria). Northern root-knot
nematode (Meloidogyne hapla). Southern root-knot nematode (Meloidogyne incognita),
Javanese root-knot nematode (Meloidogyne iavanica), Apple root-knot nematode
35 (Meloidogyne mali). Coffee root-lesion nematode (Pratvlenchus coffeae), (Pratvlenchus
drenatus), Tea root-lesion nematode (Pratvlenchus loosi), California root-lesion
nematode (Pratvlenchus neqlectus), Cobb's root-lesion nematode (Pratvlenchus
penetrans), Walnut root-lesion nematode (Pratvlenchus vulnus), Citrus burrowing
nematode (Radopholus citrophilus), Banana burrowing nematode (Radopholus similis),
40 etc.
Nematodes of the order Oxyurida such as Pinworm (Enterobius vermicularis),
Equine pinworm (Oxyuris equi). Rabbit pinworm (Passalurus ambiquus), etc.
Nematodes of the order Ascaridida such as Pig roundworm (Ascaris suum), Horse
roundworm (Parascaris equorum), Dog roundworm (Toxascaris leonina), Dog intestinal
45 roundworm (Toxocara canis), Feline roundworm (Toxocara cati), Large cattle
roundworm (Toxocara vitulorum), Anisakis spp., Pseudoterranova spp., Caecal worm
(Heterakis gallinarum), Chicken roundworm (Ascaridia galli), etc.
Nematodes of the order Spirurida such as Guinea worm (Dracunculus
48
medinensis), Gnathostoma doloresi, Gnathostoma hispidum, Gnathostoma nipponicum,
Reddish-coloured worm (Gnathostoma spinigerum), Dog stomach worm (Physaloptera
canis), Cat stomach worm (Physaloptera felidis, P. praeputialis), Feline/canine stomach
worm (Physaloptera rara), Eye worm (Thelazia callipaeda), Bovine eyeworm (Thelazia
5 rhodesi), Large mouth stomach worm (Draschia megastoma), Equine stomach worm
(Habronema microstoma), Stomach worm (Habronema muscae), Gullet worm
(Gongylonema pulchrum). Thick stomach worm (Ascarops strongylina), Parafilaria
(Parafilaria boyicola), Parafilaria multipapillosa, Stephanofilaria okinawaensis, Bancroft
filarial (Wuchereria bancrofti), Bruqia malayi, Neck threadworm (Onchocerca cervicalis),
1 o Onchocerca qibsoni, Cattle filarial worm (Onchocerca gutturosa). Onchocerca volvulus,
Bovine filarial worm (Setaria diqitata), Peritoneal worm (Setaria equina), Setaria
labiatopapillosa. Setaria marshalli, Dog heartworm (Dirofilaria immitis), African eye
worm (Loajoa), etc.
Microorganisms of the phylum Acanthocephala such as Moniliformis moniliformis,
15 Giant thorny-headed worm (Macracanthorhynchus hirudinaceus), etc.
Cestodes of the order Pseudophyllidea such as Fish tapeworm (Diphvllobothrium
latum), Diphvllobothrium nihonkaiense, Manson tapeworm (Spirometra
erinaceieuropaei), Diploqonoporus qrandis, etc.
Cestodes of the order Cyclophyllidea such as (Mesocestoides lineatus), Chicken
20 tapeworm (Raillietina cesticillus), Fowl tapeworm (Raillietina echinobothrida), Chicken
tapeworm (Raillietina tetraqona), Canine tapeworm (Taenia hydatiqena), Canine
tapeworm (Taenia multiceps). Sheep measles (Taenia ovis), Dog tapeworm (Taenia
pisiformis), Beef tapeworm (Taenia saqinata), Tapeworm (Taenia serialis). Pork
tapeworm (Taenia solium), Feline tapeworm (Taenia taeniaeformis), Hydatid tapeworm
25 (Echinococcus granulosus). Small fox tapeworm (Echinococcus multilocularis),
Echinococcus oligarthrus, Echinococcus vogeli, Rat tapeworm (Hymenolepis diminuta),
Dwarf tapeworm (Hymenolepis nana). Double-pored dog tapeworm (Dipylidium
caninum), Amoebotaenia sphenoides, Choanotaenia infundibulum, Metroliasthes
coturnix, Equine tapeworm (Anoplocephala magna), Cecal tapeworm (Anoplocephala
30 perfoliata), Dwarf equine tapeworm (Paranoplocephala mamillana), Common tapeworm
(Moniezia benedeni). Sheep tapeworm (Moniezia expansa), Stilesia spp., etc.
Trematodes of the order Strigeidida such as Pharvngostomum cordatum, Blood
fluke (Schistosoma haematobium), Blood fluke (Schistosoma iaponicum), Blood fluke
(Schistosoma mansoni), etc.
35 Trematodes of the order Echinostomida such as Echinostoma cinetorchis,
Echinostoma hortense. Giant liver fluke (Fasciola gigantica), Common liver fluke
(Fasciola hepatica), Fasciolopsis buski, Homalogaster paloniae, etc.
Trematodes of the order Plagiorchiida such as Dicrocoelium chinensis, Lancet
liver fluke (Dicrocoelium dendriticum), African lancet fluke (Dicrocoelium hospes),
40 Eurytrema coelomaticum, Pancreatic fluke (Eurvtrema pancreaticum), Paragonimus
miyazakii, Paragonimus ohirai, Lung fluke (Paragonimus westermani), etc.
Trematodes of the order Opisthorchiida such as Amphimerus spp., Chinese liver
fluke (Clonorchis sinensis), Cat liver fluke (Opisthorchis felineus). Southeast Aasian liver
fluke (Opisthorchis viverrini), Pseudamphistomum spp., Metorchis spp., Parametorchis
45 spp., Intestinal fluke (Heterophves heterophves), Metagonimus yokokawai, Pygidiopsis
summa, etc.
Amebas such as Entamoeba histolytica, E. invadens, etc.
Piroplasmida sporozoa such as Babesia bigemina, Babesia bovis, Babesia caballi,
49
Babesia can is, Babesia felis, Babesia qibsoni, Babesia ovate, Cvtauxzoon felis,
Theileria annulata. Theileria mutans, Theileria orientalis, Theileria parva, etc.
Haemosporida sporozoa such as Haemoproteus mansoni, Leucocytozoon
caulleryi, Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale,
5 Plasmodium vivax, etc.
Eucoccidiorida sporozoa such as Carvospora spp., Eimeria acervulina, Eimeria
bo vis, Eimeria brunetti, Eimeria maxima, Eimeria necatrix, Eimeria ovinoidalis, Eimeria
stiedae, Eimeria tenella, Isospora canis, Isospora felis, Isospora suis, Tvzzeria alleni,
Tyzzeria anseris, Tvzzeria perniciosa, Wenyonella anatis, Wenvonella qaqari,
10 Cryptosporidium canis, Cryptosporidium felis, Cryptosporidium hominis,
Cryptosporidium meleaqridis, Cryptosporidium muris, Cryptosporidium parvum,
Sarcocystis canis, Sarcocystis cruzi, Sarcocystis felis, Sarcocystis hominis, Sarcocystis
miescheriana, Sarcocystis neurona, Sarcocystis tenella, Sarcocystis oyalis, Toxoplasma
gondii, Hepatozoon canis, Hepatozoon felis, etc.
15 Vestibuliferida ciliata such as Balantidium coli, etc.
Trichomonadida flagellata such as Histomanas meleaqridis, Pentatrichomonas
hominis, Trichomonas tenax, etc.
Diplomonadida flagellata such as Giardia intestinalis, Giardia muris, Hexamita
meleaqridis, Hexamita parva, etc.
20 Kinetoplastida flagellata such as Leishmania donovani, Leishmania infantum,
Leishmania major, Leishmania tropica, Trypanosoma brucei qambiense, Trypanosoma
brucei rhodesiense, Trypanosoma cruzi, Trypanosoma equiperdum, Trypanosoma
evansi, etc.
Useful insects herein mean insects useful for human life by utilizing their products,
25 or useful to make agricultural work efficient e.g. by using them for pollination of orchard
trees/vegetables, and specifically, Japanese honeybee (Apis cerana iaponica), Western
honey bee (Apis mellifera), Bumblebee (Bombus consobrinus wittenburqi, B. diversus
diversus, B. hypocrita hypocrita, B. iqnitus, B. terrestris), Hornfaced bee (Osmia
cornifrons), Silkworm (Bombvx mori) may, for example, be mentioned, but the present
30 invention is not restricted thereto.
Natural enemies herein mean organisms which kill specific organisms particularly
specific organisms damaging agricultural crops by predation or parasitism or which
inhibit propagation of such organisms, and specifically, the following organisms may, for
example, be mentioned, but the present invention is not restricted thereto.
35 Parasitic wasps belonging to the family Braconidae such as Dacnusa sasakawai,
Dacnusa sibirica, Aphidius colemani, Apanteles qlomeratus, etc., the family Aphelinidae
such as Aphelinus albipodus, Aphelinus asvchis, Aphelinus qossypii, Aphelinus
maculatus, Aphelinus varipes, Encarsia formosa, Eretmocerus eremicus, Eretmocerus
mundus, etc., and the family Eulophidae such as Chrysocharis pentheus,
40 Neochrvsocharis formosa, Diqlyphus isaea, Hemiptarsenus varicornis, etc.;
Aphidophagous gall midge (Aphidoletes aphidimyza); Seven-spot ladybird (Coccinella
septempunctata); Asian lady beetle (Harmonia axyrjdjs); Predatory beetle (Propylea
iaponica); Anthocorid predatory bugs belonging to the family Anthocoridae such as
Orius minutus, Orius naqaii, Orius sauteri. Minute pirate bug (Orius strigicollis), etc.;
45 Predatory mirids belonging to the family Miridae such as Pilophorus typicus,
Nesidiocoris tenuis, etc.; Predatory thrips belonging to the family Aeolothripidae such as
Franklinothrips vespiformis, etc.; Green lacewing belonging to the family Chrysopidae
such as Dichochrvsa formosanus, Chrysoperla nipponensis, etc.; Predatory mites
50
belonging to the family Phytoseiidae such as Neoseiulus californicus, Amblvseius
cucumeris, Amblvseius degenerans, Amblvseius swirskii, Phvtoseiulus persimilis, etc.;
Wolf spider (Pardosa pseudoannulata); Crab spider (Misumenops tricuspidatus).
The compounds of the present invention represented by the formula (I) can be
5 produced, for example, by the following processes.
Process A
R2 R3 S~\ ° R2 R3 /^i(&J N^Q base W N^
R1 R1
(HI) (II) (la)
A compound represented by the formula (II) [wherein G2, R1, R2 and R3 are the
same as defined above] or its salt (such as a hydrochloride or a hydrobromide) is
10 reacted with a compound represented by the formula (III) [wherein G1 is the same as
defined above, and J1 is a chlorine atom, a bromine atom, a C1-C4 alkylcarbonyloxy
group (such as a pivaloyloxy group), a C1-C4 alkoxycarbonyloxy group (such as an
isobutyloxycarbonyloxy group), an azolyl group (such as an imidazol-1-yl group) or the
like], if necessary in a solvent such as benzene, toluene, dichloromethane, chloroform,
15 1,2-dichloroethane, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, 1,4-dioxane,
ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, water or a
mixture of two or more of them in an any ratio, if necessary in the presence of a base
such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, sodium
acetate, triethylamine, ethyl diisopropylamine, N-methylmorpholine, pyridine or 4-
20 (dimethylamino)pyridine in an amount of from 1 to 3 equivalents per 1 equivalent of the
compound represented by the formula (II), within a temperature range of from 0°C to the
refluxing temperature of the reaction mixture for from 30 minutes to 24 hours, to obtain
a compound of the present invention represented by the formula (la) [wherein G1, R1, R2
and R3 are the same as defined above] which is a compound of the formula (I) wherein
25 W is an oxygen atom, and R4 is a hydrogen atom.
Some of the compounds represented by the formula (III) used in this process are
known compounds, and some of them are commercially available. The rest of them
can be synthesized in accordance with known methods disclosed in the literature, for
example, by a method in accordance with the method disclosed in J. Med. Chem.,
30 1991, vol.34, p.1630, etc., in which a corresponding known carboxylic acid is reacted
with a halogenating agent such as thionyl chloride, phosphorus pentachloride or oxalyl
chloride, a method in accordance with the method disclosed in Tetrahedron Letters,
2003, vol.44, p.4819, J. Med. Chem., 1991, vol.34, p.222, etc., in which a corresponding
known carboxylic acid is reacted with an organic acid halide such as pivaloyl chloride or
35 isobutyl chloroformate in the presence of a base if necessary, or a method disclosed in
J. Org. Chem., 1989, vol.54, p.5620, etc., in which a corresponding known carboxylic
acid is reacted with carbonyl diimidazole, sulfonyl diimidazole or the like.
Process B
51
W R2R3
HjNO-R1
(V) ®"i R4 O
(IV)
(I)
1 Equivalent of a compound represented by the formula (IV) [wherein G\ G2, W,
R2, R3 and R4 are the same as defined above] is reacted with from 1 to 3 equivalents of
a compound represented by the formula (V) [wherein R1 is the same as defined above]
or its salt (such as a hydrochloride or a hydrobromide), if necessary in a solvent such as
benzene, toluene, methanol, ethanol, tetrahydrofuran, acetic acid, pyridine, water or a
mixture of two or more of them in any ratio, if necessary in the presence of a base such
as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,
sodium hydrogen carbonate, sodium acetate, triethylamine or pyridine in an amount of
from 1 to 4 equivalents per 1 equivalent of the compound represented by the formula
(IV), or with hydrochloric acid, sulfuric acid or the like as a catalyst in an amount of from
0.1 to 1 equivalent per 1 equivalent of the compound represented by the formula (IV),
within a temperature range of from room temperature to the refluxing temperature of the
reaction mixture for from 1 to 48 hours to obtain a compound of the present invention
represented by the formula (I) [wherein G\ G2, W, R1, R2, R3 and R4 are the same as
defined above].
Process C
&
W
II c,
i . II
H2NOH
R"
(IV)
O
OH
(VI)
J2-R'
(VII)
base
(I)
1 Equivalent of a compound represented by the formula (IV) [wherein G1, G2, W,
R2, R3 and R4 are the same as defined above] and from 1 to 3 equivalents of
hydroxylamine or its salt (such as a hydrochloride or a sulfate) are reacted, if necessary
in a solvent such as methanol, ethanol, 1,4-dioxane, acetonitrile, pyridine, water or a
mixture of two or more of them in any ratio, if necessary in the presence of a base such
as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,
sodium hydrogen carbonate, sodium acetate, ethyldiisopropylamine or pyridine in an
amount of from 1 to 4 equivalents per 1 equivalent of the compound represented by the
52
formula (IV), within a temperature range of from room temperature to the refluxing
temperature of the reaction mixture for from 1 to 24 hours to obtain a compound
represented by the formula (VI) [wherein G\ G2, W, R2, R3 and R4 are the same as
defined above]. 1 Equivalent of the obtained compound represented by the formula
5 (VI) and from 1 to 10 equivalents of a compound represented by the formula (VII)
[wherein R1 is the same as defined above, J2 is a chlorine atom, a bromine atom, an
iodine atom, a C1-C4 alkylsulfonate group (such as a methanesulfonyloxy group), a C1-
C4 haloalkylsulfoante group (such as a trifluoromethanesulfonyloxy group) or the like]
are reacted, if necessary in an atmosphere of an inert gas such as nitrogen or argon, if
10 necessary in a solvent such as benzene, toluene, dichloromethane, chloroform,
tetrahydrofuran, acetone, acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, water
or a mixture of two or more of them in any ratio, if necessary in the presence of a base
such as sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide,
potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate or
15 triethylamine in an amount of from 1 to 3 equivalents per 1 equivalent of the compound
represented by the formula (VI), if necessary with tetrabutylammonium bromide,
potassium iodide or the like as a catalyst in an amount of from 0.01 to 1 equivalent per 1
equivalent of the compound represented by the formula (VI), within a temperature range
of from room temperature to the refluxing temperature of the reaction mixture for from 1
20 to 24 hours to obtain a compound of the present invention represented by the formula
(I) [wherein G1, G2, W, R\ R2, R3 and R4 are the same as defined above].
The compounds represented by the formula (VII) used in this process are known
compounds, and some of them are commercially available. The rest of them can be
synthesized in accordance with known methods disclosed in the literature regarding
25 known compounds.
Process D
(VIII) OH
(VI)
J2-R]
(VII)
base
(I)
30
A compound represented by the formula (VIII) [wherein G\ G2, W, R2, R3 and R4
are the same as defined above] is reacted, for example, with sodium nitrite by a method
in accordance with J. Org. Chem., 2004, vol. 69, p. 8997, etc., with tin(ll) chloridephenylmercaptan
by a method in accordance with Tetrahedron, 1990, vol. 46, p. 587,
etc., or with carbon disulfide by a method in accordance with J. Org. Chem., 1983, vol.
48, p. 2766, etc., to obtain a compound represented by the formula (VI) [wherein G1, G2,
53
W, R2, R3 and R4 are the same as defined above].
The compound represented by formula (VI) thus obtained may be reacted with a
compound represented by the formula (VII) [wherein R1 and J2 are the same as defined
above] in the same manner as in process C to obtain a compound of the present
invention represented by the formula (I) [wherein G1, G2, W, R1, R2, R3 and R4 are the
same as defined above].
Process E
^~>* ®
O
II
R2
H
R3
if
C&I
R1
J3-R4
(IX)
(la)
1 Equivalent of a compound of the present invention represented by the formula
(la) [wherein G\ G2, R1, R2 and R3 are the same as defined above] which is a
10 compound of the formula (I) wherein W is an oxygen atom and R4 is a hydrogen atom,
is reacted with from 1 to 10 equivalents of a compound represented by the formula (IX)
[wherein R4 is the same as defined above except for a hydrogen atom, and J3 is a
favorable leaving group such as a chlorine atom, a bromine atom, an iodine atom, a Ci-
C4 alkylcarbonyloxy group (such as a pivaloyloxy group), a C1-C4 alkylsulfonate (such
15 as a methanesulfonyloxy group), a C1-C4 haloalkylsulfonate group (such as a
trifluoromethanesulfonyloxy group), an arylsulfonate group (such as a
benzenesulfonyloxy group or a p-toluenesulfonyloxy group), an azolyl group (such as an
imidazol-1-yl group) or the like], if necessary in a polar solvent such as tert-butyl methyl
ether, tetrahydrofuran, 1,4-dioxane, acetonitrile or N,N-dimethylformamide, if necessary
20 in the presence of a base such as sodium hydride, potassium tert-butoxide, potassium
hydroxide, potassium carbonate, triethylamine or pyridine in an amount of from 1 to 3
equivalents per 1 equivalent of the compound represented by the formula (la), within a
temperature range of from 0 to 90°C for from 10 minutes to 24 hours to obtain a
compound of the present invention represented by the formula (lb) [wherein G1, G2, R1,
25 R2 and R3 are the same as defined above, and R4 is the same as defined above except
for a hydrogen atom] which is a compound of the formula (I) wherein W is an oxygen
atom.
Some of the compounds represented by the formula (IX) used in this process are
known compounds, and some of them are commercially available. The rest of them
30 can be synthesized in accordance with known methods disclosed in the literature
regarding known compounds, for example, the method disclosed in Chem. Pharm. Bull.,
1986, vol. 34, p. 540 and 2001, vol. 49, p. 1102, J.Am. Chem. Soc, 1964, vol. 86, p.
4383, J. Org. Chem., 1983, vol. 48, p. 5280, Org. Synth., 1988, collective vol. 6, p. 101,
Synlett, 2005, p. 2847, Synthesis, 1990, p. 1159, JP05/125017, EP0,051,273,
35 GB2,161,802 or the like.
Process F
54
P2,Sa5
1 Equivalent of a compound of the present invention represented by the formula
(lb) [wherein G1, G2, R1, R2, R3 and R4 are the same as defined above] which is a
compound of the formula (I) wherein W is an oxygen atom, and from 1 to 10 equivalents
of a sulfidizing agent such as phosphorus pentasulfide, phosphorus pentasulfide-HMDO
5 (hexamethyldisiloxane) or Lawesson's Reagent (2,4-bis(4-methoxyphenyl)-1,3,2,4-
dithiadiphosphetane=2,4-disulfide) are reacted, if necessary in a solvent such as
benzene, toluene, chlorobenzene, dichloromethane, chloroform, 1,2-dimethoxyethane,
tetrahydrofuran, 1,4-dioxane or HMPA, if necessary in the presence of a base such as
sodium hydrogen carbonate, triethylamine or pyridine in an amount of from 1 to 4
10 equivalents per 1 equivalent of the compound represented by the formula (lb), within a
temperature range of from room temperature to the refluxing temperature of the reaction
mixture for from 10 minutes to 50 hours, or in pyridine as a base in an amount sufficient
as a solvent within a temperature range of from 80°C to the refluxing temperature of the
reaction mixture for from 1 to 3 hours, to obtain a compound of the present invention
15 represented by the formula (Ic) [wherein G1, G2, R\ R2, R3 and R4 are the same as
defined above] which is a compound of the formula (I) wherein W is a sulfur atom.
In processes A to F, the reaction mixture after a reaction can be worked up by an
ordinary procedure such as direct concentration, a procedure such that the reaction
mixture is dissolved in an organic solvent, washed with water and concentrated, or a
20 procedure such that the reaction mixture is poured into ince water, extracted with an
organic solvent and concentrated, to obtain the desired oxime-substituted amide
compound. If purification is needed, the desired oxime-substituted amide compound
may be isolated or purified by an optional purification method such as recrystallization
or fractionation by column chromatography, thin layer chromatography or liquid
25 chromatography.
The compound represented by the formula (II) used in process A may be
synthesized, for example, by reaction schemes 1 to 3.
Reaction Scheme 1
55
C
II o
R2R3 / "N
(X)
o
w
o
HjNO-R1
(V)
R2 R3
H2»NH2 R2N
(XII)
1 Equivalent of a compound represented by the formula (X) [wherein G2, R2 and
R3 are the same as defined above, and J4 is a chlorine atom, bromine atom, an iodine
atom or the like] and from 1 to 1.5 equivalents of potassium phthalimide are reacted, in
a solvent such as toluene, dichloromethane, tetrahydrofuran, 1,4-dioxane, acetone,
N,N-dimethylformamide, N,N-dimethylacetamide or dimethylsulfoxide, if necessary in
the presence of from 0.1 to 2 equivalents of a base such as sodium carbonate,
potassium carbonate or sodium hydrogen carbonate, if necessary with from 0.1 to 1
equivalent of tetrabutylammonium iodide, tributylhexadecylphosphonium bromide,
crown ether (18-Crown-6) or the like as a catalyst, within a temperature range of from
room temperature to the refluxing temperature of the reaction mixture for from 0.5 to 24
hours to obtain a compound represented by the formula (XI) [wherein G2, R2 and R3 are
the same as defined above]. The obtained compound represented by the formula (XI)
is reacted with a compound represented by the formula (V) [wherein R1 is the same as
defined above] under the same conditions as in process B to obtain a compound
represented by the formula (XII) [wherein G2, R1, R2 and R3 are the same as defined
above].
Then, the compound represented by the formula (XII) is reacted with hydrazine
monohydrate or aqueous hydrazine in an amount of from 1 to 4 equivalents per 1
equivalent of the compound represented by the formula (XII), if necessary in a solvent
such as toluene, dichloromethane, chloroform, methanol, ethanol, tetrahydrofuran, 1,4-
dioxane, water or a mixture of two or more of them in any ratio, if necessary in an
atmosphere of an inert gas such as nitrogen or argon, within a temperature range of
from room temperature to the refluxing temperature of the reaction mixture for from 1 to
24 hours to obtain a compound represented by the formula (II) [wherein G2, R1, R2 and
R3 are the same as defined above].
Some of the compounds represented by the formula (X) used in this process are
known compounds, and some of them are commercially available. The rest of them
can be synthesized in accordance with known methods disclosed in the literature
regarding known compounds.
Reaction Scheme 2
56
XB C
II
o
(X)
R2 R3
H2NNH2 HN
10
15
A compound represented by the formula (X) [wherein G2, R2, R3 and J4 are the
same as defined above] and the compound represented by the formula (V) [wherein R1
is the same as defined above] are reacted under the same conditions as in process B to
obtain a compound represented by the formula (XIII) [wherein G2, R1, R2, R3 and J4 are
the same as defined above], and the obtained compound represented by the formula
(XIII) is reacted with potassium phthalimide in the same manner as in reaction scheme
1 to obtain a compound represented by the formula (XII) [wherein G2, R1, R2 and R3 are
the same as defined above].
Then, the compound represented by the formula (XII) is reacted with hydrazine
monohydrate or aqueous hydrazine in the same manner as in reaction scheme 1 to
obtain a compound represented by the formula (II) [wherein G2, R1, R2, and R3are the
same as defined above].
Reaction Scheme 3
M
(XIV) (XV)
57
O R2R3
O N X
H
(XVI)
II o
R
o'
O R2R3
C N ^ C
H M
O
(XVII)
Gz
HjNO-R1
(V)
R2 R
H2N
(XVIII)
A known compound represented by the formula (XIV) [wherein G2 is the same as
defined above, and J4 is a hydrogen atom, a chlorine atom, a bromine atom, an iodine
atom or the like] is reacted with an alkyllithium, a Grignard reagent or the like in
accordance with a method disclosed in Tetrahedron Lett., 2002, vol. 43, p. 8223 and
5 2005, vol. 46, p. 8587, J. Org. Chem., 2006, vol. 71, p. 9861, etc., to prepare a
compound represented by the formula (XV) [wherein G2 is the same as defined above,
and M is Li, MgCI, MgBr, Mgl or the like], and the prepared compound represented by
the formula (XV) and a compound represented by the formula (XVI) [wherein R2 and R3
are the same as defined above, R is a tert-butyl group, a benzyl group or the like, and J5
10 is a dimethylamino group, a N-methylmethoxyamino group, a piperidin-1-yl group, a
benzotriazol-1-yl group or the like] are reacted to obtain a compound represented by the
formula (XVII) [wherein G2, R2, R3 and R are the same as defined above].
Some of the compounds represented by the formula (XVI) are known compounds,
and some of them are commercially available. The rest of them can be synthesized in
15 accordance with known methods disclosed in the literature regarding known
compounds.
Then, the compound represented by the formula (XVII) and a compound
represented by the formula (V) [wherein R1 is the same as defined above] are reacted
under the same conditions as in process B to obtain a compound represented by the
20 formula (XVIII) [wherein G2, R\ R2, R3 and R are the same as defined above]. The
obtained compound represented by the formula (XVIII) is deprotected under known
reaction conditions with respect to the substituent R to obtain a compound represented
by the formula (II) [wherein G2, R1 R2, and R3 are the same as defined above] or its salt
(such as a hydrochloride, a hydrobromide, a trifluoroacetate or a p-toluenesulfonate).
25 The compound represented by the formula (IV) used in processes B and C may
be synthesized, for example, by reaction scheme 4 or 5.
Reaction Scheme 4
58
v_y R4 o v_y R4 o
(III) (XIX) (IVb)
A compound represented by the formula (III) [wherein G1 and J1 are the same as
defined above] and a compound represented by the formula (XIX) [wherein G2, R2 and
R3 are the same as defined above, and R4 is a hydrogen atom, a C1-C6 alkyl group or
the like] or its salt (such as a hydrochloride, a hydrobromide, a trifluoroacetate or a ptoluenesulfonate)
are reacted under the same conditions as in process A to obtain a
compound represented by the formula (IVb) [wherein G\ G2, R2 and R3 are the same as
defined above, and R4 is a hydrogen atom, a C1-C6 alkyl group or the like] which is a
compound of the formula (IV) wherein W is an oxygen atom.
Reaction Scheme 5
O R2R3 O R2 R3
^ C . X OH _ / ^ X ^
v_y R4 o v_y R4 o
(XX) (XXI)
(XV) V RyRJ f G2)
O R2 R3 / ^N
*N C
v_y R4 O
(IVb)
10 A compound represented by the formula (XX) [wherein G\ R2, R3 and R4 are the
same as defined above] is reacted for example by a method disclosed in J. Med.
Chem., 2004, vol. 47, p. 6884, Bioorganic & Med. Chem. Lett., 2012, vol. 22, p. 5485,
etc. to prepare a compound represented by the formula (XXI) [wherein G1, R2, R3, R4
and J5 are the same as defined above], and the obtained compound represented by the
15 formula (XXI) is reacted with a compound represented by the formula (XV) [wherein G2
and M are the same as defined above] in the same manner as in reaction scheme 3 to
obtain a compound represented by the formula (IVb) [wherein G\ G2, R2 and R3 are the
same as defined above, and R4 is a hydrogen atom, a C1-C6 alkyl group or the like]
which is a compound of the formula (IV) wherein W is an oxygen atom.
20 Some of the compounds represented by the formula (XX) used in this process are
known compounds, and some of them are commercially available. The rest of them
can be synthesized in accordance with known methods disclosed in the literature
regarding known compounds.
Some of the compounds represented by the formula (V) used in process B are
25 known compounds, and some of them are commercially available. The rest of them
can be synthesized, for example, as follows.
Reaction Scheme 6
59
if^rx
P J6-Ri
W (XXII) f ^ ^ A /R H2^H2
[-OH *~ I N-O *• HjNO-R1
^ W (V)
o o
(XXIII)
That is, N-hydroxyphthalimide and a compound represented by the formula (XXII)
[wherein R1 is the same as defined above, and J6 is a chlorine atom, a bromine atom,
an iodine atom or hydroxy group] are reacted, for example, in accordance with a
method disclosed in J. Med. Chem., 2008, vol. 51, p. 4601, WO2008/055013, etc. to
5 obtain a compound represented by the formula (XXIII) [wherein R1 is the same as
defined above], and the obtained compound represented by the formula (XXIII) is
reacted with hydrazine monohydrate or aqueous hydrazine under the same conditions
as in reaction scheme 1 to obtain a compound represented by the formula (V) [wherein
R1 is the same as defined above].
10 Some of the compounds represented by the formula (XXII) used in this process
are known compounds, and some of them are commercially available. The rest of
them can be synthesized in accordance with known methods disclosed in the literature
regarding known compounds.
The compound represented by the formula (VIII) used in process D may be
15 synthesized, for example, as follows.
Reaction Scheme 7
O 2 O O
N (XXIV) M n &**—~&^~&Tf
(HI) (XXV) (XXVI)
r
02N
(XXVII)
That is, a compound represented by the formula (III) [wherein G1 and J1 are the
same as defined above] and a compound represented by the formula (XXIV) [wherein
R4 is a hydrogen atom, a C1-C6 alkyl group or the like] or its salt (such as a
20 hydrochloride) are reacted under the same conditions as in process A to obtain a
compound represented by the formula (XXV) [wherein G1 is the same as defined above,
and R4 is a hydrogen atom, a C1-C6 alkyl group or the like].
The primary amines represented by the formula (XXIV) used in this process are
known compounds, and some of them are commercially available. The rest of them
25 can be synthesized in accordance with known methods disclosed in the literature
regarding known primary amines.
60
Then, the obtained compound represented by the formula (XXV) is reacted, for
example, in accordance with a method disclosed in WO2007/026965, Tetrahedron Lett.,
1994, vol. 35, p. 7107, WO2006/067103, J. Org. Chem., 1987, vol. 52, p. 5475, etc. to
obtain a compound represented by the formula (XXVI) [wherein G1 is the same as
5 defined above, R4 is a hydrogen atom, a C1-C6 alkyl group or the like, and J7 is a
chlorine atom, a C1-C4 alkylcarbonyloxy group (such as an acetoxy group), a C1-C4
alkylsulfonate group (such as a methanesulfonyloxy group) or an arylsulfonate group
(such as a benzenesulfonyloxy group)].
The obtained compound represented by the formula (XXVI) and a compound
10 represented by the formula (XXVII) [wherein G2 is the same as defined above] are
reacted, for example, in accordance with a method disclosed in Bull. Chem. Soc. Jpn.,
2004, vol. 77, p. 2219, Tetrahedron Lett., 2006, vol. 47, p. 3501, J. Org. Chem., 2004,
vol. 69, p. 8997, etc. to obtain a compound represented by the formula (Vlllb) [wherein
G1 and G2 are the same as defined above, and R4 is a hydrogen atom, a C1-C6 alkyl
15 group or the like] which is the compound of the formula (VIII) wherein W is an oxygen
atom, and R2 and R3 are hydrogen atoms.
The compound represented by the formula (XIX) may be produced by
deprotecting a compound represented by the formula (XVII) obtainable by reaction
scheme 3 by a known method or may be synthesized, for example, by any of reaction
20 schemes 8 to 11.
Reaction Scheme 8
r• pN R2R3 / O i N-L-N -J4-R'R3 zO\ ^ R2R3 / Ot
Lij o J4 x r "—' ** 71 ^> v —*~ H2N' ^c
II L\ J n "
(X) (XXVIII) (XlXa)
A compound represented by the formula (X) [wherein G2, R2, R3 and J4 are the
same as defined above] and hexamethylenetetramine are reacted, for example, in
accordance with a method disclosed in J. Heterocyclic Chem., 1987, vol. 24, p. 297 etc.,
25 if necessary in a solvent such as toluene, dichloromethane, chloroform, ethanol, diethyl
ether, tetrahydrofuran, acetone, ethyl acetate, acetonitrile, water or a mixture of two or
more of them in any ratio, if necessary with sodium iodide or the like, within a
temperature range of from room temperature to the refluxing temperature of the reaction
mixture for from 1 to 24 hours to obtain a quaternary ammonium salt represented by the
30 formula (XXVIII) [wherein G2, R2, R3 and J4 are the same as defined above]. The
obtained quaternary ammonium salt represented by the formula (XXVIII) is hydrolyzed
in a solvent such as methanol, ethanol, acetonitrile, water or a mixture of two or more of
them in any ratio, in the presence of an acid catalyst such as hydrochloric acid or
hydrobromic acid within a temperature range of from room temperature to the refluxing
35 temperature of the reaction mixture for from 0.5 to 48 hours to obtain a hydrochloride or
hydrobromide of a compound represented by the formula (XlXa) [wherein G2, R2 and R3
are the same as defined above] which is a compound of the formula (XIX) wherein R4 is
a hydrogen atom. Further, after completion of the reaction, by neutralization with a
base such as sodium hydroxide or potassium hydroxide, a free amine may be isolated.
40 Reaction Scheme 9
61
ii II n
o o o
(X) (XXIX) (XlXa)
A compound represented by the formula (X) [wherein G2, R2, R3 and J4 are the
same as defined above] and sodium azide or lithium azide are reacted, for example, in
accordance with a method disclosed in J. Org. Chem., 1986, vol. 51, p. 3374, etc., if
necessary in a solvent such as toluene, methanol, tetrahydrofuran, acetone, N,N-
5 dimethylformamide, acetonitrile, dimethylsulfoxide, water or a mixture of two or more of
them in any ratio, if necessary with methyl trioctylammonium chloride, potassium iodide
or the like as a catalyst, within a temperature range of from 0 to 50°C for from 0.5 to 18
hours to obtain a compound represented by the formula (XXIX) [wherein G2, R2 and R3
are the same as defined above]. The obtained compound represented by formula
10 (XXIX) is hydrogenated in a solvent such as methanol, ethanol, diethyl ether, water or a
mixture of two or more of them in any ratio in the presence of palladium or a platinum
catalyst, if necessary with hydrochloric acid or the like, in an atmosphere of hydrogen
under 1 to 10 atm at room temperature for from 0.5 to 24 hours; is reacted with a
reducing agent such as tin(ll) chloride in a solvent such as dichloromethane, methanol,
15 ethanol or ethyl acetate within a temperature range of from room temperature to 60°C
for from 3 to 18 hours; or is reacted with triphenylphosphine and water in a solvent such
as tetrahydrofuran, water or a mixture of the two in any ratio within a temperature range
of from 0°C to room temperature for from 0.5 to 24 hours, to obtain a compound (XlXa)
[wherein G2, R2 and R3 are the same as defined above] which is a compound of the
20 formula (XIX) wherein R4 is a hydrogen atom. Further, after completion of the reaction
if necessary, the compound of the formula (XlXa) may be treated with hydrochloric acid,
hydrobromic acid, trifluoroacetic acid, p-toluenesulfonic acid or the like to obtain a salt
thereof.
Reaction Scheme 10
CHO
R 2 R 3 /7J\ Na NN ?\ Rv,R U«\ + R2R3
y (G2 ) NCHO C X X J H V
II I II L II
(X) (XXX) (XlXa)
25 A compound represented by the formula (X) [wherein G2, R2, R3 and J4 are the
same as defined above] and diformylimide sodium salt are reacted, for example, in
accordance with a method disclosed in Tetrahedron Lett., 1989, vol. 30, p. 5285 etc., in
a solvent such as N,N-dimethylformamide or acetonitrile within a temperature range of
from room temperature to the refluxing temperature of the reaction mixture for from 2 to
30 24 hours to obtain a compound represented by the formula (XXX) [wherein G2, R2 and
R3 are the same as defined above]. The obtained compound represented by the
formula (XXX) is hydrolyzed in a solvent such as methanol, ethanol, 1,4-dioxane, water
or a mixture of two or more of them in any ratio with an acid such as hydrochloric acid
within a temperature range of from room temperature to the refluxing temperature of the
35 reaction mixture for from 1 to 24 hours to obtain a hydrochloride or the like of a
62
compound represented by the formula (XlXa) [wherein G2, R2 and R3 are the same as
defined above] which is a compound of the formula (XIX) wherein R4 is a hydrogen
atom. Further, after completion of the reaction, by neutralization with a base such as
sodium hydroxide or potassium hydroxide, a free amine may be isolated.
Reaction Scheme 11
H2IN-R4
RyR3 f & ) RyR3 ( & )
n i. n
O R4 O
(X) (XIX)
A compound represented by the formula (X) [wherein G2, R2, R3 and J4 are the
same as defined above] and an amine represented by the formula (XXIV) [wherein R4 is
a hydrogen atom, a Ci-Ce alkyl group or the like] or its salt are reacted, if necessary in a
solvent such as toluene, dichloromethane, methanol, ethanol, diethyl ether,
tetrahydrofuran, 4-methyl-2-pentanone, ethyl acetate, N,N-dimethylformamide,
acetonitrile, water or a mixture of two or more of them in any ratio, in an excessive
amount of the compound represented by the formula (XXIV) or in the presence of a
base such as sodium hydroxide, potassium carbonate, sodium carbonate, sodium
hydrogen carbonate, triethylamine or ethyldiisopropylamine, within a temperature range
of from 0°C to the refluxing temperature of the reaction mixture for from 1 to 24 hours to
obtain a compound represented by the formula (XIX) [wherein G2, R2 and R3 are the
same as defined above, and R4 is a hydrogen atom, a C1-C6 alkyl group or the like].
Some of the compounds represented by the formula (XXVII) are known
compounds, and some of them are commercially available. The rest of them may be
synthesized, for example, by reaction scheme 12 or 13.
Reaction Scheme 12
AgN02
o r r ^ r ^ Y4
J4 Y5 2 N02 Y
(XXXI) (XXVIIa)
A compound represented by the formula (XXXI) [wherein Y1, Y2, Y3, Y4, Y5 and J4
are the same as defined above] is reacted with silver nitrite in accordance with a known
method disclosed in the literature, for example, a method disclosed in J. Org. Chem.,
2004, vol. 69, p. 6907, etc., if necessary in a solvent such as benzene, diethyl ether,
tert-butyl methyl ether, acetonitrile, water or a mixture of two or more of them in any
ratio, within a temperature range of from 0°C to room temperature for from 30 minutes
to 24 hours, or reacted with sodium nitrite-urea, for example, in accordance with a
method disclosed in Tetrahedron, 2009, vol. 65, p. 1660, etc., if necessary in a solvent
such as N,N-dimethylformamide within a temperature range of from -78°C to room
temperature for from 1 to 6 hours, to obtain a compound represented by the formula
(XXVIIa) [wherein Y1, Y2, Y3, Y4 and Y5 are the same as defined above] which is a
compound of the formula (XXVII) wherein G2 is G2-1.
63
The compounds represented by the formula (XXXI) used are known compounds,
and some of them are commercially available. The rest of them can be synthesized
from known compounds in accordance with known methods disclosed in the literature.
Reaction Scheme 13
CH3NO2
base
NO,
(XXXII) (XXVIIb)
5 A compound represented by the formula (XXXII) [wherein Y1, Y2, Y3, Y4 and J4 are
the same as defined above] and nitromethane are reacted in accordance with a known
method disclosed in the literature, for example, a method disclosed in Heterocycles,
1987, vol. 26, p. 3259, WO2004/096772, etc., if necessary in a solvent such as
tetrahydrofuran or dimethylsulfoxide, if necessary in the presence of a base such as
10 sodium hydride or potassium tert-butoxide within a temperature range of from 0 to 80°C
for from 1 to 24 hours to obtain a compound of the formula (XXVIIb) [wherein Y1, Y2, Y3
and Y4 are the same as defined above] which is a compound of the formula (XXVII)
wherein G2 is G2-2.
The compounds represented by the formula (XXXII) used in this process are
15 known compounds, and some of them are commercially available. The rest of them
can be synthesized in accordance with known methods disclosed in the literature
regarding known compounds.
In the respective reaction schemes, the compounds after a reaction can be
worked up by an ordinary procedure to obtain intermediates to be material compounds
20 in processes A to D.
Further, the respective intermediates produced in such procedure may be used in
the next step reaction without isolation nor purification.
As the oxime-substituted amide compounds of the present invention represented
by the formula (I) which can be produced by such processes, specifically, the following
25 compounds of a first group and compounds of a second group may, for example, be
mentioned. However, the following compounds of a first group and compounds of a
second group merely exemplify the present invention, and the oxime-substituted amide
compounds of the present invention are by no means restricted thereto.
Further, combinations of substituents in the compounds of the above respective
30 groups are shown in Tables 2 and 3. In the Tables, Et denotes ethyl group, n-Pr and
Pr-n denote normal propyl group, i-Pr and Pr-i denote isopropyl group, c-Pr and Pr-c
denote cyclopropyl group, n-Bu and Bu-n denote normal butyl group, i-Bu and Bu-i
denote isobutyl group, s-Bu and Bu-s denote secondary butyl group, c-Bu and Bu-c
denote cyclobutyl group, t-Bu and Bu-t denote tertiary butyl group, Pen denotes pentyl
35 group, c-Pen and Pen-c denote cyclopentyl group, Hex denotes hexyl group, c-Hex and
Hex-c denote cyclohexyl group, Ph denotes phenyl group, 1-Naph denotes 1-naphthyl
group, and 2-Naph denotes 2-naphthyl group.
Further, in Tables 2 and 3, aromatic heterocyclic rings represented by D-1-1a to D-
35-b have the following structures, respectively.
For example, the expression "CH2(D-5-3b)-3-G" means a 3-chloroisoxazol-5-
ylmethyl group.
In the Tables, aliphatic heterocyclic rings represented by E-2-1a to E-17-3a have
the following structures, respectively.
For example, the expression "CH2(E-4-1a)CHO" means a 1-formylazetidin-2-
ylmethyl group.
In the Tables, partial saturated heterocyclic rings represented by M-3-b to M-19-a
have the following structures, respectively.
For example, the expression "CH2(M-4-2a)CH3" means a 3-methyl-4,5-
dihydroisoxazol-5-ylmethyl group.
Further, in the Tables, T-1 to T-9 have the following structures, respectively.
Compounds of First Group ([l]-1 to [l]-68)
Combinations of substituents in the compounds of the above first group are shown
in Table 2. In Table 2, the expression (R) or (S) in the column substituent R2 means
5 that the proportion of the R isomer or the S isomer is at least 90% in a mixture ratio of
optical isomers due to the carbon atom attached to R2.
The expressions G2-1 to G2-10 in the column substituent G2 mean the following
specific structures, respectively.
The expression "-" in the columns substituents Y2, Y4 and Y5 means that there is
no corresponding substituent present.
The expression (E) or (Z) in the column substituent R1 means that the proportion
5 of the E-isomer or the Z-isomer is at least 90% in a mixture ratio of oxime geometrical
isomers attached to the substituent R1.
Compounds of Second Group ([l]-69 to [l]-92)
Combinations of substituents in the compounds of a second group are shown in
Table 3.
159
The compounds of the present invention are capable of controlling pathogens
causing plant diseases in Tracheophyta such as plants of the order Pinales, the group
magnoliids, the group monocots and the group eudicots, and pathogens causing
infections of Vertebrata such as animals of the class Mammalia, the class Aves, the
5 class Reptilia and the class Actinopterygii, and pests such as plant-parasitic or animalparasitic
nematodes, Acanthocephala, Platyhelminthes and Protozoa.
Pests against plants may, for example, be fungi of the phylum Ascomycota, fungi
of the phylum Basidiomycota, fungi of the phylum Chitridiomycota, fungi of the phylum
Blastocladiomycota, fungi of the phylum Mucoromycotina, protists of the phylum
10 Cercozoa, microorganisms of the phylum Heterokontophyta class Oomycetes, grampositive
bacteria of the phylum Actinobacteria, gram-positive bacteria of the phylum
Tenericutes, gram-negative bacteria of the phylum Proteobacteria, nematodes of the
order Aphelenchida and nematodes of the order Tylenchida. The compounds of the
present invention have excellent controlling effect particularly on plant pathogenic fungi
15 belonging to the phylum Ascomycota and the phylum Basidiomycota, and plant-parasitic
nematodes belonging to the order Aphelenchida and the order Tylenchida at low doses.
Pests against animals may, for example, be fungi of the phylum Ascomycota, fungi
of the phylum Basidiomycota, gram-positive bacteria of the phylum Actinobacteria,
gram-positive bacteria of the phylum Firmicutes, gram-positive bacteria of the phylum
20 Tenericutes, gram-negative bacteria of the phylum Proteobacteria, nematodes of the
order Enoplida, nematodes of the order Rhabditida, nematodes of the order
Strongylida, nematodes of the order Ascaridida, nematodes of the order Spirurida,
microorganisms of the phylum Acanthocephala, cestodes of the order Pseudophyllidea,
cestodes of the order Cyclophyllidea, trematodes of the order Strigeidida, trematodes of
25 the order Echinostomida, trematodes of the order Plagiorchiida, trematodes of the order
Opisthorchiida, amebas, Piroplasmida sporozoa, Haemosporida sporozoa,
Eucoccidiorida sporozoa, Vestibuliferida ciliata, Trichomonadida flagellata,
Diplomonadida flagellata and Kinetoplastida flagellata. Particularly, the compounds of
the present invention have excellent effect to control internal parasites parasitizing
30 animals of the class Mammalia belonging to the family Cebidae, the family
Cercopithecidae, the family Hominidae, the family Leporidae, the family Chinchillidae,
the family Caviidae, the family Cricetidae, the family Muridae, the family Sciuridae, the
family Camelidae, the family Suidae, the family Cervidae, the family Bovidae, the family
Felidae, the family Canidae, the family Mustelidae, the family Equidae, the family
35 Macropodidae and the like, especially animal-parasitic nematodes belonging to the
order Enoplida, the order Rhabditida, the order Strongylida, the order Aphelenchida, the
order Tylenchida, the order Ascaridida and the order Spirurida, parasitizing mammals of
the family Suidae, the family Bovidae, the family Felidae, the family Canidae and the
family Equidae.
40 The compounds of the present invention are also effective on pests which have
acquired resistance to conventional fungicides or nematicides, and the compounds of
the present invention have very useful characteristics such that they have little harmful
effect on non-target animals such as mammals, fishes, crustaceans, natural enemies
and useful insects.
45 The compounds of the present invention may be used in any dosage form such as
a soluble concentrate, an emulsifiable concentrate, a wettable powder, a water soluble
powder, a water dispersible granule, a water soluble granule, a suspension concentrate,
a concentrated emulsion, a suspoemulsion, a microemulsion, a dustable powder, a
160
granule, a tablet or an emulsifiable gel usually after mixed with an appropriate solid
carrier or a liquid carrier, and if necessary, with a surfactant, a penetrant, a spreader, a
thickener, an anti-freezing agent, a binder, an anti-caking agent, a disintegrant, an
antifoaming agent, a preservative, a stabilizer or the like. A formulation in an arbitrary
5 dosage form may be sealed in water-soluble packaging such as a water-soluble capsule
or a water-soluble film, for labor saving or improved safety.
As solid carriers, natural minerals such as quartz, calcite, meerschaum, dolomite,
chalk, kaolinite, pyrophyllite, sericite, halloysite, methahalloysite, kibushi clay, gairome
clay, pottery stone, zeeklite, allophone, Shirasu, mica, talc, bentonite, activated clay,
10 acid clay, pumice, attapulgite, zeolite and diatomaceous earth, calcined natural minerals
such as calcined clay, pearlite, Shirasu-balloons, vermiculite, attapulgus clay and
calcined diatomaceous earth, inorganic salts such as magnesium carbonate, calcium
carbonate, sodium carbonate, sodium hydrogen carbonate, ammonium sulfate, sodium
sulfate, magnesium sulfate, diammonium hydrogen phosphate, ammonium dihydrogen
15 phosphate and potassium chloride, saccharides such as glucose, fructose, sucrose and
lactose, polysaccharides such as starch, cellulose powder and dextrin, organic
substances such as urea, urea derivatives, benzoic acid and benzoic acid salts, plants
such as wood flour, powdered cork, corncob, walnut shell and tobacco stems, fly ash,
white carbon (such as hydrated synthetic silica, anhydrous synthetic silica and hydrous
20 synthetic silicate), fertilizers and the like may be mentioned.
As liquid carriers, aromatic hydrocarbons such as xylene, alkyl (C9 or C10 etc.)
benzene, phenylxylylethane and alkyl (C1 or C3 etc.)naphthalene, aliphatic
hydrocarbons such as machine oil, normal paraffin, isoparaffin and naphthene, mixtures
of aromatic hydrocarbons and aliphatic hydrocarbons such as kerosene, alcohols such
25 as ethanol, isopropanol, cyclohexanol, phenoxyethanol and benzyl alcohol, polyhydric
alcohols such as ethylene glycol, propylene glycol, diethylene glycol, hexylene glycol,
polyethylene glycol and polypropylene glycol, ethers such as propyl cellosolve, butyl
cellosolve, phenyl cellosolve, propylene glycol monomethyl ether, propylene glycol
monoethyl ether, propylene glycol monopropyl ether, propylene glycol monobutyl ether
30 and propylene glycol monophenyl ether, ketones such as acetophenone,
cyclohexanone and y-butyrolactone, esters such as fatty acid methyl esters, dialkyl
succinates, dialkyl glutamate, dialkyl adipates and dialkyl phthalates, acid amides such
as N- alkyl (C1, Cs or C12 etc.)pyrrolidone, fats and oils such as soybean oil, linseed oil,
rapeseed oil, coconut oil, cottonseed oil and castor oil, dimethyl sulfoxide, water and the
35 like may be mentioned.
These solid and liquid carriers may be used alone or in combinations of two or
more.
As surfactants, nonionic surfactants such as polyoxyethylene alkyl ether,
polyoxyethylene alkyl(mono or di)phenyl ether, polyoxyethylene(mono, di or
40 tri)styrylphenyl ether, polyoxyethylenepolyoxypropylene block copolymers,
polyoxyethylene fatty acid (mono or di)ester, sorbitan fatty acid ester, polyoxyethylene
sorbitan fatty acid ester, ethylene oxide adducts of castor oil, acetylene glycol, acetylene
alcohol, ethylene oxide adducts of acetylene glycol, ethylene oxide adducts of acetylene
alcohol and alkyl glycosides, anionic surfactants such as alkyl sulfate salts,
45 alkylbenzenesulfonic acid salts, lignin sulfonate, alkylsulfosuccinic acid salts,
naphthalenesulfonic acid salts, alkylnaphthalenesulfonic acid salts, salts of
naphthalenesulfonic acid-formalin condensates, salts of alkylnaphthalenesulfonic acidformalin
condensates, polyoxyethylene alkyl ether sulfate or phosphate salts,
161
polyoxyethylene(mono or di) alkylphenyl ether sulfate or phosphate salts,
polyoxyethylene(mono, di or tri)styrylphenyl ether sulfate or phosphate salts,
polycarboxylic acid salts (such as polyacrylates, polymaleates and copolymers of maleic
acid and an olefin) and polystyrenesulfonic acid salts, cationic surfactants such as
5 alkylamine salts and alkyl quaternary ammonium salts, amphoteric surfactants such as
amino acid types and betaine types, silicone surfactants and fluorine surfactants may be
mentioned.
The amount of these surfactants is usually preferred to be from 0.05 to 20 parts by
weight per 100 parts by weight of the agent of the present invention, though there is no
10 particular restrictions. These surfactants may be used alone or in combination of two
or more.
The suitable application dose of the compounds of the present invention is
generally about from 0.005 to 50 kg per hectare (ha) in terms of the active ingredient,
though it varies depending on the application situation, the application season, the
15 application method and the cultivated crop.
When the compounds of the present invention are used to control internal
parasites in mammals and birds as farm animals/poultry and pet animals, the
compounds of the present invention may be administered in an effective amount
together with pharmaceutical^ acceptable additives orally, parenterally by injection
20 (intramuscular, subcutaneously, intravenously or intraperitoneally); percutaneously by
dipping, spraying, bathing, washing, pouring-on and spotting-on and dusting, or
intranasally. The compounds of the present invention may be administered through
molded articles such as chips, plates, bands, collars, ear marks, limb bands and ID tags.
The compounds of the present invention are administered in an arbitrary dosage form
25 suitable for the administration route.
The dosage form may be a solid preparation such as a dust, a granule, a wettable
powder, a pellet, a tablet, a ball, a capsule and an molded article containing an active
ingredient, a liquid preparation such as an injection fluid, an oral liquid, a liquid
preparation applied to the skin or coelom, a pour-on preparation, a spot-on preparation,
30 a flowable, an emulsion, and a semisolid preparation such as an ointment and a gel.
A solid preparation may generally be used by oral administration or by
percutaneous or by environmental application after dilution with water or the like. A
solid preparation can be prepared by mixing an active ingredient with an appropriate
vehicle, and with an adjuvant if necessary, and formulating the mixture into a desired
35 dosage form. As the vehicle, an inorganic vehicle such as a carbonate, a hydrogen
carbonate, a phosphate, aluminum oxide, silica or clay or an organic vehicle such as a
saccharide, cellulose, cereal flour or starch may, for example, be mentioned.
An injection fluid may be administered intravenously, intramuscularly or
subcutaneously. An injection fluid can be prepared by dissolving an active ingredient in
40 an appropriate solvent and, if necessary, adding additives such as a solubilizer, an acid,
a base, a buffering salt, an antioxidant and a protectant. As appropriate solvents,
water, ethanol, butanol, benzyl alcohol, glycerin, propylene glycol, polyethylene glycol,
N-methylpyrrolidone and mixtures thereof, physiologically acceptable vegetable oils and
synthetic oils suitable for injection may be mentioned. As solubilizers,
45 polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan ester and
the like may be mentioned. As protectants, benzyl alcohol, trichlorobutanol, phydroxybenzoic
acid esters, n-butanol and the like may be mentioned.
An oral liquid may be administered directly or after dilution and can be prepared in
162
the same manner as an injection fluid.
A flowable, an emulsion or the like may be administered directly or after dilution
percutaneously or by environmental application.
A liquid preparation applied to the skin is administered by dripping, spreading,
5 rubbing, spraying, sprinkling or dipping (soaking, bathing or washing) and can be
prepared in the same manner as an injection fluid.
A pour-on preparation and a spot-on preparation are dripped or sprayed to a
limited area of the skin so that they permeate through the skin and act systemically. A
pour-on preparation and a spot-on preparation can be prepared by dissolving,
10 suspending or emulsifying an active ingredient in an appropriate skin-friendly solvent or
solvent mixture. If necessary, additives such as a surfactant, a colorant, an
absorbefacient, an antioxidant, a light stabilizer and an adhesive may be added.
As appropriate solvents, water, alkanol, glycol, polyethylene glycol, polypropylene
glycol, glycerin, benzyl alcohol, phenylethanol, phenoxyethanol, ethyl acetate, butyl
15 acetate, benzyl benzoate, dipropylene glycol monomethyl ether, diethylene glycol
monobutyl ether, acetone, methyl ethyl ketone, aromatic and/or aliphatic hydrocarbons,
vegetable or synthetic oils, DMF, liquid paraffin, light liquid paraffin, silicone,
dimethylacetamide, N-methylpyrrolidone or 2,2-dimethyl-4-oxy-methylene-1,3-dioxolane
may be mentioned. As absorbefacients, DMSO, isopropyl myristate, pelargonic acid
20 dipropylene glycol, silicone oil, fatty acid esters, triglycerides and aliphatic alcohols may
be mentioned. As antioxidants, sulfites, metabisulfites, ascorbic acid,
butylhydroxytoluene, butylhydroxyanisole and tocopherol may be mentioned.
An emulsion may be administered orally, percutaneously or by injection. An
emulsion can be prepared by dissolving an active ingredient in a hydrophobic phase or
25 a hydrophilic phase and homogenizing the resulting solution with another liquid phase
together with an appropriate emulsifier, and further if necessary with additives such as a
colorant, an absorbefacient, a protectant, an antioxidant, a light screen and a thickner.
As hydrophobic phases (oils), paraffin oil, silicone oil, sesame oil, almond oil,
castor oil, synthetic triglycerides, ethyl stearate, di-n-butyryl adipate, hexyl laurate,
30 pelargonic acid dipropylene glycol, esters of branched short-chain fatty acids with Ci6-
Ci8 saturated fatty acids, isopropyl myristate, isopropyl palmitate, esters of C12-C18
saturated alcohols with caprylic/capric acid, isopropyl stearate, oleyl oleate, decyl oleate,
ethyl oleate, ethyl lactate, fatty acid ester waxes, dibutyl phthalate, diisopropyl adipate,
isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol and oleyl alcohol may be
35 mentioned.
As hydrophilic phases, water, propylene glycol, glycerin and sorbitol may be
mentioned.
As emulsifiers, nonionic surfactants such as polyoxyethylated castor oil,
polyoxyethylated sorbitan monoolefinic acid, sorbitan monostearate, glycerin
40 monostearate, polyoxyethyl stearate and alkyl phenol polyglycol ether; amphoteric
surfactants such as disodium N-lauryl-(3-iminodipropionate and lecithin; anionic
surfactants such as sodium lauryl sulfate, aliphatic alcohol sulfate ether,
mono/dialkylpolyglycol orthophosphate monoethanolamine salt; and cationic surfactants
such as cetyltrimethylammonium chloride may, for example, be mentioned.
45 As other additives, carboxymethylcellulose, methylcellulose, polyacrylate, alginate,
gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, methyl vinyl ether, maleic
anhydride copolymers, polyethylene glycol, waxes and colloidal silica may be
mentioned.
163
A semisolid preparation is administered by applying or spreading onto the skin or
introducing into the coelom. A gel can be prepared by adding a thickener to a solution
prepared in the same manner as an injection fluid sufficiently to give a transparent
viscous substance like an ointment.
5 Formulation examples of preparations using the compounds of the present
invention are given below. However, formulations of the present invention are by no
means restricted thereto. In the following formulation examples, "parts" means parts
by weight.
[Wettable powder]
10 Compound of the present invention 0.1 to 80 parts
Solid carrier 5 to 98.9 parts
Surfactant 1 to 10 parts
Others 0 to 5 parts
As the others, an anti-caking agent, a stabilizer and the like may be mentioned.
15 [Emulsifiable concentrate]
Compound of the present invention 0.1 to 30 parts
Organic solvent 45 to 95 parts
Surfactant 4.9 to 30 parts
Water 0 to 50 parts
20 Others 0 to 10 parts
As the others, a spreader, a stabilizer and the like may be mentioned.
[Suspension concentrate]
Compound of the present invention 0.1 to 70 parts
Liquid carrier 15 to 98.89 parts
25 Surfactant 1 to 12 parts
Others 0.01 to 30 parts
As the others, an anti-freezing agent, a thickener and the like may be mentioned.
[Water dispersible granule]
Compound of the present invention 0.1 to 90 parts
30 Solid carrier 0 to 98.9 parts
Surfactant 1 to 20 parts
Others 0 to 10 parts
As the others, a binder, a stabilizer and the like may be mentioned.
[Soluble concentrate]
35 Compound of the present invention 0.01 to 70 parts
Liquid carrier 20 to 99.99 parts
Others 0 to 10 parts
As the others, an anti-freezing agent, a spreader and the like may be mentioned.
[Granule]
40 Compound of the present invention 0.01 to 80 parts
Solid carrier 10 to 99.99 parts
Others 0 to 10 parts
As the others, a binder, a stabilizer and the like may be mentioned.
[Dustable powder]
45 Compound of the present invention 0.01 to 30 parts
Solid carrier 65 to 99.99 parts
Others 0 to 5 parts
As the others, an anti-drift agent, a stabilizer and the like may be mentioned.
164
Next, more specific examples of preparations containing compounds of the
present invention as an active ingredient are given below. However, the present
invention is by no means restricted thereto.
In the following Formulation Examples, "parts" means parts by weight.
5 [Formulation Example 1] Wettable powder
Compound No.2-132 of the present invention 20 parts
Pyrophyllite 74 parts
Sorpol 5039 4 parts
(tradename for a mixture of a nonionic surfactant and an anionic surfactant:
10 manufactured by TOHO Chemical Industry Col., Ltd.)
CARPLEX #80D 2 parts
(hydrous synthetic silicic acid: tradename manufactured by Shionogi & Co., Ltd.)
The above ingredients are mixed and pulverized homogenously to obtain a
wettable powder.
15 [Formulation Example 2] Emulsifiable concentrate
Compound No.2-124 of the present invention 5 parts
Xylene 75 parts
N-methylpyrrolidone 15 parts
Sorpol 2680 5 parts
20 (tradename for a mixture of a nonionic surfactant and an anionic surfactant:
manufactured by TOHO Chemical Industry Co., Ltd.)
The above ingredients are mixed homogenously to obtain an emulsifiable
concentrate.
[Formulation Example 3] Emulsifiable concentrate
25 Compound No.2-117 of the present invention 4 parts
DBE 36 parts
(tradename for a mixture of dimethyl adipate, dimethyl glutarate and dimethyl succinate:
manufactured by INVISTA)
Diisobutyl adipate 30 parts
30 N-methylpyrrolidone 10 parts
SoprofolBSU 14 parts
(tradename for a nonionic surfactant: manufactured by Rhodia Nicca. Ltd.)
Rhodacal 70BC 6 parts
(tradename for an anionic surfactant: manufactured by Rhodia Nicca. Ltd.)
35 The above ingredients are mixed homogenously to obtain an emulsifiable
concentrate.
[Formulation Example 4] Emulsifiable concentrate
Compound No.2-020 of the present invention 4 parts
DBE 11 parts
40 (tradename for a mixture of dimethyl adipate, dimethyl glutarate and dimethyl succinate:
manufactured by INVISTA)
Diisobutyl adipate 30 parts
N-methylpyrrolidone 5 parts
SoprofolBSU 14 parts
45 (tradename for a nonionic surfactant: manufactured by Rhodia Nicca. Ltd.)
Rhodacal 70BC 6 parts
(tradename for an anionic surfactant: manufactured by Rhodia Nicca. Ltd.)
Propylene glycol 10 parts
165
Water 20 parts
The above ingredients are mixed homogenously to obtain an emulsifiable
concentrate.
[Formulation Example 5] Suspension concentrate
5 Compound No.2-136 of the present invention 25 parts
AGRISOLS-710 10 parts
(tradename for a nonionic surfactant: manufactured by Kao Corporation)
LunoxlOOOC 0.5 part
(tradename for an anionic surfactant: manufactured by TOHO Chemical Industry Co.,
10 Ltd.)
Xanthan gum 0.2 part
Water 64.3 parts
The above ingredients are mixed homogenously and wet-pulverized to obtain a
suspension concentration.
15 [Formulation Example 6] Water soluble granule
Compound No.2-128 of the present invention 75 parts
HITENOLNE-15 5 parts
(tradename for an anionic surfactant: manufactured by Dai-ichi Kogyo Seiyaku Co.,
Ltd.)
20 VANILLEXN 10 parts
(tradename for an anionic surfactant: manufactured by Nippon Paper Industries Co.,
LTD.)
CARPLEX#80D 10 parts
(tradename for hydrous synthetic silicic acid: manufactured by Shionogi & Co., Ltd.)
25 The above ingredients are mixed and pulverized homogenously, then kneaded
with a small amount of water, granulated through an extrusion granulator and dried to
obtain a water soluble granule.
[Formulation Example 7] Granule
Compound No.2-120 of the present invention 5 parts
30 Benton ite 50 parts
Talc 45 parts
The above ingredients are mixed and pulverized homogenously, then kneaded
with a small amount of water, granulated through an extrusion granulator and dried to
obtain a granule.
35 [Formulation Example 8] Dustable powder
Compound No.2-140 of the present invention 3 parts
CARPLEX #80D 0.5 part
(tradename for a hydrous synthetic silicic acid: manufactured by Shionogi & Co., Ltd.)
Kaolinite 95 parts
40 Diisopropyl phosphate 1.5 parts
The above ingredients are mixed and pulverized homogeneously to obtain a
dustable powder.
It is applied after diluted with water by a factor of from 1 to 20000 so as to achieve
an active ingredient concentration of from 0.005 to 50 kg/ha.
45 [Formulation Example 9] Wettable powder preparation
Compound No.2-126 of the present invention 25 parts
Sodium diisobutylnaphthalenesulfonate 1 part
Calcium n-dodecylbenzenesulfonate 10 parts
166
Alkyl aryl polyglycol ether 12 parts
Naphthalenesulfonic acid-formalin condensate sodium salt 3 parts
Silicone emulsion 1 part
Silicon dioxide 3 parts
5 Kaolin 45 parts
[Formulation Example 10] Water-soluble concentrate preparation
Compound No.2-212 of the present invention 20 parts
Polyoxyethylenelauryl ether 3 parts
Sodium dioctylsulfosuccinate 3.5 parts
10 Dimethyl sulfoxide 37 parts
2-Propanol 36.5 parts
[Formulation Example 11] Liquid preparation for spraying
Compound No.2-185 of the present invention 2 parts
Dimethyl sulfoxide 10 parts
15 2-Propanol 35 parts
Acetone 53 parts
[Formulation Example 12] Liquid preparation for percutaneous administration
Compound No.2-151 of the present invention 5 parts
Hexylene glycol 50 parts
20 Isopropanol 45 parts
[Formulation Example 13] Liquid preparation for percutaneous administration
Compound No.2-114 of the present invention 5 parts
Propylene glycol monomethyl ether 50 parts
Dipropylene glycol 45 parts
25 [Formulation Example 14] Liquid preparation for percutaneous administration (by
dripping)
Compound No.2-174 of the present invention 2 parts
Light liquid paraffin 98 parts
[Formulation Example 15] Liquid preparation for percutaneous administration (by
30 dripping)
Compound No.2-240 of the present invention 2 parts
Light liquid paraffin 58 parts
Olive oil 30 parts
ODO-H 9 parts
35 Shin-etsu silicone 1 part
For use as agricultural fungicides or nematocides, if necessary, the compounds of
the present invention may be mixed with other fungicides, other nematocides,
insecticides, miticides, plant growth regulators, herbicides, synergists, fertilizers, soil
conditioners and the like at the time of formulation or application.
40 Further, for use as internal parasiticides, the compounds of the present invention
in effective amounts may be applied alone as active ingredients, or if necessary, they
may be mixed with other antibiotics, other vermicides and the like at the time of
formulation or application.
Particularly, the combined use with other fungicides, other nematocides, other
45 antibiotics, other vermicides or the like is expected to broaden the pesticidal spectrum
by the additive or synergistic effect of the other agrochemicals, to improve the pesticidal
effect, to reduce the application cost by enabling control at lower doses, and further, to
prolong the pesticidal effect for a long period of time. Particularly, the combined use
167
with other fungicides, nematocides, antibiotics or vermicides differing in the mechanism
of action is a very useful controlling method with a view to preventing the pests from
acquiring resistance to pesticides. In such cases, they may be combined with a
plurality of known fungicides, known nematocides, known insecticides, known miticides,
5 known antibiotics or known vermicides simultaneously.
The fungicides, nematocides, insecticides, miticides, vermicides and antibiotics to
be used in combination with the compounds of the present invention include, for
example, the compounds disclosed in e.g. The Pesticidal Manual, 15th edition, 2009,
having the generic names listed below, but are not necessarily restricted thereto.
10 Fungicides: such as acibenzolar-S-methyl, acypetacs, aldimorph, ametoctradin,
amisulbrom, amobam, ampropylfos, anilazine, azaconazole, azoxystrobin, benalaxyl,
benalaxyl-M, benodanil, benomyl, benthiavalicarb-isopropyl, benthiazole,
benzovindiflupyr, biphenyl, bitertanol, bixafen, bordeaux mixture, boscalid,
bromuconazole, bupirimate, calcium polysulfide, captan, carbendazim, carboxin,
15 carpropamid, carvone, cheshunt mixture, chinomethionat, chloroneb, chloropicrin,
chlorothalonil, chlozolinate, climbazole, copper carbonate, basic, copper hydroxide,
copper naphthenate, copper oleate, copper oxychloride, copper sulfate, copper sulfate,
basic, coumoxystrobin, cresol, cufraneb, cyazofamid, cyflufenamid, cymoxanil,
cyproconazole, cyprodinil, dazomet, dichlofluanid, dichlorophen, diclobutrazol,
20 diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim,
dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap,
dinocap-4, dinocap-6, diphenylamine, dithianon, DNOC, dodemorph-acetate, dodine,
drazoxolon, edifenphos, enestrobin, enoxastrobin, epoxiconazole, etaconazole,
ethaboxam, ethirimol, ethoxyquin, etridiazole, famoxadone, fenamidone, fenaminstrobin,
25 fenarimol, fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil,
fenpropidin, fenpropimorph, fenpyrazamine, fentin, ferbam, ferimzone, fluazinam,
fludioxonil, flufenoxystrobin, flumorph, fluopicolide, fluopyram, fluoroimide, fluotrimazole,
fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol,
fluxapyroxad, folpet, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, furconazole,
30 furmecyclox, guazatine, hexachlorobenzene, hexaconazole, hymexazol, imazalil,
imibenconazole, iminoctadine-albesilate, iminoctadine-triacetate, ipconazole, iprobenfos,
iprodione, iprovalicarb, isofetamid, isoprothiolane, isopyrazam, isotianil, kasugamycin,
kresoxim-methyl, laminarin, mancopper, mancozeb, mandestrobin, mandipropamid,
maneb, mepanipyrim, mepronil, metalaxyl, metalaxyl-M, metam, metconazole,
35 methfuroxam, metiram, metominostrobin, metrafenone, metsulfovax, milneb,
myclobutanil, nabam, natamycin, nickel bis(dimethyldithiocarbamate), nitrothal-isopropy,
nuarimol, ofurace, orysastrobin, oxadixyl, oxathiapiprolin, oxine copper, oxpoconazole
fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen,
pentachlorophenol (PCP), penthiopyrad, 2-phenylphenol, phthalide, picoxystrobin,
40 piperalin, polycarbamate, polyoxins, polyoxorim, potassium azide, potassium hydrogen
carbonate, probenazole, prochloraz, procymidone, propamocarb hydrochloride,
propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin,
pyraoxystrobin, pyrazophos, pyribencarb-methyl, pyrifenox, pyrimethanil,
pyriminostrobin, pyriofenone, pyrisoxazole, pyroquilon, quinacetol-sulfate, quinoxyfen,
45 quintozene, sedaxane, silthiofam, simeconazole, sodium hydrogen carbonate, sodium
hypochlorite, spiroxamine, sulfur, tebuconazole, tebufloquin, tecoram, tetraconazole,
thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl,
tolprocarb, tolylfluanid, triadimefon, triadimenol, triazoxide, tributyltin oxide, triclopyricab,
168
tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin,
valifenalate, vinclozolin, zinc naphthenate, zinc sulfate, ziram, zoxamide, shiitake
mushroom mycelium extracts, shiitake mushroom fruiting body extracts, BCF-082
(experimental name), NNF-0721 (experimental name) and ZF-9646 (experimental
5 name).
Insecticides: such as abamectin, acephate, acetamiprid, afidopyropen, afoxolaner,
alanycarb, aldicarb, allethrin, azamethiphos, azinphos-ethyl, azinphos-methyl, bacillus
thuringiensis, bendiocarb, benfluthrin, benfuracarb, bensultap, bifenthrin, bioallethrin,
bioresmethrin, bistrifluron, buprofezin, butocarboxim, carbaryl, carbofuran, carbosulfan,
10 cartap, chlorantraniliprole, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron,
chlormephos, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyanophos,
cyantraniliprole, cyclaniliprole, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin,
gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, betacypermethrin,
zeta-cypermethrin, cyphenothrin, cyromazine, deltamethrin, diafenthiuron,
15 diazinon, dichlorvos, diflubenzuron, dimethoate, dimethylvinphos, dinotefuran,
diofenolan, disulfoton, emamectin-benzoate, empenthrin, endosulfan, alpha-endosulfan,
EPN, esfenvalerate, ethiofencarb, ethiprole, etofenprox, etrimfos, fenitrothion,
fenobucarb, fenoxycarb, fenthion, fenvalerate, fipronil, flometoquin, flonicamid,
fluazuron, flubendiamide, flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufiprole,
20 flumethrin, flupyradifurone, fluralaner, fluvalinate, tau-fluvalinate, fonofos, furathiocarb,
halofenozide, heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid, imiprothrin,
indoxacarb, indoxacarb-MP, isoprocarb, isoxathion, lepimectin, lufenuron, malathion,
meperfluthrin, metaflumizone, metaldehyde, methacrifos, methamidophos, methidathion,
methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, muscalure,
25 nitenpyram, novaluron, noviflumuron, omethoate, oxydemeton-methyl, parathion-methyl,
permethrin, phenothrin, phenthoate, phorate, phosalone, phosmet, phoxim, pirimicarb,
pirimiphos-methyl, profenofos, prothiofos, pymetrozine, pyraclofos, pyrethrins, pyridalyl,
pyrifluquinazon, pyriprole, pyriproxyfen, resmethrin, rotenone, silafluofen, spinetoram,
spinosad, spirotetramat, sulfotep, sulfoxaflor, tebufenozide, teflubenzuron, tefluthrin,
30 terbufos, tetrachlorvinphos, tetramethrin, d-T-80-phthalthrin (d-tetramethrin),
tetramethylfluthrin, thiacloprid, thiamethoxam, thiocyclam, thiodicarb, thiofanox,
thiometon, tolfenpyrad, tralomethrin, transfluthrin, triazamate, trichlorfon, triflumuron,
ME5382 (experimental name), NC-515 (experimental name) and ZDI2501 (experimental
name).
35 Miticides: such as acequinocyl, acrinathrin, amidoflumet, amitraz, azocyclotin,
benzoximate, bifenazate, bromopropylate, clofentezine, cyenopyrafen, cyflumetofen,
dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenothiocarb, fenpropathrin,
fenpyroximate, fluacrypyrim, formetanate, halfenprox, hexythiazox, milbemectin,
propargite, pyflubumide, pyridaben, pyrimidifen, spirodiclofen, spiromesifen,
40 tebufenpyrad and NA-89 (experimental name).
Nematicides: such as cadusafos, dichlofenthion, ethoprophos, fenamiphos,
fluensulfone, fosthiazate, fosthietan, imicyafos, isamidofos, isazofos, methyl bromide,
methyl isothiocyanate, oxamyl, sodium azide, BYI-1921 (experimental name) and MAI-
08015 (experimental name).
45 Vermicides: such as acriflavine, albendazole, atovaguone, azithromycin, bithionol,
bromofenofos, cambendazole, carnidazole, chloroquine, clazuril, clindamycin
hydrochloride, clorsulon, closantel, coumaphos, cymiazol, dichlorophen,
diethylcarbamazine, diminazene, disophenol, dithiazanine iodide, doxycycline
169
hydrochloride, doramectin, emodepside, eprinomectin, febantel, fenbendazole,
flubendazole, furazolidone, glycalpyramide, imidocarb, ivermectin, levamisole,
mebendazole, mefloquine, melarsamine hydrochloride, metronidazole, metyridine,
milbemycin oxime, monepantel, morantel tartrate, moxidectin, nicarbazin, niclosamide,
5 nitroscanate, nitroxynil, omphalotin, oxantel pamoate, oxantel tartrate, oxfendazolee,
oxibendazole, oxyclozanide, pamaquine, phenothiazine, piperazine adipate, piperazine
citrate, piperazine phosphate, PNU-97333 (paraherquamide A), PNU-141962 (2-
deoxyparaherquamide), praziquantel, primaquine, propetamphos, propoxur, pyrantel
pamoate, pyrimethamine, santonin, selamectin, sulfadimethoxine, sulfadoxine,
10 sulfamerazine, sulfamonomethoxine, sulfamoildapsone, thiabendazole, tinidazole,
toltrazuril, tribromsalan and triclabendazole.
Antifungal agents: such as ketoconazole and miconazole nitrate.
Antibiotics: such as amoxicillin, ampicillin, bethoxazin, bithionol, bronopol,
cefapirin, cefazolin, cefquinome, ceftiofur, chlortetracycline, clavulanic acid,
15 danofloxacin, difloxacin, dinitolmide, enrofloxacin, florfenicol, lincomycin, lomefloxacin,
marbofloxacin, miloxacin, mirosamycin, nitrapyrin, norfloxacin, octhilinone, ofloxacin,
orbifloxacin, oxolinic acid, oxytetracycline, penicillin, streptomycin, thiamphenicol,
tiamulin fumarate, tilmicosin phosphate, acetylisovaleryltylosin, tylosin phosphate,
tulathromycin, valnemulin, calcinated shell calcium (calcium oxide), Talaromvces,
20 Trichoderma and Coniothvrium.
EXAMPLES
The present invention will be described in further detail by referring to the following
specific Examples of synthesis of and tests on the compounds of the present invention.
25 However, the present invention is by no means restricted thereto.
[Synthetic Examples]
SYNTHETIC EXAMPLE 1
(Z)-N-[2-(2,4-dichlorophenyl)-2-(methoxyimino)ethyl]-2-(trifluoromethyl)benzamide
(Compound No. 1-004 of the present invention)
30 Step 1: Preparation of 2-bromo-1 -(2,4-dichlorophenyl)ethanone-0-methyloxime
To 4.00 g of 2-bromo-1-(2,4-dichlorophenyl)ethanone in 20 ml of ethanol, 1.25 g of
methoxyamine hydrochloride was added, and the mixture was stirred at room
temperature for 12 hours. After completion of the reaction, the solvent was evaporated
under reduced pressure, and the resulting residue was mixed with 20 ml of water and
35 extracted with ethyl acetate (20 mlx2). The resulting organic layers were combined,
washed with water (20 mlxl) and then dried over saturated aqueous sodium chloride
and then anhydrous sodium sulfate, and the solvent was evaporated under reduced
pressure to obtain 3.85 g of the desired crude product as a pale yellow oil. The oil was
used in the next step without further purification.
40 1 H NMR (CDCb, Me4 Si, 300MHz) 57.2-7.55 (m, 3H), 4.56 and 4.35 (s, 2H), 4.06 and
4.04 (s, 3H).
Step 2: Preparation of N-[2-(2,4-dichlorophenyl)-2-(methoxyimino)ethyl]phthalimide
To 2.17 g of 2-bromo-1-(2,4-dichlorophenyl)ethanone-0-methyloxime in 20 ml of
N,N-dimethylformamide, 3.03 g of potassium phthalimide and 1.61 g of potassium
45 carbonate were added, and the mixture was stirred at room temperature for 18 hours.
After completion of the reaction, the reaction mixture was mixed with 40 ml of water and
extracted with ethyl acetate (50 mlxl), the resulting organic layer was washed with
water (20 mlxl) and then dried over saturated aqueous sodium chloride and then
170
anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
The resulting residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 2.10 g of the
desired product as pale yellow crystals.
5 m.p.: 82.0-85.0°C
1H NMR (CDCb, Me4Si, 300MHz) 57.65-7.8 (m, 4H), 7.15-7.35 (m, 3H), 4.92 (s, 2H),
4.01 (s, 3H).
Step 3: Preparation of 2-amino-1-(2,4-dichlorophenyl)ethanone-0-methyloxime
To 316 mg of N-[2-(2,4-dichlorophenyl)-2-(methoxyimino)ethyl]phthalimide in 10 ml
10 of ethanol, 108 mg of hydrazine monohydrate was added, and the mixture was stirred at
60°C for 2 hours. After completion of the reaction, the reaction mixture was allowed to
cool to room temperature, mixed with 30 ml of water and extracted with ethyl acetate
(40 mlxl). The resulting organic layer was dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
15 reduced pressure to obtain 170 mg of the desired crude product as a colorless oil. The
oil was used in the next step without further purification.
1H NMR (CDCb, Me4Si, 300MHz) 57.25-7.45 (m, 3H), 3.99 (s, 3H), 3.82 (s, 2H).
Step 4: Preparation of (Z)-N-[2-(2,4-dichlorophenyl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
20 To a solution of 170 mg of 2-amino-1 -(2,4-dichlorophenyl)ethanone-0-
methyloxime and 74 mg of triethylamine in 5 ml of dichloromethane, 122 mg of 2-
(trifluoromethyl)benzoyl chloride was added dropwise, and the mixture was stirred at
room temperature for 1 hour. After completion of the reaction, the reaction mixture was
mixed with 10 ml of water and extracted with chloroform (20 mlxl), the resulting organic
25 layer was dried over saturated aqueous sodium chloride and then anhydrous sodium
sulfate, and the solvent was evaporated under reduced pressure. The resulting
residue was mixed with 3 ml of diisopropyl ether and crystallized to obtain 110 mg of the
desired product as white crystals.
m.p.: 146.0-148.0°C
30 1H NMR (CDCb, Me4Si, 300MHz) 57.25-7.7 (m, 6H), 7.05-7.15 (m, 1H), 6.31 (bs, 1H),
4.62 (d, J=6.3Hz, 2H), 4.02 (s, 3H).
SYNTHETIC EXAMPLE 2
(Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(ethoxyimino)ethyl]-2-(trifluoromethyl)benzamide
(Compound No. 2-120 of the present invention)
35 Step 1: Preparation of 1 -(3,5-dichloropyridin-2-yl)ethanone
To 20 g of 3,5-dichloropyridine-2-carbonitrile in 150 ml of tetrahydrofuran, 139 ml
of a 1M tetrahydrofuran solution of methylmagnesium bromide was added dropwise with
stirring under cooling with ice, and the mixture was stirred at the same temperature for 1
hour. After completion of the reaction, the reaction mixture was mixed with 15 ml of
40 concentrated hydrochloric acid and 100 ml of water and extracted with ethyl acetate
(100 mlx2), the resulting organic layers were combined, washed with water (100 mlxl)
and dried over saturated aqueous solution chloride and then anhydrous sodium sulfate,
and the solvent was evaporated under reduced pressure. The resulting residue was
dissolved in 40 ml of ethyl acetate and 10 ml of hexane, 20 g of silica gel was added,
45 the mixture was stirred at room temperature for 1 hour and then subjected to filtration,
and the solvent was evaporated under reduced pressure. The precipitated solid was
washed with 50 ml of hexane to obtain 17.16 g of the desired product as pale yellow
crystals.
171
1H NMR (CDCb, Me4Si, 300MHz) 58.50 (d, J=2.1Hz, 1H), 7.82 (d, J=2.1Hz, 1H), 2.68 (s,
3H).
Step 2: Preparation of 2-bromo-1 -(3,5-dichloropyridin-2-yl)ethanone
To 5.00 g of 1-(3,5-dichloropyridin-2-yl)ethanone in 75 ml of tetrahydrofuran, 9.94
5 g of trimethylphenylammonium tribromide was added, and the mixture was stirred at
room temperature for 16 hours. After completion of the reaction, the precipitated solid
was filtered off through celite, and the solvent was evaporated under reduced pressure.
The resulting residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 5:95 to 15:85) as the eluent to obtain 6.64 g of
10 the desired product as a brown oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.51 (d, J=1.9Hz, 1H), 7.88 (d, J=1.9Hz, 1H), 4.67 (s,
2H).
Step 3: Preparation of 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanone-0-ethyloxime
To 3.00 g of 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanone in 25 ml of ethanol, 1.09
15 g of ethoxyamine hydrochloride was added, and the mixture was stirred at room
temperature for 16 hours. After completion of the reaction, the solvent was evaporated
under reduced pressure, the resulting residue was mixed with 50 ml of water and
extracted with ethyl acetate (50 mlx2), the resulting organic layers were combined,
washed with water (50 mlxl) and dried over saturated aqueous sodium chloride and
20 then anhydrous sodium sulfate, and the solvent was evaporated under reduced
pressure. The resulting residue was purified by silica gel column chromatograph using
ethyl acetate-hexane (with a gradient of from 5:95 to 15:85) as the eluent to obtain 3.03
g of the desired product as a colorless oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.50 (d, J=2.1Hz, 1H), 7.81 (d, J=2.1Hz, 1H), 4.67
25 and 4.52 (s, 2H), 4.35 and 4.32 (q, J=7.2Hz, 2H), 1.37 and 1.36 (t, J=7.2Hz, 3H).
Step 4: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(ethoxyimino)ethyl]phthalimide
To 3.00 g of 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanone-0-ethyloxime in 20 ml
of N,N-dimethylformamide, 2.32 g of potassium phthalimide was added, and the mixture
was stirred at room temperature for 12 hours. After completion of the reaction, the
30 reaction mixture was mixed with 50 ml of water and extracted with ethyl acetate (100
mlxl), the resulting organic layer was washed with water (50 mlxl) and dried over
saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent
was evaporated under reduced pressure. The resulting residue was washed with 10
ml of diisopropyl ether to obtain 3.08 g of the desired product as white crystals.
35 m.p.: 99.0 to 101.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.29 (d, J=2.1Hz, 1H), 7.65-7.85 (m, 5H), 4.99 (s,
2H), 4.27 (q, J=7.2Hz, 2H), 1.29 (t, J=7.2Hz, 3H).
Step 5: Preparation of 2-amino-1-(3,5-dichloropyridin-2-yl)ethanone-0-ethyloxime
To 3.00 g of N-[2-(3,5-dichloropyridin-2-yl)-2-(ethoxyimino)ethyl]phthalimide in 30
40 ml of ethanol, 793 mg of hydrazine monohydrate was added, and the mixture was
stirred at 70°C for 3 hours. After completion of the reaction, the reaction mixture was
allowed to cool to room temperature, mixed with 100 ml of water and extracted with
ethyl acetate (100 mlx2). The resulting organic layers were combined, washed with
water (100 mlxl) and dried over saturated aqueous sodium chloride and then
45 anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to
obtain 1.62 g of the desired crude product as a brown oil. The oil was used in the next
step without further purification.
1H NMR (CDCb, Me4Si, 300MHz) 58.51 and 8.48 (d, J=2.0Hz, 1H), 7.79 and 7.77 (d,
172
J=2.0Hz, 1H), 4.27 and 4.13 (q, J=6.9Hz, 2H), 3.90 and 3.74 (s, 2H), 1.34 and 1.21 (t,
J=6.9Hz, 3H).
Step 6: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(ethoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-003 of the present invention)
5 To a solution of 200 mg of 2-amino-1-(3,5-dichloropyridin-2-yl)ethanone-0-
ethyloxime and 90 mg of triethylamine in 3 ml of dichloromethane, 169 mg of 2-
(trifluoromethyl)benzoyl chloride was added dropwise with stirring under cooling with ice,
and after the addition, the mixture was stirred at room temperature for another 30
minutes. After completion of the reaction, the reaction mixture was mixed with 10 ml of
10 water and extracted with ethyl acetate (15 mlxl), the resulting organic layer was
washed with water (10 mlxl) and dried over saturated aqueous sodium chloride and
then anhydrous sodium sulfate, and the solvent was evaporated under reduced
pressure. The resulting residue was purified by silica gel column chromatography
using ethyl acetate-hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain
15 190 mg of the desired product as a pale yellow resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.45 and 8.29 (d, J=2.1Hz, 1H), 7.80 and 7.78 (d,
J=2.1Hz, 1H), 7.35-7.75 (m, 4H), 6.52 (bs, 1H), 4.75 and 4.52 (d, J=6.0Hz, 2H), 4.30
and 4.13 (q, J=7.2Hz, 2H), 1.35 and 1.21 (t, J=7.2Hz, 3H).
Step 7: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(ethoxyimino)ethyl]-2-
20 (trifluoromethyl)benzamide
190 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(ethoxyimino)ethyl]-2-
(trifluoromethyl)benzamide was dissolved in 4 ml of acetonitrile, and the solution was
irradiated with light for 2.5 hours in a quartz cell (manufactured by Fine, 4 clear windows
for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO
25 INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the
solvent was evaporated under reduced pressure, and the resulting residue was purified
by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from
1:9 to 3:7) as the eluent to obtain 41.3 mg of the desired product as white crystals.
m.p.:84.0to86.0°C
30 1H NMR (CDCb, Me4Si, 300MHz) 58.51 (d, J=2.1 Hz, 1H), 7.79 (d, J=2.1 Hz, 1H), 7.5-
7.75 (m, 4H), 6.50 (bs, 1H), 4.53 (d, J=4.8Hz, 2H), 4.13 (q, J=7.2Hz, 2H), 1.21 (t,
J=7.2Hz, 3H).
SYNTHETIC EXAMPLE 3
N-[2-(3,5-dichloropyridin-2-yl)-2-(ethoxyimino)ethyl]-3-difluoromethyl-1-methyl-1H-
35 pyrazole-4-carboxamide (Compound No. 17-004 of the present invention)
To 176 mg of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid in 1 ml of
dichloromethane, 10 mg of N,N-dimethylformamide and 381 mg of oxalyl chloride were
added, and the mixture was stirred at room temperature for 1 hour. After completion of
the reaction, the solvent was evaporated under reduced pressure, and the resulting
40 residue was dissolved in 2 ml of dichloromethane, and to the solution, 190 mg of the 2-
amino-1-(3,5-dichloropyridin-2-yl)ethanone-0-ethyloxime prepared in Step 5 in
Synthetic Example 2 in 2 ml of dichloromethane and then 91 mg of pyridine were added
dropwise with stirring under cooling with ice, and after the addition, the mixture was
stirred at room temperature for another 2 hours. After completion of the reaction, the
45 reaction mixture was mixed with 10 ml of water and extracted with chloroform (20 mlxl),
the resulting organic layer was washed with water (10 mlxl) and dried over saturated
aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was
evaporated under reduced pressure. The resulting residue was purified by silica gel
173
column chromatography using ethyl acetate-hexane (with a gradient of from 1:4 to 1:1)
as the eluent to obtain 165.3 mg of a pale yellow resinous substance. The resinous
substance was dissolved in 5 ml of acetic acid and stirred at 70°C for 2 hours, the
solvent was evaporated under reduced pressure, and the resulting residue was purified
5 by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from
1:4 to 1:1) as the eluent to obtain 130.6 mg of the desired product as a colorless
resinous substance (E/Z=1/1).
1H NMR (CDCb, Me4Si, 300MHz) 58.50 and 8.47 (d, J=2.1Hz, 1H), 7.90 and 7.86 (s,
1H), 7.76 and 7.75 (d, J=2.1 Hz, 1H), 6.9-7.1 (m, 1H), 6.84 and 6.73 (t, J=54.3Hz, 1H),
10 4.71 and 4.49 (d, J=6.0Hz, 2H), 4.31 and 4.14 (q, J=7.2Hz, 2H), 3.92 and 3.89 (s, 3H),
1.36 and 1.23 (t,J=7.2Hz,3H).
SYNTHETIC EXAMPLE 4
N-[2-(3,5-dichloropyridin-2-yl)-2-(tert-butoxyimino)ethyl]-3-(trifluoromethyl)pyrazine-2-
carboxamide (Compounds Nos. 9-005 and 9-006 of the present invention)
15 Step 1: Preparation of 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanoneoxime
To 2.00 g of the 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanone prepared in Step 2
in Synthetic Example 2 in 15 ml of ethanol, 517 mg of hydroxylamine hydrochloride was
added, and the mixture was stirred at room temperature for 12 hours. After completion
of the reaction, the reaction mixture was mixed with 100 ml of water and extracted with
20 ethyl acetate (50 mlx2), the resulting organic layers were combined, washed with water
(20 mlxl) and dried over saturated aqueous sodium chloride and then anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure. The
resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 1:9 to 3:7) as the eluent to obtain 1.31 g of the desired
25 product as a pale orange oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.53 and 8.50 (d, J=2.1Hz, 1H), 7.82 and 7.81 (d,
J=2.1 Hz, 1H), 4.75 and 4.58 (s, 2H).
Step 2: Preparation of 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanone-0-(tert-butyl)oxime
To a solution of 1.31 g of 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanoneoxime and
30 1.71 g of tert-butanol in 20 ml of dichloromethane, 3.27 g of boron trifluoride diethyl
ether complex was added, and the mixture was stirred at room temperature for 48 hours.
After completion of the reaction, the solvent was evaporated under reduced pressure,
and the resulting residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 0:100 to 15:85) as the eluent to obtain 140 mg
35 of the desired product as a colorless oil.
1H NMR (CDCb, Me4Si, 300MHz) 68.50 and 8.48 (d, J=2.1Hz, 1H), 7.81 and 7.77 (d,
J=2.1 Hz, 1H), 4.70 and 4.53 (s, 2H), 1.39 and 1.38 (s, 9H).
Step 3: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(tertbutoxyimino)
ethyl]phthalimide
40 To 140 mg of 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanone-0-(tert-butyl)oxime in
2 ml of N,N-dimethylformamide, 91 mg of potassium phthalimide was added, and the
mixture was stirred at room temperature for 5 hours. After completion of the reaction,
the reaction mixture was mixed with 10 ml of water and extracted with ethyl acetate (15
mlxl), the resulting organic layer was washed with water (10 mlxl) and dried over
45 saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent
was evaporated under reduced pressure. The resulting residue was purified by silica
gel column chromatography using ethyl acetate-hexane (with a gradient of from 2:8 to
4:6) as the eluent to obtain 162 mg of the desired product as a colorless resinous
174
substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.30 (d, J=2.1Hz, 1H), 7.7-7.85 (m, 2H), 7.74 (d,
J=2.1Hz, 1H), 7.6-7.7 (m, 2H), 4.97 (s, 2H), 1.27 (s, 9H).
Step 4: Preparation of 2-amino-1-(3,5-dichloropyridin-2-yl)ethanone-0-(tert-butyl)oxime
5 To 162 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(tert-butoxyimino)ethyl]phthalimide
in 10 ml of ethanol, 40 mg of hydrazine monohydrate was added, and the mixture was
stirred at 80°C for 1 hour. After completion of the reaction, the solvent was evaporated
under reduced pressure, and the reaction mixture was mixed with 30 ml of water and
extracted with ethyl acetate (25 mlx2). The resulting organic layers were combined,
10 washed with water (20 mlxl) and dried over saturated aqueous sodium chloride and
then anhydrous sodium sulfate, and the solvent was evaporated under reduced
pressure to obtain 89 mg of the desired crude product as a colorless oil. The oil was
used in the next step without further purification.
1H NMR (CDCb, Me4Si, 300MHz) 58.47 (d, J=2.4Hz, 1H), 7.79 (d, J=2.4Hz, 1H), 3.88
15 (bs, 2H), 1.36 (s, 9H).
Step 5: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(tert-butoxyimino)ethyl]-3-
(trifluoromethyl)pyrazine-2-carboxamide
To 74 mg of 3-(trifluoromethyl)pyrazine-2-carboxylic acid in 3 ml of
dichloromethane, 10 mg of N,N-dimethylformamide and 57 mg of oxalyl chloride were
20 added, and the mixture was stirred at room temperature for 1 hour. After completion of
the reaction, the solvent was evaporated under reduced pressure, and the resulting
residue was dissolved in 10 ml of dichloromethane. To the solution, 89 mg of 2-amino-
1-(3,5-dichloropyridin-2-yl)ethanone-0-(tert-butyl)oxime and 39 mg of triethylamine
were added with stirring under cooling with ice, and the mixture was stirred at room
25 temperature for another 1 hour. After completion of the reaction, the reaction mixture
was mixed with 10 ml of water and extracted with chloroform (10 mlxl), the resulting
organic layer was dried over saturated aqueous sodium chloride and then anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure. The
resulting residue was purified by silica gel column chromatography using ethyl acetate-
30 hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 22 mg of geometrical
isomer A and 111 mg of geometrical isomer B of the desired product as colorless
resinous substances.
Isomer A:
1H NMR (CDCb, Me4Si, 300MHz) 58.77 (d, J=2.4Hz, 1H), 8.69 (d, J=2.4Hz, 1H), 8.46 (d,
35 J=2.1 Hz, 1H), 8.14 (bs, 1H), 7.78 (d, J=2.1 Hz, 1H), 4.77 (d, J=6.0Hz, 2H), 1.42 (s, 9H).
Isomer B:
1H NMR (CDCb, Me4Si, 300MHz) 58.77 (d, J=2.4Hz, 1H), 8.70 (d, J=2.4Hz, 1H), 8.46 (d,
J=2.1Hz, 1H), 8.17 (bs, 1H), 7.78 (d, J=2.1Hz, 1H), 4.79 (d, J=6.0Hz, 2H), 1.39 (s, 9H).
SYNTHETIC EXAMPLE 5
40 (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(propoxyimino)ethyl]-2-(trifluoromethyl)benzamide
(Compound No. 2-126 of the present invention)
Step 1: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]phthalimide
To 3.00 g of the 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanone prepared in Step 2
in Synthetic Example 2 in 30 ml of N,N-dimethylformamide, 4.13 g of potassium
45 phthalimide was added, and the mixture was stirred at 80°C for 3 hours and then at
room temperature for 18 hours. After completion of the reaction, the reaction mixture
was mixed with 150 ml of water and extracted with ethyl acetate (50 mlx2), the resulting
organic layers were combined, washed with water (50 mlxl) and dried over saturated
175
aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was
evaporated under reduced pressure. The resulting residue was mixed with 40 ml of a
mixture of diisopropyl ether and hexane (1:1), the insolubles were filtered off, and the
solvent was evaporated under reduced pressure. The resulting residue was purified by
5 silica gel column chromatography using ethyl acetate-hexane (with a gradient of from
15:85 to 25:75) as the eluent to obtain 0.32 g of the desired product as a dark brown
resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.58 (d, J=2.0Hz, 1H), 7.65-7.8 (m, 5H), 5.30 (s, 2H).
Step 2: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]phthalimide
10 To 0.32 g of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]phthalimide in 15 ml of
ethanol, 0.66 g of hydroxylamine hydrochloride was added and refluxed with heating for
4 hours with stirring. After completion of the reaction, the solvent was evaporated
under reduced pressure, and the reaction mixture was mixed with 30 ml of water and 50
ml of ethyl acetate, and the resulting organic layer was collected. The organic layer
15 was washed with water (30 mlxl) and dried over saturated aqueous sodium chloride
and then anhydrous sodium sulfate, the solvent was evaporated under reduced
pressure, and the resulting residue was washed with 10 ml of hexane to obtain 265 mg
of the desired product as yellow crystals.
m.p.: 138.0 to 141.0 °C
20 1H NMR (CDCb, Me4Si, 300MHz) 58.47 and 8.30 (d, J=2.0Hz, 1H), 8.13 and 7.52 (s,
1H), 7.65-7.9 (m, 5H), 5.05 and 4.78 (s, 2H).
Step 3: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(propoxyimino)ethyl]phthalimide
To 265 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]phthalimide in 2
ml of N,N-dimethylformamide, 310 mg of potassium carbonate and 387 mg of 1-
25 iodopropane were added, and the mixture was stirred at room temperature for 18 hours.
After completion of the reaction, the reaction mixture was mixed with 30 ml of water and
extracted with ethyl acetate (50 mlxl), the resulting organic layer was washed with
water (50 mlxl) and dried over saturated aqueous sodium chloride and then anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure. The
30 resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 15:85 to 25:75) as the eluent to obtain 235 mg of the
desired product as a yellow resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.42 and 8.29 (d, J=2.0Hz, 1H), 7.65-7.9 (m, 5H),
4.99 and 4.76 (s, 2H), 4.18 and 4.00 (t, J=6.7Hz, 2H), 1.5-1.75 (m, 2H), 0.93 and 0.81 (t,
35 J=7.5Hz, 3H).
Step 4: Preparation of 2-amino-1 -(3,5-dichloropyridin-2-yl)ethanone-0-propyloxime
To 235 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(propoxyimino)ethyl]phthalimide in 5
ml of ethanol, 90 mg of hydrazine monohydrate was added and refluxed with heating for
3 hours with stirring. After completion of the reaction, the reaction mixture was allowed
40 to cool to room temperature, mixed with 20 ml of water and extracted with ethyl acetate
(35 mlx2). The resulting organic layers were combined, washed with water (20 mlxl)
and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate,
and the solvent was evaporated under reduced pressure to obtain 151 mg of the
desired crude product as a brown oil. The oil was used in the next step without further
45 purification.
1H NMR (CDCb, Me4Si, 300MHz) 58.49 and 8.48 (d, J=2.0Hz, 1H), 7.78 and 7.76 (d,
J=2.0Hz, 1H), 4.17 and 4.01 (t, J=6.6Hz, 2H), 3.89 and 3.73 (s, 2H), 1.5-1.85 (m, 2H),
0.98 and 0.86 (t, J=7.4Hz, 3H).
176
Step 5: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(propoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-004 of the present invention)
In a solution of 151 mg of 2-amino-1-(3,5-dichloropyridin-2-yl)ethanone-0-
propyloxime and 86 mg of triethylamine in 4 ml of dichloromethane, 154 mg of 2-
5 (trifluoromethyl)benzoyl chloride was added dropwise with stirring under cooling with ice,
and after the addition, the mixture was stirred at room temperature for another 2 hours.
After completion of the reaction, the reaction mixture was mixed with 10 ml of water and
extracted with chloroform (30 mlxl), the resulting organic layer was washed with water
(10 mlxl) and dried over saturated aqueous sodium chloride and then anhydrous
10 sodium sulfate, and the solvent was evaporated under reduced pressure. The
resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 2:8 to 3:7) as the eluent to obtain 218 mg of the desired
product as a pale yellow resinous substance.
1H NMR (CDCIa, Me4Si, 300MHz) 58.49 and 8.44 (d, J=2.1Hz, 1H), 7.80 and 7.78 (d,
15 J=2.1 Hz, 1H), 7.35-7.7 (m, 4H), 6.53 and 6.49 (bs, 1H), 4.75 and 4.52 (d, J=6.3Hz, 2H),
4.21 and 4.03 (t, J=6.9Hz, 2H), 1.7-1.8 and 1.55-4.65 (m, 2H), 0.96 and 0.86 (t, J=7.5Hz,
3H).
Step 6: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(propoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
20 To 218 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(propoxyimino)ethyl]-2-
(trifluoromethyl)benzamide in 3 ml of acetonitrile, 5 mg of benzophenone was added,
and the mixture was irradiated with light for 48 hours in a quartz cell (manufactured by
Fine, 4 clear windows for spectroscopy) using a 100 W high-pressure mercury lamp
(manufactured by USHIO INC., lamp: UM-102, power supply UM-103B-B). After
25 completion of the reaction, the solvent was evaporated under reduced pressure, and the
resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 25:75 to 35:65) as the eluent to obtain 83 mg of the
desired product as white crystals.
m.p.:80.0to83.0°C
30 1H NMR (CDCIa, Me4Si, 300MHz) 58.51 (d, J=1.9Hz, 1H), 7.79 (d, J=1.9Hz, 1H), 7.5-
7.75 (m, 4H), 6.50 (bs, 1H), 4.53 (d, J=5.2Hz, 2H), 4.04 (t, J=6.6Hz, 2H), 1.5-1.7 (m,
2H), 0.86 (t, J=7.4Hz, 3H)
SYNTHETIC EXAMPLE 6
(Z)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-(cyclopropylmethoxyimino)ethyl]-2-
35 (trifluoromethyl)benzamide (Compound No. 2-024 of the present invention)
Step 1: Preparation of 2-bromo-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethanone
To 0.82 g of 1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethanone in 10 ml of
tetrahydrofuran, 1.38 g of trimethylphenylammonium tribromide was added, and the
mixture was stirred at room temperature for 16 hours. After completion of the reaction,
40 the precipitated solid was filtered off through celite, and the solvent was evaporated
under reduced pressure. The resulting residue was purified by silica gel column
chromatography using diethyl ether as the eluent to obtain 1.43 g of the desired product
as a brown oil. The oil was used in the next step without further purification.
Step 2: Preparation of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
45 oxoethyl]phthalimide
To 1.43 g of 2-bromo-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethanone in 10 ml
of N.N-dimethylformamide, 0.68 g of potassium phthalimide and 0.01 g of potassium
iodide were added, and the mixture was stirred at 85°C for 1 hour. After completion of
177
the reaction, the reaction mixture was allowed to cool to room temperature, mixed with
10 ml of water and extracted with ethyl acetate (10 mlx3), the resulting organic layers
were combined, washed with water and dried over saturated aqueous sodium chloride
and then anhydrous sodium sulfate, and the solvent was evaporated under reduced
5 pressure. The resulting residue was purified by preparative medium pressure liquid
chromatography (preparative medium pressure chromatograph: YFLC-Wprep
manufactured by Yamazen Science, Inc.) using ethyl acetate-hexane (with a gradient of
from 5:95 to 46:60) as the eluent to obtain 0.47 g of the desired product as a pale yellow
resinous substance.
10 1H NMR (CDCIs, Me4Si, 300MHz) 58.87 (d, J=1.8Hz, 1H), 8.10 (d, J=1.8Hz, 1H), 7.85-
7.95 (m, 2H), 7.7-7.8 (m, 2H), 5.32 (s, 2H).
Step 3: Preparation of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(hydroxyimino)ethyl]phthalimide
To a solution of 0.47 g of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
15 oxoethyl]phthalimide and 0.54 g of hydroxylamine hydrochloride in 5 ml of ethanol, 0.94
g of pyridine was added, and the mixture was stirred at room temperature for 24 hours.
After completion of the reaction, the reaction mixture was mixed with 5 ml of water and
extracted with ethyl acetate (5 mlx3), the resulting organic layers were combined, dried
over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the
20 solvent was distilled off under reduced pressure. The resulting residue was purified by
preparative medium pressure liquid chromatography (preparative medium pressure
chromatograph: YFLC-Wprep manufactured by Yamazen Science, Inc.) using ethyl
acetate-hexane (with a gradient of from 1:3 to 2:2) as the eluent to obtain 325 mg of the
desired product as white crystals.
25 1H NMR (CDCIs, Me4Si, 300MHz) 610.57 and 9.75 (s, 1H), 8.7-8.8 (m, 1H), 7.9-7.95 (m,
1H), 7.6-7.85 (m, 4H), 5.07 and 4.80 (s, 2H)
Step 4: Preparation of (E)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(cyclopropylmethoxyimino)ethyl]phthalimide
To 300 mg of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
30 (hydroxyimino)ethyl]phthalimide in 5 ml of N,N-dimethylformamide, 324 mg of
potassium carbonate and 158 mg of cyclopropylmethyl bromide were added, and the
mixture was stirred at room temperature for 18 hours. After completion of the reaction,
the reaction mixture was mixed with 5 ml of water and extracted with ethyl acetate (5
mlx3), the resulting organic layers were combined, washed with water and dried over
35 saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent
was evaporated under reduced pressure. The resulting residue was purified by
preparative medium pressure liquid chromatography (preparative medium pressure
chromatograph: YFLC-Wprep manufactured by Yamazen Science, Inc.) using ethyl
acetate-hexane (with a gradient of from 1:19 to 4:16) as the eluent to obtain 98 mg of
40 the desired product as a pale yellow resinous substance.
1H NMR (CDCIs, Me4Si, 300MHz) 68.61 (d, J=1.5Hz, 1H), 7.97 (d, J=1.5Hz, 1H), 7.75-
7.85 (m, 2H), 7.65-7.75 (m, 2H), 5.03 (s, 2H), 4.03 (d, J=7.5Hz, 2H), 1.05-1.25 (m, 1H),
0.4-0.5 (m, 2H), 0.15-0.25 (m, 2H).
Step 5: Preparation of (E)-2-amino-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethanone-
45 0-(cyclopropylmethyl)oxime
To 98 mg of (E)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(cyclopropylmethoxyimino)ethyl]phthalimide in 3 ml of ethanol, 76 mg of hydrazine
monohydrate was added, and the mixture was stirred at 80°C for 1 hour. After
178
completion of the reaction, the reaction mixture was allowed to cool to room
temperature, mixed with 5 ml of water and extracted with ethyl acetate (5 mlx3). The
resulting organic layers were combined, dried over saturated aqueous sodium chloride
and then anhydrous sodium sulfate, and the solvent was evaporated under reduced
5 pressure. The resulting residue was purified by silica gel column chromatography
using methanol-chloroform (1:10) as the eluent to obtain 65 mg of the desired product
as a pale yellow oil. The oil was used in the next step without further purification.
1H NMR (CDCb, Me4Si, 300MHz) 68.78 (d, J=1.5Hz, 1H), 8.00 (d, J=1.5Hz, 1H), 4.05 (d,
J=7.2Hz, 2H), 3.96 (s, 2H), 1.66 (bs, 2H), 1.15-1.35 (m, 1H), 0.55-0.65 (m, 2H), 0.3-0.4
10 (m,2H).
Step 6: Preparation of (E)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(cyclopropylmethoxyimino)ethyl]-2-(trifluoromethyl)benzamide (Compound No. 2-023 of
the present invention)
In a solution of 65 mg of (E)-2-amino-1-[3-chloro-5-(trifluoromethyl)pyridin-2-
15 yl]ethanone-0-(cyclopropylmethyl)oxime and 32 mg of triethylarnine in 2 ml of
dichloromethane, 39 mg of 2-(trifluoromethyl)benzoyl chloride was added dropwise with
stirring under cooling with ice, and after the addition, the mixture was stirred at room
temperature for another 1 hour. After completion of the reaction, the reaction mixture
was mixed with 2 ml of water and extracted with dichloromethane (2 mlxl), the resulting
20 organic layer was dried over saturated aqueous sodium chloride and then anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure. The
resulting residue was purified by preparative medium pressure liquid chromatography
(preparative medium pressure chromatograph: YFLC-Wprep manufactured by Yamazen
Science, Inc.) using ethyl acetate-hexane (with a gradient of from 2:18 to 5:15) as the
25 eluent to obtain 85 mg of the desired product as white crystals.
m.p.:98.0to 101.0°C
1H NMR (CDCb, Me4Si, 300MHz) 68.75 (d, J=1.5Hz, 1H), 8.02 (d, J=1.5Hz, 1H), 7.6-7.7
(m, 1H), 7.45-7.6 (m, 2H), 7.35-7.45 (m, 1H), 6.55 (bs, 1H), 4.81 (d, J=6.0Hz, 2H), 4.19
(d, J=7.2Hz, 2H), 1.15-1.3 (m, 1H), 0.3-0.4 (m, 2H), 0.5-0.6 (m, 2H).
30 Step 7: Preparation of (Z)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(cyclopropylmethoxyimino)ethyl]-2-(trifluoromethyl)benzamide
To 85 mg of (E)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(cyclopropylmethoxyimino)ethyl]-2-(trifluoromethyl)benzamide in 3 ml of acetonitrile, 1
mg of benzophenone was added, and the mixture was irradiated with light for 5 hours in
35 a quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100 W
high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power
supply: UM-103B-B). After completion of the reaction, the solvent was evaporated
under reduced pressure, and the resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to 5:5) as the
40 eluent to obtain 47 mg of the desired product as white crystals.
m.p.: 73.0 to 74.0°C
1H NMR (CDCb, Me4Si, 300MHz) 68.80 (d, J=1.5Hz, 1H), 8.01 (d, J=1.5Hz, 1H), 7.65-
7.75 (m, 1H), 7.5-7.65 (m, 3H), 6.52 (bs, 1H), 4.58 (d, J=6.0Hz, 2H), 3.91 (d, J=7.2Hz,
2H), 1.0-1.15 (m, 1H), 0.45-0.55 (m, 2H), 0.2-0.3 (m, 2H).
45 SYNTHETIC EXAMPLE 7
(Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-methoxyimino-1-methylethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-117 of the present invention)
Step 1: Preparation of 1-(3,5-dichloropyridin-2-yl)-1-propanone
179
To 5.0 g of 3,5-dichloropyridin-2-carbonitrile in 50 ml of tetrahydrofuran, 38 ml of
13% ethylmagnesium bromide in tetrahydrofuran was added dropwise with stirring
under cooling with ice, and after the addition, the mixture was stirred at room
temperature for 1 hour. After completion of the reaction, the reaction mixture was
5 added dropwise to 55 ml of 1N aqueous hydrochloric acid with stirring under cooling
with ice, and extracted with ethyl acetate (50 mlx2). The resulting organic layers were
combined, washed with water (50 mlxl) and dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure. The resulting residue was purified by silica gel column
10 chromatography using ethyl acetate-hexane (with a gradient of 5:95 to 15:85) as the
eluent to obtain 4.4 g of the desired product as pale yellow crystals.
1H NMR (CDCIs, Me4Si, 300MHz) 58.48 (d, J=2.1Hz, 1H), 7.81 (d, J=2.1Hz, 1H), 3.10 (q,
J=7.2Hz, 2H), 1.20 (t, J=7.2Hz, 3H).
Step 2: Preparation of 2-bromo-1-(3,5-dichloropyridin-2-yl)-1-propanone
15 To 4.40 g of 1 -(3,5-dichloropyridin-2-yl)-1 -propanone in 20 ml of ethyl acetatechloroform
(1:1), 10.12 g of copper(l) bromide was added, and the mixture was stirred
at room temperature for 12 hours. After completion of the reaction, the reaction
mixture was mixed with 30 ml of saturated aqueous sodium hydrogencarbonate, and
the precipitated solid was filtered off through celite and washed with 20 ml of ethyl
20 acetate. The filtrate was mixed with 100 ml of ethyl acetate, the resulting organic layer
was collected, washed with water (30 mlxl) and dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 15:85) as
25 the eluent to obtain 5.00 g of the desired product as a pale orange oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.49 (d, J=2.1Hz, 1H), 7.86 (d, J=2.1Hz, 1H), 5.76 (q,
J=6.9Hz, 1H), 1.89 (d, J=6.9Hz, 3H).
Step 3: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-1-methyl-2-oxoethyl)phthalimide
To 5.00 g of 2-bromo-1-(3,5-dichloropyridin-2-yl)-1 -propanone in 20 ml of N,N-
30 dimethylformamide, 3.27 g of potassium phthalimide was added, and the mixture was
stirred at room temperature for 2 hours. After completion of the reaction, the reaction
mixture was mixed with 50 ml of water and extracted with ethyl acetate (50 mlx2), and
the resulting organic layers were combined, washed with water (30 mlxl) and dried
over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the
35 solvent was evaporated under reduced pressure to obtain 2.02 g of the desired crude
product as brown crystals. The crystals were used in the next step without further
purification.
1H NMR (CDCb, Me4Si, 300MHz) 58.34 (d, J=2.1Hz, 1H), 7.65-7.9 (m, 5H), 5.57 (q,
J=6.9Hz, 1H), 1.68 (d, J=6.9Hz, 3H).
40 Step 4: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-methoxyimino-1-
methylethyljphthalimide
To 1.00 g of N-[2-(3,5-dichloropyridin-2-yl)-1-methyl-2-oxoethyl]phthalimide in 10
ml of ethanol, 2.39 g of methoxyamine hydrochloride and 3.40 g of pyridine were added
and refluxed with heating for 18 hours with stirring. After completion of the reaction,
45 the reaction mixture was allowed to cool to room temperature, mixed with 30 ml of 1N
aqueous hydrochloric acid and extracted with ethyl acetate (40 mlx2). The resulting
organic layers were combined, washed with 30 ml of 1N aqueous hydrochloric acid and
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
180
the solvent was evaporated under reduced pressure. The resulting residue was
purified by silica gel column chromatography using ethyl acetate-hexane (with a
gradient of from 1:9 to 3:7) as the eluent to obtain 0.81 g of the desired product as a
colorless resinous substance.
5 1H NMR (CDCb, Me4Si, 300MHz) 58.34 and 8.20 (bs, 1H), 7.65-7.85 (m, 5H), 5.95-6.05
and 5.3-5.65 (m, 1H), 4.01 and 3.86 (bs, 3H), 1.75-1.85 (m, 3H).
Step 5: Preparation of 2-amino-1-(3,5-dichloropyridin-2-yl)-1-propanone-0-methyloxime
To 810 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-methoxyimino-1-
methylethyl]phthalimide in 30 ml of ethanol, 161 mg of hydrazine monohydrate was
10 added and refluxed with heating for 1 hour with stirring. After completion of the
reaction, the solvent was evaporated under reduced pressure, and the resulting residue
was mixed with 20 ml of water and extracted with ethyl acetate (30 mlxl). The
resulting organic layer was washed with water (20 mlxl) and dried over saturated
aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was
15 evaporated under reduced pressure to obtain 430 mg of the desired crude product as a
pale yellow oil. The oil was used in the next step without further purification.
1H NMR (CDCb, Me4Si, 300MHz) 58.51 and 8.48 (d, J=2.1Hz, 1H), 7.79 and 7.77 (d,
J=2.1Hz, 1H), 4.4-4.5 and 3.9-3.05 (m, 1H), 3.99 and 3.84 (s, 3H), 1.32 and 1.27 (d,
J=6.9Hz, 3H).
20 Step 6: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-methoxyimino-1-methylethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-115 of the present invention)
To a solution of 430 mg of 2-amino-1-(3,5-dichloropyridin-2-yl)-1-propanone-0-
methyloxime and 210 mg of triethylamine in 20 ml of dichloromethane, 361 mg of 2-
(trifluoromethyl)benzoyl chloride was added dropwise with stirring under cooling with ice,
25 and after the addition, the mixture was stirred at room temperature for another 1 hour.
After completion of the reaction, the reaction mixture was mixed with 30 ml of water and
extracted with chloroform (20 mlxl), the resulting organic layer was washed with water
(20 mlxl) and dried over saturated aqueous sodium chloride and then anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure. The
30 resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 1:9 to 3:7) as the eluent to obtain 296 mg of the desired
product as a colorless resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.50 and 8.41 (d, J=1.8Hz, 1H), 7.82 and 7.79 (d,
J=1.8Hz, 1H), 7.4-7.75 (m, 4H), 6.65-7.0 (m, 1H), 5.7-5.85 and 5.2-5.3 (m, 1H), 4.05
35 and 3.87 (s, 3H), 1.56 and 1.45 (d, J=6.6Hz, 3H).
Step 7: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-methoxyimino-1-methylethyl]-
2-(trifluoromethyl)benzamide
160 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-methoxyimino-1-methylethyl]-2-
(trifluoromethyl)benzamide in 4 ml of acetonitrile was irradiated with light for 12 hours in
40 a quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100 W
high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power
supply: UM-103B-B). After completion of the reaction, the solvent was evaporated
under reduced pressure, and the precipitated solid was washed with 5 ml of diisopropyl
ether to obtain 33 mg of the desired product as white crystals.
45 m.p.: 104.0 to 105.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.50 (d, J=2.1Hz, 1H), 7.80 (d, J=2.1Hz, 1H), 7.5-
7.75 (m, 4H), 6.78 (bs, 1H), 5.2-5.35 (m, 1H), 3.87 (s, 3H), 1.45 (d, J=6.6Hz, 3H).
SYNTHETIC EXAMPLE 8
181
(Z)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-(ethoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-185 of the present invention)
Step 1: Preparation of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(ethoxyimino)ethyl]phthalimide
5 To 214 mg of the N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
oxoethyl]phthalimide prepared in Step 2 in Synthetic Example 6 in 3 ml of ethanol, 84
mg of ethoxyamine hydrochloride was added, and the mixture was stirred at room
temperature for 18 hours. After completion of the reaction, the reaction mixture was
mixed with 5 ml of water and extracted with ethyl acetate (5 mlx3), and the resulting
10 organic layers were combined, dried over saturated aqueous sodium chloride and then
anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
The resulting residue was purified by preparative medium pressure liquid
chromatography (preparative medium pressure chromatograph: YFLC-Wprep
manufactured by Yamazen Science, Inc.) using ethyl acetate-hexane (with a gradient of
15 from 2:18 to 5:15) as the eluent to obtain 111 mg of the desired product as a brown
resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.60 (d, J=1.5Hz, 1H), 7.97 (d, J=1.5Hz, 1H), 7.8-7.9
(m, 2H), 7.65-7.75 (m, 2H), 5.02 and 4.80 (s, 2H), 4.29 and 4.11 (q, J=7.2Hz, 2H), 1.30
and 1.17 (t,J=7.2Hz,3H).
20 Step 2: Preparation of 2-amino-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethanone-0-
ethyloxime
To 111 mg of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(ethoxyimino)ethyl]phthalimide in 3 ml of ethanol, 86 mg of hydrazine monohydrate was
added, and the mixture was stirred at 80°C for 1 hour. After completion of the reaction,
25 the reaction mixture was allowed to cool to room temperature, mixed with 5 ml of water
and extracted with ethyl acetate (5 mlx3). The resulting organic layers were combined,
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, the
solvent was evaporated under reduced pressure, and the resulting residue was purified
by silica gel column chromatography using methanol-chloroform (1:10) as the eluent to
30 obtain 47 mg of the desired product as a yellow oil. The oil was used in the next step
without further purification.
1H NMR (CDCb, Me4Si, 300MHz) 58.80 and 8.77 (d, J=1.5Hz, 1H), 8.00 and 7.97 (d,
J=1.5Hz, 1H), 4.29 and 4.13 (q, J=7.2Hz, 2H), 3.93 and 3.77 (s, 2H), 1.70 (bs, 2H), 1.35
and 1.22 (t, J=7.2z, 3H).
35 Step 3: Preparation of N:[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(ethoxyimino)ethyl]-2-(trifluoromethyl)benzamide (Compound No. 2-016 of the present
invention)
To a solution of 47 mg of 2-amino-1-[3-chloro-5-(trifluoromethyl)pyridin-2-
yl]ethanone-0-ethyloxime and 25 mg of triethylamine in 2 ml of dichlorornethane, 31 mg
40 of 2-(trif luoromethyl)benzoyl chloride was added dropwise with stirring under cooling
with ice, and after the addition, the mixture was stirred at room temperature for another
1 hour. After completion of the reaction, the reaction mixture was mixed with 2 ml of
water and extracted with dichlorornethane (2 mlxl), the resulting organic layer was
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
45 the solvent was evaporated under reduced pressure. The resulting residue was
purified by preparative medium pressure liquid chromatography (preparative medium
pressure chromatograph: YFLC-Wprep manufactured by Yamazen Science, Inc.) using
ethyl acetate-hexane (with a gradient of from 2:18 to 5:15) as the eluent to obtain 48 mg
182
of the desired product as a colorless resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.81 and 8.75 (d, J=1.5Hz, 1H), 8.03 and 8.00 (d,
J=1.5Hz, 1H), 7.35-7.55 (m, 4H), 6.51 (bs, 1H), 4.79 and 4.58 (d, J=5.4Hz, 2H), 4.34
and 4.16 (q, J=7.2Hz, 2H), 1.38 and 1.24 (t, J=7.2Hz, 3H).
5 Step 4: Preparation of (Z)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(ethoxyimino)ethyl]-2-(trifluoromethyl)benzamide
To 48 mg of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-(ethoxyimino)ethyl]-2-
(trifluoromethyl)benzamide in 3 ml of acetonitrile, 1 mg of benzophenone was added,
and the mixture was irradiated with light for 4 hours in a quartz cell (manufactured by
10 Fine, 4 clear windows for spectroscopy) using a 100 W high-pressure mercury lamp
(manufactured by USHIO INC., lamp: UM-102, power supply: UM-103B-B). After
completion of the reaction, the solvent was evaporated under reduced pressure, and the
resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 1:9 to 5:5) as the eluent to obtain 42 mg of the desired
15 product as white crystals.
m.p.:60.0to62.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.81 (d, J=1.5Hz, 1H), 8.00 (d, J=1.5Hz, 1H), 7.5-
7.55 (m, 4H), 6.51 (bs, 1H), 4.79 (d, J=5.4Hz, 2H), 4.16 (q, J=7.2Hz, 2H), 1.24 (t,
J=7.2Hz, 3H).
20 SYNTHETIC EXAMPLE 9
N-[2-(3-chloro-5-methoxypyridin-2-yl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (compound No. 2-083 of the present invention)
Step 1: Preparation of 2-bromo-1-(3-chloro-5-methoxypyridin-2-yl)ethanone
To 0.90 g of 1-(3-chloro-5-methoxypyridin-2-yl)ethanone in 10 ml of
25 tetrahydrofuran, 1.82 g of trimethylphenylammonium tribromide was added, and the
mixture was stirred at room temperature for 16 hours. After completion of the reaction,
the precipitated solid was filtered off, and the solvent was evaporated under reduced
pressure. The resulting residue was purified by silica gel column chromatography
using ethyl acetate-hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain
30 0.57 g of the desired product as pale yellow crystals.
1H NMR (CDCb, Me4Si, 300MHz) 58.23 (d, J=2.4Hz, 1H), 7.28 (d, J=2.4Hz, 1H), 4.74
(s, 2H), 3.95 (s, 3H).
Step 2: Preparation of N-[2-(3-chloro-5-methoxypyridin-2-yl)-2-oxoethyl]phthalimide
To 570 mg of 2-bromo-1-(3-chloro-5-methoxypyridin-2-yl)ethanone in 10 ml of
35 N,N-dimethylformamide, 800 mg of potassium phthalimide and 36 mg of potassium
iodide were added, and the mixture was stirred at 80°C for 5 hours. After completion
of the reaction, the reaction mixture was allowed to cool to room temperature, mixed
with 20 ml of water and extracted with ethyl acetate (40 mlxl), the resulting organic
layer was dried over saturated aqueous sodium chloride and then anhydrous sodium
40 sulfate, and the solvent was evaporated under reduced pressure. The resulting
residue was purified by silica gel column chromatography using ethyl acetate-hexane
(with a gradient of from 1:9 to 3:7) as the eluent to obtain 0.12 g of the desired product
as white crystals.
1H NMR (CDCb, Me4Si, 300MHz) 58.30 (d, J=2.4Hz, 1H), 7.85-7.95 (m, 2H), 7.7-7.8
45 (m, 2H), 7.27 (d, J=2.4Hz, 2H), 5.31 (s, 2H), 3.96 (s, 3H).
Step 3: Preparation of N-[2-(3-chloro-5-methoxypyridin-2-yl)-2-
(methoxyimino)ethyl]phthalimide
To a solution of 120 mg of N-[2-(3-chloro-5-methoxypyridin-2-yl)-2-
183
oxoethyl]phthalimide and 60 mg of methoxyamine hydrochloride in 5 ml of ethanol, 85
mg of pyridine was added, and the mixture was stirred at 80°C for 6 hours. After
completion of the reaction, the solvent was evaporated under reduced pressure, and the
resulting residue was purified by silica gel column chromatography using ethyl acetate-
5 hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 101 mg of the desired
product as a pale yellow oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.17 and 8.01 (d, J=2.7Hz, 1H), 7.65-7.9 (m, 4H),
7.20 and 7.19 (d, J=2.7Hz, 1H), 4.99 and 4.77 (s, 2H), 4.04 and 3.84 (s, 3H), 3.84 and
3.78 (s, 3H).
10 Step 4: Preparation of N-[2-(3-chloro-5-methoxypyridin-2-yl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
To 101 mg of N-[2-(3-chloro-5-methoxypyridin-2-yl)-2-
(methoxyimino)ethyl]phthalimide in 5 ml of ethanol, 42 mg of hydrazine monohydrate
was added, and the mixture was stirred at room temperature for 12 hours. After
15 completion of the reaction, the reaction mixture was mixed with 15 ml of water and
extracted with ethyl acetate (30 mlxl), the resulting organic layer was washed with
water (20 mlxl) and dried over saturated aqueous sodium chloride and then anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure. The
resulting residue was dissolved in 5 ml of dichloromethane, and to the solution, 46 mg
20 of 2-(trifluoromethyl)benzoyl chloride and then 33 mg of triethylamine were added, and
the mixture was stirred at room temperature for one hour. After completion of the
reaction, the reaction mixture was mixed with 5 ml of water and extracted with ethyl
acetate (15 mlxl), the resulting organic layer was washed with water (20 mlxl) and
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
25 the solvent was evaporated under reduced pressure. The resulting residue was
purified by silica gel column chromatography using ethyl acetate-hexane (with a
gradient of from 1:9 to 3:7) as the eluent to obtain 87 mg of a pale yellow resinous
substance. The resinous substance was dissolved in 5 ml of ethanol, and 0.5 ml of a
1,4-dioxane solution (4 mol/L) of hydrogen chloride, and the mixture was stirred at 70°C
30 for 2 hours. The solvent was evaporated under reduced pressure, and the resulting
residue was purified by silica gel column chromatography using ethyl acetate-hexane
(with a gradient of from 1:9 to 3:7) as the eluent to obtain 80 mg of the desired product
as a colorless resinous substance (E/Z=55/45).
1H NMR (CDCb, Me4Si, 300MHz) 58.23 and 8.19 (d, J=2.7Hz, 1H), 7.35-7.75 (m, 4H),
35 7.28 and 7.27 (d, J=2.7Hz, 1H), 6.57 and 6.50 (bs, 1H), 4.74 and 4.52 (d, J=6.0Hz, 2H),
4.05 and 3.87 (s, 3H), 3.84 (bs, 3H).
SYNTHETIC EXAMPLE 10
(Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-128 of the present invention)
40 Step 1: Preparation of 1 -[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-1,3,5,7-
tetraazatricyclo[3,3,1,13'7]decan-1 -ium bromide
5.00 g of the 2-bromo-1-(3,5-dichloropyridin-2-yl)ethanone prepared in Step 2 in
Synthetic Example 2 in 30 ml of chloroform was added dropwise to 2.61 g of 1,3,5,7-
tetraazatricyclo[3,3,1,13'7]decane in 50 ml of chloroform with stirring at room
45 temperature, and the mixture was stirred at the same temperature for 2 hours. After
completion of the reaction, the precipitated crystals were collected by filtration and
washed with 30 ml of chloroform to obtain 7.40 g of the desired product as white
crystals.
184
m.p.>177.0°C (decomposition)
Step 2: Preparation of 2-amino-1-(3,5-dichloropyridin-2-yl)ethanone hydrochloride
To a suspension of 7.0 g of 1-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-1,3,5,7-
tetraazatricyclo[3,3,1,13'7]decan-1-ium bromide in 70 ml of ethanol, 7 ml of concentrated
5 hydrochloric acid was added, and the mixture was stirred at room temperature for 14
hours. After completion of the reaction, the solid was collected by filtration and washed
with 15 ml of ethanol to obtain 3.7 g of the desired product as white crystals.
m.p.>207.0°C (decomposition)
1H NMR (CDCb, Me4Si-DMSO-d6, 300MHz) 58.83 (bs, 1H), 8.51 (bs, 1H), 4.54 (bs,
10 2H).
Step 3: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-
(trifluoromethyl)benzamide
To a suspension of 3.7 g of 2-amino-1-(3,5-dichloropyridin-2-yl)ethanone
hydrochloride in 50 ml of ethyl acetate, 30 ml of water and 3.5 g of 2-
15 (trifluoromethyl)benzoyl chloride were added, and 6.1 g of potassium carbonate in 30 ml
of water was added dropwise with stirring under cooling with ice, and the mixture was
stirred at the same temperature for 30 minutes. After completion of the reaction, the
reaction mixture was mixed with 20 ml of ethyl acetate, the resulting organic layer was
collected, washed with water (20 mlxl) and dried over saturated aqueous sodium
20 chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 2:8 to 6:4) as the
eluent to obtain 3.8 g of the desired product as pale yellow crystals.
m.p.: 123.0 to 125.0°C
25 1H NMR (CDCb, Me4Si, 300MHz) 58.55 (d, J=2.1 Hz, 1H), 7.88 (d, J=2.1 Hz, 1H), 7.5-
7.75 (m, 4H), 6.69 (bs, 1H), 5.10 (d, J=4.8Hz, 2H).
Step 4: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]-2-
(trifluoromethyl)benzamide
To a solution of 3.38 g of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-
30 (trifluoromethyl)benzamide and 0.934 g of hydroxylamine hydrochloride in 20 ml of
ethanol, 1.10 g of sodium acetate was added, and the mixture was stirred at room
temperature for 12 hours. After completion of the reaction, the solvent was evaporated
under reduced pressure, the resulting residue was mixed with 40 ml of water and
extracted with ethyl acetate (20 mlx2), the resulting organic layers were combined,
35 washed with water (20 mlxl) and dried over saturated aqueous sodium chloride and
then anhydrous sodium sulfate, and the solvent was evaporated under reduced
pressure. The resulting residue was purified by silica gel column chromatography
using ethyl acetate-hexane (with a gradient of from 2:8 to 4:6) as the eluent to obtain
1.90 g of the desired product as white crystals.
40 m.p.: 134.0 to 136.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.52 and 8.45 (d, J=2.4Hz, 1H), 7.81 and 7.80 (d,
J=2.4Hz, 1H), 7.35-7.75 (m, 4H), 6.53 (bs, 1H), 4.80 and 4.55 (d, J=6.3Hz, 2H).
Step 5: Preparation of (E)-N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-239 of the present invention)
45 To a suspension of 300 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-
(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide and 315 mg of potassium carbonate
in 3 ml of N,N-dimethylformamide, 195 mg of 2-iodopropane was added, and the
mixture was stirred at room temperature for 6 hours. After completion of the reaction,
185
the reaction mixture was mixed with 20 ml of water and extracted with ethyl acetate (10
mlx2), the resulting organic layers were combined, washed with water (10 mlx2), the
resulting organic layer was dried over saturated aqueous sodium chloride and then
anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
5 The resulting residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 258 mg of the
desired product as white crystals.
m.p.: 54.0 to 57.0°C
1H NMR (CDCIs, Me4Si, 300MHz) 58.45 (d, J=2.1Hz, 1H), 7.81 (d, J=2.1Hz, 1H), 7.35-
10 7.7 (m, 4H), 6.49 (bs, 1H), 4.76 (d, J=6.3Hz, 2H), 4.45-4.6 (m, 1H), 1.33 (d, J=6.0Hz,
6H).
Step 6: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
To 258 mg of (E)-N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)ethyl]-2-
15 (trifluoromethyl)benzamide in 4 ml of acetonitrile, 2 mg of benzophenone was added,
and the mixture was irradiated with light for 12 hours in a quartz cell (manufactured by
Fine, 4 clear windows for spectroscopy) using a 100 W high-pressure mercury lamp
(manufactured by USHIO INC., lamp: UM-102, power supply: UM-103B-B). After
completion of the reaction, the solvent was evaporated under reduced pressure, and the
20 resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 1:9 to 3:7) as the eluent to obtain 231 mg of the desired
product as white crystals.
m.p.: 107.0 to 108.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.50 (d, J=2.1Hz, 1H), 7.78 (d, J=2.1Hz, 1H), 7.5-7.8
25 (m, 4H), 6.54 (bs, 1H), 4.53 (d, J=5.1Hz, 2H), 4.3-4.45 (m, 1H), 1.18 (d, J=6.3Hz, 6H).
SYNTHETIC EXAMPLE 11
(Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(tert-butoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (compound No. 2-140 of the present invention)
Step 1: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(tert- butoxyimino)ethyl]-2-
30 (trifluoromethyl)benzamide (compound No. 2-139 of the present invention)
To a solution of 200 mg of the N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-
(trifluoromethyl)benzamide prepared in Step 3 in Synthetic Example 10 and 199 mg of
0-(tert-butyl)hydroxylamine hydrochloride in 2.6 ml of ethanol, 167 mg of pyridine was
added, and the mixture was stirred at 70°C for 18 hours. After completion of the
35 reaction, the solvent was evaporated under reduced pressure, the resulting residue was
mixed with 2 ml of water and extracted with ethyl acetate (2 mlx2), the resulting organic
layers were combined, dried over saturated aqueous sodium chloride and then
anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
The resulting residue was purified by silica gel column chromatography using ethyl
40 acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 207 mg of
the desired product as a colorless resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.50 and 8.44 (d, J=2.4Hz, 1H), 7.25-7.85 (m, 5H),
6.54 (bs, 1H), 4.77 and 4.54 (d, J=5.7Hz, 2H), 1.37 and 1.24 (s, 9H).
Step 2: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(tert-butoxyimino)ethyl]-2-
45 (trifluoromethyl)benzamide
207 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(tert-butoxyimino)ethyl]-2-
(trifluoromethyl)benzamide in 4 ml of acetonitrile was irradiated with light for 8 hours in a
quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100 W
186
high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power
supply: UM-103B-B). After completion of the reaction, the solvent was evaporated
under reduced pressure, and the resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to 5:5) to obtain
5 190 mg of the desired product as a colorless resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.50 (d, J=2.0Hz, 1H), 7.77 (d, J=2.0Hz, 1H), 7.5-
7.75 (m, 4H), 6.56 (bs, 1H), 4.53 (d, J=5.1Hz, 2H), 1.24 (s, 9H).
SYNTHETIC EXAMPLE 12
(Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(2,2,2-trifluoroethoxyimino)ethyl]-2-
10 (trifluoromethyl)benzamide (compound No. 2-212 of the present invention)
Step 1: Preparation of tert-butyl N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]carbamate
To 35.1 g of 2-bromo-3,5-dichloropyridine in 10 ml of tetrahydrofuran, 116.3 ml of
a 1.3 M tetrahydrofuran solution of isopropylmagnesium chloride-lithium chloride
complex was added dropwise with stirring at -20°C, and after the addition, the mixture
15 was stirred at the same temperature for 15 minutes. Then, to the reaction mixture,
15.0 g of N-methoxy-N-methyl-2-(tert-butoxycarbonylamino)acetamide in 114 ml of
tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at
the same temperature for another 2 hours. After completion of the reaction, the
reaction mixture was mixed with 100 ml of saturated aqueous ammonium chloride and
20 100 ml of water and extracted with ethyl acetate (200 mlx2), the resulting organic layers
were combined, washed with water (100 mlxl) and dried over saturated aqueous
sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated
under reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 0:10 to 3:7) as the
25 eluent to obtain 12.5 g of the desired product as pale yellow crystals.
m.p.: 82.0 to 84.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.51 (d, J=2.1Hz, 1H), 7.85 (d, J=2.1Hz, 1H), 5.31
(bs, 1H), 4.76 (bs, 2H), 1.47 (s, 9H).
Step 2: Preparation of tert-butyl N-[2-(3,5-dichloropyridin-2-yl)-2-
30 (hydroxyimino)ethyl]carbamate
To a solution of 10.6 g of tert-butyl N-[2-(3,5-dichloropyridin-2-yl)-2-
oxoethyl]carbamate and 4.8 g of hydroxylamine hydrochloride in 87 ml of ethanol, 6.1 g
of pyridine was added, and the mixture was stirred at room temperature for 24 hours.
After completion of the reaction, the solvent was evaporated under reduced pressure,
35 the resulting residue was mixed with 50 ml of water and extracted with ethyl acetate
(100 mlx2), the resulting organic layers were combined, dried over saturated aqueous
sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated
under reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 40:60) as
40 the eluent to obtain 10.1 g of the desired product as a pale yellow resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.52 and 8.47 (d, J=2.4Hz, 1H), 7.82 and 7.79 (d,
J=2.4Hz, 1H), 5.65 and 5.16 (bs, 1H), 4.46 and 4.24 (d, J=5.4Hz, 2H), 1.39 and 1.34 (s,
9H).
Step 3: Preparation of tert-butyl N-[2-(3,5-dichloropyridin-2-yl)-2-(2,2,2-
45 trifluoroethoxyimino)ethyl]carbamate
To 5.0 g of tert-butyl N-[2-(3,5-dichloropyridin-2-yl)-2-
(hydroxyimino)ethyl]carbamate in 16.0 ml of N,N-dimethylformamide, 4.3 g of potassium
carbonate and 5.4 g of 2,2,2-trifluoroethyl trifluoromethanesulfonate were added, and
187
the mixture was stirred at room temperature for 18 hours. After completion of the
reaction, the reaction mixture was mixed with 100 ml of water and extracted with ethyl
acetate (100 mlx2), the resulting organic layers were combined, washed with water (50
mlx2) and dried over saturated aqueous sodium chloride and then anhydrous sodium
5 sulfate, and the solvent was evaporated under reduced pressure. The resulting
residue was purified by silica gel column chromatography using ethyl acetate-hexane
(with a gradient of from 0:10 to 3:7) as the eluent to obtain 4.8 g of the desired product
as a pale yellow oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.51 and 8.49 (d, J=1.8Hz, 1H), 7.80 and 7.78 (d,
10 J=1.8Hz, 1H), 4.94 (bs, 1H), 4.0-4.65 (m, 4H), 1.39 and 1.34 (s, 9H).
Step 4: Preparation of 2-amino1 -(3,5-dichloropyridin-2-yl)ethanone-0-(2,2,2-
trifluoroethyl)oxime hydrochloride
To 4.9 g of tert-butyl N-[2-(3,5-dichloropyridin-2-yl)-2-(2,2,2-
trif luoroethoxyimino)ethyl]carbamate in 5 ml of 1,4-dioxane, 25 ml of a 1,4-dioxane
15 solution (4 mol/L) of hydrogen chloride was added, and the mixture was stirred at room
temperature for 3 hours. After completion of the reaction, the solvent was evaporated
under reduced pressure, and the resulting residue was washed with 20 ml of hexane to
obtain 3.1 g of the desired product as pale brown crystals.
m.p.: 141.0 to 143.0°C
20 1H NMR (CDCb, Me4Si, 300MHz) 58.98 (bs, 3H), 8.56 and 8.52 (d, J=2.1 Hz, 1H), 7.83
and 7.80 (d, J=2.1Hz, 1H), 4.72 and 4.54 (q, J=8.7Hz, 2H), 4.28 and 4.10 (bs, 2H).
Step 5: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(2,2,2-trifluoroethoxyimino)ethyl]-
2-(trifluoromethyl)benzamide (compound No. 2-011 of the present invention)
To 2.0 g of 2-amino1-(3,5-dichloropyridin-2-yl)ethanone-0-(2,2,2-
25 trifluoroethyl)oxime hydrochloride in 12.0 ml of water, 1.4 g of 2-(trifluoromethyl)benzoyl
chloride in 12.0 ml of dichloromethane and 2.4 g of potassium carbonate were added at
room temperature with stirring, and the mixture was stirred at the same temperature for
2 hours. After completion of the reaction, the resulting organic layer was collected and
dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced
30 pressure. The resulting residue was purified by silica gel column chromatography
using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to
obtain 2.6 g of the desired product as a pale yellow resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.51 and 8.46 (d, J=2.1Hz, 1H), 7.82 and 7.81 (d,
J=2.1Hz, 1H), 7.35-7.75 (m, 4H), 6.39 (bs, 1H), 4.80 and 4.57 (d, J=6.0Hz, 2H), 4.61
35 and 4.42 (q, J=8.4Hz, 2H).
Step 6: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(2,2,2-
trifluoroethoxyimino)ethyl]-2-(trifluoromethyl)benzamide
2.6 g of N-[2-(3,5-dichloropyridin-2-yl)-2-(2,2,2-trifluoroethoxyimino)ethyl]-2-
(trifluoromethyl)benzamide was dissolved in 12.0 ml of acetonitrile, and the solution was
40 irradiated with light for 48 hours in a quartz cell (manufactured by Fine, 4 clear windows
for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO
INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the
solvent was evaporated under reduced pressure, and the resulting residue was washed
with 20 ml of hexane to obtain 2.1 g of the desired product as white crystals.
45 m.p.: 100.0 to 102.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.52 (d, J=2.1Hz, 1H), 7.45-7.85 (m, 5H), 6.39 (bs,
1H), 4.57 (d, J=5.4Hz, 2H), 4.42 (q, J=8.7Hz, 2H).
SYNTHETIC EXAMPLE 13
188
(S)-N-[2-(3,5-dichloropyridin-2-yl)-2-(Z)-(isopropoxyimino)-1-methylethyl]-2-
(trifluoromethyl)benzamide (compound No. 2-132 of the present invention)
Step 1: Preparation of (S)-N-methoxy-N-methyl-2-(tertbutoxycarbonylamino)
propionamide
5 To 20.0 g of N-(tert-butoxycarbonyl)-L-alanine in 352 ml of dichloromethane, 12.4
g of N,0-dimethylhydroxylamine hydrochloride, 15.7 g of 1-hydroxybenzotriazole
monohydrate, 24.3 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
and 42.7 g of triethylamine were added, and the mixture was stirred at room
temperature for 1.5 hours. After completion of the reaction, the reaction mixture was
10 washed with 500 ml of saturated aqueous sodium hydrogen carbonate, 500 ml of 1N
aqueous hydrochloric acid and 500 ml of water in this order, the resulting organic layer
was dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate,
and the solvent was evaporated under reduced pressure. The resulting residue was
washed with 200 ml of hexane to obtain 13.1 g of the desired product as white crystals.
15 m.p.: 144.0 to 145.0°C
1H NMR (CDCIa, Me4Si, 300MHz) 55.22 (bs, 1H), 4.68 (bs, 1H), 3.77 (s, 3H), 3.21 (s,
3H), 1.44 (s, 9H), 1.31 (d, J=6.9Hz, 3H).
Step 2: Preparation of tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-1-methyl-2-
oxoethyl]carbamate
20 To 11.0 g of 2-bromo-3,5-dichloropyridine in 5 ml of tetrahydrofuran, 36.4 ml of a
1.3 M tetrahydrofuran solution of isopropylmagnesium chloride-lithium chloride complex
was added dropwise with stirring at -20°C, and after the addition, the mixture was stirred
at the same temperature for 15 minutes. Then, to the reaction mixture, 5.0 g of (S)-Nmethoxy-
N-methyl-2-(tert-butoxycarbonylamino)propionamide in 36 ml of
25 tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at
the same temperature for another 2 hours. After completion of the reaction, the
reaction mixture was mixed with 30 ml of saturated aqueous ammonium chloride and 10
ml of water and extracted with ethyl acetate (40 mlx2), the resulting organic layers were
combined, washed with water (40 mlxl) and dried over saturated aqueous sodium
30 chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 10:0 to 3:7) to
obtain 4.5 g of the desired product as a pale yellow oil.
1H NMR (CDCIa, Me4Si, 300MHz) 58.51 (d, J=2.1Hz, 1H), 7.84 (d, J=2.1Hz, 1H), 5.50
35 (bs, 1H), 5.32 (bs, 1H), 1.46 (s, 9H), 1.36 (d, J=7.2Hz, 3H).
Optical purity: 95% e.e.
Optical rotation: [a]D17-5-20.20°(CHCI3, c=0.10)
Step 3: Preparation of tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-hydroxyimino-1-
methylethyl]carbamate
40 To a solution of 1.0 g of tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-1-methyl-2-
oxoethyl]carbamate and 239 mg of hydroxylamine hydrochloride in 5 ml of ethanol, 272
mg of pyridine was added, and the mixture was stirred at room temperature for 18
hours. After completion of the reaction, the solvent was evaporated under reduced
pressure, the resulting residue was mixed with 10 ml of water and extracted with ethyl
45 acetate (10 mlx2), the resulting organic layers were combined, dried over saturated
aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was
evaporated under reduced pressure. The resulting residue was purified by silica gel
column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to
189
40:60) as the eluent to obtain 740 mg of the desired product as pale yellow crystals.
m.p.:51.0to53.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.53 (d, J=2.1Hz, 1H), 7.78 (d, J=2.1Hz, 1H), 5.15
(bs, 1H), 4.81 (bs, 1H), 1.3-1.65 (m, 12H).
5 Optical purity: 95% e.e.
Optical rotation: [a]D
17-8-27.40o(CHCb, c=0.10)
Step 4: Preparation of tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)-
1 -methylethyl]carbamate
To 655 mg of tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-hydroxyimino-1-
10 methylethyl]carbamate in 1.6 ml of N,N-dimethylformamide, 445 mg of potassium
carbonate and 789 mg of 2-iodopropane were added, and the mixture was stirred at
room temperature for 18 hours. After completion of the reaction, the reaction mixture
was mixed with 5 ml of water and extracted with ethyl acetate (10 mlx2), the resulting
organic layers were combined, washed with water (10 mlx2) and dried over saturated
15 aqueous sodium chloride and then aqueous sodium sulfate, and the solvent was
evaporated under reduced pressure. The resulting residue was purified by silica gel
column chromatography using ethyl acetate-hexane (with a gradient of from 0:10 to 3:7)
as the eluent to obtain 411 mg of the desired product as a colorless oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.49 and 8.44 (d, J=2.1Hz, 1H), 7.77 and 7.73 (d,
20 J=2.1 Hz, 1H), 5.20 (bs, 1H), 4.74 (bs, 1H), 4.25-4.5 (m, 1H), 1.1 -1.6 (m, 18H).
Optical purity: 95% e.e.
Optical rotation: [a]D
180-29.90o(CHCb, c=0.14)
Step 5: Preparation of (S)-2-amino-1-(3,5-dichloropyridin-2-yl)propanone-0-
isopropyloxime hydrochloride
25 To 350 mg of tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)-1-
methylethyl]carbamate in 3 ml of 1,4-dioxane, 5 ml of a 1,4-dioxane solution (4 mol/L) of
hydrogen chloride was added, and the mixture was stirred at room temperature for 6
hours. After completion of the reaction, the solvent was evaporated under reduced
pressure, and the resulting residue was washed with 20 ml of hexane to obtain 253 mg
30 of the desired product as white crystals.
m.p.: 215.0 to 216.0°C
1H NMR (CDCb, Me4Si, 300MHz) 59.00 (bs, 3H), 8.51 (d, J=2.1Hz, 1H), 7.76 (d,
J=2.1Hz, 1H), 4.35-4.6 (m, 2H), 1.73 and 1.57 (d, J=6.9Hz, 3H), 1.15-1.4 (m, 6H).
Optical purity: 95% e.e.
35 Optical rotation: [a]D18-6-15.50°(CHCb, c=0.10)
Step 6: Preparation of (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)-1 -
methylethyl]-2-(trifluoromethyl)benzamide (compound No. 2-130 of the present
invention)
To 210 mg of (S)-2-amino-1-(3,5-dichloropyridin-2-yl)propanone-0-isopropyloxime
40 hydrochloride in 1.3 ml of water, 151 mg of 2-(trifluoromethyl)benzoyl chloride in 1.3 ml
of dichloromethane and 278 mg of potassium carbonate were added with stirring at
room temperature, and the mixture was stirred at the same temperature for 2 hours.
After completion of the reaction, the resulting organic layer was collected and dried over
anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
45 The resulting residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 221 mg of
the desired product as a colorless resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.48 and 8.40 (d, J=1.8Hz, 1H), 7.4-7.85 (m, 5H),
190
7.00 and 6.85 (bs, 1H), 5.7-5.85 and 5.15-5.3 (m, 1H), 4.25-4.55 (m, 1H), 1.15-1.6 (m,
9H).
Optical purity: 95% e.e.
Optical rotation: [a]D
190-13.20°(EtOH, c=0.10)
5 Step 7: Preparation of (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-[(Z)-isopropoxyimino]-1-
methylethyl]-2-(trifluoromethyl)benzamide
240 mg of (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)-1-methylethyl]-2-
(trifluoromethyl)benzamide was dissolved in 4 ml of acetonitrile, and the solution was
irradiated with light for 8 hours in a quartz cell (manufactured by Fine, 4 clear windows
10 for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO
INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the
solvent was evaporated under reduced pressure, and the resulting residue was purified
by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from
1:9 to 5:5) as the eluent to obtain 153 mg of the desired product as a colorless resinous
15 substance.
1H NMR (CDCI3, Me4Si, 300MHz) 58.48 (d, J=2.1Hz, 1H), 7.78 (d, J=2.1Hz, 1H), 7.45-
7.75 (m, 4H), 6.84 (bs, 1H), 5.15-5.3 (m, 1H), 4.25-4.45 (m, 1H), 1.44 (d, J=6.6Hz, 3H),
1.18 (d, J=6.0Hz, 6H).
Optical purity: 95% e.e.
20 Optical rotation: [a]D
21-8 -8.60°(EtOH, c=0.10)
SYNTHETIC EXAMPLE 14
(S)-N-[2-(3,5-dichloropyridin-2-yl)-2-[(Z)-ethoxyimino]-1-methylethyl]-2-
(trifluoromethyl)benzamide (compound No. 2-124 of the present invention)
Step 1: Preparation of tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-ethoxyimino-1-
25 methylethyl]carbamate
To a solution of 1.0 g of the tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-1-methyl-
2-oxoethyl]carbamate prepared in Step 2 in Synthetic Example 13 and 336 mg of
ethoxyamine hydrochloride in 6.3 ml of ethanol, 272 mg of pyridine was added, and the
mixture was stirred at room temperature for 18 hours. After completion of the reaction,
30 the solvent was distilled off under reduced pressure, the resulting residue was mixed
with 10 ml of water and extracted with ethyl acetate (10 mlx2), the resulting organic
layers were combined, dried over saturated aqueous sodium chloride and then
anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
The resulting residue was purified by silica gel column chromatography using ethyl
35 acetate-hexane (with a gradient of from 5:95 to 40:60) as the eluent to obtain 824 mg of
the desired produced as a pale yellow oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.50 (d, J=2.1Hz, 1H), 7.74 (d, J=2.1Hz, 1H), 5.19
(bs, 1H),4.75(bs, 1H), 4.26 and 4.11 (q, J=7.2Hz, 2H), 1.1-1.55 (m, 15H).
Optical purity: 95% e.e.
40 Optical rotation: [a]D
17-9-30.00°(CHCI3, c=0.10)
Step 2: Preparation of (S)-2-amino-1-(3,5-dichloropyridin-2-yl)propanone-0-ethyloxime
hydrochloride
To 780 mg of tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-ethoxyimino-1-
methylethyl]carbamate in 3 ml of 1,4-dioxane, 5 ml of a 1,4-dioxane solution (4 mol/L) of
45 hydrogen chloride was added, and the mixture was stirred at room temperature for 6
hours. After completion of the reaction, the solvent was evaporated under reduced
pressure, and the resulting residue was washed with 20 ml of hexane to obtain 643 mg
of the desired product as beige crystals.
191
m.p.:209.0to210.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.98 (bs, 3H), 8.52 (d, J=2.1Hz, 1H), 7.77 (d,
J=2.1Hz, 1H), 4.51 (bs, 1H), 4.35 and 4.20 (q, J=7.2Hz, 2H), 1.73 and 1.59 (d, J=7.2Hz,
3H), 1.38 and 1.25 (t, J=7.2Hz, 3H).
5 Optical purity: 95% e.e.
Optical rotation: [a]D18-5-10.90o(CHCb, c=0.10)
Step 3: Preparation of (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-ethoxyimino-1-methylethyl]-
2-(trifluoromethyl)benzamide (compound No. 2-122 of the present invention)
To 550 mg of (S)-2-amino-1-(3,5-dichloropyridin-2-yl)propanone-0-ethyloxime
10 hydrochloride in 3.7 ml of water, 423 mg of 2-(trifluoromethyl)benzoyl chloride in 3.7 ml
of dichloromethane and 763 mg of potassium carbonate were added with stirring at
room temperature, and the mixture was stirred at the same temperature for 2 hours.
After completion of the reaction, the organic layer was collected and dried over
anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
15 The resulting residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 800 mg of
the desired product as a colorless resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.49 (d, J=2.1Hz, 1H), 7.4-7.85 (m, 5H), 6.98 and
6.81 (bs, 1H), 5.75-5.85 and 5.15-5.35 (m, 1H), 4.29 and 4.12 (q, J=7.2Hz, 2H), 1.15-
20 1.65 (m,6H).
Optical purity: 95% e.e.
Optical rotation: [a]D
190-13.10°(EtOH, c=0.10)
Step 4: Preparation of (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-[(Z)-ethoxyimino]-1-
methylethyl]-2-(trifluoromethyl)benzamide
25 580 mg of (S)-N-[2-(3,5-dichloropyridin-2-yl)-2-ethoxyimino-1 -methylethyl]-2-
(trifluoromethyl)benzamide was dissolved in 3 ml of acetonitrile, and the solution was
irradiated with light for 8 hours in a quartz cell (manufactured by Fine, 4 clear windows
for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO
INC., lamp: UM-102, power supply. UM-103B-B). After completion of the reaction, the
30 solvent was evaporated under reduced pressure, and the resulting residue was purified
by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from
1:9 to 5:5) as the eluent to obtain 557 mg of the desired product as a colorless resinous
substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.49 (d, J=2.1Hz, 1H), 7.4-7.85 (m, 5H), 6.81 (bs,
35 1H), 5.15-5.35 (m, 1H), 4.12 (q, J=7.2Hz, 2H), 1.45 (d, J=6.9Hz, 3H), 1.20 (t, J=7.2Hz,
3H).
Optical purity: 95% e.e.
Optical rotation: [a]D
217-11.40°(EtOH, c=0.10)
SYNTHETIC EXAMPLE 15
40 (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(sec-butoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (compound No. 2-136 of the present invention)
Step 1: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-
(trifluoromethyl)benzamide
To 5.0 g of the tert-butyl N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]carbamate
45 prepared in Step 1 in Synthetic Example 12 in 2 ml of 1,4-dioxane, 25 ml of a 1,4-
dioxane solution (4 mol/L) of hydrogen chloride was added, and the mixture was stirred
at room temperature for 1.5 hours. After completion of the reaction, the solvent was
evaporated under reduced pressure, the resulting residue was dissolved in 33 ml of
192
water and 33 ml of dichloromethane, and to the resulting solution, 4.5 g of potassium
carbonate was added and further, 3.8 g of 2-(trifluoromethyl)benzoyl chloride was
added with stirring under cooling with ice, and the mixture was stirred at room
temperature for 2 hours. After completion of the reaction, the resulting organic layer
5 was collected and dried over anhydrous sodium sulfate, and the solvent was
evaporated under reduced pressure. The resulting residue was purified by silica gel
column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to
50:50) as the eluent to obtain 2.8 g of the desired product as pale yellow crystals.
m.p.: 123.0to125.0°C
10 1H NMR (CDCIa, Me4Si, 300MHz) 58.56 (d, J=2.1Hz, 1H), 7.88 (d, J=2.1Hz, 1H), 7.5-7.8
(m, 4H), 6.69 (bs, 1H), 5.10 (d, J=5.1Hz, 2H).
Step 2: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]-2-
(trifluoromethyl)benzamide
To 2.8 g of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-(trifluoromethyl)benzamide
15 in 19 ml of ethanol, 1.0 g of hydroxylamine hydrochloride was added, and the mixture
was stirred at room temperature for 96 hours. After completion of the reaction, the
solvent was evaporated under reduced pressure, the resulting residue was mixed with
50 ml of water and extracted with ethyl acetate (50 mlx2), the resulting organic layers
were combined, dried over saturated aqueous sodium chloride and then anhydrous
20 sodium sulfate, and the solvent was evaporated under reduced pressure. The
resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 5:95 to 50:50) as the eluent to obtain 2.8 g of the
desired product as pale yellow crystals.
m.p.: 134.0 to 136.0°C
25 1H NMR (CDCI3, Me4Si, 300MHz) 58.52 and 8.45 (d, J=2.4Hz, 1H), 7.81 and 7.80 (d,
J=2.4Hz, 1H), 7.35-7.75 (m, 4H), 6.53 (bs, 1H), 4.80 and 4.55 (d, J=6.3Hz, 2H).
Step 3: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(sec-butoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-009 of the present invention)
To a suspension of 500 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-
30 (hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide and 352 mg of potassium carbonate
in 1.3 ml of N,N-dimethylformamide, 704 mg of 2-iodobutane was added, and the
mixture was stirred at room temperature for 12 hours. After completion the reaction,
the reaction mixture was mixed with 3 ml of water and extracted with ethyl acetate (3
mlx2), the resulting organic layers were combined, washed with water (3 mlxl) and
35 dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
the solvent was evaporated under reduced pressure. The resulting residue was
purified by silica gel column chromatography using ethyl acetate-hexane (with a
gradient of from 5:95 to 50:50) as the eluent to obtain 522 mg of the desired product as
a pale yellow resinous substance.
40 1H NMR (CDCI3, Me4Si, 300MHz) 58.50 and 8.44 (d, J=2.1 Hz, 1H), 7.81 and 7.78 (d,
J=2.1Hz, 1H), 7.35-7.75 (m, 4H), 6.53 (bs, 1H), 4.76 and 4.52 (d, J=5.7Hz, 2H), 4.25-
4.35 and 4.1-4.2 (m, 1H), 1.35-1.85 (m, 2H), 1.30 and 1.17 (d, J=6.3Hz, 3H), 0.94 and
0.83 (t, J=7.2Hz, 3H).
Step 4: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(sec-butoxyimino)ethyl]-2-
45 (trifluoromethyl)benzamide
To 522 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(sec-butoxyimino)ethyl]-2-
(trifluoromethyl)benzamide in 3 ml of acetonitrile, 1 mg of benzophenone was added,
and the mixture was irradiated with light for 12 hours in a quartz cell (manufactured by
193
Fine, 4 clear windows for spectroscopy) using a 100 W high-pressure mercury lamp
(manufactured by USHIO INC., lamp: UM-102, power supply: UM-103B-B). After
completion of the reaction, the solvent was evaporated under reduced pressure, and the
resulting residue was purified by silica gel column chromatography using ethyl acetate-
5 hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 416 mg of the
desired product as white crystals.
m.p.:68.0to70.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.50 (d, J=2.1Hz, 1H), 7.45-7.8 (m, 5H), 6.53 (bs,
1H), 4.53 (d, J=4.8Hz, 2H), 4.05-4.2 (m, 1H), 1.35-1.7 (m, 2H), 1.18 (d, J=6.3Hz, 3H),
10 0.84 (t, J=7.5Hz, 3H).
SYNTHETIC EXAMPLE 16
(Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-(trifluoromethyl)benzamide
(Compound No. 2-114 of the present invention)
Step 1: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
15 (trifluoromethyl)benzamide (Compound No. 2-002 of the present invention)
To a solution of 200 mg of the N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-
(trifluoromethyl)benzamide prepared in Step 1 in Synthetic Example 15 and 133 mg of
methoxyamine hydrochloride in 2.7 ml of ethanol, 168 mg of pyridine was added, and
the mixture was stirred at 80°C for 6 hours. After completion of the reaction, the
20 reaction mixture was mixed with 10 ml of water and extracted with ethyl acetate (10
mlxl), the resulting organic layer was washed with water (10 mlxl) and dried over
saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent
was evaporated under reduced pressure. The resulting residue was purified by silica
gel column chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to
25 3:7) as the eluent to obtain 191 mg of the desired product as a pale yellow resinous
substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.50 and 8.45 (d, J=2.1Hz, 1H), 7.80 and 7.78 (d,
J=2.1Hz, 1H), 7.35-7.75 (m, 4H), 6.48 and 6.43 (bs, 1H), 4.73 and 4.53 (d, J=6.3Hz,
2H), 4.06 and 4.02 (s, 3H).
30 Step 2: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
191 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide in 4 ml of acetonitrile was irradiated with light for 11 hours in
a quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100 W
35 high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power
supply: UM-103B-B). After completion of the reaction, the solvent was evaporated
under reduced pressure, and the resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to 3:7) as the
eluent to obtain 149 mg of the desired product as white crystals.
40 m.p.:88.0to89.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.50 (d, J=2.0Hz, 1H), 7.78 (d, J=2.0Hz, 1H), 7.35-
7.75 (m, 4H), 6.45 (bs, 1H), 4.53 (d, J=4.8Hz, 2H), 4.02 (s, 3H).
SYNTHETIC EXAMPLE 17
(Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-[1-(4-fluorophenyl)ethoxyimino]ethyl]-2-
45 (trifluoromethyl)benzamide (Compound No. 2-174 of the present invention)
Step 1: Preparation of N-[2-methoxy(methyl)amino-2-oxoethyl]-2-
(trifluoromethyl)benzamide
To 45.2 g of 2-[2-(trifluoromethyl)benzoylamino]acetic acid in 609 ml of
194
dichloromethane, 21.4 g of N,0-dimethylhydroxylamine hydrochloride, 42.0 g of 1-(3-
dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 73.8 g of triethylamine and 2.2
g of 4-(dimethylamino)pyridine were added, and the mixture was stirred at room
temperature for 18 hours. After completion of the reaction, the reaction mixture was
5 washed with 500 ml of saturated anhydrous sodium hydrogen carbonate, 500 ml of 1N
aqueous hydrochloric acid twice and 500 ml of water in this order, the resulting organic
layer was dried over saturated aqueous sodium chloride and then anhydrous sodium
sulfate, and the solvent was evaporated under reduced pressure. The resulting
residue was washed with 200 ml of hexane to obtain 31.4 g of the desired product as
10 white crystals.
m.p.: 106.0to107.0°C
1H NMR (CDCIa, Me4Si, 300MHz) 57.5-7.75 (m, 4H), 6.70 (bs, 1H), 4.40 (d, J=3.9Hz,
2H), 3.77 (s, 3H), 3.25 (s, 3H).
Step 2: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-
15 (trifluoromethyl)benzamide
To 17.6 g of 2-bromo-3,5-dichloropyridin in 5 ml of tetrahydrofuran, 58.3 ml of a
1,3M tetrahydrofuran solution of isopropylmagnesium chloride-lithium chloride complex
was added dropwise with stirring at -20°C, and after the addition, the mixture was stirred
at the same temperature for 30 minutes. Then, to the reaction mixture, 10.0 g of N-[2-
20 methoxy(methyl)amino-2-oxoethyl]-2-(trifluoromethyl)benzamide in 57.4 ml of
tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at
room temperature for another 3 hours. After completion of the reaction, the reaction
mixture was mixed with 100 ml of saturated aqueous ammonium chloride and 100 ml of
water and extracted with ethyl acetate (150 mlx2), the resulting organic layers were
25 combined, washed with water (100 mlxl) and dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was distilled off under
reduced pressure. The residue was purified by silica gel column chromatography
using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to
obtain 3.0 g of the desired product as pale yellow crystals.
30 m.p.: 123.0 to 125.0°C
1H NMR (CDCIa, Me4Si, 300MHz) 58.56 (d, J=2.1Hz, 1H), 7.88 (d, J=2.1Hz, 1H), 7.5-7.8
(m, 4H), 6.69 (bs, 1H), 5.10 (d, J=5.1Hz, 2H).
Step 3: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]-2-
(trifluoromethyl)benzamide
35 To 2.8 g of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-(trifluoromethyl)benzamide
in 19 ml of ethanol, 1.0 g of hydroxylamine hydrochloride was added, and the mixture
was stirred at room temperature for 96 hours. After completion of the reaction, the
solvent was evaporated under reduced pressure, the resulting residue was mixed with
50 ml of water and extracted with ethyl acetate (50 mlx2), the resulting organic layers
40 were combined, dried over saturated aqueous sodium chloride and then anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure. The
resulting residue was purified by silica gel column chromatography using ethyl acetatehexane
(with a gradient of from 5:95 to 50:50) as the eluent to obtain 2.8 g of the
desired product as white crystals.
45 m.p.: 134.0 to 136.0°C
1H NMR (CDCIa, Me4Si, 300MHz) 68.52 and 8.45 (d, J=2.4Hz, 1H), 7.81 and 7.80 (d,
J=2.4Hz, 1H), 7.35-7.75 (m, 4H), 6.53 (bs, 1H), 4.80 and 4.55 (d, J=6.3Hz, 2H).
Step. 4: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-[1-(4-
195
fluorophenyl)ethoxyimino]ethyl]-2-(trifluoromethyl)benzamide (Compound No. 2-173 of
the present invention)
To a suspension of 200 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-
(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide and 211 mg of potassium carbonate
5 in 2 ml of N,N-dimethylformamide, 155 mg of 1 -(1 -bromoethyl)-4-fluorobenzene was
added, and the mixture was stirred at room temperature for 18 hours. After completion
of the reaction, the reaction mixture was mixed with 3 ml of water and extracted with
ethyl acetate (3 mlx2), the resulting organic layers were combined, washed with water
(3 mlxl) and dried over saturated aqueous sodium chloride and then anhydrous sodium
10 sulfate, and the solvent was evaporated under reduced pressure. The resulting
residue was purified by silica gel column chromatography using ethyl acetate-hexane
(with a gradient of from 5:95 to 50:50) as the eluent to obtain 171 mg of the desired
product as a pale yellow resinous substance.
1H NMR (CDCIa, Me4Si, 300MHz) 58.52 and 8.42 (d, J=2.1 Hz, 1H), 7.80 and 7.77 (d,
15 J=2.1 Hz, 1H), 6.0-7.75 (m, 8H), 6.40 (bs, 1H), 5.38 and 5.21 (q, J=6.9Hz, 1H), 4.81 and
4.49 (d, J=5.7Hz, 2H), 1.64 and 1.45 (d, J=6.9Hz, 3H).
Step 5: Preparation of (Z)-N-[2-(3,5-dichloropyridin-2-yl)-2-[1-(4-
fluorophenyl)ethoxyimino]ethyl]-2-(trifluoromethyl)benzamide
To 171 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-[1-(4-
20 fluorophenyl)ethoxyimino]ethyl]-2-(trifluoromethyl)benzamide in 3 ml of acetonitrile, 1
mg of benzophenone was added, and the mixture was irradiated with light for 12 hours
in a quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100
W high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power
supply: UM-103B-B). After completion of the reaction, the solvent was evaporated
25 under reduced pressure, and the resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as
the eluent to obtain 98 mg of the desired product as a pale yellow resinous substance.
1H NMR (CDCI3, Me4Si, 300MHz) 58.52 (d, J=2.0Hz, 1H), 7.80 (d, J=2.0Hz, 1H), 6.85-
7.75 (m, 8H), 6.38 (bs, 1H), 5.22 (q, J=6.6Hz, 1H), 4.50 (d, J=5.5Hz, 2H), 1.45 (d,
30 J=6.6Hz, 3H).
SYNTHETIC EXAMPLE 18
(Z)-N-[2-(3,5-dibromopyridin-2-yl)-2-(ethoxyimino)ethyl]-2-(trifluoromethyl)benzamide
(Compound No. 2-236 of the present invention)
Step 1: Preparation of N-[2-(3,5-dibromopyridin-2-yl)-2-oxoethyl]-2-
35 (trifluoromethyl)benzamide
To 5.5 g of 3,5-dibromopyridine in 1 ml of tetrahydrofuran, 22.7 ml of a 1.0M
tetrahydrofuran-toluene solution of 2,2,6,6-tetramethylpiperidinylmagnesium chloridelithium
chloride complex was added dropwise with stirring at -20°C, and after the
addition, the mixture was stirred at the same temperature for 30 minutes. Then, to the
40 reaction mixture, 3.0 g of the N-[2-methoxy(methyl)amino-2-oxoethyl]-2-
(trifluoromethyl)benzamide prepared in Step 1 in Synthetic Example 17 in 17 ml of
tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at
the same temperature for another 1 hour. After completion of the reaction, the reaction
mixture was mixed with 30 ml of saturated aqueous ammonium chloride and 20 ml of
45 water and extracted with ethyl acetate (50 mlx2), the resulting organic layers were
combined, washed with water (50 mlxl) and dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure. The resulting residue was purified by silica gel column
196
chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as
the eluent to obtain 659 mg of the desired product as a pale yellow oil.
1H NMR (CDCIs, Me4Si, 300MHz) 58.69 (d, J=2.1Hz, 1H), 8.25 (d, J=2.1Hz, 1H), 7.1-7.8
(m, 4H), 6.68 (bs, 1H), 5.10 (d, J=4.8Hz, 2H).
5 Step 2: Preparation of N-[2-(3,5-dibromopyridin-2-yl)-2-(ethoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-235 of the present invention)
To 200 mg of N-[2-(3,5-dibromopyridin-2-yl)-2-oxoethyl]-2-
(trifluoromethyl)benzamide in 1.4 ml of ethanol, 63 mg of ethoxyamine hydrochloride
was added, and the mixture was stirred at room temperature for 18 hours. After
10 completion of the reaction, the solvent was evaporated under reduced pressure, the
resulting residue was mixed with 4 ml of water and extracted with ethyl acetate (4 mlx2),
the resulting organic layers were combined, dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure. The residue was purified by silica gel column chromatography
15 using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to
obtain 195 mg of the desired product as a pale yellow resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.63 and 8.58 (d, J=2.1Hz, 1H), 8.14 and 8.10 (d,
J=2.1Hz, 1H), 7.1-7.75 (m, 4H), 6.43 (bs, 1H), 4.75 and 4.53 (d, J=5.7Hz, 2H), 4.30 and
4.13 (q, J=7.2Hz, 2H), 1.36 and 1.22 (t, J=7.2Hz, 3H).
20 Step 3: Preparation of (Z)-N-[2-(3,5-dibromopyridin-2-yl)-2-(ethoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
195 mg of N-[2-(3,5-dibromopyridin-2-yl)-2-(ethoxyimino)ethyl]-2-
(trifluoromethyl)benzamide was dissolved in 3 ml of acetonitrile, and the solution was
irradiated with light for 12 hours in a quartz cell (manufactured by Fine, 4 clear windows
25 for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO
INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the
solvent was evaporated under reduced pressure, and the resulting residue was purified
by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from
1:9 to 5:5) as the eluent to obtain 125 mg of the desired product as a pale yellow
30 resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.63 (d, J=2.1Hz, 1H), 8.10 (d, J=2.1Hz, 1H), 7.1-
7.75 (m, 4H), 6.52 (bs, 1H), 4.53 (d, J=5.7Hz, 2H), 4.13 (q, J=7.2Hz, 2H), 1.22 (t,
J=7.2Hz, 3H).
SYNTHETIC EXAMPLE 19
35 N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)ethyl]-2-(trifluoromethyl)benzamide
(Compound No. 2-005 of the present invention)
Step 1: Preparation of 3,5-dichloro-2-(nitromethyl)pyridine
To 30.74 g of potassium tert-butoxide in 100 ml of dimethylsulfoxide, 16.72 g of
nitromethane was added dropwise with stirring under cooling with ice, and after the
40 addition, the mixture was stirred at room temperature for another 1 hour. Then, the
reaction mixture was cooled with ice again, and to the reaction mixture, 25.00 g of 2,3,5-
trichloropyridine in 100 ml of dimethylsulfoxide was added dropwise with stirring, and
after the addition, the mixture was stirred at 70°C for another 6 hours. After completion
of the reaction, the reaction mixture was allowed to cool to room temperature, poured
45 into 200 ml of 10% aqueous hydrochloric acid with stirring under cooling with ice and
extracted with ethyl acetate (200 mlxl). The resulting organic layer was washed with
water (100 mlxl) and dried over saturated aqueous sodium chloride and then
anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
197
The resulting residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 5:95 to 10:90) as the eluent to obtain 10.10 g of
the desired product as a pale yellow oil.
1H NMR (CDCb, Me4Si, 300MHz) 58.53 (d, J=2.4Hz, 1H), 7.84 (d, J=2.4Hz, 1H), 5.76 (s,
5 2H).
Step 2: Preparation of N-chloromethyl-2-(trifluoromethyl)benzamide
To 15.50 g of N-hydroxymethyl-2-(trifluoromethyl)benzamide in 200 ml of
dichloromethane, 16.83 g of thionyl chloride was added dropwise with stirring under
cooling with ice, and after the addition, the mixture was stirred at room temperature for
10 another 3 hours. After completion of the reaction, the solvent was evaporated under
reduced pressure, and the precipitated solid was washed with 50 ml of hexane to obtain
16.90 g of the desired product as white crystals.
1H NMR (CDCb, Me4Si, 300MHz) 57.5-7.75 (m, 4H), 6.40 (bs, 1H), 5.32 (d, J=7.5Hz,
2H).
15 Step 3: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-nitroethyl]-2-
(trifluoromethyl)benzamide
To 6.57 g of potassium tert-butoxide in 100 ml of N,N-dimethylformamide, 10.10 g
of 3,5-dichloro-2-(nitromethyl)pyridine was added dropwise with stirring under cooling
with ice, and after the addition, the mixture was stirred at the same temperature for
20 another 30 minutes. Then, to the reaction mixture, 11.59 g of N-chloromethyl-2-
(trifluoromethyl)benzamide in 50 ml of N,N-dimethylformamide was added dropwise with
stirring under cooing with ice, and after the addition, the mixture was stirred at room
temperature for another 2 hours. After completion of the reaction, the reaction mixture
was carefully poured into 100 ml of ice-water, acidified with 10% aqueous hydrochloric
25 acid and extracted with ethyl acetate (100 mlx2). The resulting organic layers were
combined, washed with water (100 mlxl) and dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to 3:7) as the
30 eluent to obtain 14.00 g of the desired product as a pale yellow resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.48 (d, J=2.1Hz, 1H), 7.87 (d, J=2.1Hz, 1H), 7.45-
7.75 (m, 4H), 6.49 (bs, 1H), 6.35 (dd, J=7.2, 4.5Hz, 1H), 4.3-4.5 (m, 2H).
Step 4: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]-2-
(trifluoromethyl)benzamide
35 To 14.00 g of N-[2-(3,5-dichloropyridin-2-yl)-2-nitroethyl]-2-
(trifluoromethyl)benzamide in 70 ml of a mixture of N,N-dimethylformamide-water (7:1),
16.62 g of sodium nitrite was added, and the mixture was stirred at 60°C for 18 hours.
After completion of the reaction, the reaction mixture was allowed to cool to room
temperature, poured into 100 ml of water and extracted with ethyl acetate (100 mlx2).
40 The resulting organic layers were combined, washed with water (50 mlxl) and dried
over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the
solvent was evaporated under reduced pressure. The resulting residue was purified by
silica gel column chromatography using ethyl acetate-hexane (with a gradient of from
3:7 to 1:1) as the eluent to obtain 5.90 g of the desired product as pale yellow crystals.
45 1H NMR (CDCb, Me4Si, 300MHz) 58.52 and 8.45 (d, J=2.4Hz, 1H), 7.81 and 7.80 (d,
J=2.4Hz, 1H), 7.35-7.75 (m, 4H), 6.53 (bs, 1H), 4.80 and 4.55 (d, J=6.3Hz, 2H).
Step 5: Preparation of N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
198
To a suspension of 450 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-
(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide and 476 mg of potassium carbonate
in 5 ml of N,N-dimethylformamide, 313 mg of 2-iodopropane was added, and the
mixture was stirred at room temperature for 12 hours. After completion of the reaction,
5 the reaction mixture was mixed with 20 ml of water and extracted with ethyl acetate (25
mlx2), the resulting organic layers were combined, washed with water (20 mlxl) and
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
the solvent was evaporated under reduced pressure. The resulting residue was
purified by silica gel column chromatography using ethyl acetate-hexane (with a
10 gradient of from 1:9 to 3:7) as the eluent to obtain 121 mg of a colorless resinous
substance. The resinous substance was dissolved in 10 ml of ethanol, the solution
was mixed with 1 ml of a 1,4-dioxane solution (4 mol/L) of hydrogen chloride and stirred
at 70°C for 5 hours, and the solvent was evaporated under reduced pressure. The
resulting residue was purified by silica gel column chromatography using ethyl acetate-
15 hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 99 mg of the desired
product as a colorless resinous substance (E/Z=50/50).
1H NMR (CDCIa, Me4Si, 300MHz) 58.50 and 8.45 (d, J=2.1Hz, 1H), 7.81 and 7.78 (d,
J=2.1Hz, 1H), 7.35-7.75 (m, 4H), 6.53 and 6.49 (bs, 1H), 4.76 and 4.53 (d, J=6.0Hz,
2H), 4.45-4.55 and 4.3-4.45 (m, 1H), 1.33 and 1.18 (d, J=6.3Hz, 6H).
20 SYNTHETIC EXAMPLE 20
(Z)-N-[2-(5-bromo-3-chloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-216 of the present invention)
Step 1: Preparation of 5-bromo-3-chloro-2-(nitromethyl)pyridine
To 12.4 g of potassium tert-butoxide in 79 ml of dimethylsulfoxide, 6.7 g of
25 nitromethane was added dropwise with stirring under cooling with ice, and after the
addition, the mixture was stirred at room temperature for another 1 hour. Then, the
reaction mixture was added dropwise to 25.0 g of 5-bromo-2,3-dichloropyridine in 20 ml
of dimethylsulfoxide with stirring under cooling with ice, and after the addition, the
mixture was stirred at room temperature for 23 hours and at 50°C for 6 hours. After
30 completion of the reaction, the reaction mixture was allowed to cool to room
temperature, mixed with 100 ml of water and 100 ml of saturated aqueous ammonium
chloride and extracted with ethyl acetate (200 mlx2). The resulting organic layers were
combined, washed with water (100 mlx3) and dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
35 reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 30:70) as
the eluent to obtain 7.8 g of the desired product as a pale yellow oil.
1H NMR (CDCI3, Me4Si, 300MHz) 58.62 (d, J=2.1Hz, 1H), 7.98 (d, J=2.1Hz, 1H), 5.74 (s,
2H).
40 Step 2: Preparation of N-[2-(5-bromo-3-chloropyridin-2-yl)-2-nitroethyl]-2-
(trifluoromethyl)benzamide
To 4.2 g of potassium tert-butoxide in 72 ml of N,N-dimethylformamide, 7.8 g of 5-
bromo-3-chloro-2-(nitromethyl)pyridine was added dropwise with stirring under cooling
with ice, and after the addition, the mixture was stirred at the same temperature for
45 another 1 hour. Then, to the reaction mixture, 4.7 g of the N-chloromethyl-2-
(trifluoromethyl)benzamide prepared in Step 2 in Synthetic Example 19 in 30 ml of N,Ndimethylformamide
was added dropwise with stirring under cooling with ice, and after
the addition, the mixture was stirred at room temperature for another 2 hours. After
199
completion of the reaction, the reaction mixture was carefully poured into 100 ml of icewater,
acidified with 10% aqueous hydrochloric acid and extracted with ethyl acetate
(100 mlx2). The resulting organic layers were combined, washed with water (100
mlx2) and dried over saturated aqueous sodium chloride and then anhydrous sodium
5 sulfate, and the solvent was distilled off under reduced pressure. The resulting residue
was purified by silica gel column chromatography using ethyl acetate-hexane (with a
gradient of from 5:95 to 50:50) as the eluent to obtain 6.0 g of the desired product as a
pale yellow oil.
1H NMR (CDCIa, Me4Si, 300MHz) 58.57 (d, J=1.8Hz, 1H), 8.01 (d, J=1.8Hz, 1H), 7.4-
10 7.75 (m, 4H), 6.48 (bs, 1H), 6.25-6.4 (m, 1H), 4.25-4.5 (m, 2H).
Step 3: Preparation of N-[2-(5-bromo-3-chloropyridin-2-yl)-2-(hydroxyimino)ethyl]-2-
(trifluoromethyl)benzamide
To 6.0 g of N-[2-(5-bromo-3-chloropyridin-2-yl)-2-nitroethyl]-2-
(trifluoromethyl)benzamide in 65 ml of a mixture of N,N-dimethylformamide-water (7:1),
15 6.4 g of sodium nitrite was added, and the mixture was stirred at 60°C for 18 hours.
After completion of the reaction, the reaction mixture was allowed to cool to room
temperature, poured into 100 ml of water, mixed with 20 ml of saturated aqueous
ammonium chloride and extracted with ethyl acetate (100 mlx2). The resulting organic
layers were combined, washed with water (50 mlxl) and dried over saturated aqueous
20 sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated
under reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 2:8 to 6:4) as the
eluent to obtain 3.1 g of the desired product as a pale yellow resinous substance.
1H NMR (CDCI3, Me4Si, 300MHz) 58.6-8.65 and 8.5-8.6 (m, 1H), 7.9-8.0 (m, 1H), 7.35-
25 7.75 (m, 4H), 6.51 (bs, 1H), 4.75-4.85 and 4.5-4.6 (m, 2H).
Step 4: Preparation of N-[2-(5-bromo-3-chloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
To a suspension of 200 mg of N-[2-(5-bromo-3-chloropyridin-2-yl)-2-
(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide and 189 mg of potassium carbonate
30 in 1 ml of N.N-dimethylformamide, 97 mg of iodomethane was added, and the mixture
was stirred at room temperature for 23 hours. After completion of the reaction, the
reaction mixture was mixed with 10 ml of water and extracted with ethyl acetate (20
mlx2), the resulting organic layers were combined, washed with water (10 mlx2) and
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
35 the solvent was evaporated under reduced pressure. The resulting residue was
purified by silica gel column chromatography using ethyl acetate-hexane (with a
gradient of from 5:95 to 50:50) as the eluent to obtain 143 mg of the desired product as
a pale yellow resinous substance.
1H NMR (CDCI3, Me4Si, 300MHz) 58.61 and 8.56 (d, J=1.8Hz, 1H), 7.96 and 7.94 (d,
40 J=1.8Hz, 1H), 7.35-7.75 (m, 4H), 6.48 (bs, 1H), 4.74 and 4.54 (d, J=5.4Hz, 2H), 4.07
and 3.88 (s, 3H).
Step 5: Preparation of (Z)-N-[2-(5-bromo-3-chloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide
143 mg of N-[2-(5-bromo-3-chloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
45 (trifluoromethyl)benzamide was dissolved in 3 ml of acetonitrile, and the solution was
irradiated with light for 12 hours in a quartz cell (manufactured by Fine, 4 clear windows
for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO
INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the
200
solvent was evaporated under reduced pressure, and the resulting residue was washed
with 10 ml of hexane to obtain 63 mg of the desired product as pale yellow crystals.
m.p.:85.0to86.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.61 (d, J=1.8Hz, 1H), 7.94 (d, J=1.8Hz, 1H), 7.5-
5 7.75 (m, 4H), 6.48 (bs, 1H), 4.54 (d, J=5.4Hz, 2H), 3.88 (s, 3H).
SYNTHETIC EXAMPLE 21
(Z)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-(isopropoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-020 of the present invention)
Step 1: Preparation of N-[2-[3-chloro-5-(trifluoromethyl)pyhdin-2-yl]-2-nitroethyl]-2-
10 (trifluoromethyl)benzamide
To 10.26 g of potassium tert-butoxide in 80 ml of N,N-dimethylformamide, 20.00 g
of 3-chloro-2-nitromethyl-5-(trifluoromethyl)pyridine was added dropwise with stirring
under cooling with ice, and after the addition, the mixture was stirred at the same
temperature for another 30 minutes. Then, to the reaction mixture, 18.77 g of the N-
15 chloromethyl-2-(trifluoromethyl)benzamide prepared in Step 2 in Synthetic Example 19
in 20 ml of N,N-dimethylformamide was added dropwise with stirring under cooling with
ice, and after the addition, the mixture was stirred at room temperature for another 3
hours. After completion of the reaction, the reaction mixture was carefully poured into
150 ml of 5% aqueous hydrochloric acid under cooling with ice and extracted with ethyl
20 acetate (100 mlx2). The resulting organic layers were combined, washed with water
(100 mlx2) and dried over saturated aqueous sodium chloride and then anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure. The
precipitated solid was purified with 30 ml of diisopropyl ether to obtain 19.80 g of the
desired product as white crystals.
25 m.p.: 100.0 to 102.0°C
1H NMR (CDCIa, Me4Si, 300MHz) 58.78 (s, 1H), 8.09 (s, 1H), 7.45-7.75 (m, 4H), 6.50
(bs, 1H), 6.4-6.5 (m, 1H), 4.35-4.5 (m, 2H).
Step 2: Preparation of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide
30 To 19.80 g of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-nitroethyl]-2-
(trifluoromethyl)benzamide in 100 ml of a mixture of N,N-dimethylformamide-water (7:1),
21.65 g of sodium nitrite was added, and the mixture was stirred at from 45 to 50°C for
12 hours. After completion of the reaction, the reaction mixture was allowed to cool to
room temperature, poured into 150 ml of water and extracted with ethyl acetate (100
35 mlx2). The resulting organic layers were combined, washed with water (100 mlx1) and
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
the solvent was evaporated under reduced pressure. The resulting residue was
purified by silica gel column chromatography using ethyl acetate-hexane (with a
gradient of from 3:7 to 1:1) as the eluent to obtain 11.10 g of the desired product as
40 white crystals.
m.p.: 110.0to113.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.82 and 8.75 (s, 1H), 8.04 (s, 1H), 7.35-7.7 (m, 4H),
6.52 (bs, 1H), 4.83 and 4.59 (d, J=6.3Hz, 2H).
Step 3: Preparation of (E)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
45 (isopropoxyimino)ethyl]-2-(trifluoromethyl)benzamide (Compound No. 2-019 of the
present invention)
To a suspension of 20.00 g of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide and 19.48 g of potassium carbonate
201
in 105 ml of N,N-dimethylformamide, 10.38 g of 2-iodopropane was added, and the
mixture was stirred at room temperature for 12 hours. After completion of the reaction,
the reaction mixture was mixed with 200 ml of water and extracted with ethyl acetate
(100 mlx3), the resulting organic layers were combined, washed with water (100 mlxl)
5 and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate,
and the solvent was evaporated under reduced pressure. The resulting residue was
purified by silica gel column chromatography using ethyl acetate-hexane (with a
gradient of from 1:9 to 3:7) as the eluent to obtain 11.00 g of the desired product as
white crystals.
10 m.p.: 81.0to83.0°C
1H NMR (CDCIa, Me4Si, 300MHz) 68.73 (s, 1H), 8.01 (s, 1H), 7.35-7.75 (m, 4H), 6.48
(bs, 1H), 4.78 (d, J=5.1Hz, 2H), 4.45-4.6 (m, 1H), 1.34 (d, J=6.0Hz, 6H).
Step 4: Preparation of (Z)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(isopropoxyimino)ethyl]-2-(trifluoromethyl)benzamide
15 11.00 g of (E)-N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-
(isopropoxyimino)ethyl]-2-(trifluoromethyl)benzamide was dissolved in 30 ml of acetic
acid and stirred at 70°C for 1 hour. After completion of the reaction, the solvent was
evaporated under reduced pressure, and the resulting residue was purified by silica gel
column chromatography using ethyl acetate-chloroform (with a gradient of from 0:100 to
20 5:95) as the eluent to obtain 5.63 g of the desired product as white crystals.
m.p.:97.0to98.0°C
1H NMR (CDCIa, Me4Si, 300MHz) 58.79 (s, 1H), 7.99 (s, 1H), 7.5-7.75 (m, 4H), 6.49 (bs,
1H), 4.56 (d, J=5.1Hz, 2H), 4.3-4.45 (m, 1H), 1.19 (d, J=6.0Hz, 6H).
SYNTHETIC EXAMPLE 22
25 N-[2-[3-chloro-5-(3,3-dimethyl-1-butynyl)pyridin-2-yl]-2-(isopropoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-248 of the present invention)
Step 1: Preparation of N-[2-(5-bromo-3-chloropyridin-2-yl)-2-(isopropoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-181 of the present invention)
To a suspension of 1.80 g of the N-[2-(5-bromo-3-chloropyridin-2-yl)-2-
30 (hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide prepared in Step 3 in Synthetic
Example 20 and 0.86 g of potassium carbonate in 10 ml of N,N-dimethylformamide,
1.30 g of 2-iodopropane was added, and the mixture was stirred at room temperature
for 13 hours. After completion of the reaction, the reaction mixture was mixed with 100
ml of water and extracted with ethyl acetate (50 mlx2), the resulting organic layers were
35 combined, washed with water (100 mlxl) and dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure. The resulting residue was purified by silica gel column
chromatography using ethyl acetate-hexane (with a gradient of from 1:4 to 2:2) as the
eluent to obtain 1.26 g of the desired product as a pale yellow resinous substance.
40 1H NMR (CDCIa, Me4Si, 300MHz) 58.60 and 8.54 (d, J=1.9Hz, 1H), 7.96 and 7.93 (d,
J=1.9Hz, 1H), 7.35-7.75 (m, 4H), 6.53 and 6.49 (bs, 1H), 4.75 and 4.53 (d, J=6.1 and
5.0Hz, 2H), 4.51 and 4.37 (sep, J=6.3Hz, 1H), 1.33 and 1.19 (d, J=6.3Hz, 6H).
Step 2: Preparation of N-[2-[3-chloro-5-(3,3-dimethyl-1-butynyl)pyridin-2-yl]-2-
(isopropoxyimino)ethyl]-2-(trifluoromethyl)benzamide
45 To a solution of 0.15 g of N-[2-(5-bromo-3-chloropyridin-2-yl)-2-
(isopropoxyimino)ethyl]-2-(trifluoromethyl)benzamide and 0.05 g of 3,3-dimethyl-1-
butyne in 3 ml of triethylamine, 0.04 g of copper(l) iodide and 0.02 g of
dichlorobistriphenylphosphine palladium(ll) were added, and the mixture was stirred at
202
80°C for 3 hours. After completion of the reaction, the reaction mixture was allowed to
cool to room temperature, mixed with 10 ml of water and extracted with ethyl acetate
(20 mlxl). The resulting organic layer was washed with water (10 mlxl) and dried
over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the
5 solvent was evaporated under reduced pressure. The residue was purified by silica
gel column chromatography using ethyl acetate-hexane (with a gradient of from 1:5 to
2:4) as the eluent to obtain 0.15 g of the desired product as a yellow resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.49 and 8.43 (d, J=1.7Hz, 1H), 7.76 and 7.73 (d,
J=1.7Hz, 1H), 7.45-7.8 (m, 4H), 6.60 (bs, 1H), 4.77 and 4.52 (d, J=5.8 and 4.8Hz, 2H),
10 4.50 and 4.35 (sep, J=6.3Hz, 1H), 1.32 (s, 9H), 1.31 and 1.17 (d, J=6.3Hz, 6H).
SYNTHETIC EXAMPLE 23
N-[2-(5-bromo-3-chloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzthioamide (Compound No. 5-001 of the present invention)
To 222 mg of the N-[2-(5-bromo-3-chloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-
15 (trifluoromethyl)benzamide prepared in Step 4 in Synthetic Example 20 in 5 ml of 1,4-
dioxane, 200 mg of Lawesson's Reagent (2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-
diphosphetane-2,4-disulfide) was added, and the mixture was stirred at 80°C for 3 hours
and then at room temperature for 12 hours. After completion of the reaction, the
reaction mixture was mixed with 40 ml of 0.05M aqueous sodium hydroxide and
20 extracted with a mixture of ethyl acetate-diethyl ether (2:1) (30 mlxl), the resulting
organic layer was washed with 40 ml of 0.2M aqueous sodium hydroxide and dried over
saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent
was evaporated under reduced pressure. The resulting residue was purified by silica
gel column chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to
25 2:8) as the eluent to obtain 133 mg of the desired product as a brown resinous
substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.61 and 8.53 (d, J=2.0Hz, 1H), 8.33 and 8.08 (bs,
1H), 7.98 and 7.96 (d, J=2.0Hz, 1H), 7.35-7.7 (m, 4H), 5.10 and 4.80 (d, J=5.1 and
4.4Hz, 2H), 4.09 and 3.89 (s, 3H).
30 SYNTHETIC EXAMPLE 24
N-[2-(3,5-dichloropyridin-2-yl)-2-(methoxyimino)ethyl]-N-methyl-2-
(trifluoromethyl)benzamide (Compound No. 4-005 of the present invention)
To 33 mg of 60% sodium hydride in oil in 5 ml of tetrahydrofuran, 300 mg of the N-
[2-(3,5-dichloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-(trifluoromethyl)benzamide
35 prepared in Step 1 in Synthetic Example 16 in 3 ml of tetrahydrofuran was added
dropwise with stirring and cooling with ice, and the mixture was stirred at the same
temperature for 30 minutes. Then, the reaction mixture was mixed with 157 mg of
methyl iodide, warmed to room temperature and stirred for another 1 hour. After
completion of the reaction, the reaction mixture was poured into 20 ml of ice-water and
40 extracted with ethyl acetate (50 mlxl), the organic layer was washed with water (20
mlxl) and dried over saturated aqueous sodium chloride and then anhydrous sodium
sulfate, and the solvent was evaporated under reduced pressure. The resulting
residue was purified by silica gel column chromatography using ethyl acetate-hexane
(with a gradient of from 1:9 to 2:8) as the eluent to obtain 203 mg of the desired product
45 as a pale yellow resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.51 and 8.40 (d, J=2.0Hz, 1H), 7.81 and 7.80 (d,
J=2.0Hz, 1H), 7.4-7.75 (m, 3H), 6.9-7.15 (m, 1H), 5.00 and 4.53 (d, J=15.0Hz, 1H), 4.75
and 4.34 (d, J=15.0Hz, 1H), 4.06 and 3.96 (s, 3H), 3.02 and 2.82 (s, 3H).
203
SYNTHETIC EXAMPLE 25
N-cyclopropyl-N-[2-(3,5-dichloropyridin-2-yl)-2-(methoxyimino)ethyl]-5-fluoro-1-methyl-3-
trifluoromethyl-1H-pyrazole-4-carboxamide (Compound No. 17-009 of the present
invention)
5 Step 1: Preparation of 2-cyclopropylamino-1-(3,5-dichloropyridin-2-yl)ethanone-0-
methyloxime
To 700 mg of 2-bromo-1 -(3,5-dichloropyridin-2-yl)ethanone-0-methyloxime
prepared in the same manner as in Steps 1 to 3 in Synthetic Example 2 in 10 ml of
acetonitrile, 402 mg of cyclopropylamine in 5 ml of acetonitrile was added, and the
10 mixture was stirred at room temperature for 18 hours. After completion of the reaction,
the reaction mixture was mixed with 30 ml of water and extracted with ethyl acetate (40
mlx2, the resulting organic layers were combined, washed with water (30 mlxl) and
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
the solvent was evaporated under reduced pressure. The resulting residue was
15 purified by silica gel column chromatography using ethyl acetate-hexane (with a
gradient of from 3:7 to 5:5) as the eluent to obtain 450 mg of the desired product as a
colorless resinous substance.
1H NMR (CDCIs, Me4Si, 300MHz) 58.48 (bs, 1H), 7.78 (bs, 1H), 3.8-4.05 (m, 5H), 1.95-
2.1 (m, 1H), 0.15-0.4 (m,4H).
20 Step 2: Preparation of N-cyclopropyl-N-[2-(3,5-dichloropyridin-2-yl)-2-
(methoxyimino)ethyl]-5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxamide
To 204 mg of 5-fluoro-1-methyl-3-trifluoromethyl-1 H-pyrazole-4-carboxylic acid in
3 ml of dichloromethane, 16 mg of N,N-dimethylformamide and 161 mg of oxalyl
chloride were added, and the mixture was stirred at room temperature for 1 hour. After
25 completion of the reaction, the solvent was evaporated under reduced pressure, the
resulting residue was dissolved in 5 ml of dichloromethane, and added dropwise to a
solution of 220 mg of 2-cyclopropylamino-1-(3,5-dichloropyridin-2-yl)ethanone-0-
methyloxime and 162 mg of triethylamine in 10 ml of dichloromethane with stirring under
cooling with ice, and after the addition, the mixture was stirred at room temperature for
30 another 1 hour. After completion of the reaction, the reaction mixture was mixed with
20 ml of water and extracted with chloroform (20 mlxl), the resulting organic layer was
washed with water (20 mlxl) and dried over saturated aqueous sodium chloride and
then anhydrous sodium sulfate, and the solvent was evaporated under reduced
pressure. The resulting residue was purified by silica gel column chromatography
35 using ethyl acetate-hexane (with a gradient of from 1:4 to 2:3) as the eluent to obtain
252 mg of the desired product as white crystals.
m.p.:95.0to97.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.43 (d, J=2.1Hz, 1H), 7.77 (d, J=2.1Hz, 1H), 4.81
(bs, 2H), 4.04 (s, 3H), 3.78 (s, 3H), 2.7-2.8 (m, 1H), 0.55-0.7 (m, 4H).
40 SYNTHETIC EXAMPLE 26
N-[2-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]-2-(methoxyimino)ethyl]-2-
(trifluoromethyl)benzamide (Compound No. 2-223 of the present invention)
Step 1: Preparation of 1-(3-chloro-5-hydroxypyridin-2-yl)ethanone
To a solution of 3.8 g of the 1-(3,5-dichloropyridin-2-yl)ethanone prepared in Step
45 1 in Synthetic Example 2 and 13.8 g of potassium carbonate in 20 ml of
dimethylsulfoxide, 5.9 g of acetaldoxime was added, and the mixture was stirred at
80°C for 4 hours. After completion of the reaction, the reaction mixture was allowed to
cool to room temperature, mixed with 50 ml of water and washed with diethyl ether (30
204
mlxl), the resulting aqueous layer was acidified with 6N aqueous hydrochloric acid and
extracted with ethyl acetate (25 mlx2). The resulting organic layers were combined,
dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and
the solvent was evaporated under reduced pressure to obtain 1.0 g of desired crude
5 product as brown crystals. The crystals were used in the next step without further
purification.
m.p.: 143.0to145.0°C
1H NMR (CDCb, Me4Si, 300MHz) 68.20 (d, J=2.4Hz, 1H), 7.30 (d, J=2.4Hz, 1H), 2.68 (s,
3H).
10 Step 2: Preparation of 1-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethanone
To 1.0 g of 1-(3-chloro-5-hydroxypyridin-2-yl)ethanone in 15 ml of N,Ndimethylformamide,
1.2 g of potassium carbonate and 1.6 g of 2,2,2-trifluoroethyl
trifluoromethanesulfonate were added, and the mixture was stirred at room temperature
for 12 hours. After completion of the reaction, the reaction mixture was mixed with 40
15 ml of water and extracted with ethyl acetate (50 mlxl), the resulting organic layer was
washed with water (20 mlxl) and dried over saturated aqueous sodium chloride and
then anhydrous sodium sulfate, and the solvent was evaporated under reduced
pressure. The residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 1.2 g of the
20 desired product as white crystals.
m.p.:52.0to55.0°C
1H NMR (CDCb, Me4Si, 300MHz) 58.30 (d, J=2.7Hz, 1H), 7.33 (d, J=2.7Hz, 1H), 4.47 (q,
J=7.8Hz, 2H), 2.68 (s, 3H).
Step 3: Preparation of 2-bromo-1-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethanone
25 To 1.1 g of 1-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethanone in 20 ml of
tetrahydrofuran, 1.6 g of trimethylphenylammonium tribromide was added, and the
mixture was stirred at room temperature for 12 hours. After completion of the reaction,
the precipitated solid was filtered off through celite, and the solvent was evaporated
under reduced pressure to obtain 1.3 g of the desired crude product as a pale yellow oil.
30 The oil was used in the next step without further purification.
1H NMR (CDCb, Me4Si, 300MHz) 68.32 (d, J=2.7Hz, 1H), 7.37 (d, J=2.7Hz, 1H), 4.72 (s,
2H), 4.50 (q, J=7.8Hz, 2H).
Step 4: Preparation of 2-bromo-1-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-
yl]ethanone-0-methyloxime
35 To 1.3 g of 2-bromo-1 -[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethanone in 10
ml of ethanol, 362 mg of methoxyamine hydrochloride was added, and the mixture was
stirred at room temperature for 13 hours. After completion of the reaction, the solvent
was evaporated under reduced pressure, and the resulting residue was purified by silica
gel column chromatography using ethyl acetate-hexane (with a gradient of from 0:100 to
40 5:95) to obtain 1.2 g of the desired product as a colorless oil.
1H NMR (CDCb, Me4Si, 300MHz) 68.30 (d, J=2.4Hz, 1H), 7.37 (d, J=2.4Hz, 1H), 4.51 (s,
2H), 4.44 (q, J=7.5Hz, 2H), 4.10 (s, 3H).
Step 5: Preparation of N-[2-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]-2-
(methoxyimino)ethyl]phthalimide
45 To 1.0 g of 2-bromo-1 -[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethanone-0-
methyloxime in 10 ml of N,N-dimethylformamide, 615 mg of potassium phthalimide was
added, and the mixture was stirred at room temperature for 13 hours. After completion
of the reaction, the reaction mixture was mixed with 30 ml of water and extracted with
205
ethyl acetate (20 mlxl), the resulting organic layer was washed with water (20 mlxl)
and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate,
and the solvent was evaporated under reduced pressure. The resulting residue was
washed with 10 ml of diisopropyl ether to obtain 790 mg of the desired product as pale
5 orange crystals.
1H NMR (CDCIs, Me4Si, 300MHz) 58.08 (d, J=2.4Hz, 1H), 7.55-7.9 (m, 4H), 7.28 (d,
J=2.4Hz, 1H), 4.98 (s, 2H), 4.33 (q, J=7.8Hz, 2H), 4.04 (s, 3H).
Step 6: Preparation of 2-amino-1 -[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-
yl]ethanone-0-methyloxime
10 To 790 mg of N-[2-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]-2-
(methoxyimino)ethyl]phthalimide in 10 ml of ethanol, 187 mg of hydrazine monohydrate
was added and refluxed with heating for 1 hour with stirring. After completion of the
reaction, the reaction mixture was allowed to cool to room temperature, mixed with 30
ml of water and extracted with ethyl acetate (25 mlx2). The resulting organic layers
15 were combined, washed with water (20 mlxl) and dried over saturated aqueous sodium
chloride and then anhydrous sodium sulfate, and the solvent was evaporated under
reduced pressure to obtain 446 mg of the desired crude product as a brown oil. The oil
was used in the next step without further purification.
1H NMR (CDCb, Me4Si, 300MHz) 58.32 and 8.31 (d, J=2.4Hz, 1H), 7.38 and 7.37 (d,
20 J=2.4Hz, 1H), 4.4-4.5 (m, 2H), 4.03 and 3.91 (s, 2H), 3.88 and 3.75 (s, 3H).
Step 7: Preparation of N-[2-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]-2-
(methoxyimino)ethyl]-2-(trifluoromethyl)benzamide
To a solution of 227 mg of 2-amino-1-[3-chloro-5-(2,2,2-trifluoroethoxy)pyridin-2-
yl]ethanone-0-methyloxime and 92 mg of triethylarnine in 5 ml of dichlorornethane, 175
25 mg of 2-(trifluoromethyl)benzoyl chloride was added dropwise with stirring under cooling
with ice, and after the addition, the mixture was stirred at room temperature for another
1 hour. After completion of the reaction, the reaction mixture was mixed with 10 ml of
water and extracted with chloroform (10 mlxl), the resulting organic layer was washed
with water (10 mlxl) and dried over saturated aqueous sodium chloride and then
30 anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure.
The resulting residue was purified by silica gel column chromatography using ethyl
acetate-hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 249 mg of the
desired product as a colorless resinous substance.
1H NMR (CDCb, Me4Si, 300MHz) 58.31 and 8.27 (d, J=3.0Hz, 1H), 7.35-7.75 (m, 5H),
35 6.52 and 6.45 (bs, 1H), 4.75 and 4.53 (d, J=6.0Hz, 2H), 4.43 (q, J=7.8Hz, 2H), 4.06 and
3.88 (s, 3H).
The compounds of the present invention can be produced in accordance with the
processes and Examples previously described. Examples of the oxime-substituted
amide compounds of the present invention produced in the same manners as in
40 Synthetic Examples 1 to 26 are shown in Tables 4 to 32, and examples of their
intermediates are shown in Tables 33 to 45. However, the oxime-substituted amide
compounds of the present invention and their intermediates are by no means restricted
thereto.
In the Tables, Et denotes ethyl group, n-Pr denotes normal propyl group, i-Pr and
45 Pr-i denote isopropyl group, c-Pr and Pr-c denote cyclopropyl group, n-Bu denotes
normal butyl group, i-Bu denotes isobutyl group, s-Bu denotes sec-butyl group, c-Bu
and Bu-c denote cyclobutyl group, t-Bu and Bu-t denote tert-butyl group, Pen denotes
pentyl group, c-Pen and Pen-c denote cyclopentyl group, Hex denotes hexyl group, c206
Hex and Hex-c denote cyclohexyl group, Ph denotes phenyl group, and Naph denotes
naphthyl group.
In the Tables, aromatic heterocyclic rings represented by D-1-1b to D-32-3b have
the following structures, respectively.
(Z)„
„-,-lb : JP*f* D-3-a:^Q D-5-3b : V Ti
o'
N
D-7-a : ^ ) >
N
5 4
D-7-b : N »
In the Tables, T-3 to T-6 have the following structures, respectively.
T-3 : T-4 T-5
OH OH
^
T-6
Further, in the Tables, the expression (R) or (S) in the column substituent R2
means that the proportion of the R-isomer or the S-isomer is at least 90% in a mixture
ratio of optical isomers due to the carbon atom attached to R2, and the expression (E) or
(Z) in the column substituent R1 means that the proportion of the E-isomer or the Zisomer
is at least 90% in a mixture ratio of oxime geometrical isomers attached to the
substituent R1. In the column m.p., " * 1 " means that the compound was oily or resinous.
TABLE 4
10
In the Tables, the expression "(HCI)" in the column substituent R1 means the
compound being a hydrochloride.
5 [Table 40]
241
Among the compounds shown in Tables 4 to 45, 1H NMR data of compounds of
which melting points are not disclosed in the Tables are shown in Table 46.
[Table 46-1]
5 Table 46
No. XH NMR (CDC13, Me4Si, 300MHz)
1-002 5 7.05-7.75 (a, 13H), 5. 45-5, 55 and 5, 1-5. 2 (m, IH),
5.13 and 5.02 (s, 2H), 1.53 and 1.36 (d, J=7.2Hz, 3H)„
1-003 8 7. 05-7. 75 (a, 7H), 6. 48 and 6. 34 (bs, IH),
4.61 and 4.43 (d, J=6.3Hz, 2H), 4.02 and 3.85 (s, 3H)„
1-005 8 7.1-7.9 (a, 7H), 6.72 and 6.64 (d, J=6.9Hz, IH),
5.31 and 5.05 (dq, J=6. 9 and 6.6Hz, IH), 3.96 and 3.83 (s, 3H),
1.59 and 1.45 (d, J=6. 6Hz, 3H)„
1-006 8 7.1-7.75 (a, 7H), 6.84 and 6.69 (d, J=7. 2Hz, IH),
5.2-5.35 and 4.95-5.1 (a, IH), 4.35-4.5 and 4.25-4.35 (a, IH),
1.58 and 1.43 (d, J=6. 9Hz, 3H), 1.1-1.5 (a, 6H),
1-007 8 7.15-7.75 (a, 7H), 6.48 and 6.45 (bs, IH),
5.3-5.45 and 5.0-5.25 (a, IH), 4.54 and 4.38 (q, J=8.4Hz, 2H),
1.63 and 1.46 (d, J=6.9Hz, 3H)„
1-008 §7.1-7.75 (a, 11H), 6. 60 and 6.50 (d, J=7.5Hz, IH),
5. 25-5. 4 and 4. 95-5. 1 (m, IH), 5. 16 and 5. 01 (s, 2H),
1.56 and 1.42 (d, J=6.9Hz, 3H).
1-009 §7.45-7.75 (a, 4H), 7.7-7.1 (m, IH), 6.96 (bs, IH), 6.7-6.8 (a, 2H),
5. 25-5, 4 and 4. 85-5. 0 (ffi, IH), 4.45-4.65 (a, IH),
4.35-4.45 and 4.2-4. 35 (a, IH), 2.36 and 2.19 (s, 3H),
1. 1-1.4 (a, 15H).
1-010 §6.6-7.75 (DI, 12H), 5. 3-5, 4 and 4. 9-5. 05 (m, IH), 5. 12 and 4.99 (s, 2H),
4.5-4.65 (a, IH), 2.25 and 2. 15 (s, 3H), 1.25-1.55 (a, 9H)„
1-013 §6.8-7.75 (a, 9H), 5.5-5.65 and 5. 15-5.25 (a, IH), 4.0-4.25 (a, 2H),
1.58 and 1.39 (d, J=7.2Hz, 3H), 1.34 and 1.33 (s, 9H), 1.1-1.3 (a, 3H)
1-020 §6.8-7.75 (m, 14H), 5. 45-5. 6 and 5. 1-5. 25 (a, IH),
4.15-4.25 and 4. 05-4. 16 (a, 2H), 1.58 and 1.40 (d, J=7. 2Hz, 3H),
1.28 and 1.23 (t, J=7.2Hz, 3H)„
1-022 §8.36 and 8.30 (d, J=2. 1Hz, IH), 6.5-7.75 (a, 16H), 5.0-5.6 (a, 3H),
1.54 and 1.38 (d, J=7.2Hz, 3H)S
1-023 §6.8-7.8 (a, 14H), 5.55-5.7 and 5. 15-5. 3 (a, IH),
4.2-4.3 and 4.05-4.2 (a, 2H), 1.61 and 1.43 (d, J=7.2Hz, 3H),
1.30 and 1.25 (t, J=7.2Hz, 3H)„
1-024 § 6. 85-7. 85 (a, 14H), 5. 55-5. 7 and 5. 2-5. 35 (a, IH),
4. 4-4. 5 and 4. 25-4. 4 (m, IH), 1.15-1.65 (a, 9H)C
1-025 8 3.6-7.85 (a, 14H), 5.55-5.7 and 5.2-5.3 (a, IH), 3.8-4.05 (a, 2H),
1.63 and 1.43 (d, J=6.9Hz, 3H), 1.0-1.25 (a, IH), 0.4-0.55 (a, 2H),
0. 15-0.3 (m, 2H).
1-027 8 8.38 and 8.32 (d, J=2. 1Hz, IH), 7.2-7.8 (a, 15H),
6.58 and 6. 19 (bs, IH), 5.05-5.7 (a, 3H),
1.57 and 1.40 (d, J=6.9Hz, 3H).
1-034 §6.4-7.8 (a, 13H), 4.85-5.55 (a, 2H), 1.2-1.7 (a, 6H).
242
[Table 46-2]
Table 46 (continued)
No. *H NMR (CDC13, Me4Si, 300MHs)
1-035 6 7.45-8.1 (m, 7H), 6.70 and 6.64 (bs, IH),
5.35-5.55 and 5. 1-5. 25 (m, IH), 4.2-4.3 and 4.05-4,2 (m, 2H),
1.59 and 1.41 (d, J=6.9Hz, 3H), 1.30 and 1.22 (t, J=7.2Hz, 3H)C
1-036 6 6.8-7.75 (m, 9H), 5.45-5.6 and 5. 1-5.2 On, IH), 4,5-4.7 (m, IH),
4.0-4.3 (n, 2H), 1.1-1.6 On, 12H)„
1-037 6 6.85-8.25 (a, 12H), 4.8-5.65 (m, IH), 3.95-4.35 On, 2H),
1. 1-1.65 (m, 6H)„
1-038 6 6.4-8.25 (m, 12H), 4.85-5.85 On, IH), 4.3-4.65 On, 2H),
1, 15-1.7 (n, 3H)0
1-039 6 6.6-8.45 0B, 15H), 4.8-5.8 (m, 3H), 1.5-1.65 (m, 3H)„
1-041 6 6.6-7.75 (a, 8H), 5. 35-5. 5 and 5. 0-5. 15 On, IH),
3.95-4,05 and 3.8-3.9 On, 2H), 1.6-1.65 and 1.4-1.45 On, 3H),
0.95-1.3 (m, IH), 0.45-0.55 (m, 2H), 0.15-0.3 On, 2H).
1-042 6 6.4-7.75 (m, 7H), 5.3-5.45 and 5. 0-5. 15 On, IH),
4.00 and 3.87 (d, J=6. 9Hz, 2H), 1.75 and 1.43 (d, J=6. 9Hz, 3H),
1.0-1.3 (m, IH), 0.45-0.6 (a, 2H), 0.15-0.3 (in, 2H)„
1-043 6 7.1-7.75 (a, 7H), 6.66 and 6.55 (bs, IH),
5. 35-5, 5 and 5. 0-5. 15 Oft IH), 4. 25 and 4, 10 (q, J=7.2Hz, 2H),
1.60 and 1.21 (d, J=6.6Hz, 3H), 1.32 and 1.19 (t, J=7.2Hz, 3H)„
1-044 6 7.1-7.75 (m, 7H), 6.69 and 6.61 (bs, IH),
5. 35-5.5 and 5.0-5. 15 On, IH), 4.25-4.5 (rn, IH), 1.1-1.65 (tn, 9H)„
1-045 6 7.1-7.75 (m, 7H), 6.64 and 6.53 (bs, IH),
5. 35-5. 5 and 5. 0-5. 15 On, IH), 4. 25 and 4. 10 (q, J=7.2Hz, 2H),
1.55-1.65 and 1.35-1.45 On, 3H), 1.31 and 1.19 (t, J=7.2Hz, 3H).
1-046 6 7.1-7.75 (m, 7H), 6. 67 and 6, 59 (bs, IH), 5. 3-5. 5 and 5. 0-5. 15 On, IH),
4.25-4.5 (m, IH), 1.1-1.65 (no, 9H)0
1-047 6 7.15-7.75 On, 7H), 6.71 and 6.64 (bs, IH),
5. 35-5. 5 and 5. 0-5. 15 On, IH), 3. 95-4. 05 and 3. 8-3. 9 On, 2H),
1.6-1.65 and 1.4-1.45 On, 3H), 0.95-1.3 (m, IH), 0.4-0.55 On, 2H),
0. 15-0.3 (n, 2H)0
1-048 6 7.05-7.75 (u, 7H), 6.42 and 6.28 (bs, IH),
5, 35-5. 5 and 5. 05-5. 2 On, IH), 4. 5-4, 65 and 4. 3-4. 45 On, 2H),
1.6-1.65 and 1.4-1.45 On, 3H)0
1-049 6 6.95-7.75 (m, 6H), 6.55 (bs, IH), 5.3-5,45 and 5.0-5.1 On, IH),
4. 2-4. 3 and 4. 05-4. 2 On, 2H), 1.15-1.65 (no, 6H)Q
1-050 6 7.0-7.75 (a, 7H), 6.47 and 6.59 (bs, IH),
5. 35-5. 5 and 5. 05-5. 15 (ra, IH), 4.05-4.35 On, 2H),
1.6-1.65 and 1.4-1.45 On, 3H), 1.33 and 1.19 (t, J=7.2Hz, 3H)„
1-051 6 6.95-7.75 (m, 6H), 6.56 and 6.47 (bs, IH),
5.3-5.45 and 5.0-5.15 On, IH), 4.01 and 3.85 (s, 3H),
1.55-1.65 and 1.4-1.45 (m, 3H)„
1-052 6 6.95-7.75 (m, 6H), 6.5-6,7 On, IH), 5.3-5.45 and 5.0-5. 15 On, IH),
4.2-4,35 and 4.05-4.2 On, 2H), 1.6-1.65 and 1.4-1.5 (a, 3H),
1.33 and 1.21 (t, J=7.2Hz, 3H)„
243
[Table 46-3]
Table 46 (continued)
No. XH NMR (CDC13, Me4Si, 300MHz)
1-053 6 6.6-7.75 (m, 8H), 5.25-5. 4 and 5.0-5. 15 (ra, IH), 4.05-4.3 (m, 2H),
1.6L and 1.46 (d, J=6.9Hz, 3H), 1.31 and 1.19 (t, J=7.2Hz, 3H),
1-054 6 7.2-7.75 (m, 7H), 6. 77 and 6. 64 (bs, IH), 5. 25-5. 4 and 5. 0-5. 1 (n, IH),
4.24 and 4.09 (q, J=7. 2Hz, 2H), 1.59 and 1.46 (d, J=6. 9Hz, 3H),
1.31 and 1.19 (t, J=7.2Hz, 3H)0
1-055 67.1-7.75 (m, 12H), 6.49 (bs, IH), 4.85-5.45 (m, 2H), 1.35-1.7 (m, 6H)„
1-057 6 6.95-7.75 (m, 7H), 6.80 and 6.69 (bs, IH),
5. 25-5. 4 and 4. 95-5. 1 (m, IH), 4.0-4.3 (m, 2H),
1.60 and 1.45 (d, J=7.2Hz, 3H), 1.15-1.35 (m, 3H)0
1-058 6 7.15-7.75 (ra, 7H), 6.78 and 6.66 (bs, IH),
5. 25-5. 35 and 4. 95-5. 1 (m, IH), 4. 0-4. 3 (ra, 2H),
1.55-1.65 and 1.4-1.5 (m, 3H), 1.15-1.35 (tn, 3H)„
1-060 6 7.15-7.8 (m, 7H), 6.62 (bs, IH), 5. 15-5. 3 and 4.95-5. 15 (m, IH),
4.05-4.35 (m, 2H), 3.45-3.65 (m, 2H), 3.28 and 2.96 (s, 3H),
1.61 and 1.45 (d, J=6.9Hz, 3H).
1-061 67.15-7.75 (ra, 11H), 6.41 (bs, IH), 5.0-5.5 (m, 3H),
1.60 and 1.43 (d, J=6.9Hz, 3H)0
1-062 6 7.1-7.75 (o, 7H), 6.3-6.75 (m, 3H), 4.95-5.35 (ra, 3H),
1.56 and 1.43 (d, J=6.9Hz, 3H)Q
1-063 6 8.38 and 8.28 (d, J=2. 1Hz, IH), 7.15-7.75 On, 9H), 6.41 (bs, IH),
5.0-5.45 (ra, 3H), 1.57 and 1.42 (d, J-7.2Hz, 3H).
1-064 6 8.25-8.45 (ra, IH), 7.05-7.75 (m, 9H), 6.3-6.45 (tn, IH),
5.0-5.55 (m, 3H), 1.64 and 1.44 (d., J=6. 9Hz, 3H)„
1-065 6 7.05-7.75 (m, 7H), 6.78 and 6.66 (bs, IH),
5.2-5.45 and 4.95-5. 1 (m, IH), 4.0-4.3 (tn, 2H), 1.4-1.65 (ra, 3H),
1. 15-1.35 (ra, 3H)„
1-066 6 7.05-7.75 (ra, 7H), 6.82 and 6.68 (bs, IH),
5.2-5.45 and 4. 95-5. 1 (m, IH), 4.2-4.5 (m, IH), 1.1-1.65 (m, 9H).
1-067 6 7.05-7.8 (m, 7H), 6.68 and 6.67 (bs, IH), 4.95-5.45 (a, IH),
3.98 and 3.85 (d, J=7.2Hz, 2H), 1.61 and 1.45 (d, J=7.2Hz, 3H),
0.95-1,2 (m, IH), 0.4-0.55 (m, 2H), 0.15-0.25 (m, 2H)„
1-068 6 7.1-7.8 (ra, 7H), 6.46 (bs, IH), 5.3-5.45 and 5.0-5.2 (tn, IH),
4.45-4.6 and 4.3-4.45 (m., 2H), 1.63 and 1.46 (d, J=6..9Hz, 3H),
1-069 6 8.25-8.4 (m, IH), 6.4-7.75 (m, 10H), 5.0-5.45 (ra, 3H),
1.56 and 1.42 (d, J=6.9Hz, 3H),
1-070 6 7.05-7.75 (ra, 7H), 6.72 (bs, IH), 5,3-5.45 and 4.95-5. 1 (m, IH),
3.97 and 3.83 (s, 3H), 2,36 and 2.35 (s, 3H), 1.4-1.6 (m, 3H).
1-071 6 7.05-7.75 (m, 7H), 6.7-6.85 (m, IH), 5.3-5.45 and 4.95-5.1 (tn, IH),
4.0-4.3 (ra, 2H), 2.36 and 2.35 (s, 3H), 1.58 and 1.44 (d, J=6.9Hz, 3H),
1. 15-1.35 (ra, 3H),
1-072 6 6.5-8.0 (ra, 8H), 5. 25-5. 4 and 5. 0-5. 15 (m, IH),
4.2-4.3 and 4.0-4.2 (ra, 2H), 1.63 and 1.47 (d, J=6.9Hz, 3H),
1. 15-1.35 (ra, 3H)„
244
[Table 46-4]
Table 46 (continued)
No. *H NMR (CDC13, Me4Si, 300MHz)
1-073 §6.65-7.75 (o, 8H), 5. 25-5.4 and 5. 0-5. 1 (a, IH), 3.75-4.0 (m, 6H),
1.57 and 1.43 (d, J=6.9Hz, 3H).
1-074 6 6.7-7.75 (a, 8H), 5.25-5.4 and 4.95-5. 1 (a, IH), 4.0-4.3 (a, 2H),
3.82 and 3.81 (s, 3H), 1.58 and 1.43 (d, J=6.9Hz, 3H),
1. 15-1.35 (a, 3H)„
1-075 6 7. 0-7. 75 (a, 7H), 6. 6-6. 9 (a, IH), 5. 25-5. 4 and 4. 95-5. 1 (a, IH),
4.15-4.3 and 4.0-4.15 (m, 2H), 2.50 and 2.48 (Sj 3H), 1.4-1.65 (m, 3H),
1.15-1,35 (a, 3H)a
1-076 6 7.3-7.8 (a, 7H), 6.59 (bs, IH), 5. 2-5. 4 and 5. 0-5. 2 (a, IH),
4.05-4.3 (a, 2H), 2.7-2.8 (a, 3H), 1.45-1.7 (a, 3H), 1.15-1.35 (a, 3H)
o
1-077 6 7.3-8.05 (a, 7H), 6.72 and 6.55 (bs, IH),
5.25-5, 35 and 5. 0-5. 15 (a, IH), 4. 26 and 4. 10 (q, J=7. 2Hz, 2H),
3.11 and 3.06 (s, 3H), 1.65 and 1.48 (d, J=6. 9Hz, 3H),
1.32 and 1.19 (t, J=7.2Hz, 3H),
1-078 6 7.3-8.05 (a, 7H), 6.65 (bs, IH), 5.25-5. 4 and 5. 0-5. 2 (a, IH),
4.25 and 4.09 (q, J=7.2Hz, 2H), 2.62 and 2.61 (s, 3H),
1.63 and 1.47 (d, J=6.9Hz, 3H), 1.32 and 1.18 (t, J=7.2Hz, 3H).
1-079 6 7.2-7.8 (a, 7H), 6.65-6.85 (a, IH), 5, 3-5.45 and 5.0-5. 15 (a, IH),
3.95-4.3 (a, 5H), 2.15-2.25 (n, 3H), 1.60 and 1.45 (d, J=6.9Hz, 3H),
1.15-1.35 (a, 3H)0
1-080 6 7.2-7.75 (a, 7H), 6.45-6.75 (a, IH), 5.2-5.35 and 5. 0-5. 15 (a, IH),
4.01 and 3.84 (s, 3H), 1.63 and 1.47 (d, J=6.9Hz, 3H)Q
1-081 6 7.2-7.75 (a, 7H), 6.75 and 6.55 (bs, IH),
5. 2-5. 35 and 5. 0-5. 15 (a, IH), 4. 05-4. 3 (a, 2H),
1.63 and 1.47 (d, J=6.9Hz, 3H), 1.15-1.35 (a, 3H)„
1-083 6 7.15-7.75 (a, 7H), 6.6-6.8 (a, 2H), 5.7-5.85 (a, IH), 5.0-5.4 (a, 2H),
3.99 and 3.84 (s, 3H), 1.59 and 1.45 (d, J=7.2Hz, 3H)a
1-084 6 7.15-7.75 (a, 7H), 6.55-6.85 (a, 2H), 5.7-5.85 (a, IH),
5.0-5.4 (a, 2H), 4.15-4.3 and 4.0-4.15 (a, 2H),
1.60 and 1.45 (d, J=6.9Hz, 3H), 1.15-1.35 (a, 3H)„
1-085 6 7.25-7.75 (a, 12H), 6.72 (bs, IH), 5.35-5.45 and 5.05-5.2 (a, IH),
4.00 and 3.87 (s, 3H), 1.63 and 1.49 (d, J=6.9Hz, 3H)„
1-086 6 7.25-7.75 (a, 12H), 6.7-6.85 (m, IH), 5.35-5.5 and 5.05~5.2 (a, IH),
4.0-4.3 (a, 2H), 1.64 and 1,49 (d, J=6.9Hz, 3H), 1.15-1.35 (a, 3H)Q
1-087 67.25-7.75 (m, 11H), 6.65-6.8 (a, IH), 5.35-5.45 and 5.05-5.2 (a, IH),
4.01 and 3.87 (s, 3H), 1.63 and 1.49 (d, J=6.9Hz, 3H)„
1-088 67.25-7.75 (a, 11H), 6.73 (bs, IH), 5.3-5.45 and 5.05-5.2 (a, IH),
4.0-4.3 (a, 2H), 1.64 and 1.49 (d, J=6.9Hz, 3H), 1.15-1.35 (a, 3H)„
1-089 67.2-7.75 (a, 7H), 7.1-7.65 (a, 2H), 6.6-6.9 (m, IH), 6.3-6.4 (a, 2H),
5.3-5.45 and 5. 0-5. 15 (a, IH), 4.0-4.3 (a, 2H),
1.62 and 1.48 (d, J=6.9Hz, 3H), 1.15-1.35 (a, 3H)C
1-090 6 7.25-7.95 (a, 10H), 6.4-6.8 (a, IH), 5.25-5.45 and 5.0-5.2 On, IH),
4.05-4.3 (a, 2H), 1.62 and 1.47 (d, J=6.9Hz, 3H), 1.15-1.35 (a, 3H)„
245
[Table 46-5]
Table 46 (continued)
No. lH NMR (CDC13J Me4Si, 300MHz)
1-091 6 7.2-8.0 (m, 8H), 6.6-6.85 (a, 2H), 5.25-5.4 and 5.0-5.2 (m, IH),
4.05-4.3 (m, 2H), 1.63 and 1,48 (d, J=6.9Hs, 3H), 1.15-1.35 (m, 3H).
1-092 6 7.0-7.75 (m, 7H), 6.70 (bs, IH), 5.25-5.4 and 5.0-5. 15 (m, IH),
4.05-4.3 On, 2H), 1.61 and 1.45 (d, J=6.9Hz, 3H), 1.15-1.35 On, 3H)a
1-093 6 6.6-7.75 (m, 8H), 5.25-5.4 and 5.0-5. 15 (m, IH), 4.05-4.3 (m, 2H),
1.15-1.65 (m, 6H)„
1-094 6 6.9-7.75 (m, 7H), 6.61 (bs, IH), 5.0-5.3 (m, IH), 4.15-4.35 OB, 2H),
3.5-3.6 (ta, 2D, 3.29 and 2.96 (s, 3H), 1.4-1.85 (m, 3H)„
1-095 6 6.4-7.75 (m, 7H), 5. 3-5.5 and 5.0-5. 1 (m, IH),
4.2-4.35 and 4.05-4.2 (m, 2H), 1.4-1.65 (o, 3H), 1.15-1.4 (m, 3H),
1-096 6 7.15-7.8 (m, 7H), 7. 10 and 6.81 (bs, IH), 5. 2-5.4 and 4.9-5.05 (m, IH),
4.20 and 4.07 (q, J=6.9Hz, 2H), 3.38 and 2.23 (s, 3H),
1.35-1.6 (m, 3H), 1.29 and 1.18 (t, J=6.9Hz, 3H).
1-097 6 7.0-8.05 (m, 7H), 6.91 (bs, IH), 5.2-5.4 and 4.85-5. 05 (m, IH),
4.19 and 4.06 (q, J=7. 0Hz, 2H), 2.35 and 2.34 (s, 3H),
2.32 and 2.21 (s, 3H), 1.52 and 1.38 (d, J=7.2Hz, 3H),
1.28 and 1. 18 (t, J=7. 0Hz, 3H)„
1-098 6 7.4-7.8 (m, 7H), 6.54 (bs, IH), 5.0-5.2 (to, IH), 4.0-4.3 (en, 2H),
1.1-1.65 (m, 6H)„
1-099 6 6.7-7.8 (n, 8H), 5.35-5.5 and 5.0-5. 15 (m, IH), 4.0-4.25 (m, 2H),
3.75-3.85 (m, 3H), 1.15-1.6 (m, 6H).
1-100 6 6.7-8.25 (m, 9H), 4.95-5.4 (m, IH), 4.0-4.3 (m, 4H), 1.0-1.6 (a, 9H)C
1-101 6 6.7-8.0 (o, 8H), 5.0-5.85 (m, 2H), 3.45-4.35 (o, 6H), 1.15-1.7 (a, 6H)
1-102 6 6.65-8.35 (n>, 11H), 5.5-5.65 and 5.05-5.2 (m, IH), 4.0-4.35 (m, 2H),
1.05-1.65 (ID, 6H)„
2-006 6 8.49 and 8.44 (d, J=2. 1Hz, IH), 7.80 and 7.78 (d, J=2. 1Hz, IH),
7.35-7.75 On, 4H), 6.48 (bs, IH), 4.75 and 4.52 (d, J=6. 0Hz, 2H),
4.26 and 4.07 (t, J=6.9Hz, 2H), 1.65-1.8 and 1.5-1.65 (m, 2H),
1.35-1.5 and 1.2-1.35 (m, 2H), 0.93 and 0.89 (t, J=7.2Hz, 3H)„
2-007 6 8. 50 and 8.45 (d, J=2. 1Hz, IH), 7. 80 and 7. 78 (d, J=2. 1Hz, IH),
7.35-7.75 (m, 4H), 6.48 (bs, IH), 4.77 and 4.53 (d, J=5.7Hz, 2H),
4.02 and 3.85 (d, J=6.9Hz, 2H), 1.85-2.15 (m, IH),
0.96 and 0.83 (d, J=6.9Hz, 6H)B
2-008 6 8.50 and 8.45 (bs, IH), 7.75-7.85 (m, IH), 7.35-7.7 (to, 4H),
6.59 (bs, IH), 4. 78 and 4. 53 (d, J=6. 0Hz, 2H),
4.07 and 3.89 (d, J=7.2Hz, 2H), 1,0-1.25 (o, IH), 0.4-0.6 (m, 2H),
0. 15-0.35 On, 2H)„
2-010 6 8.51 and 8.44 (d, J-2. 1Hz, IH), 7. 80 and 7. 79 (d, J=2. 1Hz, IH),
7.35-7.75 (m, 4H), 6.49 (bs, IH), 4.75-4.9 and 4.6-4.75 (m, IH),
4.77 and 4.53 (d, J=6.0Hz, 2H), 1.95-2.4 (m, 4H), 1.5-1.85 (m, 2H)„
2-012 68.49 and 8.44 (d, J=2. 1Hz, IH), 7. 80 and 7.79 (d, J=2. 1Hz, IH),
7.3-7.75 (m, 4H), 6,45-6.6 (m, IH), 5.8-6.1 (m, IH), 5.1-5.4 (m, 2H),
4.7-4.8 (m, 2H), 4.5-4.6 (m, 2H)a
246
[Table 46-6]
Table 46 (continued)
No. XH NMR (CDC13, Me4Si, 300MHz)
2-013 6 8.50 and 8.43 (d, J=2. 1Hz, IH), 7.79 and 7.77 (d, J=2. 1Hz, IH),
7.15-7.75 (m, 8H), 6.39 (bs, IH), 5.24 and 5.06 (s, 2H),
4.77 and 4. 52 (d, J=6. 3Hz, 2H)„
2-014 § 8.80 and 8.75 (s, IH), 8.03 and 8.01 (Sj IH), 7.35-7.75 (m, 4H),
6.44 (bs, IH), 4.77 and 4.57 (d, J=5. 1Hz, 2H), 4.09 and 3.89 (s, 3H)a
2-015 6 8.79 and 8.70 (s, IH), 8.02 and 8.00 (s, IH), 7.35-7.75 (m, 4H),
6.85 and 6.70 (bs, IH), 5.78 and 5.29 (n, IH), 4.07 and 3.88 (s, 3H),
1.59 and 1.48 (d, J=6.9Hz, 3H)„
2-017 §8.80 and 8.75 (s, IH), 8.03 and 8.00 (s, IH), 7.3-7.75 (m, 4H),
6. 46 (bs, IH), 4. 79 and 4. 57 (d, J=6. 0Hz, 2H),
4.24 and 4.05 (t, J=6.9Hz, 2H), 1.7-1.85 and 1.55-1.7 , 4H)0
2-029 6 8.79 and 8.74 (s, IH), 8.03 and 7.99 (s, IH), 7.3-7.7 On, 4H),
6. 4-6. 55 (m, IH), 4. 85-4. 9 and 4. 7-4. 75 (m, IH),
4. 77 and 4.56 (d, J=6. 3Hz, 2H), 1.5-1,95 (a, 8H)0
2-030 §8.80 and 8.76 (s, IH), 8.40 and 8.02 (s, IH), 7.3-7.75 (m, 4H),
6.39 (bs, IH), 6. 06 and 5, 95 (tt, J=55. 8 and 4. 2Hz, IH),
4.81 and 4.60 (d, J=5.7Hz, 2H), 4. 44 and 4.25 (td, J=13. 5, 4.2Hz, 2H)0
2-031 §8.76 (s, IH), 8.05 (s, IH), 7.35-7.7 (n, 4H), 6.39 (bs, IH),
6.77 (tt, J=55.2 and 4.2Hz, IH), 4.81 (d, J=6.3Hz, 2H),
4.44 (td, J=13.2, 4.2Hz, 2H)„
247
[Table 46-7]
Table 46 (continued)
No. XH NMR (CDC13J Me4Si, 300MHz)
2-032 §8.81 and 8,76 (s, IH), 8.04 and 8,03 (s, IH), 7.3-7.75 (a, 4H),
6.34 (bs, IH), 4. 82 and 4.61 (d, J=6. 3Hz, 2H),
4.63 and 4.43 (q, J=8.7Hz, 2H).
2-033 6 8.82 and 8.73 (s, IH), S. 06 and 8.03 (s, IH), 7.25-7.75 (a, 4H),
6.62 (bs, IH), 5.82 and 5.36 (m, IH), 4,62 and 4.43 (q, J=8.7Hz, 2H),
1.65 and 1.49 (d, J=6.9Hz, 3H)„
2-034 6 8.80 and 8.77 (s, IH), 8.03 and 8.01 (s, IH), 7.35-7.75 (m, 4H),
6.44 and 6.80 (bs, IH), 4.78 and 4. 58 (d, J=6. 0Hz, 2H),
4.42 and 4.24 (t, J=6.6Hz, 2H), 2.85 and 2.72 (t, J=6.6Hs, 2H),
2.06 and 2.05 (s, 3H)a
2-035 6 8.80 and 8.75 (s, IH), 8.03 and 8.00 (s, IH), 7.3-7.75 (a, 4H),
6.44 and 6.54 (bs, IH), 4.05-5.0 (a, 5H), 2.7-3.15 (a, 2H),
1.99 and 1.90 (s, 3H)„
2-036 6 8.82 and 8.76 (s, IH), 8.07 and 8.03 (s, IH), 7.3-7.75 (a, 4H),
6.39 (bs, IH), 4.93 and 4.72 (s, 2H), 4.81 and 4.64 (d, J=6.0Hz, 2H)„
2-037 68.83 and 8.75 (s, IH), 8.07 and 8.03 (s, IH), 7.35-7.75 (a, 4H),
6.41 (bs, IH), 5. 10 and 4.94 (q, J=6.9Hz, IH),
4.78 and 4.63 (d, J=6.0Hz, 2H), 1.77 and 1.58 (d, J=6.9Hz, 3H)„
2-038 68.81 and 8.77 (s, IH), 8.05 and 8.03 (s, IH), 7.35-7.75 (a, 4H),
6.44 (bs, IH), 4.81 and 4.60 (d, J=6. 0Hz, 2H),
4.48 and 4.30 (t, J=6.3Hz, 2H), 2.84 and 2. 71 (t, J=6.3Hz, 2H)„
2-039 6 8.83 and 8.72 (s, IH), 8. 10 and 8.06 (s, IH), 7.35-7.75 (a, 5H),
6.44 and 6.32 (bs, IH), 4.91 and 4.89 (bs, 2H), 4.66 and 4.64 (bs, 2H),
3.9-4.05 (m, 2H)„
2-040 6 8.79 and 8.73 (s, IH), 8.01 and 7.99 (s, IH), 7.3-7.7 (a, 4H),
6.45-6,55 (a, IH), 5.8-6.2 (a, IH), 5.15-5.4 (a, 2H),
4. 80 and 4. 57 (d, J=6. 3Hz, 2H), 4. 75-4. 8 and 4. 55-4. 6 (a, 2H)„
2-041 6 8.80 and 8,74 (s, IH), S. 01 (bs, IH), 7.3-7.75 (a, 4H), 6.43 (bs, IH),
4.85-5.05 (a, 2H), 4.82 and 4.57 (d, J=6.0Hz, 2H),
4.70 and 4.50 (s, 2H), 1.80 and 1.69 (s, 3H)a
2-042 6 8.81 and 8.74 (s, IH), 8.02 and 8.00 (s, IH), 7.35-7.75 (a, 4H),
6.45 (bs, IH), 5.75-6.05 (a, IH), 5.05-5.35 (a, 2H),
4. 8-4. 9 and 4. 65-4. 75 (a, IH), 4.81 and 4. 57 (d, J=6. 3Hz, 2H),
1.44 and 1.27 (d, J=6.6Hz, 3H)„
2-044 6 8.81 and 8.75 (s, IH), 8.04 and 8.02 (s, IH), 7.35-7.75 (m, 4H),
6.41 (bs, IH), 4.87 and 4,68 (d, J=2.7Hz, 2H),
4.81 and 4.61 (d, J=6.0Hz, 2H), 2,51 and 2.46 (t, J=2.7Hz, IH),
2-046 6 8. 77 and 8. 72 (s, IH), 7. 99 and 7. 97 (s, IH), 7. 2-7. 7 (a, 6H),
6.85-7.15 On, 2H), 6.48 (bs, IH), 5.37 and 5. 18 (s, 2H),
4.78 and 4.55 (d, J=6.0Hz, 2H)„
2-048 8 8.77 and 8.71 (s, IH), 8.00 and 7.97 (s, IH), 7.2-7.7 (a, 6H),
6. 95-7. 1 (a, 2H), 6. 45 (bs, IH), 5. 26 and 5. 06 (s, 2H),
4.78 and 4.55 (d, J=6.0Hz, 2H)„
248
[Table 46-8]
Table 46 (continued)
No. XH NMR (CDC13, Me4Si, 300MHz)
2-050 68.80 and 8.72 (s, IH), 8.00 (bs, IH), 7.1-7.7 (m, 8H), 6.41 (bs, IH),
5.26 and 5.07 (s, 2H), 4.80 and 4.56 (d, J=6. OHz, 2H).
2-051 6 8.79 and 8.73 (s, IH), 8.01 and 7.99 (s, IH), 7.2-7.7 (m, 8H),
6.41 (bs, IH), 5.26 and 5.07 (s, 2H)., 4.80 and 4.56 (d, J=6. OHz, 2H)„
2-053 6 8.77 and 8.72 (s, IH), 8.00 and 7.97 (s, IH), 7.05-7.7 (o, 8H),
6.4-6.5 (ID, IH), 5.26 and 5.08 (s, 2H), 4.78 and 4.55 (d, J=6.3Hi, 2H),
2,33 and 2.31 (s, 3H)„
2-054 6 8.76 and 8.71 (s, IH), 7.99 and 7.96 (s, IH), 7.05-7.7 (is, 8H),
6.4-6.5 (ffl, IH), 5.25 and 5.07 (s, 2H), 4.77 and 4.54 (d, J=6. 3Hz, 2H),
2. 34 and 2. 32 (s, 3H) e
2-055 68.78 and 8.73 (s, IH), 8.00 and 7.98 (s, IH), 7.15-7.75 (a, 8H),
6.4-6.5 {m, IH), 5.27 and 5.10 (s, 2H), 4.79 and 4.57 (d, J=6.OHz, 2H),
1.32 and 1.30 (s, 9H)0
2-056 68.81 and 8.73 (s, IH), 8.00 (bs, IH), 7.25-7.7 (n, 8H), 6.45 (bs, IH),
5.51 and 5.33 (s, 2H), 4.83 and 4.57 (d, J=6.0Hz, 2H)C
2-057 6 8.79 and 8.72 (s, IH), 8.00 and 7.99 (s, IH), 7.25-7.7 (m, 8H),
6.43 (bs, IH), 5.34 and 5.15 (s, 2H), 4.81 and 4.55 (d, J=6. OHz, 2H)„
2-058 6 8.80 and 8.72 (s, IH), 8,00 (bs, IH), 7.25-7.7 (n, 8H), 6.40 (bs, IH),
5.35 and 5.16 (s, 2H), 4.83 and 4.56 (d, J=6.0Hz, 2H)0
2-059 6 8.78 and 8.72 (s, IH), 8.00 and 7.98 (s, IH), 7.2-7.7 (m, 5H),
6.75-7.0 (m, 3H), 6.44 (bs, IH), 5.28 and 5.09 (s, 2H),
4.80 and 4.56 (d, J =6.OHz, 2H), 3.79 and 3. 76 (s, 3H)a
2-060 6 8.78 and 8.74 (s, IH), 8.01 and 7.97 (s, IH), 7.2-7.75 (m, 6H),
6.8-6.95 (a, 2H), 6.4-6.5 (m, IH), 5.24 and 5.05 (s, 2H),
4.77 and 4.56 (d, J=6. OHz, 2H), 3.81 and 3.79 (s, 3H)«,
2-061 6 8.79 and 8.73 (s, IH), 7.99 (bs, IH), 7.15-7.7 (m, 8H), 6.45 (bs, IH),
5.39 and 5.21 (s, 2H), 4.80 and 4.56 (d, J=6.3Hz, 2H)„
2-062 68.81 and 8.73 (s, IH), 8.00 (bs, IH), 7.1-7.7 (m, 8H), 6.39 (bs, IH),
5.30 and 5.11 (s, 2H), 4.82 and 4.57 (d, J=6. 3Hz, 2H).
2-063 6 8.79 and 8.72 (s, IH), 8.01 and 7.99 (s, IH), 7.1-7.7 (m, 8H),
6.40 (bs, IH), 5.29 and 5.10 (s, 2H), 4.81 and 4.56 (d, J=6. OHz, 2H)„
2-064 6 8.82 and 8.72 (s, IH), 7.25-8.25 (m, 9H), 6.3-6.5 (m, IH),
5.40 and 5.20 (s, 2H), 4,86 and 4.57 (d, J=6.3Hz, 2H)„
2-065 6 8.79 and 8.72 (s, IH), 8.00 and 7.97 (s, IH), 7.3-7.7 (m, 8H),
6.63 and 6,56 (bs, IH), 5.47 and 5.29 (s, 2H),
4.84 and 4.55 (d, J=5.7Hz, 2H).
2-066 6 8.81 and 8.72 (s, IH), 8.01 (bs, IH), 7.25-7.75 (m, 8H), 6.39 (bs, IH),
5.31 and 5.12 (s, 2H), 4.82 and 4.56 (d, J=6. 3Hz, 2H)a
2-067 6 8.81 and 8.72 (s, IH), 8.00 (bs, IH), 7.25-7.7 (m, 8H), 6.43 (bs, IH),
5.36 and 5.15 (s, 2H), 4.84 and 4.56 (d, J=6. OHz, 2H)„
2-068 6 8.80 and 8.74 (s, IH), 8.01 and 7.99 (s, IH), 7.25-7.7 (tu, 13H),
6.41 (bs, IH), 5.35 and 5.16 (s, 2H), 4.82 and 4.58 (d, J=6.3Hz, 2H)„
249
[Table 46-9]
Table 46 (continued)
No. *H NMR (CDC1S, Me4Si, 300MHz)
2-069 6 8.78 and 8.72 (s, IH), 8.00 and 7.98 (s, IH), 7.25-7.75 (m, 5H),
6.6-6.9 (a, 2H), 6.43 (bs, IH), 5.31 and 5. 12 (s, 2H),
4.78 and 4.55 (d, J=6. 3Hz, 2H).
2-071 §8.80 and 8.73 (s, IH), 8.01 and 8.00 (s, IH), 6.95-7.75 (ro, 7H),
6.38 (bs, IH), 5.23 and 5.04 (s, 2H), 4.80 and 4.56 (d, J=6.0Hz, 2H),
2-072 6 8.82 and 8.73 (s, IH), 8.02 (bs, IH), 7.3-7,7 (to, 4H),
6.65-7.0 (m, 3H), 6.3-6.45 (a, IH), 5.26 and 5.06 (s, 2H),
4.83 and 4.57 (d, J=6.0Hz, 2H).
2-073 6 8.80 and 8.72 (s, IH), 8.00 (bs, IH), 7.05-7.7 (a, 7H),
6.3-6.5 (a, IH), 5.23 and 5.04 (s, 2H), 4.80 and 4.56 (d, J=6.3Hz, 2H)
c
2-074 6 8.80 and 8,72 (s, IH), 8.01 (bs, IH), 7.25-7.7 (a, 4H),
6.85-7.1 (a, 2H), 6.35-6.5 (a, IH), 5.20 and 5.00 (s, 2H),
4.81 and 4.56 (d: J=6.0Hz, 2H)„
2-075 6 8.79 and 8.73 (s, IH), 7.98 (bs, IH), 7.35-7.9 (a, 11H), 6.40 (bs, IH),
5.46 and 5.27 (s, 2H), 4.81 and 4.56 (d, J=6.0Hz, 2H)„
2-077 6 8.83 and 8.76 (s, IH), 8.52 and 8.01 (d, J=4.5Hz, IH),
8.00 and 7,99 (s, IH), 7.05-7.7 (a, 7H), 6.45 (bs, IH),
5.44 and 5.25 (s, 2H), 4.85 and 4.59 (d( J=5.4Hz, 2H)„
2-078 6 8.81 and 8.74 (s, IH), 8.5-8.7 (m, 2H), 8.02 and 8.00 (s, IH),
7.80 and 7.78 (t, J=2. 1Hz, IH), 7.25-7.75 (a, 5H), 6.40 (bs, IH),
5.32 and 5.13 (s, 2H), 4.81 and 4.57 (d, J=6. 3Hz, 2H)0
2-079 68.80 and 8.72 (s, IH), 8.41 and 8.31 (s, IH), 8.01 and 7.99 (s, IH),
7.77 and 7.75 (d, J=2.4Hz, IH), 7.25-7.7 (a, 5H), 6.39 (bs, IH),
5.28 and 5.09 (s, 2H), 4.80 and 4.55 (d, J=6. 3Hz, 2H)„
2-080 68.84 and 8.74 (s, IH), 8.5-8.6 (a, 2H), 8.03 and 8.01 (s, IH),
7.15-7.7 (a, 6H), 6.47 (bs, IH), 5.33 and 5. 12 (s, 2H),
4.88 and 4.58 (d, J=6.0Hz, 2H).
2-081 6 8.81 and 8.70 (s, IH), 8.00 and 7,97 (s, IH), 7.0-7.7 (a, 9H),
6.42 and 6.36 (bs, IH), 5.41 and 5. 25 (q, J=6. 9Hz, IH),
4,8-4.9 (a, IH), 4,5-4.55 (o, IH), 1.67 and 1.47 (d, J=6.9Hz, 3H)„
2-084 6 8.21 and 8.19 (d, J=2. 1Hz, IH), 7.35-7.75 (a, 4H),
7.28 and 7.27 (d, J=2. 1Hz, IH), 6. 54 and 6. 47 (bs, IH),
4.71 and 4,51 (d, J=6. 0Hz, 2H), 4, 06 and 3.89 (s, 3H),
3.88 and 3.85 (s, 3H)a
2-085 6 8.44 and 8.39 (d, J=2. 1Hz, IH), 7.4-7.8 (ro, 5H),
6.63 and 6.58 (bs, IH), 4.83 and 4.60 (d, J=5. 7Hz, 2H),
4.45-4.65 and 4. 35-4. 55 (a, IH), 1.33 and 1.20 (d, J=6. 3Hz, 6H)„
2-086 6 8. 48 and 8.43 (d, J=2. 1Hz, IH), 7. 80 and 7. 77 (d, J=2. 1Hz, IH),
7.35-7.75 (a, 4H), 6.53 and 6.46 (bs, IH), 4.5-4.9 (a, 3H),
1.4-2.0 (a, 8H)„
2-087 6 8.45-8.55 (a, IH), 7.75-7.85 (m, IH), 7,35-7.75 (a, 4H),
6.59 and 6.46 (bs, IH), 4.78 and 4.55 (d, J=5. 7Hz, 2H),
4.47 and 4.29 (t, J=6.0Hz, 2H), 3.79 and 3.67 (t, J=6,0Hz, 2H)„
250
[Table 46-10]
Table 46 (continued)
No. *H NMR (CDC13, Me4Si, 300MHz)
2-088 5 8.50 and 8.45 (d, J=2. 1Hz, IH), 7.81 and 7.79 (d, J=2. lHa, IH),
7.35-7.75 On, 4H), 6.52 (bs, IH)., 5.41 and 5.24 (q, J=5. 1Hz, IH),
4.5-4.9 , 2H), 1.33 and 1.20 (d, J=6.9Hz, 3H)0
252
[Table 46-12]
Table 46 (continued)
No. *H NMR (CDC13, Me4Si, 300MHz)
2-118 68.49 (d, J=2. 1Hz, IH), 7.4-7.85 (m, 5H), 6.78 (bs, IH),
5.2-5.3 (in, IH), 3.86 (s, 3H), 1.45 (d., J=6.6Hz, 3H) „
2-119 68.49 and 8.40 (d, J=1.8Hz, IH), 7.82 and 7.78 (d, J=1.8Hz, IH),
7.5-7.7 (n, 4H), 5.15-5.25 (m, IH), 4.05 and 3.88 (s, 3H),
1.85-2.05 (XD, IH), 1.6-1.75 (m, IH), 1.04 (t, J=7. 5Hz, 3H).
2-121 68,50 and 8,41 (d, J=1.8Hz, IH), 7.82 and 7.79 (d, J=1.8Hz, IH),
7.4-7,75 (m, 4H), 6.65-7.05 (m, IH), 5.75-5.85 and 5.2-5.35 (m, IH),
4.29 and 4.12 (q, .1=6.9Hz, 2H), 1.56 and 1.44 (d, J=6,9Hz, 3H),
1.26 and 1.21 (t, J=6.9Hz, 3H)„
2-123 6 8.50 (d, J=2.0Hz, IH), 7.79 (d, J=2.0Hz, IH), 7.4-7.75 (m, 4H),
6.80 (bs, IH), 5.25 (dq, J=7.4, 6.8Hz, IH), 4.12 (q, J=7.0Hz, 2H),
1.45 (d, J=6.8Hz, 3H), 1.20 (t, J=7. 0Hz, 3H),
2-125 67.25-8,7 (a, 6H), 5.0-6.8 (m, IH), 4.1-4.35 (m, 2H), 1.15-1.35 (a, 3H),
1.00 and 0.94 (s, 9H)„
2-127 6 8.50 (d, J=1.9Hz, IH)., 7.79 (d, J=l. 9Hz, IH), 7.45-7.75 (m, 4H),
6.81 (bs, IH), 5.15-5.35 (a, IH), 4.02 (t, J=6.7Hz, 2H),
1.5-1.7 (a, 2H), 1.45 (d, J=6.9Hz, 3H), 0.85 (t, J=7.4Hz, 3H).
2-129 6 8.49 and 8.40 (d, J=1.8Hz, IH), 7.81 and 7.78 (d, J=l. 8Hz, IH),
7.4-7.75 (a, 4H), 6.7-7.05 (m, IH), 5,7-5.85 and 5.15-5.3 (a, IH),
4.4-4.55 and 4.4.3-4.4 On, IH), 1.56 and 1.43 (d, J=6.6Hz, 3H),
1.05-1.35 On, 6H)o
2-131 6 8.49 (d, J=2.0Hz, IH), 7.78 (d, J=2.0Hz, IH), 7.45-7.75 (a, 4H),
6.84 (bs, IH), 5.24 (dq, J=7.8, 6, 8Hz, IH), 4.35 (sep, J=6. 3Hz, IH),
1.44 (d, J=6.8Hz, 3H), 1.18 (d, J=6.3Hz, 6H)„
2-137 6 8.49 (d, J=2.0Hz, IH), 7.78 (d, J=2.0Hz, IH), 7.45-7.75 On, 4H),
6.83 (bs, IH), 5.15-5.3 (a, IH), 4.05-4,2 (n, IH), 1.35-1,7 (a, 2H),
1.44 (d, J=€.8Hz, 3H), 1.16 (d, J=6. 5Hz, 3H), 0.82 (t, J=7. 4Hz, 3H)„
2-141 6 8. 50 and 8.45 (d, J=2. 1Hz, IH), 7. 80 and 7. 78 (d, J=2. 1Hz, IH),
7.35-7.75 On, 4H), 6.49 (bs, IH), 4.75 and 4.53 (d, J=5. 4Hz, 2H),
4.24 and 4.06 (t, J=6.6Hz, 2H), 1.15-1.8 (a, 6H), 0.8-0.95 (a, 3H).
2-144 6 8.50 and 8,45 (d, J=2, 1Hz, IH), 7.75-7.85 (a, IH), 7.35-7,75 (a, 4H),
6.54 (bs, IH), 4.78 and 4,52 (d, J=5. 7Hz, 2H),
4.0-4.2 and 3.9-4.0 (a, IH), 1.4-1.8 On, 4H),
0.94 and 0.83 (t, J-7.5Hz, 6H)„
2-146 6 8. 50 and 8.45 (d, J=2. 1Hz, IH), 7. 80 and 7. 78 (d, J=2. 1Hz, IH),
7.35-7.75 On, 4H), 6.49 (bs, IH), 4.75 and 4.53 (d, J=5.7Hz, 2H),
4.24 and 4.06 (t, .1=6.9Hz, 2H), 1.15-1.8 (n, 8H), 0.8-0.95 (a, 3H).
2-149 6 8. 50 and 8.45 (d, J=2. 1Hz, IH), 7. 80 and 7. 78 (d, J=2. 1Hz, IH),
7.35-7.75 On, 4H), 6.47 (bs, IH), 4. 75 and 4.52 (d, J=5.7Hz, 2H),
4.06 and 3.88 (d, J=6.6Hz, 2H), 0.75-1.85 (a, UH).
2-150 6 8.51 and 8.46 (d, J=2. 1Hz, IH), 7. 82 and 7.80 (d, J=2. 1Hz, IH),
7.35-7,75 On, 4H), 6.39 (bs, IH),
6.06 and 5,95 (tt, J=55.5 and 4. 5Hz, IH),
4.78 and 4.56 (d, J=5.7Hz, 2H), 4.41 and 4.24 (td, J=13. 2, 4. 5Hz, 2H)0
253
[Table 46-13]
Table 46 (continued)
No. *H NMR (CDC13J Me4Si, 300MHz)
2-151 a 8.52 (d, J=2,0Hz, IH), 7.82 (d, J=2.0Hz, IH), 7.45-7.8 (a, 4H),
6.60 (bs, IH), 5.32 (dq, J=7.8, 6. 8Hz, IH).. 4.41 (q, J=8.5Hz, 2H),
1.47 (d, J=6.8Ha, 3H),
2-152 8 8. 50 and 8.48 (d, J=2. 1Hz, IH), 7.81 and 7.79 (d, J=2. 1Hz, IH),
7.4-7.75 (m, 4H), 6.90 and 6. 52 (bs, 1H)„
4.75 and 4,54 (d, J=5.7Hz, 2H), 4.38 and 4.23 (t, J=5. 1Hz, 2H),
3.64 and 3.58 (t, J=5. 1Hz, 2H), 3.30 and 3.13 (s, 3H)„
2-153 58.50 and 8.43 (d, J=2. 1Hz, IH), 7.75-7.85 {m, IH), 7.3-7.75 , 8H), 6.57 and 6.51 (bs, IH), 5.47 and 5.29 (s, 2H),
4.83 and 4.54 (d, J=5.7Hz, 2H).
2-164 6 8. 52 and 8.47 (d, J=2. 1Hz, IH), 7. 80 and 7. 73 (d, J=2. 1Hz, IH),
7.3-7.75 (m, 6H), 6.91 and 6.49 (bs, IH), 5.57 and 4.39 (s, 2H),
4.82 and 4.58 (d, J=5.7Hz, 2H).
2-165 6 8.45-8.8 (m, 2H), 7.79 (t, J=2. 1Hz, IH), 7.2-7.75 (m, 5H),
6.98 and 6.48 (bs, IH), 5,46 and 5.31 (bs, 2H),
4. 79 and 4. 56 (d, J=6. 0Hz, 2H).
254
[Table 46-14]
Table 46 (continued)
No. JH NMR (CDC13, Me4Si, 300MHz)
2-166 6 8. 51 and 8.45 (d, J=2. 1Hz, IH), 7. 80 and 7.79 (d, J=2. 1Hz, IH),
7.35-7.75 On, 4H), 7.30 and 7.08 (s, IH), 6.57 and 6.42 (bs, IH),
5.32 and 5.16 (bs, 2H), 4.80 and 4.55 (d, J=5. 7Hz, 2H)„
2-167 6 8.51 and 8.46 (d, J=2.4Hz, IH), 7.83 and 7.79 (d, J=2.4Hz, IH),
7.3-7.75 (m, 5H), 6.40 (bs, IH), 5.34 and 5. 16 (bs, 2H),
4.76 and 4.57 (d, J=6.0Hz, 2H)„
2-168 6 8. 51 and 8,44 (d, J=2. 1Hz, IH), 8. 42 and 8.31 (d, J=2. 1Hz, IH),
7.25-7.85 (ro, 7H), 6.37 (bs, IH), 5.27 and 5.09 (s, 2H),
4.78 and 4.53 (d, J=5. 7Hz, 2H).
2-169 6 8. 54 and 8.43 (d, J=2. 1Hz, IH), 8.25-8.4 (m, IH),
7.83 and 7.80 (d, J=2. 1Hz, IH), 7.05-7.75 On, 6H), 6.51 (bs, IH),
5.28 and 5.08 (s, 2H), 4.84 and 4.54 (d, J=5. 7Hz, 2H).
2-171 68.52 and 8.42 (d, J=2. 1Hz, IH), 7.81 and 7.77 (d, J=2. 1Hz, IH),
7.2-7.7 (a, 9H), 6.45 and 6.40 (bs, IH),
5.41 and 5.25 (q, J=6.6Hz, IH), 4.75-7.85 and 4.45-4.55 (m, 2H),
1.66 and 1.47 (d, J=6.6Hz, 3H)»
2-172 6 8.52 (d, J=2.0Hz, IH), 7.80 (d, J=2. 0Hz, IH), 7.15-7.75 (m, 9H),
6.40 (bs, IH), 5.25 (q, J=6.6Hz, IH), 4.50 (dd, J=5. 1, 1.7Hz, 2H),
1.47 (d, J=6.6Hz, 3H)„
2-175 6 8.54 and 8.39 (d, J=2. 1Hz, IH), 7.82 and 7.74 (d, J=2. 1Hz, IH),
7.2-7.7 (to, 9H), 6. 55 and 6.35 (bs, IH),
4.87 and 4.49 (d, J=6. 3Hz, 2H), 1.74 and 1.62 (s, 6H)„
2-176 6 8. 50 and 8.47 (d, J=2. 1Hz, IH), 7.82 and 7.76 (d, J=2. 1Hz, IH),
7.0-7.75 (m, 9H), 6.44 and 6.27 (bs, IH),
4.69 and 4.54 (d, J=5.7Hz, 2H), 4.47 and 4.28 (t, J=7. 2Hz, 2H),
3.06 and 2.92 (t, J=7.2Hz, 2H).
2-177 6 8.54 and 8.48 (dd, J=2. 1, 0.9Hz, IH), 7.0-7.9 (m, 10H), 6.61 (bs, IH),
4.99 and 4.70 (d, J=5.7Hz, 2H)„
2-178 6 7.92 and 7.90 (d, J=7.7Hz, IH), 7.4-7.75 (to, 4H), 6.39 (bs, IH),
4.70 and 4.51 (d, J=6. 3 and 5.2Hz, 2H), 4.32 and 4.14 (q, J=7.0Hz, 2H),
1.35 and 1.22 (t, J=7.0Hz, 3H)„
2-179 6 7.92 and 8.89 (d, J=8.3Hz, IH), 7.4-7.75 (m, 4H), 6.39 (bs, IH),
4.70 and 4.51 (d, J=6. 3 and 5.6Hz, 2H),
4.52 and 4.38 (sep, J=6.3Hz, IH), 1.33 and 1.19 (d, J=6. 3Hz, 6H)„
2-180 6 7.4-7.75 (m, 5H), 6.53 and 6.43 (s, IH), 4.75-4.8 and 4.5-4.6 (m, 2H),
4.3-4.4 and 3.6-3.7 (m, IH), 4.00 and 3.99 (bs, 3H),
1.33 and 1.21 (d, J=6.3Hz, 6H)„
2-184 6 8.79 (bs, IH), 8.00 (bs, IH), 7.5-7.7 (m, 4H), 6.72 (bs, IH),
5.25-5.35 (m, IH), 3.88 (s, 3H), 1.47 (d, J=6.9Hz, 3H)0
2-186 6 8.79 (bs, IH), 7.99 (bs, IH), 7.5-7.7 (m, 4H), 6.74 (bs, IH),
5.2-5.35 (m, IH), 4.12 (q, J=7.2Hz, 2H), 1.47 (d, J=6.9Hz, 3H),
1.21 (t, J=7.2Hz,, 3H)a
255
[Table 46-15]
Table 46 (continued)
No. JH NMR (CDC13J Me4Si, 300MHz)
2-188 6 8.78 (bs, IH), 7.98 (bs, IH), 7.5-7.7 (m, 4H), 6.78 (bs, IH),
5.2-5.35 (m, IH), 4.3-4.45 (m, IH)., 1.46 (d, J=6.9Hz, 3H),
1. 18 (d, J=6.3Hz, 6H)0
2-195 68.82 (d, J=1.9Hz, IH), 8.02 (d, J=l. 9Hz, IH), 7.15-7.8 (a, 9H),
6.37 (bs, IH), 5.26 (q, J=6.4Hz, IH), 4.54 (dd, J=5. 5, 1.8Hz, 2H),
1.48 (d, J=6.4Hz, 3H)„
2-196 6 8.82 (d, J=2.0Hz, IH), 8.02 (d, J=2. OHz, IH), 6.85-7.75 (m, 8H),
6.35 (bs, IH), 5.24 (q, J=6.5Hz, IH), 4.53 (d, J=5.5Hz, 2H),
1.46 (d, J=6.5Hz, 3H).
2-197 6 8.23 and 8.20 (d, J=2. 8Hz, IH), 7.35-7.75 (a, 4H),
7. 29 and 7. 27 (d, J=2. 8Hz, IH), 6. 64 and 6. 59 (bs, IH),
4.76 and 4,52 (d, J=5. 8 and 5.0Hz, 2H),
4. 50 and 4. 36 (sep, J=6.2Hz, IH), 3. 89 and 3. 88 (s, 3H),
1.33 and 1.19 (d, J=6.2Hz, 6H),
2-198 6 8. 75 and 8.72 (d, J=l. 8Hz, IH), 8. 06 and 8. 04 (d, J=l. 8Hz, IH),
7.35-7.75 (m, 4H), 6.62 (bs, IH),
4. 79 and 4. 54 (d, J=6. 0 and 4. 9Hz, 2H),
4.55 and 4.37 (sep, J=6. 3Hz, IH), 4. 04 and 4. 03 (s, 3H),
2.24 and 2.21 (s, 3H), 1.34 and 1.18 (d, J=6.3Hz, 6H)„
2-199 68.80 and 8.74 (d, J=1.7Hz, IH), 8. 05 and 8. 03 (d, J=l. 7Hz, IH),
7.35-7.75 (a, 4H), 6.42 (bs, IH),
4.77 and 4.56 (d, J=6. 1 and 5.1Hz, 2H), 4.34 and 4.15 (q, J=7. OHz, 2H),
1.37 and 1.22 (t, J=7. OHz, 3H)„
2-200 6 8.80 and 8.74 (d, J=2. 1Hz, IH), 8. 05 and 8.02 (d, J=2. 1Hz, IH),
7.35-7.8 (a, 4H), 6.44 (bs, IH), 4.77 and 4.56 (d, J=6.0Hz, 2H),
4.54 and 4,39 (sep, J=6.3Hz, IH), 1.35 and 1.19 (d, J=6. 3Hz, 6H) „
2-201 6 8.80 and 8.75 (d, J=2. 0 and 1. 7Hz, IH),
8.05 and 8.04 (d, J=2.0 and 1.7Hz, IH), 7.4-7.75 (m, 4H),
6.49 and 6.42 (bs, IH), 4.79 and 4.57 (d, J=6. 1 and 5. 5Hz, 2H),
4.34 and 4.15 (d, J=7.2Hz, 2H), 1.0-1.3 (m, IH), 0.45-0.65 (pa, 2H),
0. 15-0. 35 On, 2H) „
2-202 6 8.81 and 8.70 (d, J=2. OHz, IH), 8.04 and 8.00 (d, J=2. OHz, IH),
7.15-7.55 (n, 9H), 6.40 and 6.32 (bs, IH),
5.43 and 5.26 (q, J=6.6Hz, IH), 4.5-4.85 (n, 2H),
1.68 and 1,47 (d, J=6.6Hz, 3H).
2-204 6 8.44 and 8.39 (d, J=2.4Hz, IH), 7.45-7.75 (DI, 5H), 6.52 (bs, IH),
4.77 and 4.53 (d, J=6. 1 and 5.1Hz, 2H), 4.21 and 4.03 (t, J=6.8Hz, 2H),
1.7-1.85 and 1.55-1.7 (m, 2H), 0.97 and 0. 86 (t, J=7.3Hz, 3H)„
2-206 6 7.2-8.5 (m, 12H), 6.28 (d, J=7.2Hz, IH), 3.92 (s, 3H).
2-207 6 8.49 (d, J=2.1Hz, IH), 7.45-7.8 fcn, 5H), 6.78 (bs, IH),
5.15-5.3 (m, IH), 4.06 (t, J=6.9Hz, 2H), 1.5-1.65 (ro, 2H),
1.44 (d, J=6.9Hz, 3H), 1.2-1.4 (m, 2H), 0.87 (t, J=6.9Hz, 3H),
256
[Table 46-16]
Table 46 (continued)
No. XH NMR (CDC13, Me4Si, 300MHz)
2-208 6 8.49 (d, J=2. 1Hz, IH), 7,45-7.8 (m, 5H), 6.75 (bs, IH),
5.15-5.3 (m, IH), 3.84 (d, J=6.6Hz, 2H), 1.8-2.0 (m, IH),
1.45 (d, J=6.6Hz, 3H), 0.83 (d, J=6.6Hz, 6H)„
2-209 6 8.50 (d, J=2. 1Hz, IH), 7.45-7.85 (m, 5H), 6.81 (bs, IH),
5.15-5.35 On, IH), 3.88 (d, J=7.2Hz, 2H), 1.44 (d, J =6.9Hz, 3H),
1.0-1.15 (m, IH), 0.45-0.55 (m, 2H), 0.15-0.25 (in, 2H)0
2-210 6 8.49 (d, J=2. 1Hz, IH), 7.78 (d, J=2, 1Hz, IH), 7.5-7.65 On, 4H),
6.87 (bs, IH), 5.2-5.3 On, IH), 1.44 (d, J=6.6Hz, 3H), 1.23 (s, 9H)„
2-211 6 8.49 (d, J=2. 1Hz, IH), 7.45-7.8 (in, 5H), 6.52 (bs, IH),
4.51 (d, J=5. 1Hz, 2H), 3.85-4.0 (m, IH), 1.4-1.65 (m, 4H),
0.83 (t, J=7.5Hz, 6H)„
2-213 6 8.49 (d, J=2. 1Hz, IH), 7.45-7.8 On, 5H), 6.49 (bs, IH),
5.75-5.9 (DI, IH), 5.05-5.2 (m, 2H), 4.6-4.75 (in, IH),
4.53 (d, J=5.1Hz, 2H), 1.26 (d, J=6. 6Hz, 3H)„
2-214 6 7.90 (d, J=7.8Hz, IH), 7.45-7.75 (m, 4H), 6.3-6.45 (m, IH),
4.52 (d, J=4.9Hz, 2H), 4.14 (q, J=7. 1Hz, 2H), 1.22 (t, J=7. 1Hz, 3H)„
2-219 6 8.80 (d, J=2.0Hz, IH), 8.00 (d, J=2. 0Hz, IH), 7.45-7.75 (m, 4H),
6.49 (bs, IH), 4.56 (d, .1=5.5Hz, 2H), 3.97 (qui, J=6. 1Hz, IH),
1.45-1,65 On, 4H), 0.83 (t, J=7.3Hz, 6H)„
2-220 6 8.80 (d, J=2.0Hz, IH), 8.00 (d, J=2.0Hz, IH), 7.45-7.75 On, 4H),
6.47 (bs, IH), 5.85 (ddd, J=17.3, 10.7, 6. 2Hz, IH), 5.05-5.2 On, 2H),
4.71 (qd, J=6.8, 6.2Hz, IH), 4.58 (d, J=5. 1Hz, 2H),
1.27 (d, J=6.8Hz, 3H)„
2-222 6 8.43 and 8.39 (d, J=2.4Hz, IH), 7.3-7.75 (a, 5H),
6.59 and 6.57 (t, J=72. OHz, IH), 6.49 and 6. 42 (bs, IH),
4.75 and 4,54 (d, J=6.3Hz, 2H), 4.07 and 3.89 (s, 3H).
2-224 6 8.51 and 8,40 (d, J-2. 1Hz, IH), 7.35-7.85 (m, 5H), 6.55-6.75 On, 2H),
5.75-5.95 (in, IH), 5.35-5,55 (m, IH), 4.3-4.8 (m, 3H),
1.33 and 1.19 (d, J=6. OHz, 6H)„
2-226 6 8.56 (d, J=1.7Hz, IH), 7.80 (d, J=l. 7Hz, IH), 7.5-7.75 (m, 4H),
6.57 (bs, IH), 4,53 (d, J=5. 1Hz, 2H), 4.36 (sep, J=6.3Hz, IH),
1.17 (d, J=6.3Hz, 6H), 0.27 (s, 9H)0
2-227 6 8.45-8.65 On, IH), 6.35-7.8 (m, 10H), 4.3-4.85 (a, 3H),
1. 15-1.4 (m, 6H)„
2-228 6 8.85-8.95 On, IH), 6.35-8.2 (m, 9H), 4.3-4.85 (m, 3H),
1, 15-1.4 (a, 6H)„
2-229 6 8.91 (d, J=2.1Hz, IH), 8.65 (bs, IH), 8.15-8.2 (m, 2H),
7.5-7.75 (m, 4H), 6.55 (bs, IH), 4.58 (d, J=6.6Hz, 2H),
4.3-4.45 (m, IH), 1.20 (d, J=6. 6Hz, 6H)„
2-232 6 8,70 and 8.64 (s, IH), 7.4-7.8 (m, 4H), 6.40 (bs, IH),
4.3-4.75 (in, 3H), 1.33 and 1.20 (d, J=6.6Hz, 6H)„
2-234 6 8.63 (d, J=2. 1Hz, IH), 8.11 (d, J=2. 1Hz, IH), 7.5-7.75 (in, 4H),
6,5-7.0 (m, IH), 5.15-5.35 (m, IH), 3.87 (s, 3H),
1.47 (d, J=6.6Hz, 3H)0
257
[Table 46-17]
Table 46 (continued)
No. XH NMR (CDC13J Me4Si, 300MHz)
2-237 3 8.63 (bs, IH), 8.1-8.15 (m, IH), 7.5-7.75 (m, 4H), 6.5-7.0 (m, IH),
5.15-5.35 (m, IH)., 4.13 (q, J=7.2Hz, 2H), 1.46 (d, J=6.9Hz, 3H),
1.21 (t, J=7.2Hz, 3H)„
2-238 6 8. 63 and 8.58 (d, J=2. 1Hz, IH), 8. 14 and 8. 10 (d, J=2. 1Hz, IH),
7.1-7.75 (m, 4H), 6.43 (bs, IH), 4.75 and 4.52 (d, J=5.7Hz, 2H),
4.21 and 4.03 (t, J=6.9Hz, 2H), 1.3-1.85 (a, 2H),
0.97 and 0.86 (t, J=7.5Hz, 3H)„
2-242 3 8.51 (d, J=2. 1Hz, IH), 7.15-7.8 {a, 9H), 6,41 (bs, IH), 5.06 (s, 2H),
4.53 (d, J=5.1Hz, 2H).
2-243 6 8.51 (d, J =2. 1Hz, IH), 6.9-7.85 (m, 8H), 6.39 (bs, IH), 5.03 (s, 2H),
4.54 (d, J=5.4Hz, 2H)„
2-244 6 8.59 (d, J=2.0Hz, IH), 7.94 (d, J=2.0Hz, IH), 7.15-7.7 (a, 9H),
6.41 (bs, IH), 5.24 (q, J=6.5Hz, IH), 4,99 (dd, J=5. 1, 1.7Hz, 2H),
1.47 (d, J=6.5Hz, 3H),
2-247 5 8.31 and 8.27 (d, J=2.7Hz, IH), 7,25-7.75 (a, 7H), 6.95-7.1 (a, 2H),
6.52 (bs, IH), 4.76 and 4.54 (d, J=5.8 and 5.1Hz, 2H),
4.06 and 3.89 (s, 3H)„
2-249 6 8.65 and 8.59 (d, J=1.7Hz, IH), 7.91 and 7.87 (d, J=1.7Hz, IH),
7.35-7.75 (a, 9H), 6.59 (bs, IH),
4.80 and 4.56 (d, J=5. 8 and 5. 1Hz, 2H),
4. 54 and 4. 38 (sep, J=6.3Hz, IH), 1. 34 and 1.19 (d, J=6. 3Hz, 6H) „
2-251 68.63 and 8.58 (d, J=1.5Hz, IH), 8. 15 and 8. 12 (d, J=1.5Hz, IH),
7. 45-7. 9 (a, 4H), 6, 48 (bs, IH), 4. 78 and 4. 55 (d, J=5. 4Hz, 2H),
4.61 and 4.41 (q, J=8.4Hz, 2H).
2-254 6 8.50 (d, J=2. 1Hz, IH), 7.79 (d, J=2. 1Hz, IH), 7.5-7.75 (a,, 4H),
6.80 (bs, IH), 5.15-5.35 (a, IH), 4.02 (t, J=6.9Hz, 2H),
1.5-1.7 (a, 2H), 1.45 (d, J=6. 9Hz, 3H), 0.86 (t, J=7.5Hz, 3H)„
2-255 6 8.30 and 8.26 (d, J=2.4Hz, IH), 7.3-7,75 (a, 6H),
7.33 and 7.30 (d, J=2.4Hz, IH), 6.95-7.1 (a, 2H), 6.58 (bs, IH),
4. 77 and 4. 53 (d, J=5. 8 and 4. 8Hz, 2H),
4.51 and 4.37 (sep, J=6.3Hz, IH), 1.33 and 1.20 (d, J=6.3Hz, 6H)„
2-256 68.50 and 8.44 (d, J=1.7Hz, IH), 7.75 and 7.72 (d, J=1.7Hz, 1.H),
7.35-7.75 On, 4H), 6.55 (bs, IH),
4.77 and 4.52 (d, J=6. 1 and 5. 1Hz, 2H),
4.51 and 4.36 (sep, J=6.5Hz, IH), 2.09 and 2.08 (s, 3H),
1.33 and 1.18 (d, J=6.5Hz, 6H)„
2-257 6 8.43 (d, J=l,7Hz, IH), 7.35-7.75 (m, 4H), 7.74 (d, J=1.7Hz, IH),
6,59 (bs, IH), 4.77 (d, J=5. 1Hz, 2H), 4.36 (sep, J=4.4Hz, IH),
1.45-1.55 (a, IH), 1.20 (d, J=4.4Hz, 6H), 0.85-0.95 (m, 4H)„
2-258 6 8.49 and 8.44 (d, J=1.7Hz, IH), 7. 76 and 7.73 (d, J=1.7Hz, IH),
7.3-7.7 (a, 4H), 6.62 (bs, IH), 4.78 and 4.53 (d, J=5.8 and 4. SHs, 2H),
4.52 and 4.36 (sep, J=6.5Hz, IH), 2.75-2.95 (a, IH), 1.9-2.15 (m, 2H),
1.5-1.9 (a, 6H), 1.34 and 1.18 (d, J=6.5Hz, 6H).
258
[Table 46-18]
Table 46 (continued)
No. *H NMR (CDC13J Me4Si, 300MHz;)
2-259 6 8.57 and 8.51 (d, J=1.7Hz, IH), 7.82 and 7.79 (d, J=l. 7Hz, IH),
7.3-7.75 (a, 4H), 6.52 (bs, IH),
4.77 and 4.53 (d, J=5. 8 and 5.1Hz, 2H),
4.52 and 4.38 (sep, J=6. 5Hz, IH), 1.33 and 1.18 (d, J=6. 5Hz, 6H)„
2-260 6 8. 57 and 8.52 (d, J=2.0Hz, IH), 7. 83 and 7.79 (d, J=2. 0Hz, IH),
7.25-7.75 (a, 4H), 6.52 (bs, IH),
4. 77 and 4. 53 (d, J=5. 8 and 4. 8Hz, 2H),,
4.50 and 4.36 (sep, J=6. 1Hz, IH), 1.33 and 1.18 (d, J=6. 1Hz, 6H)„
2-261 68.56 and 8.50 (d, J=1.7Hz, IH), 7.81 and 7.77 (d, J=1.7Hz, IH),
7.3-7.75 (a, 4H), 6.52 (bs, IH),
4.77 and 4.53 (d, J=6. 1 and 5.1Hz, 2H),
4.52 and 4.36 (sep, J=6.3Hz, IH), 1.33 and 1.18 (d, J=6. 3Hs, 6H)„
2-262 6 8.54 and 8.48 (d, J=1.7Hz, IH), 7.80 and 7.77 (d, J=1.7Hz, IH),
7.35-7.75 (a, 4H), 6.55 (bs, IH), 4.78 and 4.54 (d, J=5. 1Hz, 2H),
4.53 and 4.36 (sep, J=6.5Hz, IH), 2.07 (bs, IH), 1.64 and 1.57 (s, 6H),
1.34 and 1.19 (d, J=6.5Hz, 6H).
2-263 6 8.53 and 8.47 (d, J=1.7Hz, IH), 7,79 and 7.76 (d, J=1.7Hz, IH),
7.3-7.75 (a, 4H), 6.54 (bs, IH),
4.77 and 4.53 (d, J=6. 1 and 4. 8Hz, 2H),
4.51 and 4.36 (sep, J=6.3Hz, IH), 1.7-2.15 (a, BE),
1.33 and 1.18 (d, J=6.3Hz, 6H).
2-264 6 8,55 and 8.49 (d, J=1.7Hz, IH), 7.81 and 7.78 (d, J=l. 7Hz, IH),
7.45-7.75 (a, 4H), 6.57 (bs, IH),
4.77 and 4.53 (d, J=6. 1 and 5.1Hz, 2H),
4.50 and 4.36 (sep, J=6.3Hz, IH), 1.55-2.05 On, 10H),
1.33 and 1.18 (d, J=6.3Hz, 6H)„
2-265 6 8.54 and 8.49 (d, J=1.7Hz, IH), 7.81 and 7.77 (d, J=l. 7Hz, IH),
7.35-7.75 (a, 4H), 6.59 (bs, IH), 6.24 (bs, IH),
4.78 and 4.53 (d, J=6. 1 and 4. 8Hz, 2H),
4.52 and 4.36 (sep, J=6.1Hz, IH), 2.45-2.65 (a, 4H), 1.9-2.05 (a, 2H),
1.33 and 1.18 (d, J=6. 1Hz, 6H)„
2-266 6 8.52 and 8,46 (d, J=1.7Hz, IH), 7,78 and 7.75 (d, J=1.7Hz, IH),
7.3-7.75 (a, 4H), 6.56 (bs, IH), 6.30 (bs, IH),
4.78 and 4.53 (d, J=5.8 and 4, 8Hz, 2H),
4.52 and 4.36 (sep, J=6.5Hz, IH), 2.1-2.3 (a, 4H), 1.55-1.75 (a, 4H),
1.33 and 1.18 (d, J=6.5Hz, 6H).
2-267 6 8.63 and 8.58 (d, J=1.7Hz, IH), 7.90 and 7.86 (d, J=1.7Hz, IH),
7.35-7.75 (a, 8H), 6.63 (bs, IH),
4.80 and 4.56 (d, J=5. 8 and 5.1Hz, 2H),
4.55 and 4.38 (sep, J=6.5Hz, IH), 1.35 and 1.20 (d, J=6.5Hz, 6H),
1.34 (s, 9H).
259
[Table 46-19]
Table 46 (continued)
No. XH NMR (CDC13J Me4Si, 300MHz)
2-268 6 8.72 and 8.66 (d, J=1.7Hz, IH), 8.6-8.65 (a, IH),
7.98 and 7.94 (d, J=l. 7Hz, IH), 7.3-7.75 On, 7H), 6.59 (bs, IH),
4.81 and 4. 57 (d, J=5. 1Hz, 2H), 4. 54 and 4.38 (sep, J=6. 1Hz, IH),
1.36 and 1.21 (d, J=6. 1Hz, 6H),
2-269 6 8.78 and 8.77 (d, J=1.0Hz, IH), 8.67 and 8.62 (d, J=l. 7Hz, IH),
8.55-8.6 (m, IH), 7.93 and 7.90 (d, J=l. 7Hz, IH),
7.85 and 7.82 (t, J=2. OHz, IH), 7.3-7.8 (m, 5H), 6.70 (bs, IH),
4.81 and 4.57 (d, J=5. 1Hz, 2H), 4.53 and 4.35 (sep, J=6. 5Hz, IH),
1.36 and 1.21 (d, J=6.5Hz, 6H).
2-270 5 8.55-8.7 (m, 3H), 7.94 and 7.91 (d, J=2. OHz, IH), 7.45-7.75 OB, 4H),
7.40 (d, J=6.3Hz, 2H), 6.72 (bs, IH), 4.81 and 4.57 (d, J=5. SHz, 2H),
4.52 and 4.39 (sep, J=6. 1Hz, IH), 1.36 and 1.21 (d, J=6. 1Hz, 6H)„
2-271 5 8.72 and 8.71 (d, J=2. OHz, IH), 7.89 and 7.83 (d, J=2. OHz, IH),
7.05-7.75 (m, 8H), 6.81 and 6.64 (bs, IH),
4.75 and 4.58 (d, J=6. 1 and 5.1Hz, 2H),
4.39 and 4.06 (sep, J=6.3Hz, IH), 1.21 and 0.98 (d, J=6. 3Hz, 6H)„
3-002 6 6.75-7.75 On, 12H), 5. 45-5. 6 and 5. 1-5. 2 (n, IH),
5.17 and 5.04 (ds, 2H), 1.54 and 1.37 (d, J=7.2Hz, 3H).
3-003 5 7.1-7.5 (m, 7H), 6.51 (bs, IH), 5.25-5.4 and 5.0-5. 15 (m, IH),
4.00 and 3.85 (s, 3H), 2.44 and 2.35 (s, 3H),
1.60 and 1.45 (d, J=6.9Hz, 3H)0
3-004 6 8.51 and 8.49 (d, J=2. OHz, IH), 7.95-8.15 (m, IH),
7.78 and 7.77 (d, J=2. OHz, IH), 7.0-7.65 (m, 3H), 7.53 (bs, IH),
4.79 and 4.57 (dd, J=6. 1, 1.5Hz and 4.8, 1.5Hz, 2H),
4. 34 and 4. 17 (q, J=7. OHz, 2H), 1. 38 and 1.25 (t, J=7. OHz, 3H)„
3-005 6 8.51 and 8.47 (d, J=2. OHz, IH), 7.80 and 7.78 (d, J=2. OHz, IH),
7.25-7.45 On, IH), 6.85-7.0 (to, 2H), 6.66 and 6.61 (bs, IH),
4.76 and 4.56 (d, J=6. 1 and 5.1Hz, 2H), 4.32 and 4.15 (q, J=7.2Hz, 2H),
1.36 and 1.22 (t, J=7.2Hz, 3H)„
3-006 5 8.51 and 8.47 (d, J=2. OHz, IH), 7.79 and 7.78 (d, J=2. OHz, IH),
7. 25-7. 7 (m, 4H), 6. 97 and 6. 89 (bs, IH),
4.77 and 4.56 (d, J=6. 1 and 5.1Hz, 2H), 4.32 and 4.15 (q, J=7. OHz, 2H),
1.37 and 1.23 (t, J=7. OHz, 3H).
3-007 6 8.50 (d, J=2. 1Hz, IH), 7.77 (d, J=2. 1Hz, IH), 7.6-7.7 (m, IH),
7.25-7.45 On, 3H), 6.96 (bs, IH), 4.55 (d, J=5. 1Hz, 2H),
4.05 (t, J=6.9Hz, 2H), 1.55-1.7 (m, 2H), 0.87 (t, J=7.5Hz, 3H)a
3-008 6 8.51 and 8.46 (d, J=2. OHz, IH), 7.80 and 7. 78 (d, J=2, OHz, IH),
7.1-7.35 (m, 2H), 6.9-7.1 (n, IH), 6.48 and 6.40 (bs, IH),
4.79 and 4.58 (d, J=6. 1 and 5.1Hz, 2H), 4.31 and 4.14 (q, J=7.0Hz, 2H),
1.36 and 1.22 (t, J=7. OHz, 3H)0
260
[Table 46-20]
Table 46 (continued)
No. *H NMR (CDC13, lfe4Si, 300MHz)
3-009 6 8.51 and 8.46 (d, J=2. OHz, IH), 7,80 and 7.78 (d, J=2. OHz, IH),
7.15-7.35 On, 3H), 6. 40 and 6.34 (bs, IH),
4.81 and 4.60 (d, J=6. 1 and 5.1Hz, 2H), 4,31 and 4.14 (q, J=7. OHz, 2H),
1.36 and 1.22 (t, J=6. 3Hz, 3H).
3-010 6 8.51 and 8.47 (d, J=2. OHz, IH), 7.80 and 7.78 (d, J=2. OHz, IH),
7.2-7.65 (m, 4H), 6.71 and 6.66 (bs, IH),
4.77 and 4.55 (d, J=6. 1 and 5.1Hz, 2H), 4.32 and 4.15 (q, J=7. OHz, 2H),
1.37 and 1.23 (t, J=7.0Hz, 3H)»
3-011 6 8.51 (d, J=2. 1Hz, IH), 7.78 (d, J=2. 1Hz, IH), 7.2-7.65 (a, 4H),
6.71 (bs, IH), 4.55 (d, J=5. 1Hz, 2H), 4.04 (t, J=6.9Hz, 2H),
1.55-1.7 (a, 2H), 0.86 (t, J=7.5Hz, 3H)„
3-013 5 7.8-7.9 (a, IH), 7.05-7.5 (a, 6H), 6.59 (bs, IH),
5. 25-5, 4 and 5. 0-5. 1 On, IH), 4.26 and 4.11 (q, J=7. 2Hz, 2H),
1.45-1.65 (m, 3H), 1.34 and 1.20 (t, J=7.2Hz, 3H).
3-014 6 8.52 and 8.47 (d, JN2.0Hz, IH), 7.8-7.9 On, IH),
7.80 and 7.78 (d, J=2. OHz, IH), 7.2-7.45 (m, 2H), 7.0-7.15 On, IH),
6.48 (bs, IH), 4.77 and 4.54 (d, J=6. 1 and 5.1Hz, 2H),
4.32 and 4.15 (q, J=7. OHz, 2H), 1.37 and 1.22 (t, J=7. OHz, 3H)„
3-015 6 8.51 (d, J=2. 1Hz, IH), 7.87 (d, J=7. SHz, IH), 7.78 (d, J=2. 1Hz, IH),
7.05-7.45 On, 3H), 6.47 (bs, IH), 4.54 (d, J=5.4Hz, 2H),
4.04 (t, J=6.6Hz, 2H), 1.5-1.7 On, 2H), 0.86 (t, J=7.5Hz, 3H)„
3-016 6 8.51 and 8.47 (d, J=2. OHz, IH), 7.7-8.1 (m, IH),
7.80 and 7.78 (d, J=2. OHz, IH), 7.05-7.45 (n, 3H),
6.52 and 6.48 (bs, IH), 4.77 and 4.54 (d, J=6. 1 and 5.1Hz, 2H),
4.53 and 4.48 (sep, J=6.3Hz, IH), 1.34 and 1.19 (d, J=6.3Hz, 6H)0
3-017 68.52 and 8.48 (d, J=2. OHz, IH), 7.8-7.9 On, IH),
7.80 and 7.79 (d, J=2. OHz, IH), 7.2-7.45 (m, 2H), 7.0-7.15 (in, IH),
6.48 (bs, IH), 4.79 and 4.55 (d, J=6. 1 and 5.1Hz, 2H),
4.08 and 3.91 (d, J=7.2Hz, 2H), 1.0-1.3 (m, IH), 0.4-0.65 (m, 2H),
0. 15-0.35 On, 2H)0
3-018 6 8.52 and 8.43 (d, J=2. OHz, IH), 7.7-7.9 On, IH),
7.80 and 7.75 (d, J=2. OHz, IH), 7.0-7.45 On, 8H), 6.45 (bs, IH),
5.42 and 5.27 (q, J=6.6Hz, IH), 4.45-4.85 On, 2H),
1.68 and 1,47 (d, J=6.6Hz, 3H).
3-019 6 8.50 (d, J =2. 1Hz, IH), 7,78 (d, J=2. 1Hz, IH), 7.15-7.45 On, 4H),
6.41 (bs, IH), 4.52 (d, J=5.4Hz, 2H), 4.03 (t, J=6.9Hz, 2H),
2.41 (s, 3H), 1.55-1.7 On, 2H), 0.86 (t, J=7. 8Hz, 3H)Q
3-020 6 8.51 and 8.47 (d, J=2. OHz, IH), 7,81 and 7.77 (d, J=2. OHz, IH),
7.1-7.5 (a, 4H), 6.52 (bs, IH), 4.73 and 4.53 (d, J=6. 0 and 5.5Hz, 2H),
4.52 and 4.38 (sep, J=6.3Hz, IH), 2.41 and 2.32 (s, 3H),
1.34 and 1.19 (d, J=6.3Hz, 6H)„
261
[Table 46-21]
Table 46 (continued)
No. XH NMR (CDC13J Me4Si, 300MHz)
3-021 5 8.51 and 8.48 (d, J=2. OHz, IH), 7.81 and 7.79 (d, J=2. 0Hz, IH),
6.95-7.3 (a, 3H), 6.42 (bs, IH),
4.72 and 4.52 (d, J=6. 1 and 5.1Hz, 2H), 4.31 and 4.14 (q, J=7.0Hz, 2H),
2.30 and 2.21 (d, J=2.4Hz, 3H), 1.36 and 1.22 (t, J=7.OHz, 3H)„
3-023 8 8.50 and 8.47 (d, J=2. OHz, IH), 7.81 and 7.79 (d, J=2.0Hz, 1H),
7.3-8.1 (a, 4H), 7.23 and 7.12 (t, J=55. 6Hz, IH), 6.64 (bs, IH),
4.74 and 4.52 (d, J=6.2 and 4.8Hz, 2H), 4.3-4.65 (a, IH),
1.34 and 1.20 (d, J=6.3Hz, 6H).
3-024 5 8.50 and 8.45 (d, J=2.OHz, IH), 7.81 and 7.78 (d, J=2. OHz, IH),
7.25-7.65 On, 3H), 6.53 (bs, IH),
4.74 and 4.51 (d, J=6. 1 and 4. 9Hz, 2H),
4.51 and 4.37 (sep, J=6. 1Hz, 1H),1.33 and 1.19 (d, J=6. 1Hz, 6H).
3-025 5 8.50 and 8.45 (d, J=2.OHz, IH), 7.81 and 7.79 (d, J=2.0Hz, IH),
7.4-7.6 (m, 2H)., 7.25-7.4 (a, IH), 6.52 and 6.45 (bs, IH),
4.79 and 4.57 (d, J=6. 1 and 5.1Hz, 2H), 4.31 and 4.14 (q, J=7.0Hz, 2H),
1.35 and 1.21 (t, J=7. OHz, 3H)„
3-026 8 8.60 and 8.31 (bs, IH), 8.50 and 8.48 (d, J=2. OHz, IH),
8.17 and 8.12 (dd, J=8.0, 1.8Hz, IH), 7.76 (d, J=2.0Hz, IH),
7.35-7.5 (a, IH), 6.85-7.1 (a, 2H),
4.79 and 4.57 (d, J=5.8 and 4.8Hz, 2H), 4.33 and 4.18 (q, J=7.OHz, 2H),
3.99 and 3.89 (s, 3H), 1.38 and 1.26 (t, J=7. OHz, 3H)C
3-027 5 8.51 and 8.48 (d, J=2. OHz, IH), 8.09 and 8.02 (dd, J-7.8, 1.9Hz, IH),
7.78 and 7.77 (d, J=2. OHz, IH), 7.62 (bs., IH), 7.05-7.7 (a, 3H),
6.63 and 6.53 (d, J=73. 1Hz, IH),
4.77 and 4.55 (d, J=6. 1 and 4.8Hz, 2H), 4.33 and 4.17 (q, J=7.0Hz, 2H),
1.37 and 1.24 (t, J=7. OHz, 3H),
3-028 5 8.51 and 8.47 (d, J=2. 0 and 2. 4Hz, IH),
8.02 and 7.94 (dd, J=7.9, 2.1Hz, IH),
7.79 and 7.78 (d, J=2.0 and 2.4Hz, IH), 7.2-7.6 (a, 3H), 7.44 (bs, IH),
4.77 and 4.54 (d, J=6. 1 and 4. 8Hz, 2H), 4.33 and 4.16 (q, J=7. OHz, 2H),
1.37 and 1.22 (t, J=7. OHz, 3H)0
3-029 5 8. 50 and 8.47 (d, J=2. OHz, IH), 7. 79 and 7.77 (d, J=2. OHz, IH),
7.1-7.6 (a, 4H), 7.01 (bs, IH), 4.77 and 4.56 (d, J=6. 1 and 5.1Hz, 2H),
4.32 and 4.15 (q, J=7. OHz, 2H), 2.44 and 2.39 (s, 3H),
1.37 and 1.23 (t, J=7. OHz, 3H)„
3-030 5 8.51 and 8,45 (d, J=2. OHz, IH), 8.05 and 8.00 (dd, J=7.8, 1.2Hz, IH),
7.83 and 7.80 (d, J=2. OHz, IH), 7.35-7.75 (a, 3H), 6.50 (bs, IH),
4. 78 and 4. 56 (d, J=5. 8 and 5. 5Hz, 2H), 4. 32 and 4.15 (q, J=7. OHz, 2H),
1.36 and 1.22 (t, J=7. OHz, 3H).
3-031 8 8.51 and 8.48 (d, J=2. OHz, IH), 7.81 and 7. 79 (d, J=2. OHz, IH),
7.35-7.85 (a, 4H), 7.07 and 6.99 (bs, IH),
4.80 and 4.57 (d, J=5.8 and 5.1Hz, 2H), 4.34 and 4.17 (q, J=7. OHz, 2H),
1.37 and 1.23 (t, J=7. OHz, 3H),
262
[Table 46-22]
Table 46 (continued)
No. XH NMR (CDC13, Me4Si, 300MHz)
3-032 6 8.42 and 8.31 (d, J=2. 0Hz, IH), 7.72 and 7.71 (d, J=2. 0Hz, IH),
7.25-7.7 (m, 9H), 6.05 and 6.03 (bs, IH),
4.50 and 4.25 (d, J=6. 1 and 5.1Hz, 2H), 4.18 and 4.01 (q, J=7.0Hz, 2H),
1.27 and 1.14 (t, J=7. 0Hz, 3H).
3-033 6 8.45-8.55 (a, IH), 7.2-7.8 (ro, 5H), 6.95 (bs, IH),
4.75 and 4.55 (d, J=5.7Hz, 2H), 4.07 and 3.89 (s, 3H)0
3-035 6 8.50 (d, J=2. 1Hz, IH), 7.7-7.8 (m, 2H), 7.3-7.45 (m, 3H),
7.17 (bs, IH), 4.56 (d, J=4.8Hz, 2H), 1.26 (s, 9H)„
3-037 6 8.45-8.55 (m, IH), 7.2-7.85 (n, 5H), 6.73 (bs, IH),
4.5-4.6 (a, 2H), 3.88 (s, 3H)0
3-038 6 8.51 (d, 5=2. 1Hz, IH), 7.77 (d, J=2. 1Hz, IH), 7.5-7.65 (m, 2H),
7.2-7.4 (m, 2H), 6.75 (bs, IH), 4.55 (d, J=5. 1Hz, 2H),
4.05-4.25 (a, IH), 1.15-1.7 (n, 5H), 0.84 (t, J=7. 8Hz, 3H).
3-039 6 8.50 (d, J=2. 1Hz, IH), 7.77 (d, J=2. 1Hz, IH), 7.55-7.65 (m, 2H),
7.2-7.4 (is, 2H), 6.83 (bs, IH), 4.55 (d, J=5.4Hz, 2H), 1.26 (s, 9H)„
3-040 5 8.52 (d, J=2. 1Hz, IH), 7.81 (d, J=2. 1Hz, IH), 7.25-7.7 (m, 4H),
6.68 (bs, IH), 4.58 (d, J=5.4Hz, 2H), 4,44 (q, J=8. 4Hz, 2H),
3-042 6 8.4-8.55 (m, IH), 7.0-7.9 (m, 5H), 6.54 (bs, IH),
4. 7-4. 8 and 4. 5-4. 6 (m, 2H), 3. 85-4. 1 (m, 3H) a
3-043 6 8.51 (d, J=2. 1Hz, IH), 7,87 (d, J=8. 1Hz, IH), 7.77 (d, J=2. 1Hz, IH),
7.3-7.45 (m, 2H), 7.05-7.15 {m, IH), 6.49 (bs, IH),
4.54 (d, J=5.1Hz, 2H), 4.05-4.25 (m, IH), 1.15-1.7 (m, 5H),
0.84 (t, J-7.5Hz, 3H)„
3-044 6 8.51 and 8.46 (d, J=2. 1Hz, IH), 7.75-7.9 (n, 2H), 7.0-7.45 (m, 3H),
6.52 (bs, IH), 4.78 and 4.54 (d, J=5.4Hz, 2H), 1.39 and 1.26 (s, 9H)„
3-045 6 8.53 and 8.49 (d, J=2. 1Hz, IH), 7.8-7.95 (m, 2H), 7.0-7.45 (m, 3H),
6.37 (bs, IH), 4.35-4.85 (m, 4H)„
3-046 6 8.50 and 8,47 (d, J=2. 1Hz, IH), 7. 79 and 7.78 (d, J=2. 1Hz, IH),
7.1-7.5 (m, 4H), 6.48 and 6.40 (bs, IH),
4.71 and 4.53 (d, J=6,0Hz, 2H), 4. 06 and 3.88 (s, 3H),
2.40 and 2.30 (s, 3H)„
3-048 6 8.50 (d, J=2. 1Hz, IH), 7.77 (d, J=2. 1Hz, IH), 7.15-7.45 On, 4H),
6.45 (bs, IH), 4.53 (d, J=5. 1Hz, 2H), 2.43 (s, 3H), 1.26 (s, 9H)„
3-051 68.64 and 8.60 (d, J=1.5Hz, IH), 8, 14 and 8. 11 (d, J=1.5Hz, IH),
7.1-7.4 (ID, 4H), 6.35 and 6.27 (bs, IH),
4.76 and 4.56 (d, J=5.4Hz, 2H), 4.61 and 4.41 (q, J-8.4Hz, 2H),
2.40 (s, 3H)„
4-001 6 8.43 and 8.36 (d, J=2. 1Hz, IH), 7.82 (d, J=2. 1Hz, IH),
7.75 (d, J=7.8Hz, IH), 7.2-7.35 (m, IH), 6.95-7.1 (m, IH),
6.59 (d, J=7.8Hz, IH), 5.83 and 4. 14 (s, IH), 3.79 and 3.62 (s, 3H),
1.84 and 1.55 (s, 6H)C
263
[Table 46-23]
Table 46 (continued)
No. *H NMR (CDC13J Me4Si, 300MHz)
4-002 6 8.47 (d, J=2.4Hz, IH), 7.79 (d, J=2.4Hz, IH), 7.45-7.75 (m, 4H),
7.21 (bs, IH), 4.0-4.2 (m, 2H), 1.82 (s, 3H)., 1.75 (s, 3H),
1. 17 (t, J=7.2Hz, 3H)0
4-004 6 8.45-8.55 (a, IH), 7.35-7.75 (a, 5H), 6.59 and 6.43 (bs, IH),
4.05-4.3 (a, 2H), 2.5-3.0 Cm, 4H), 1.75-2.15 (a, 2H), 1.2-1.35 (m, 3H)
4-006 6 8.50 and 8.40 (d, J=2. 0Hz, IH), 7.80 (d, J=2. 0Hz, IH),
7.35-7.7 (a, 3H), 6.9-7.15 (a, IH),
4.88 and 4.62, 4,25 (d, J=3. 1, 15.3, 15.3Hs, 2H),
4.07 and 3.96 (s, 3H), 2.95-3.30 (a, 2H),
1.22 and 1.09 (t, J=7. 2Hz, 3HL
4-008 6 8.47 and 8.38 (d, J=2.4 and 2.0Hz, IH),
7.80 and 7.78 (d, J=2.4 and 2. GHz, IH), 7.4-7.75 (a, 3H),
7.15-7.25 On, IH), 4.25-5.3 (a, 4H), 4.08 and 3.91 (s, 3H),
3.38 and 3.15 (s, 3H)a
4-009 6 8.50 and 8.40 (d, J=2.4Hz, IH), 7.80 (d, J=2.4Hz, IH),
7.35-7.7 (a, 3H), 6.95-7.2 (a, IH), 5.5-6.0 (a, IH), 5.0-5.35 (m, 2H),
4.89 and 4.57 (d, J=15. 0Hz, IH), 4.76 and 4. 28 (d, J=15. 0Hz, 1H),
4.06 and 3.93 (s, 3H), 3.4-3.9 (a, 2H)„
4-010 6 8. 47 and 8. 38 (d, J=2. 4Hz, IH), 7.81 and 7. 79 (d, J=2. 4Hz, IH),
7.4-7.75 (a, 3H), 7.1-7.25 (m, IH), 5.09 and 4.73 (d, J=9.6Hz, IH),
4.80 and 4.42 (d, J=9.6Hz, IH), 3.7-4.3 (a, 2H), 4.08 and 3.95 (s, 3H),
2.28 and 2.22 (t, J=2.6Hz, IH).
4-011 68.81 and 8.79 (s, IH), 8.00 and 7.98 (s, IH), 7.35-7.7 (a, 4H),
4.6-5.4 (n, 2H), 4.09 and 3.92 (s, 3H), 2.75-2.85 and 2.6-2.7 (m, IH),
0.35-0.9 (a, 4H).
4-012 6 8.52 and 8.40 (d, J=2. 0Hz, IH), 7.3-7.86 On, 4H),
7.09 and 7.02 (d, J=6.8Hz, IH), 3.95-5.1 On, 4H),
4.27 and 3.94 (s, 3H)Q
4-013 6 8.47 and 8.44 (d, J=2.0Hz, IH), 7.81 and 7. 75 (d, J=2. 0Hz, IH),
7.45-7.75 (m, 4H), 4.82 and 4.73 (s, 2H), 3.94 and 3.87 (s, 3H),
2.42 and 2.28 (s, 3H)Q
4-014 6 8. 53 and 8.44 (d, J=2. 0Hz, IH), 7. 82 and 7. 79 (d, J=2. 0Hz, IH),
7.35-7.75 0», 4H), 4.98 (bs, 2H), 4.06 and 3.90 (s, 3H),
3.63 and 3.59 (s, 3H).
4-015 6 8.52 (bs, IH), 7.4-7.9 On, 5H), 5,67 (bs, IH), 4.82 (bs, IH),
3.94 (s, 3H)Q
6-001 6 8.25-8.5 (a, 3H), 7.7-7.85 (m, 2H), 7.3-7.4 (a, IH),
4. 76 and 4.54 (d, J=6. 0Hz, 2H), 4. 34 and 4. 16 (q, J=7. 2Hz, 2H),
1.38 and 1.23 (t, J=7.2Hz, 3H)5
6-003 6 8.25-8.55 (a, 3H), 7.7-7.85 (a, 2H), 7.2-7.3 (a, IH),
4. 76 and 4.54 (d, J=5. 7Hz, 2H), 4. 33 and 4. 16 (q, J=7. 2Hz, 2H),
1.38 and 1.23 (t, J=7.2Hz, 3H),
264
[Table 46-24]
Table 46 (continued)
No. XH NMR (CDC13, Me4Si, 300MHz)
6-004 §8.3-8.7 (m, 3H), 7.7-7.8 (m, IH), 7.5-7.6 (m, IH), 7.2-7.35 (m, IH),
4. 74 and 4. 52 (d, J=5. 7Hz, 2H), 4. 33 and 4, 16 (q, J=7. 2Hz, 2H),
2.67 and 2.66 (s, 3H), 1.38 and 1.23 (t, J=7.2Hz, 3H)„
6-005 §8,75 (dd, J=4.8, 1.0Hz, IH), 8.49 (d, J=2, 0Hz, IH), 8.23 (bs, IH),
8.15 (dd, J=8.2, 1.0Hz, IH), 7.75 (d, J=2.0Hz, IH),
7.56 (dd, J=8.2, 4.8Hz,, IH), 4.55 (d, J=5. 5Hz, 2H),
4.16 (q, J=7.0Hz, 2H), 1.23 (t, J=7. 0Hz, 3H)„
6-006 6 8.45-8.5 (o, 2H), 8.32 (bs, IH), 7.79 (dd, J=8. 1, 1.5Hz, IH),
7.73 (d, J=1.8Hz, IH), 7.35 (dd, J=8. 1, 4. 5Hz, IH),
4.52 (d, J=5.7Hz, 2H), 4.35-4.45 (to, IH), 1.20 (d, J =6.0Hz, 6H).
6-007 §8.51 (dd, J=4.5, 1. 5Hz, IH), 8.48 (d, J=2. 1Hz, IH), 8.32 (bs, IH),
8.00 (dd, J=8. 1, 1.5Hz, IH), 7.73 (d, J=2. 1Hz, IH),
7.26 (dd, J=8. 1, 4. 5Hz, IH), 4.52 (d, J=5. 7Hz, 2H), 4.35-4.45 (m, IH),
1.20 (d, J=6.0Hz, 6H)0
6-008 §8.75 (dd, J=4.8, 1.5Hz, IH), 8.48 (d, J=2. 1Hz, IH), 8.25 (bs, IH),
8,15 (d, J=7.8Hz, IH), 7.74 (d, J=2. 1Hz, IH),
7.56 (dd, J=7.8, 4. 8Hz, IH), 4.55 (d, J=5. 4Hz, 2H),
4.35-4.45 (m, IH), 1.20 (d, J=6.3Hz, 6H)„
7-001 § 8. 4-8. 5 and 8. 3-8. 4 (m, IH), 8. 0-8. 1 and 7. 8-7. 85 (m, IH),
7.15-7.5 (K, 5H), 4.65 and 4.60 (d, J=6. 3Hz, 2H),
4. 04 and 3.87 (s, 3H)„
7-002 §8.50 and 8.47 (d, J=2. 1Hz, IH), 8.4-8.5 (ro, IH), 8.05-8.2 (m, IH),
7.80 and 7.78 (d, J=2. 1Hz, IH), 7.25-7.4 (tn, IH),
6.44 and 6.27 (bs, IH), 4.78 and 4. 56 (d, J=6. 0Hz, 2H),
4.33 and 4.16 (q, J=7.2Hz, 2H), 1.38 and 1.24 (t, J=7.2Hz, 3H)„
7-003 §8. 51 and 8.48 (d, J=2. 1Hz, IH), 8. 08 and 8.00 (d, J=7. 8Hz, IH),
7.81 and 7.79 (d, J=2. 1Hz, IH), 7.72 and 7.69 (d, J=7.8Hz, IH),
7.07 and 7.01 (bs, IH), 4,78 and 4.56 (d, J=6. 3Hz, 2H),
4.34 and 4.16 (q, J=7.2Hz, 2H), 1.38 and 1.23 (t, J=7.2Hs, 3H)„
7-004 §8.7-8.8 (m, IH), 7.89 and 7,73 (d, J=7.8Hz, IH), 7.1-7.6 (m, 4H),
6. 95 and 6.81 (bs, IH), 5. 2-5. 35 and 4. 95-5. 1 (m, IH),
4.36 and 4.09 (q, J=7.2Hz, 2H), 1.60 and 1.45 (d, J=7.2Hz, 3H),
1.31 and 1.18 (t, J=7.2Hz, 3H)„
7-006 §8.4-8.55 (n, 2H), 8.05-8.15 (a, IH), 7.78 (d, J=1.8Hz, IH),
7,25-7.4 (m, 2H), 4.55 (d, J=5. 1Hz, 2H), 3.89 (s, 3H).
7-007 §8.51 (d, J=2. 1Hz, IH), 8.45-8.5 (m, IH), 8.1-8.2 (m, IH),
7.78 (d, J=2.1Hz, IH), 7.3-7.4 (m, 2H), 4.56 (d, J=4.8Hz, 2H),
4.06 (t, J=6.9Hz, 2H), 1.55-1.75 (m, 2H), 0.87 (t, J=7.5Hz, 3H)Q
7-008 §8.4-8.55 (m, 2H), 8.15-8.25 {a, IH), 7.78 (d, J=2.4Hz, IH),
7.58 (bs, IH), 7.3-7.4 (m, IH), 4.56 (d, J=4.8Hz, 2H), 1.27 (s, 9H)a
7-009 §8.5-8.55 (tn, IH), 8.45-8.5 (m, IH), 8.05-8.15 (m, IH),
7.8-7.85 (m, IH), 7.25-7.4 (in, 2H), 4.60 (d, J=5.4Hz, 2H),
4.45 (q, J=8.7Hz, 2H),
265
[Table 46-25]
Table 46 (continued)
No. :H NMR (CDC13, Me4Si, 300MHz)
8-001 6 8.98 (s, IH), 8.89 (d, J=4. 8Hz, IH), 8.51 (d, J=2.0Hz, IH),
7.80 (d, J=2.0Hz, IH), 7.48 (d, J=4.8Hz, IH), 6.62 (bs., IH),
4.53 (d, J=5. 1Hz, 2H), 4.14 (q, J=7. 0Hz, 2H), 1.22 (t, J=7.0Hz, 3H)a
9-001 6 8.81 (d, J=2. 1Hz, IH), 8.76 (d, J=2. 1Hz, IH), 8.48 (d, J=2. 1Hz, IH),
8.03 (bs, IH), 7.77 (d, J=2. 1Hz, IH), 4.56 (d, J=5.8Hz, 2H),
3.90 (s, 3HL
9-002 6 8.81 (d, J=2.4Hz, IH), 8.77 (d, J=2. 4Hz, IH), 8.10 (bs, IH),
7.44 (d, J=2. 1Hz, IH), 7.30 (dd, J=8. 1, 2.1Hz, IH),
7.16 (d, J=8.1Hz, IH), 5.0-5.15 (a, IH), 4.12 (q, J=7.2Hz, 2H),
1.48 (d, J=6.9Hz, 3H), 1.21 (t, J=7.2Hz, 3H)a
9-004 6 8.82 and 8.79 (d, J=2.4Hz, IH), 8. 77 and 8.71 (d, J=2. 4Hz, IH),
8.50 and 8.48 (d, J=2.0Hz, IH), 8.08 (bs, IH),
7.78 and 7.77 (d, J=2.0Hz, IH), 4.82 and 4,57 (d, J=6. 1 and 5.5Hz, 2H),
4.01 and 3.92 (d, J=7.0Hz, 2H), 1.0-1.2 (m, IH), 0.45-0.65 (m, 2H),
0. 15-0.4 (m, 2H)0
9-007 6 8.82 (d, J=2.7Hz, IH), 8.76 (d, J=2. 7Hz, IH), 8.49 (d, J=1.8Hz, IH),
8.05 (bs, IH), 7.76 (d, J=l, 8Hz, IH), 4.56 (d, J=5.1Hz, 2H),
4.35-4.45 On, IH), 1.20 (d, J=6.3Hz, 6H)„
10-001 6 8. 50 and 8.48 (d, J=2. 1Hz, IH), 7. 78 and 7. 76 (d, J=2. 1Hz, IH),
7.44 and 7.40 (d, J=2. 1Hz, IH), 7.16 (bs, IH),
6.57 and 6.54 (d, J=2. 1Hz, IH), 4.74 and 4,51 (d, J=5.4Hz, 2H),
4. 25-4. 4 and 4. 05-4. 25 Co, 2H), 1.38 and 1.24 (t, J=7. 2Hz, 3H).
10-002 6 8.50 (d, J=2.0Hz, IH), 7.76 (d, J=2.0Hz, IH), 7.31 (d, J=1.4Hz, IH),
6.91 (s, IH), 6.32 (d, J=1.4Hz, IH), 4.48 (d, J=5. 1Hz, 2H),
4.16 (q, J=7.0Hz, 2H), 2.36 (s, 3H), 1.23 (t, J=7.0Hz, 3H)a
11-001 6 8.49 and 8.46 (d, J=2.0Hz, IH), 7.77 and 7.75 (d, J=2.0Hz, IH),
6.33 (bs, IH), 6. 00 and 5.86 (s, IH),
4.66 and 4.44 (d, J=6. 1 and 5.1Hz, 2H), 4.31 and 4.14 (q, J=7.0Hz, 2H),
2.50 and 2.45 (s, 3H), 2.24 and 2.22 (s, 3H),
1.36 and 1.23 (t, J=7.0Hz, 3H)C
11-002 6 8.50 and 8.46 (d, J=2.0Hz, IH), 7.79 and 7.77 (d, J=2.0Hz, IH),
6.69 (bs, IH), 6. 34 and 6.27 (s, IH),
4.69 and 4.47 (d, J=5.5 and 4.8Hz, 2H), 4.31 and 4.15 (q, J=7.0Hz, 2H),
2.36 and 2.33 (s, 3H), 1.36 and 1.23 (t, J=7.0Hz, 3H)C
11-003 6 8.51 and 8.48 (d, J=2.4 and 2.0Hz, IH),
7.81 and 7.79 (d, J=2.4 and 2.0Hz, IH), 7.65-7.75 (m, 2H),
7.3-7.5 (m, 3H), 6.95 and 6.88 (s, IH), 6.82 and 6.80 (bs, IH),
4.74 and 4.51 (d, J=5.8 and 4.8Hz, 2H), 4,33 and 4.16 (q, J=7.0Hz, 2H),
1.37 and 1.24 (t, J=7.0Hz, 3H).
12-001 6 6.85-7.8 (m, 7H), 5. 4-5.55 and 5. 05-5. 15 (a, IH),
4.03 and 3.88 (s, 3H), 2.55 and 2.51 (s, 3H),
1.54 and 1.35 (d, J=6.9Hz, 3H).
266
[Table 46-26]
Table 46 (continued)
No. lH NMR (CDC13, Me4Si, 300MHz)
12-002 6 6.85-7.75 On, 1 IH), 5. 4-5. 55 and 5. 05-5. 15 (m, IH),
5.20 and 5.07 (s, 2H), 2.47 and 2.37 (s, 3H),
1.54 and 1.34 (d, J=6.9Hz, 3H),
12-003 8 7.1-7.45 (ni, 4H), 6.88 and 6.82 , 6H), 5.2-5.45 and 5.0-5. 15 (m, IH), 4.05-4.35 (m, 2H),
1.2-1.65 (m, 6H)6
27-001 6 7.45-7.7 (m, 5H), 5.95-6.1 (m, IH), 4.8-4.9 (a, IH), 4.02 (s, 3H),
3.60 (s, 3H), 1.51 (d, J=6.9Hz, 3H), 1.35 (d, J=6.0Hz, 6H).
27-002 6 7.5-7.75 («, 4H), 6.97 (d, J=7.8Hz, IH), 5.15-5.25 (m, IH),
4.75-4.9 (E, IH), 3.90 (s, 3H), 3.64 (s, 3H), 1.40 (d, J=7.2Hz, 3H),
1.37 (d, J=6.6Hz, 6H)0
29-001 6 7.4-7.85 (a, 4H), 6.58 and 6.41 (bs, IH),
4.85 and 4.73 (d, J=5.7Hz, 2H), 4.05 and 4.03 (s, 3H)0
29-002 6 7.4-7.8 (n, 4H), 6.61 and 6.42 (bs, IH),
4.87 and 4.74 (d, J=5.4Hz, 2H), 4.2-4.4 (ro, 2H), 1.25-1.4 (m, 3H)„
30-007 6 6.5-8.65 (m, 13H), 4.85-5.85 (m, IH), 1.4-1.7 (m, 3H)„
30-009 6 6.95-7.75 (a, 6H), 6.3-6.7 (m, IH), 5.0-5.3 , 2H),
0.85-1.5 (n, 21H)„
41-009 8 8. 50 and 8.47 (d, J=2. 1Hz, IH), 7. 78 and 7. 75 (d, J=2. 1Hz, IH),
5.02 (bs, IH), 3.95-4.45 (m, 4H), 1,4-1,85 (n, 2H),
1.39 and 1.35 (s, 9H), 0,98 and 0.86 (t, J-7.5Hz, 3H)0
41-010 8 8.49 and 8.46 (d, J=2.4Hz, IH), 7.77 and 7.74 (d, J=2.4Hz, IH),
5.01 (bs, IH), 4.1-4.55 (B, 3H)f 1.39 and 1.35 (s, 9H),
1.31 and 1.17 (d, J=6.3Hz, 6H)„
41-011 88.45-8.6 (m, IH), 7.7-7.8 (m, IH), 4.25-5.3 (m, 3H), 1.1-1.6 (n, 18H),
41-013 8 8.49 and 8.46 (d, J=2. 1Hz, IH), 7.77 and 7.75 (d, J=2, 1Hz, IH),
5.05 (bs, IH), 4. 42 and 4, 19 (d, J=6. 3Hz, 2H),
4.03 and 3.88 (d, J=7.2Hz, 2H), L 39 and 1.35 (s, 9H), 1.1-1.3 (m, IH),
0. 55-0. 65 and 0. 45-0. 55 (m, 2H), 0. 3-0. 35 and 0, 2-0. 25 (m, 2H)„
41-014 8 8. 48 and 8.46 (d, J=2. 1Hz, IH), 7. 77 and 7. 73 (d, J=2. 1Hz, IH),
5.03 (bs, IH), 4.05-4.45 (to, 3H), 0,8-1.85 (a, 17H)C
41-015 8 8.4-8.5 (m, IH), 7.7-7.8 (m, IH), 5,05 (bs, IH), 4.35-4.45 (m, 2H),
1.3-1.4 (m, 18H).
41-017 8 8. 50 and 8.43 (d, J=2. 1Hz, IH), 7. 76 and 7. 72 (d, J=2. 1Hz, IH),
7. 2-7. 4 (n, 5H), 5. 36 and 5. 24 (q, J=6. 6Hz, IH), 4.8-5. 05 (m, IH),
4.45 and 4.15 (d, J=5.4Hz, 2H), 1.63 and 1.45 (d, J=6.6Hz, 3H),
1.36 and 1.35 (s, 9H)0
41-018 8 8. 50 and 8.44 (d, J=2. 1Hz, IH), 7. 76 and 7.73 (d, J=2. 1Hz, IH),
6.9-7.4 (a, 4H), 5.34 and 5.22 (q, J=6.9Hz, IH), 4.97 (bs, IH),
4.4-4.5 and 4. 1-4.2 (m, 2H), 1.3-1.65 (m, 12H).
41-019 8 8.50 (d, J=2.1Hz, IH), 7.75 (d, J=2. 1Hz, IH), 5.21 (bs, IH),
4.75 (bs, IH), 4.02 (t, J=6.9Hz, 2H), 1.6-1.7 (in, 2H), 1.41 (s, 9H),
1.36 (d, J=6.9Hz, 3H), 0.86 (t, J=7.5Hz, 3H)0
42-001 8 7.54 (d, J=7.5Hz, IH), 7.45-7.5 (m, IH), 7.3-7.4 (n, IH),
5.30 (bs, IH), 4.95-5.1 (o, IH), 1.43 (s, 9H), 1.33 (d, J=7.2Hz, 3H).
42-005 8 8.55 (d, J=1.8Hz, IH), 7.83 (d, J=1.8Hz, IH), 5.65 (bs, IH),
5.37 (bs, IH), 1.44 (s, 9H), 0.91 (s, 9H)<,
42-006 8 8.64 (d, J=2.1Hz, IH), 8,21 (d, J=2. 1Hz, IH), 5.31 (bs, IH),
4.75 (d, J=4.5Hz, 2H), 1.47 (s, 9H)Q
275
[Test Example]
Now, usefulness of the compounds of the present invention as pesticides will be
described in detail by referring to the following Test Examples, but the present invention
is by no restricted thereto.
5 Preparation of test solutions A:
Compounds of the present invention were dissolved in a solvent for emulsion (a
mixture of Sorpol (registered trademark) 3005XL (manufactured by Toho Chemical
Industry Co., Ltd.): N-methylpyrrolidone:Solvesso (registered trademark) 200
(manufactured by ExxonMobil Chemical) in a ratio of 1:5:2) to prepare 20% emulsifiable
10 concentrates. Then, distilled water was added to dilute the emulsifiable concentrates
to the predetermined concentration (500 ppm), and the obtained solutions were used in
the following Test Examples 1 to 7.
Preparation of test solutions B:
Compounds of the present invention were dissolved in dimethylsulfoxide to
15 prepare 1% solutions. Then, distilled water was added to dilute the solutions to the
predetermined concentration (100 ppm), and the obtained solutions were used in the
following Test Examples 8 to 12.
TEST EXAMPLE 1: Test on the preventive effect against cucumber powdery mildew
Cucumber (cultivar: Sagami Hanjiro) was planted in 90 cm3 plastic pots, and in the
20 seed leaf stage, 5 ml per pot of test solutions A of the compounds of the present
invention were spray-inoculated. After drying in air, the pots were placed in an airconditioned
greenhouse (20°C), and a suspension of conidium of Erysiphe polygoni
(synonym: Erysiphe betae) was sprayed. After the pots were placed at the same
temperature for 9 days, the proportion of the formed lesion in the inoculated leaves was
25 measured to calculate the control value in accordance with the following formula. Here,
the test was carried out in duplicate.
Control value = [1-(lesion area ratio in treated plot/lesion area ratio in non-treated
plot)] x 100
As a result, among the compounds tested, the following compounds showed a
30 control value of at least 70%.
Compounds Nos. 1-001 to 1-015, 1-018 to 1-021, 1-023 to 1-025, 1-028 to 1-030,1-032
to 1-034, 1-036 to 1-038, 1-040 to 1-076, 1-078 to 1-102, 2-002 to 2-019, 2-020*, 2-021
to 2-081, 2-083 to 2-089, 2-090*, 2-091, 2-092, 2-093*, 2-095 to 2-111,2-113, 2-115, 2-
117 to 2-121, 2-123, 2-124, 2-126, 2-127, 2-128, 2-129, 2-131 to 2-139, 2-141 to 2-205,
35 2-207 to 2-214, 2-215*, 2-216 to 2-228, 2-230, 2-231, 2-233 to 2-235, 2-237, 2-238, 2-
240 to 2-251, 3-001, 3-003, 3-004, 3-006, 3-007, 3-010 to 3-030, 3-033 to 3-051, 4-002
to 4-006, 4-008 to 4-011, 5-001, 6-001 to 6-005, 7-001 to 7-009, 9-001 to 9-006, 10-001,
11-001, 11-002, 12-001, 12-003 to 12-017, 13-001, 13-002, 15-001, 17-001, 17-002*,
17-003 to 17-006, 17-007*, 17-008 to 17-010, 19-001, 20-001 to 20-003, 20-004*, 20-
40 005 to 20-007, 21 -001, 22-001 to 22-003, 23-001, 23-002, 23-004, 25-001 to 25-004,
26-001 to 26-003, 27-002, 28-001, 30-017, 31-007, 32-026, 32-028 and 32-032 of the
present invention.
The symbol * means that the test was carried out using a 100 ppm solution.
TEST EXAMPLE 2: Test on the preventive effect against cucumber gray mold (spore
45 inoculation)
Cucumber (cultivar: Sagami Hanjiro) was planted in 90 cm3 plastic pots, and in the
seed leaf stage, 5 ml per pot of test solutions A of the compounds of the present
invention were applied. After drying in air, the treated leaves were cut and put in
276
plastic containers. 30 ul of a mixture of a suspension of conidium of Botrytis cinerea
and a dissolved PDA medium in a ratio of 1:1 was dropped on each treated leaf and
inoculated. After the inoculation, the plastic containers were placed at 20°C in humid
conditions for 3 days, and the proportion of the formed lesion in the inoculated leaves
5 was measured to calculate the control value in accordance with the same formula as in
Test Example 1. Here, the test was carried out in duplicate.
As a result, among the compounds tested, the following compounds showed a
control value of at least 70%.
Compounds Nos. 1-001, 1-005 to 1-007, 1-009, 1-024, 1-040 to 1-044, 1-046, 1-049 to
10 1-054, 1-057 to 1-060, 1-063, 1-065 to 1-067, 1-070 to 1-075, 1-079, 1-082, 1-083, 1-
085, 1-090, 1-092, 1-093, 1-096, 1-097, 1-099, 1-100, 1-102, 2-002 to 2-019, 2-020*, 2-
021 to 2-030, 2-032 to 2-034, 2-040 to 2-051, 2-053 to 2-069, 2-071 to 2-086, 2-088, 2-
089, 2-091, 2-092, 2-096 to 2-101, 2-104, 2-105, 2-107, 2-111, 2-114*, 2-115, 2-117, 2-
118, 2-120, 2-121, 2-123, 2-124, 2-126 to 2-129, 2-131 to 2-144, 2-146 to 2-150, 2-152
15 to 2-162, 2-164 to 2-166, 2-169, 2-171 to 2-175, 2-177 to 2-179, 2-181 to 2-202, 2-204,
2-205, 2-207 to 2-214, 2-215*, 2-216 to 2-228, 2-230 to 2-235, 2-237, 2-238, 2-240 to 2-
251, 3-003 to 3-007, 3-010 to 3-020, 3-022 to 3-024, 3-026, 3-027, 3-029, 3-030, 3-033
to 3-051, 4-013, 4-015, 5-001, 6-001, 6-003 to 6-005, 7-001, 7-002, 7-004 to 7-009, 9-
001 to 9-006, 10-001, 10-002, 11-001, 11-002, 12-001, 12-003 to 12-006, 12-008 to 12-
20 013, 12-015 to 12-017, 13-001, 13-002, 15-001, 17-001 to 17-007, 17-009, 17-010, 18-
001, 19-001, 20-001 to 20-003, 20-005, 20-006, 21-001, 22-001 to 22-003, 23-001 to
23-004, 24-001, 25-001, 25-002, 26-001, 26-003, 27-002 and 32-028 of the present
invention.
The symbol * means that the test was carried out using a 100 ppm solution.
25 TEST EXAMPLE 3: Test on the preventive effect against cucumber gray mold
(mycelium inoculation)
Cucumber (cultivar: Sagami Hanjiro) was planted in 90 cm3 plastic pots, and in the
seed leaf stage, 5 ml per pot of test solutions A of the compounds of the present
invention were applied. On the next day, the pots were put in a plastic container, and
30 agar blocks (diameter: 5 mm) containing Botrytis cinerea preliminarily cultivated in a
PDA medium were inoculated to the seed leaves of the cucumber treated with the
solutions. After the inoculation, the plastic container was covered with a plastic sheet
and humidified, and placed at 20°C for 2 days, whereupon the proportion of the formed
lesion in the inoculated leaves was measured to calculate the control value in
35 accordance with the same formula as in Test Example 1. Here, the test was carried
out in duplicate.
As a result, among the compounds tested, the following compounds showed a
control value of at least 70%.
Compounds Nos. 1-005, 1-040, 1-041, 1-043, 1-050 to 1-052, 1-057, 1-058, 1-065, 1-
40 070, 1 -072 to 1 -075, 1 -080, 1 -083, 1 -090, 1 -093, 1 -094, 1 -099, 1 -100, 2-002 to 2-018,
2-020*, 2-021, 2-022, 2-024 to 2-027, 2-029, 2-032, 2-040, 2-042, 2-044, 2-045, 2-047,
2-048, 2-051 to 2-054, 2-060, 2-065, 2-069, 2-071, 2-074, 2-075, 2-081, 2-083, 2-085,
2-092, 2-096, 2-098, 2-113, 2-114*, 2-115, 2-117, 2-118, 2-120, 2-121, 2-123, 2-124, 2-
126 to 2-129, 2-131 to 2-143, 2-146, 2-149, 2-152, 2-154, 2-156 to 2-158, 2-160 to 2-
45 162, 2-166 to 2-169, 2-171 to 2-174, 2-176, 2-178, 2-179, 2-181 to 2-196, 2-200 to 2-
202, 2-204, 2-205, 2-207 to 2-214, 2-215*, 2-216 to 2-220, 2-222, 2-223, 2-225 to 2-228,
2-230 to 2-235, 2-237, 2-238, 2-244 to 2-251, 3-004, 3-006, 3-007, 3-010, 3-011, 3-014,
3-015, 3-018 to 3-020, 3-022, 3-023, 3-026, 3-027, 3-029, 3-033 to 3-048, 3-051, 4-013,
277
4-015, 5-001, 6-001, 6-003, 6-005, 7-002, 7-004 to 7-009, 9-001 to 9-004, 9-006, 10-
001, 11-001, 11-002, 12-004, 12-008 to 12-013, 12-015 to 12-017, 13-001, 13-002, 15-
001, 17-002 to 17-004, 17-006, 17-007, 17-010, 19-001, 20-001, 20-003, 20-005, 20-
006, 21-001, 22-001 to 22-003, 23-001, 24-001 and 32-028 of the present invention.
5 The symbol * means that the test was carried out using a 100 ppm solution.
TEST EXAMPLE 4: Test on the preventive effect against cucumber stem rot
Cucumber (cultivar: Sagami Hanjiro) was planted in 90 cm3 plastic pots, and in the
seed leaf stage, 5 ml per pot of test solutions A of the compounds of the present
invention were applied. After drying in air, the pots were put in a plastic container, and
10 agar blocks (diameter: 5 mm) containing Sclerotinia sclerotiorum preliminarily cultivated
in a PDA medium were inoculated to the seed leaves of the cucumber treated with the
solutions. After the inoculation, the plastic container was covered with a plastic sheet
and humidified, and placed at 20°C for 2 days, whereupon the proportion of the formed
lesion in the inoculated leaves was measured to calculate the control value in
15 accordance with the same formula as in Test Example 1. Here, the test was carried
out in duplicate.
As a result, among the compounds tested, the following compounds showed a
control value of at least 70%.
Compounds Nos. 1-001, 1-003, 1-005, 1-006, 1-036 to 1-038, 1-040, 1-041, 1-043 to 1-
20 045, 1 -051, 1 -053, 1 -054, 1 -057, 1 -058, 1 -060, 1 -065, 1 -070, 1 -071, 1 -073 to 1 -075, 1 -
079, 1-080, 1-092, 1-093, 1-096, 1-099, 2-002 to 2-019, 2-020*, 2-021, 2-022, 2-024 to
2-030, 2-032 to 2-034, 2-040 to 2-048, 2-050, 2-051, 2-053, 2-054, 2-056, 2-059, 2-060,
2-064 to 2-067, 2-069, 2-071, 2-072, 2-076, 2-079, 2-081, 2-083 to 2-089, 2-091, 2-092,
2-093*, 2-096 to 2-102, 2-104 to 2-111, 2-113, 2-114*, 2-115, 2-117 to 2-121, 2-123, 2-
25 124, 2-126 to 2-129, 2-131 to 2-144, 2-146 to 2-169, 2-171 to 2-174, 2-176 to 2-179, 2-
181 to 2-205, 2-207 to 2-214, 2-215*, 2-216 to 2-228, 2-230 to 2-235, 2-237, 2-238, 2-
240 to 2-251, 3-003, 3-005 to 3-007, 3-010, 3-011, 3-014 to 3-020, 3-022 to 3-024, 3-
026, 3-027, 3-029, 3-030, 3-033 to 3-049, 3-051, 4-002 to 4-004, 4-013, 4-015, 5-001,
6-001, 6-003 to 6-005, 7-002, 7-004 to 7-009, 9-001 to 9-004, 9-006, 10-001, 10-002,
30 11-001, 11-002, 12-001, 12-004, 12-005, 12-009 to 12-013, 12-015 to 12-017, 13-001,
13-002, 15-001, 17-002 to 17-004, 17-006, 17-007, 17-009, 17-010, 19-001, 20-001 to
20-003, 20-005 to 20-007, 21-001, 22-001 to 22-003, 24-001, 25-001, 26-001, 27-002
and 32-028 of the present invention.
The symbol * means that the test was carried out using a 100 ppm solution.
35 TEST EXAMPLE 5: Test on the preventive effect against wheat powdery mildew
To wheat (cultivar: Norin-61-go) in 1.3-leaf stage planted in 90 cm3 plastic pots, 5
ml per pot of test solutions A of the compounds of the present invention were applied.
On the next day, the pots were placed in an air-conditioned greenhouse (20°C), and
conidium of Blumeria qraminis f. sp. tritici was inoculated to the wheat. 7 Days after,
40 the proportion of the formed lesion in the inoculated leaves was measured to calculate
the control value in accordance with the same formula as in Test Example 1. Here, the
test was carried out in duplicate.
As a result, among the compounds tested, the following compounds showed a
control value of at least 70%.
45 Compounds Nos. 1 -001, 1 -003, 1 -005 to 1 -011, 1 -014, 1 -040 to 1 -046, 1 -048 to 1 -060,
1-062, 1-063, 1-065 to 1-068, 1-070 to 1-075, 1-078 to 1-088, 1-090 to 1-093, 1-095 to
1-102, 2-002 to 2-019, 2-020*, 2-021 to 2-034, 2-036 to 2-038, 2-040 to 2-051, 2-053 to
2-075, 2-077, 2-079, 2-081, 2-083 to 2-089, 2-090*, 2-091, 2-092, 2-095 to 2-111, 2-113,
278
2-115, 2-117 to 2-121, 2-123, 2-124, 2-126 to 2-129, 2-131 to 2-134, 2-136 to 2-139, 2-
141 to 2-155, 2-157 to 2-192, 2-194 to 2-205, 2-207 to 2-214, 2-215*, 2-216 to 2-223, 2-
225 to 2-228, 2-230 to 2-235, 2-237, 2-238, 2-240 to 2-251, 3-001, 3-003, 3-006, 3-007,
3-010 to 3-020, 3-022 to 3-025, 3-027, 3-028, 3-030, 3-033 to 3-051, 4-002 to 4-006, 4-
5 008 to 4-011, 5-001, 6-001, 6-003, 6-005, 7-001, 7-002, 7-004 to 7-009, 9-001 to 9-006,
11-002, 12-001, 12-003 to 12-006, 12-008 to 12-013, 12-015 to 12-017, 13-001, 13-002,
15-001, 17-002 to 17-010, 18-001, 19-001, 20-001 to 20-003, 20-005 to 20-007, 21-001,
22-001 to 22-003, 23-001, 23-002, 23-004, 24-001, 25-001 to 25-004, 26-001, 26-003
and 31-007 of the present invention.
10 The symbol * means that the test was carried out using a 100 ppm solution.
TEST EXAMPLE 6: Test on the preventive effective against wheat glume blotch
To wheat (cultivar: Haruyutaka) in 1.3-leaf stage planted in 90 cm3 plastic pots, 5
ml per pot of test solutions A of the compounds of the present invention were applied.
On the next day, a suspension of conidium of Phaeosphaeria nodorum synonym:
15 Septoria nodorum) was spray-inoculated to the wheat, and the pots were placed in an
inoculation chamber at 20°C under a humidity of 100% for 2 days. Then, the pots were
placed in an air-conditioned greenhouse (20°C) for 6 days. The proportion of the
formed lesion in the inoculated leaves was measured to calculate the control value in
accordance with the same formula as in Test Example 1. Here, the test was carried
20 out in duplicate.
As a result, among the compounds tested, the following compounds showed a
control value of at least 70%.
Compounds Nos. 1-041, 1-044, 1-045, 1-058, 1-067, 1-075, 1-079, 1-082 to 1-084, 1-
101,1-102, 2-002 to 2-006, 2-008 to 2-010, 2-012 to 2-018, 2-020*, 2-021, 2-022, 2-024
25 to 2-029, 2-037, 2-040 to 2-042, 2-044, 2-047, 2-048, 2-063, 2-064, 2-066, 2-067, 2-071,
2-072, 2-074, 2-081, 2-086, 2-087, 2-092, 2-096 to 2-099, 2-101, 2-102, 2-105, 2-012 to
2-018, 2-115, 2-118, 2-120, 2-121, 2-123, 2-124, 2-127 to 2-129, 2-131, 2-132, 2-134 to
2-136, 2-139, 2-141 to 2-146, 2-148, 2-158, 2-159, 2-162, 2-167, 2-168, 2-171 to 2-179,
2-181, 2-183 to 2-187, 2-190 to 2-196, 2-198, 2-202, 2-204, 2-205, 2-207 to 2-211, 2-
30 214, 2-215*, 2-216, 2-217, 2-219, 2-220, 2-225 to 2-227, 2-231 to 2-235, 2-237, 2-238,
2-244 to 2-251, 3-007, 3-015, 3-016, 3-018, 3-020, 3-023, 3-034, 3-035, 3-038 to 3-041,
3-043, 3-047, 3-050, 4-003, 5-001, 6-003, 6-005, 7-007 to 7-009, 9-002, 9-003, 10-001,
12-008, 12-009, 12-011, 12-013, 12-015, 13-001, 15-001, 17-004, 17-009, 20-001 to 20-
003, 20-006, 22-001, 22-003 and 25-001 to 25-004 of the present invention.
35 The symbol * means that the test was carried out using a 100 ppm solution.
TEST EXAMPLE 7: Test on the preventive effect against wheat brown leaf rust
To wheat (cultivar: Norin-61 -go) in 1.3-leaf stage planted in 90 cm3 plastic pots, 5
ml per pot of test solutions A of the compounds of the present invention were applied.
On the next day, a suspension of spore of Puccinia recondita was spray-inoculated to
40 the wheat, and the pots were placed in an inoculation chamber at 20°C under a
humidity of 100% for 1 day. Then, the pots were placed in an air-conditioned
greenhouse (20°C) for 8 days. The proportion of the formed lesion in the inoculated
leaves was measured to calculate the control value in accordance with the same
formula as in Test Example 1. Here, the test was carried out in duplicate.
45 As a result, among the compounds tested, the following compounds showed a
control value of at least 70%.
Compounds Nos. 1-013, 1-046, 1-049, 1-053, 1-054, 1-057, 1-065 to 1-068, 1-071, 1-
075, 1-079, 1-084 to 1-086, 1-090 to 1-092, 1-095, 2-005, 2-033, 2-075, 2-102, 2-106 to
279
2-110, 2-115, 2-117, 2-118, 2-120, 2-121, 2-123, 2-124, 2-126, 2-127, 2-129, 2-131 to 2-
133, 2-136, 2-137, 2-141, 2-142, 2-158, 2-172, 2-174, 2-178, 2-179, 2-184, 2-186 to 2-
188, 2-207 to 2-210, 2-214, 2-226, 2-232, 2-234, 2-237, 2-238, 2-248, 2-249, 3-016 to
3-018, 3-038, 3-039, 3-043, 3-044, 4-004, 5-001, 6-003, 7-004, 9-002, 12-009, 12-013,
5 12-016, 13-001, 17-010, 22-003, 25-001, 26-003, 30-011, 31-007 and 32-012 of the
present invention.
TEST EXAMPLE 8: Test on the antibacterial activity on Aspergillus niger
60 uJ of a potato dextrose 1 % agar medium was added to each well of a 96 well
plate, and 30 uJ of sterilized water containing spores of Aspergillus niger (10 spores/3
10 u.l) was added to each well. Further, 10 u.l per well of test solutions B of the
compounds of the present invention were added, and the plate was left at rest at 25°C
under dark conditions. 2 Days after addition of the solutions, the flora area ratio (%)
was determined to calculate the efficacy (%) relative to the non-treated plot in
accordance with the following formula.
15 Efficacy (%) = [1-(flora area ratio in treated plot/flora area ratio in non-treated
plot)] x 100
As a result, among the compounds tested, the following compounds showed an
efficacy of at least 50%.
Compounds Nos. 1-001, 1-003, 1-005 to 1-008, 1-020, 1-036 to 1-038, 1-040, 1-041, 1-
20 043 to 1-054, 1-056 to 1-070, 1-072 to 1-074, 1-080, 1-081, 1-083 to 1-087, 1-089, 1-
090, 1-092 to 1-094, 1-096, 1-097, 1-099 to 1-102, 2-002 to 2-005, 2-007 to 2-019, 2-
021, 2-024, 2-026 to 2-030, 2-032 to 2-034, 2-037, 2-040 to 2-042, 2-044 to 2-051, 2-
053, 2-054, 2-056 to 2-061, 2-064 to 2-076, 2-079 to 2-081, 2-084, 2-086 to 2-089, 2-
091 to 2-111, 2-114, 2-115, 2-117 to 2-124, 2-126 to 2-129, 2-132 to 2-137, 2-139 to 2-
25 152, 2-154, 2-156 to 2-164, 2-166 to 2-169, 2-171 to 2-176, 2-181 to 2-197, 2-199 to 2-
205, 2-207 to 2-212, 2-216 to 2-221, 2-223 to 2-227, 2-230 to 2-238, 2-245, 2-246, 3-
003, 3-006, 3-007, 3-010 to 3-025, 3-029, 3-030, 3-036, 3-040, 4-002, 4-003, 7-001, 7-
002, 7-004, 7-005, 7-007, 7-009, 9-001, 9-002, 9-004, 10-002, 12-001, 12-005, 12-006,
12-008, 12-010, 12-011, 13-001, 15-001, 17-001 to 17-010, 19-001, 20-001 to 20-003,
30 21-001, 22-001 to 22-003, 23-001 to 23-004, 26-001, 26-003 and 28-001 of the present
invention.
TEST EXAMPLE 9: Insecticidal test on Meloidogvne incognita
60 u.l of a potato dextrose 1% agar medium was added to each well of a 96 well
plate, and 30 uJ of sterilized water containing eggs of Meloidogvne incognita (10 eggs/3
35 uJ) was added to each well. Further, 10 u.i per well of test solutions B of the
compounds of the present invention were added, and the plate was left at rest at 25°C
under dark conditions. 4 Days after addition of the solutions, unhatched eggs and
inactive larvae were counted, to calculate the efficacy (%) relative to the non-treated
plot in accordance with the following formula.
40 Efficacy (%) = [(number of unhatched eggs+inactive larvae in treated plot)/
number of active larvae in non-treated plot] x 100
As a result, among the compounds tested, the following compounds showed an
efficacy of at least 50%.
Compounds Nos. 1-001, 1-003, 1-005 to 1-007, 1-009, 1-020, 1-021, 1-023, 1-025, 1-
45 040, 1 -043, 1 -047 to 1 -053, 1 -058 to 1 -061, 1 -063 to 1 -069, 1 -072, 1 -078, 1 -081, 1 -083,
1-092 to 1-096, 1-099 to 1-102, 2-002 to 2-019, 2-022, 2-024, 2-027 to 2-030, 2-032, 2-
033, 2-036 to 2-040, 2-042, 2-044 to 2-048, 2-050, 2-051, 2-053 to 2-061, 2-064 to 2-
067, 2-069, 2-071 to 2-075, 2-079 to 2-081, 2-083 to 2-085, 2-087, 2-088, 2-091 to 2-
280
094, 2-096 to 2-111, 2-114, 2-115, 2-117 to 2-124, 2-126 to 2-133, 2-135 to 2-142, 2-146,
2-150 to 2-152, 2-157 to 2-164, 2-166 to 2-174, 2-176, 2-178, 2-180 to 2-189, 2-192, 2-
194 to 2-197, 2-199 to 2-202, 2-204, 2-205, 2-207 to 2-210, 2-212, 2-216, 2-217, 2-220,
2-221, 2-223, 2-226, 2-227, 2-230 to 2-238, 2-245, 2-246, 2-248, 2-249, 2-251, 3-001,
5 3-002, 3-004 to 3-008, 3-010, 3-011, 3-014 to 3-025, 3-029, 3-030, 3-036, 3-040, 3-045,
3-049, 3-051, 4-002, 4-003, 7-002, 7-004, 7-005, 7-007, 7-009, 9-001 to 9-004, 12-001,
12-002, 12-005, 12-008, 12-010, 12-011, 12-013, 12-017, 13-001, 17-002, 23-001, 26-
001 and 26-003 of the present invention.
TEST EXAMPLE 10: Test on the preventive effect on Meloidogvne incognita
10 1 ml per seedling of test solutions B of the compounds of the present invention
were treated to the bases of garden balsam seedlings (about 2 weeks after budding)
planted in a cell tray of which each cell was filled with 10 g of soil. 1 Hour after the
application, 1 ml per cell of water containing Meloidogvne incognita 2L larvae (100 2L
larvae/1 ml) was applied to the bases. The tray was placed in a greenhouse for 3
15 weeks, and the root knot level formed on the root was determined in accordance with
the following damage index and the damage degree to calculate the efficacy (%)
relative to the non-treated plot in accordance with the following formula.
0: No knot observed.
20 1: Knot observed on a part of the root system.
2: Knot observed on the entire root system.
3: Large knot observed.
4: Large knot observed on the entire root system.
[Damage degree]=[I(damage index x number of seedlings at each index)/
25 (4 x number of seedlings investigated)] x 100
Efficacy (%) = [1-(damage degree in treated plot/damage degree in non-treated
plot)] x 100
As a result, among the compounds tested, the following compounds showed an
efficacy of at least 50%.
30 Compounds Nos. 1 -006, 1 -061, 1 -063, 1 -099, 2-002 to 2-006, 2-008, 2-009, 2-011 to 2-
013, 2-022, 2-024, 2-030, 2-032, 2-033, 2-044, 2-048, 2-051, 2-057, 2-058, 2-060, 2-
061, 2-064, 2-066, 2-067, 2-069, 2-071 to 2-074, 2-079, 2-087, 2-088, 2-097 to 2-100,
2-102 to 2-105, 2-114, 2-115, 2-117, 2-120, 2-121, 2-126, 2-128, 2-129, 2-133, 2-135, 2-
141,2-142, 2-150, 2-151, 2-160 to 2-163, 2-166 to 2-171,2-173, 2-174, 2-176, 2-178,
35 2-181,2-182, 2-196, 2-199, 2-201, 2-202, 2-205, 2-209, 2-212, 2-216, 2-217, 2-237, 3-
006, 3-010, 3-014, 3-016 to 3-018, 3-020, 3-021, 3-029, 3-030, 7-002, 7-005 and 12-010
of the present invention.
TEST EXAMPLE 11: Insecticidal test on Pratvlenchus coffeae
60 U.I of a potato dextrose 1 % agar medium was added to each well of a 96 well
40 plate, and 30 uJ of sterilized water containing Pratvlenchus coffeae 2L larvae cultured in
callus was added to each well. Further, 10 u.l per well of test solutions B of the
compounds of the present invention were added, and the plate was left at rest at 25°C
under dark conditions. 4 Days after addition of the solutions, inactive larvae were
counted to calculate the efficacy (%) relative to the non-treated plot in accordance with
45 the following formula.
Efficacy (%) = (number of inactive larvae in treated plot/number of active larvae
in non-treated plot) x 100
As a result, among the compounds tested, the following compounds showed an
281
efficacy of at least 50%.
Compounds Nos. 1-001, 1-003, 1-005 to 1-007, 1-058 to 1-061, 1-063, 1-064, 1-099, 2-
002 to 2-018, 2-022, 2-024, 2-027, 2-029, 2-030, 2-032 to 2-034, 2-036 to 2-040, 2-042,
2-044, 2-046 to 2-048, 2-050, 2-051, 2-053 to 2-058, 2-060, 2-061, 2-064 to 2-067, 2-
5 069, 2-071 to 2-075, 2-079 to 2-081, 2-083 to 2-085, 2-087, 2-088, 2-091, 2-093, 2-094,
2-096 to 2-108, 2-110,2-115, 2-117, 2-120, 2-121, 2-129, 2-139, 2-141,2-146, 2-150, 2-
159 to 2-164, 2-166 to 2-171,2-173, 2-176, 2-178, 2-181, 2-197, 2-199 to 2-202, 3-002,
3-005, 3-006, 3-008, 3-010, 3-014, 3-016 to 3-018, 3-020 to 3-023, 3-025, 3-030, 3-031,
7-002, 7-005, 12-002, 12-005, 12-008, 12-010 and 17-002 of the present invention.
10 TEST EXAMPLE 12: Insecticidal test on Haemonchus contortus
60 uJ of a potato dextrose 1 % agar medium was added to each plate of a 96 well
plate, and 30 ul of sterilized water containing eggs of Haemonchus contortus (10 eggs/3
|il) was added to each well. Further, 10 uJ per well of test solutions B of the
compounds of the present invention were added, and the plate was left at rest at 25°C
15 under dark conditions. 4 Days after addition of the solutions, unhatched eggs and
inactive larvae were counted to calculate the efficacy (%) relative to the non-treated plot
in accordance with the same formula as in Test Example 9.
As a result, among the compounds tested, the following compounds showed an
efficacy of at least 50%.
20 Compounds Nos. 1 -001 to 1 -013, 1 -017 to 1 -021, 1 -023, 1 -024, 1 -026, 1 -028, 1 -029, 1 -
031, 1-032, 1-034, 1-036 to 1-074, 1-080, 1-081, 1-083 to 1-094, 1-096, 1-097, 1-099 to
1-102, 2-001 to 2-019, 2-021 to 2-027, 2-029, 2-030, 2-032 to 2-051, 2-053 to 2-061, 2-
064 to 2-089, 2-091 to 2-115, 2-117 to 2-129, 2-132 to 2-137, 2-139 to 2-164, 2-166 to
2-178, 2-180 to 2-197, 2-199 to 2-212, 2-216 to 2-221, 2-223 to 2-227, 2-230 to 2-238,
25 2-245, 2-246, 3-001 to 3-008, 3-010, 3-011, 3-013 to 3-030, 3-036, 3-040, 3-049, 4-002,
4-003, 7-001, 7-002, 7-004, 7-005, 7-007, 7-009, 8-001, 9-002, 9-004, 10-002, 12-001
to 12-008, 12-010, 12-011, 13-001, 15-001, 17-001, 17-003, 17-004, 17-006, 20-002,
20-003, 22-001, 22-002, 23-001 to 23-004, 26-001 to 26-003, 29-001 and 29-002 of the
present invention.
30
INDUSTRIAL APPLICABILITY
The oxime-substituted amide compounds of the present invention are very useful
compounds which are excellent in pesticidal activities, especially in fungicidal and
nematocidal activities, and have little harmful effect on non-target organisms such as
35 mammals, fishes and useful insects.
The entire disclosures of Japanese Patent Application No. 2012-156398 filed on
July 12, 2012, Japanese Patent Application No. 2013-019666 filed on February 4, 2013
and Japanese Patent Application No. 2013-103989 filed on May 16, 2013 including
40 specifications, claims and summaries are incorporated herein by reference in their
entireties.
282
CLAIMS
1. An oxime-substituted amide compound represented by the formula (I), or its Noxide
or salt:
W R2R3
V y R4 N
i
R1
wherein G1 is a structure represented by any one of G1-1 to G1-51:
G2 is a structure represented by any one of G2-1 to G2-19:
W is an oxygen atom or a sulfur atom,
X1 is a halogen atom, cyano, nitro, -SFs, C1-C6 alkyl, (Ci-C6)alkyl optionally
substituted with R6, C3-C8 cycloalkyi, C3-C8 halocycloalkyl, C2-C6 alkenyl, C2-C6
haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, -OR7, -S(0)rR7, -N(R9)R8, -C(0)NH2, -
5 C(S)NH2, tri(Ci-C6 alkyl)silyl, phenyl, phenyl substituted with (Z)m or D-3,
each of X2, X3, X4 and X5 is independently a hydrogen atom, a halogen atom,
cyano, nitro, C1-C6 alkyl, (Ci-Ce)alkyl optionally substituted with R6, C3-C8 cycloalkyi,
C3-C8 halocycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6
haloalkynyl, -OH, -OR7, -SH, -S(0)rR7, -N(R9)R8, Ci-C6 alkylcarbonyl, Ci-C6
10 alkoxycarbonyl, -C(0)NH2, -C(S)NH2, phenyl, phenyl substituted with (Z)m, D-2 or D-
32,
provided that when G1 is a structure represented by G1-27 and X1 is
dihalomethyl, X2 is a hydrogen atom,
each of Y1 and Y3 is independently a hydrogen atom, a halogen atom, cyano,
15 nitro, -SCN, -SF5, Ci-Cs alkyl, (Ci-C6)alkyl optionally substituted with R6, C3-C10
cycloalkyi, (C3-Cio)cycloalkyl optionally substituted with R6, E-1 to E-22, C2-C6 alkenyl,
(C2-C6)alkenyl optionally substituted with R6, C5-C10 cycloalkenyl, C5-C10
halocycloalkenyl, C2-C6 alkynyl, (C2-C6)alkynyl optionally substituted with R6, -OH, -
286
OR7, -OS(0)2R7, -SH, -S(0)rR7, -N(R9)R8, -N=C(R9a)R8a, -C(0)R1°, -C(R10)=NOH, -
C(R10)=NOR1\ M-3, M-13, M-30, -C(0)OH, -C(0)OR1\ -C(0)SR11, -C(0)N(R13)R12, M-
7, M-17, M-23, M-26, -C(S)OR11, -C(S)SR11, -C(S)N(R13)R12, M-9, M-19, M-23, M-24,
M-28, M-25, M-29, -S(0)2OR11, -S(0)2N(R13)R12, -Si(R14a)(R14b)R14, phenyl, phenyl
5 substituted with (Z)m, or D-1 to D-38,
each of Y2, Y4 and Y5 is independently a hydrogen atom, a halogen atom, cyano,
nitro, -SCN, -SF5, Ci-C6 alkyl, (Ci-Ce)alkyl optionally substituted with R6, C3-C8
cycloalkyl, C3-C8 halocycloalkyl, -OH, -OR7, -SH, -S(0)rR7, -NH2, Ci-C6 alkylamino,
di(Ci-Ce alkyl)amino, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6
10 haloalkynyl, Ci-Ce alkoxycarbonyl, -C(0)NH2 or -C(S)NH2,
or, Y1, Y2, Y3 and Y4 represent that Y1 or Y3 and Y2, or Y3 and Y4, together form -
CH2CH2CH2-, -CH2CH2O-, -CH2OCH2-, -OCH2O-, -CH2CH2CH2CH2-, -CH2CH2S-, -
CH2SCH2-, -SCH2S-, -CH2CH2N(R5)-, -CH2N(R5)CH2-, -CH2CH2CH2CH2-, -
CH2CH2CH20-, -CH2CH2OCH2-, -CH2OCH2O-, -OCH2CH2O-, -OCH2CH2S-, -
15 SCH2CH2S-, -CH2CH=CH-, -N(R5)N=CH-, -OCH2CH=CH-, -CH=CHCH=CH-, -
CH=CHCH=N-, -CH=CHN=CH-, -CH=NCH=N- or -N=CHCH=N- to form a 5-membered
ring or a 6-membered ring together with the carbon atoms attached to Y1, Y2, Y3 and
Y4, wherein hydrogen atoms on the respective ring-constituting carbon atoms may
optionally be substituted with a halogen atom, cyano, nitro, C1-C4 alkyl or C1-C4
20 haloalkyl,
and further, when G1 is a structure represented by G1-1, G1-9, G1-10, G1-12, G1-
13, G1-16toG1-20, G1-22 to G1-24, G1-26, G1-27, G1-30, G1-32, G1-35, G1-38, G1-40
or GM2 to G1-50, Y1 and Y2, Y2 and Y3, or Y3 and Y4, together may form -OCH=CH-, -
SCH=CH-, -N(R5)CH=CH-, -OCH=N-, -SCH=N- or -N(R5)CH=N- to form a 5-
25 membered ring together with the carbon atoms attached to Y\ Y2, Y3 and Y4, wherein
hydrogen atoms on the respective ring-constituting carbon atoms may optionally be
substituted with a halogen atom, cyano, nitro, C1-C4 alkyl or C1-C4 haloalkyl,
D-1 to D-38 are aromatic heterocyclic rings represented by the following
structural formulae, respectively:
E-1 to E-22 are saturated heterocyclic rings represented by the following
structural formulae, respectively:
Z is a halogen atom, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy(Ci-
C4)alkyl, C1-C4 haloalkoxy(Ci-C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, C1-C4
haloalkylthio(Ci-C4)alkyl, C1-C4 alkylsulfinyl(Ci-C4)alkyl, C1-C4 haloalkylsulfinyl(Ci-
C4)alkyl, C1-C4 alkylsulfonyl(Ci-C4)alkyl, C1-C4 haloalkylsulfonyl(Ci-C4)alkyl, C3-C6
cycloalkyl, C3-C6 halocycloalkyl, -OH, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4
alkylsulfonyloxy, C1-C4 haloalkylsulfonyloxy, C1-C4 alkylthio, C1-C4 haloalkylthio, C1-C4
alkylsulfinyl, C1-C4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, -NH2,
C1-C4 alkylamino, di(Ci-C4 alkyl)amino, C1-C4 alkoxycarbonyl, C1-C4
haloalkoxycarbonyl, -C(0)NH2, C1-C4 alkylaminocarbonyl, di(Ci-C4
alkyl)aminocarbonyl, -C(S)NH2, -S(0)2NH2 or phenyl,
when m or n is an integer of at least 2, the respective Z's may be identical with or
290
different from one another, and when there are two neighboring Z's, the two
neighboring Z's may form -CH2CH2CH2-, -ChbChfcO-, -CH2OCH2-, -OCH2O-, -
CH2CH2S-, -CH2SCH2-, -CH2CH2CH2CH2-, -CH2CH2CH2O-, -CH2CH2OCH2-, -
CH2OCH20-, -OCH2CH2O-, -CH2CH2CH2S-, -OCH2CH2S- or -CH=CH-CH=CH- to form
a 5-membered ring or a 6-membered ring together with the carbon atoms attached to
the two Z's, wherein hydrogen atoms on the respective ring-constituting carbon atoms
may optionally be substituted with a halogen atom, a cyano group, a nitro group, a
methyl group, a trifluoromethyl group, a methoxy group or a methylthio group,
R1 is Ci-Cs alkyl, (Ci-Cs)alkyl optionally substituted with R18, C3-C10 cycloalkyl,
C3-C10 halocycloalkyi, E-2 to E-8, E-14 to E-18, E-21, Cs-Ce alkenyl, Ca-Ce haloalkenyl,
C5-C10 cycloalkenyl, C5-C10 halocycloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl,
phenyl(C3-C6)alkynyl, phenyl or phenyl substituted with (Z)m,
R2 is a hydrogen atom, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C4 alkoxy(Ci-
C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 alkylsulfinyl(Ci-C4)alkyl, C1-C4
alkylsulfonyl(Ci-C4)alkyl, C3-C6 cycloalkyl or phenyl, or may form the after-mentioned
ring together with R3,
provided that when G1 is a structure represented by G1-1, X1 is a chlorine atom,
X2, X3 and X5 are hydrogen atoms, X4 is a hydrogen atom or a chlorine atom, G2 is a
structure represented by G2-1, Y3 is a chlorine atom, and Y1, Y2, Y4 and Y5 are
hydrogen atoms, R2 is cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C4 alkoxy(Ci-C4)alkyl,
C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 alkylsulfinyl(Ci-C4)alkyl, C1-C4 alkylsulfonyl(Ci-
C4)alkyl, C3-C6 cycloalkyl or phenyl,
R3 is a hydrogen atom or C1-C6 alkyl,
or R3 may form, together with R2, a C2-C5 alkylene chain to form a 3- to 6-
membered ring together with the carbon atom attached to R2 and R3, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a C1-C4 alkyl group, a -CHO group, a C1-C4 alkylcarbonyl
group, a C1-C4 alkoxycarbonyl group, a C1-C4 alkylaminocarbonyl group, a C1-C4
haloalkylaminocarbonyl group, a di(Ci-C4 alkyl)aminocarbonyl group or a phenyl
group,
R4 is a hydrogen atom, cyano, nitro, C1-C6 alkyl, (Ci-Ce)alkyl optionally
substituted with R19, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C5-C10
cycloalkenyl, C5-C10 halocycloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, -C(0)R20, -
C(0)OR21, -C(0)SR21, -C(0)N(R23)R22, -C(0)C(0)OR21, -C(S)0R21, -C(S)SR21, -
C(S)N(R23)R22, -OH, -OR21, -SR21, -N(R25)R24, -N=C(R25a)R24a, -S(0)2R21, -
S(0)2N(R23)R22 or -SN(R27)R26,
R5 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl(Ci-C4)alkyl,
C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl or C2-C6 haloalkynyl,
R6 is a halogen atom, cyano, nitro, C3-C8 cycloalkyl, C3-C8 halocycloalkyi,
hydroxy(C3-C8)cycloalkyl, C1-C6 alkoxy(C3-C8)cycloalkyl, C3-C6 alkenyl, C3-C8
cycloalkenyl, E-1 to E-22, -OH, -OR7, -SH, -S(0)rR7, -N(R9)R8, -C(R10)=NOH, -
C(R10)=NOR11, -C(0)OR11, -C(0)N(R13)R12, -Si(R14a)(R14b)R14, phenyl, phenyl
substituted with (Z)m or D-1 to D-38,
R7 is Ci-Ce alkyl, (Ci-Ce) alkyl optionally substituted with R28, Cs-Ce cycloalkyl,
(C3-C8)cycloalkyl optionally substituted with R28, E-2 to E-8, E-14 to E-18, E-21, C2-C6
alkenyl, (C2-C6)alkenyl optionally substituted with R28, C5-C10 cycloalkenyl, C5-C10
halocycloalkenyl, C3-C6 alkynyl, (C3-C6)alkynyl optionally substituted with R28, C1-C6
alkylcarbonyl, C1-C6 alkoxycarbonyl, phenyl, phenyl substituted with (Z)m, D-1, D-2, D291
4 to D-6, D-8 to D-10, D-12 to D-19, D-21, D-23, D-25, D-27 or D-30 to D-38,
R8 is a hydrogen atom, C1-C6 alkyl, (Ci-Cejalkyl optionally substituted with R28,
C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl,
Cs-Ce haloalkynyl, -C(0)R10, -C(0)C(0)R11, -C(0)OR11, -C(0)C(0)OR11, -C(0)SR11, -
C(0)N(R13)R12, -C(S)OR11, -C(S)SR11, -C(S)N(R13)R12, -OH, -S(0)2R11 or-
S(0)2N(R13)R12, or may form the after-mentioned ring together with R9,
R9 is a hydrogen atom, Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R28,
C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, -
CHO, C1-C6 alkylcarbonyl, C1-C6 haloalkylcarbonyl or C1-C6 alkoxycarbonyl,
or R9 may form, together with R8, a C2-C6 alkylene chain to form a 3- to 7-
membered ring together with the nitrogen atom attached to R8 and R9, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl
group, an oxo group or a thioxo group,
R8a is Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkoxy, C3-C6 alkenyloxy, phenoxy or
phenoxy substituted with (Z)m, or may form the after-mentioned ring together with R9a,
R9a is a hydrogen atom, Ci-Ce alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, phenyl or
phenyl substituted with (Z)m,
or R9a may form, together with R8a, a C4-C6 alkylene chain to form a 5- to 7-
membered ring together with the carbon atom attached to R8a and R9a, wherein the
alkylene chain may contain an oxygen atom or sulfur atom,
R10 is a hydrogen atom, Ci-Ce alkyl, (Ci-C6)alkyl optionally substituted with R28,
C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C5-C10
cycloalkenyl, C5-C10 halocycloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, phenyl, phenyl
substituted with (Z)m, or D-1 to D-38,
R11 is Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R28, Cs-Cs cycloalkyl,
C3-C8 halocycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C5-C10 cycloalkenyl, C5-C10
halocycloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, phenyl, phenyl substituted with
(Z)m, D-1, D-2, D-4 to D-6, D-8 to D-10, D-12 to D-19, D-21, D-23, D-25, D-27 or D-30
i to D-38,
R12 is a hydrogen atom, C1-C6 alkyl, (Ci-C6)alkyl optionally substituted with R28,
C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl,
C3-C6 haloalkynyl, C1-C6 alkylcarbonyl, C1-C6 haloalkylcarbonyl, phenylcarbonyl, C1-C6
alkoxycarbonyl, phenyl, phenyl substituted with (Z)m, D-1 to D-25 or D-27 to D-38, or
i may form the after-mentioned ring together with R13,
R13 is a hydrogen atom, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl(Ci-C4)alkyl,
C1-C4 alkoxy(Ci-C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 alkylsulfonyl(Ci-C4)alkyl,
cyano(Ci-C4)alkyl, C3-C6 alkenyl or C3-C6 alkynyl,
or R13 may form, together with R12, a C2-C6 alkylene chain to form a 3- to 7-
) membered ring together with the nitrogen atom attached to R12 and R13, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy
group, a -CHO group, a C1-C4 alkylcarbonyl group or a C1-C4 alkoxycarbonyl group,
R14 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, phenyl or phenyl substituted with
3 (Z)m,
each of R14a and R14b is independently Ci-Ce alkyl, Ci-Ce haloalkyl or Ci-Ce
alkoxy,
R15 is a hydrogen atom, cyano, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl(Ci292
C4)alkyl, hydroxy(Ci-C4)alkyl, C1-C4 alkoxy(Ci-C4)alkyl, C1-C4 haloalkoxy(Ci-C4)alkyl,
C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 haloalkylthio(Ci-C4)alkyl, C1-C4 alkylamino(Ci-
C4)alkyl, di(Ci-C4 alkyl)amino(Ci-C4)alkyl, cyano(Ci-C4)alkyl, C1-C4 alkoxycarbonyl(Ci-
C4)alkyl, C1-C4 haloalkoxycarbonyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl
substituted with (Z)m, C3-C6 cycloalkyi, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl,
C2-C6 haloalkynyl, C1-C6 alkylcarbonyl, phenylcarbonyl, phenylcarbonyl substituted
with (Z)m, Ci-Ce alkoxycarbonyl, Ci-Ce haloalkoxycarbonyl, di(Ci-Ce
alkyl)aminocarbonyl, C1-C6 alkylsulfonyl, phenylsulfonyl, phenylsulfonyl substituted
with (Z)m, di(Ci-Ce alkyl)aminosulfonyl, phenyl, phenyl substituted with (Z)m, or Ci-Ce
alkoxy,
and further, when R15 and Z are neighboring, the neighboring R15 and Z may form
-CH2CH2CH2CH2-, -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CHN=
CH- or -CH=CH-CH=N- to form a 6-membered ring together with the atoms
respectively attached to R15 and Z, wherein hydrogen atoms on the respective ringconstituting
carbon atoms may optionally be substituted with a halogen atom, a methyl
group or a trifluoromethyl group,
R16 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyi, C3-C6
halocycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, -
C(0)R1°, -C(0)C(0)R11, -C(0)OR11, -C(0)C(0)OR11, -C(0)SR11, -C(0)N(R13)R12, -
C(S)OR11, -C(S)SR11, -C(S)N(R13)R12, -S(0)2R11, -S(0)2N(R13)R12, phenyl, phenyl
substituted with (Z)m or D-3,
R16a is a hydrogen atom, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, Ci-Ce
alkylcarbonyl, Ci-Ce haloalkylcarbonyl, Ci-Ce alkoxycarbonyl, C1-C6
haloalkoxycarbonyl, C1-C6 alkylsulfonyl or Ci-Ce haloalkylsulfonyl,
R17 is a halogen atom, cyano, C1-C6 alkyl, C1-C6 haloalkyl, hydroxy(Ci-C4)alkyl,
C1-C4 alkoxy(Ci-C4) alkyl, C1-C4 alkoxycarbonyl(Ci-C4)alkyl, Ci-Ce alkoxy, Ci-Ce
alkylthio, Ci-Ce alkylamino, di(Ci-Ce alkyl)amino, C1-C6 alkoxycarbonyl, phenyl or
phenyl substituted with (Z)m,
when p is an integer of at least 2, the respective R17's may be identical with or
different from one another, and further, when two R17's are on the same carbon atom,
the two R17's together may form C1-C4 alkylidene, oxo, thioxo, imino, C1-C4 alkylimino
or C1-C4 alkoxyimino,
R18 is a halogen atom, cyano, nitro, C3-C10 cycloalkyi, C3-C10 halocycloalkyl, E-1
to E-22, C5-C10 cycloalkenyl, C5-C10 halocycloalkenyl, -OR29, -N(R30)R29, -SH, -
S(0)rR31, -S(0)t(R31)=NR16a, -C(0)R32, -C(R32)=NOH, -C(R32)=NOR33, -C(0)OH, -
C(0)OR33, -C(0)SR33, -C(0)N(R35)R34, -C(0)C(0)OR33, -C(S)OR33, -C(S)SR33, -
C(S)N(R35)R34, -S(0)2OH, -S(0)2OR33, -S(0)2N(R35)R34, -Si(R14a)(R14b)R14, M-1 to M-
30, phenyl, phenyl substituted with (Z)m or D-1 to D-38,
M-1 to M-30 are partial saturated heterocyclic rings represented by the following
structural formulae, respectively:
R19 is a halogen atom, cyano, nitro, C3-C8 cycloalkyi, E-5, E-6, E-14, E-15, C5-C10
cycloalkenyl, -OR36, -S(0)rR37, -C(R32)=NOH, -C(R32)=NOR33, M-3, -C(0)OR33, -
C(0)SR33, -C(0)NH2, M-7, M-17, -C(0)C(0)OR33, -C(S)OR33, -C(S)SR33, -C(S)NH2, M294
9, M-19, -S(0)2N(R35)R34or-Si(R14a)(R14b)R14,
R20 is a hydrogen atom, C1-C6 alkyl, (Ci-Ce)alkyl optionally substituted with R28,
C3-C8 cycloalkyi, C3-C8 halocycloalkyi, C2-C6 alkenyl, C2-C6 haloalkenyl, C5-C10
cycloalkenyl, C5-C10 halocycloalkenyl, C2-C6 alkynyl or C2-C6 haloalkynyl,
R21 is Ci-Ce alkyl, (Ci-C6)alkyl optionally substituted with R28, Ca-Cs cycloalkyi,
C3-C8 halocycloalkyi, C3-C6 alkenyl, C3-C6 haloalkenyl, C5-C10 cycloalkenyl, C5-C10
halocycloalkenyl, C3-C6 alkynyl or C3-C6 haloalkynyl,
R22 is a hydrogen atom, C1-C6 alkyl, (Ci-Ce)alkyl optionally substituted with R28,
C3-C8 cycloalkyi, C3-C8 halocycloalkyi, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl,
C3-C6 haloalkynyl, Ci-C6alkylcarbonyl, C1-C6 haloalkylcarbonyl, phenylcarbonyl, C1-C6
alkoxycarbonyl, phenyl, phenyl substituted with (Z)m, D-1 to D-25 or D-27 to D-38, or
may form the after-mentioned ring together with R23,
R23 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 cycloalkyl(Ci-C4)alkyl,
C1-C4 alkoxy(Ci-C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, C1-C4 alkylsulfonyl(Ci-C4)alkyl,
cyano(Ci-C4)alkyl, C3-C6 alkenyl or C3-C6 alkynyl,
or R23 may form, together with R22, a C2-C6 alkylene chain to form a 3- to 7-
membered ring together with the nitrogen atom attached to R22 and R23, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy
group, a -CHO group, a C1-C4 alkylcarbonyl group or a C1-C4 alkoxycarbonyl group,
R24 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C8 cycloalkyi, C3-C8
halocycloalkyi, C3-C8 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, -
S(0)2R33 or -S(0)2N(R35)R34, or may form the after-mentioned ring together with R25,
R25 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C6 alkenyl, C3-C6
haloalkenyl, C3-C6 alkynyl or C3-C6 haloalkynyl,
or R25 may form, together with R24, a C4-C5 alkylene chain to form a 5- to 6-
membered ring together with the nitrogen atom attached to R24 and R25, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl
group, a C1-C4 alkoxy group, a -CHO group, a C1-C4 alkylcarbonyl group, a C1-C4
alkoxycarbonyl group, an oxo group or a thioxo group,
R24a is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-C8 cycloalkyi, phenyl or
phenyl substituted with (Z)m, or may form the after-mentioned ring together with R25a,
R25a is a hydrogen atom, Ci-Ce alkyl, C1-C6 alkoxy, Ci-Ce alkylthio or di(Ci-Ce
alkyl)amino,
or R25a may form, together with R24a, a C3-C5 alkylene chain to form a 4- to 6-
membered ring together with the carbon atom attached to R24a and R25a, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl
group, a -CHO group, a C1-C4 alkylcarbonyl group or a C1-C4 alkoxycarbonyl group,
R26 is C1-C12 alkyl, C1-C12 haloalkyl, C1-C12 alkoxy(Ci-Ci2)alkyl, cyano(Ci-
Ci2)alkyl, C1-C12 alkoxycarbonyl(Ci-Ci2)alkyl, phenyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl
substituted with (Z)m, C3-C12 alkenyl, C3-C12 haloalkenyl, C3-C12 alkynyl, C3-C12
haloalkynyl, C1-C12 alkylcarbonyl, C1-C12 alkoxycarbonyl, -C(0)ON=C(CH3)SCH3, -
C(0)ON=C(SCH3)C(0)N(CH3)2, phenyl or phenyl substituted with (Z)m, or may form
the after-mentioned ring together with R27,
R27 is C1-C12 alkyl, C1-C12 haloalkyl, C1-C12 alkoxy(Ci-Ci2 alkyl), cyano(Ci-Ci2)
alkyl, C1-C12 alkoxycarbonyl(Ci-Ci2)alkyl, phenyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl
295
substituted with (Z)m, C3-C12 alkenyl, C3-C12 haloalkenyl, C3-C12 alkynyl, C3-C12
haloalkynyl, phenyl or phenyl substituted with (Z)m,
or R27 may form, together with R26, a C4-C7 alkylene chain to form a 5- to 8-
membered ring together with the nitrogen atom attached to R26 and R27, wherein the
alkylene chain may contain an oxygen atom or sulfur atom, and may optionally be
substituted with a C1-C4 alkyl group or a C1-C4 alkoxy group,
R28 is a halogen atom, cyano, nitro, C3-C8 cycloalkyi, C3-C8 halocycloalkyl, C1-C6
alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6
haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, di(Ci-
C6 alkyl)amino, C1-C6 alkoxycarbonyl, C1-C6 haloalkoxycarbonyl, -C(0)NH2, C1-C6
alkylaminocarbonyl, di(Ci-C6 alkyl)aminocarbonyl, -C(S)NH2, phenyl, phenyl
substituted with (Z)m, or D-1 to D-38,
R29 is a hydrogen atom, Ci-Cs alkyl, (Ci-Cs)alkyl optionally substituted with R38,
Cs-Cs cycloalkyi, (C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14
to E-21, C3-C8 alkenyl, (C3-Cs)alkenyl optionally substituted with R38, C3-C8 alkynyl,
(C3-C8)alkynyl optionally substituted with R38, -C(0)R39, -C(0)C(0)R40, -C(0)OR4°, -
C(0)C(0)OR4°, -C(0)SR40, -C(0)N(R42)R41, -C(S)R39, -C(S)OR40, -C(S)SR40, -
C(S)N(R42)R41, -S(0)2R4°, -S(0)2N(R42)R41, -Si(R14a)(R14b)R14, -P(0)(OR43)2, -
P(S)(OR43)2, phenyl, phenyl substituted with (Z)m, D-1, D-2, D-4 to D-6, D-8 to D-10, D-
12 to D-19, D-21, D-23, D-25, D-27 or D-30 to D-38, or may form the after-mentioned
ring together with R30,
R30 is a hydrogen atom, C1-C6 alkyl, C1-C6 haloalkyl, C3-C4 cycloalkyl(Ci-C4)alkyl,
C1-C4 alkoxy(Ci-C4)alkyl, C1-C4 alkylthio(Ci-C4)alkyl, cyano(Ci-C4)alkyl, C3-Ce
cycloalkyi, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 haloalkylcarbonyl, C1-C6 alkoxycarbonyl,
C1-C6 alkoxy, C1-C6 alkylsulfonyl, phenyl or phenyl substituted with (Z)m,
or R30 may form, together with R29, a C2-C6 alkylene chain to form a 3- to 7-
membered ring together with the nitrogen atom attached to R29 and R30, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl
group, a C1-C4 alkoxy group, a -CHO group, a C1-C4 alkylcarbonyl group, a C1-C4
alkoxycarbonyl group, a phenyl group, a phenyl group substituted with (Z)m, an oxo
group or a thioxo group,
R31 is Ci-C8 alkyl, (Ci-C8)alkyl optionally substituted with R38, C3-C8 cycloalkyi,
(C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14 to E-21, C3-Cs
alkenyl, (C3-Cs)alkenyl optionally substituted with R38, C3-C8 alkynyl, (C3-Cs)alkynyl
optionally substituted with R38, -C(0)R39, -C(0)C(0)R40, -C(0)OR4°, -C(0)C(0)OR40, -
C(0)SR40, -C(0)N(R42)R41, -C(S)R39, -C(S)OR40, -C(S)SR40, -C(S)N(R42)R41, -SH, Ci-
Ce alkylthio, C1-C6 haloalkylthio, phenylthio, phenylthio substituted with (Z)m, -
P(0)(OR43)2, -P(S)(OR43)2, phenyl, phenyl substituted with (Z)m, D-9, D-10, D-12, D-14
to D-17, D-30 or D-32 to D-35,
R32 is a hydrogen atom, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyi(Ci-C4)alkyl,
Ci-Ce alkoxy(Ci-C4)alkyl, Ci-Ce haloalkoxy(Ci-C4)alkyl, Ci-Ce alkylthio(Ci-C4)alkyl, Ci-
Ce haloalkylthio(Ci-C4)alkyl, Ci-Ce alkylsulfonyl(Ci-C4)alkyl, Ci-Ce haloalkylsulfonyl(Ci-
C4)alkyl, phenyl(Ci-C4)alkyl, phenyl(Ci-C4)alkyl substituted with (Z)m, C3-C6 cycloalkyi,
phenyl or phenyl substituted with (Z)m,
R33 is Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R38, Cs-Cs cycloalkyi,
(C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14 to E-21, C2-C6
alkenyl, (C2-C6)alkenyl optionally substituted with R38, C3-C6 alkynyl, (C3-C6)alkynyl
296
optionally substituted with R38, phenyl, phenyl substituted with (Z)m, D-1, D-2, D-4 to D-
6, D-8 to D-10, D-12 to D-19, D-21, D-23, D-25, D-27 or D-30 to D-38,
R34 is a hydrogen atom, Ci-Ce alkyl, (Ci-C6)alkyl optionally substituted with R38,
C3-Ce cycloalkyi, (C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14
to E-21, C2-C6 alkenyl, (C2-Ce)alkenyl optionally substituted with R38, C3-C8 alkynyl,
(C3-Ce)alkynyl optionally substituted with R38, phenyl, phenyl substituted with (Z)m, D-1
to D25 or D-27 to D-38, or may form the after-mentioned ring together with R35,
R35 is a hydrogen atom, Ci-Ce alkyl, (Ci-Ce)alkyl optionally substituted with R38,
C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, phenyl or phenyl
substituted with (Z)m,
or R35 may form, together with R34, a C2-C5 alkylene chain to form a 3- to 6-
membered ring together with the nitrogen atom attached to R34 and R35, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy
group, a -CHO group, a C1-C4 alkylcarbonyl group, a C1-C4 alkoxycarbonyl group, a
phenyl group, a phenyl group substituted with (Z)m or an oxo group,
R36 is a hydrogen atom, Ci-Ce alkyl, (Ci-C8)alkyl optionally substituted with R38,
C3-C8 cycloalkyi, (C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14
to E-21, C3-C8 alkenyl, (C3-Ce)alkenyl optionally substituted with R38, C3-C8 alkynyl,
(C3-C8)alkynyl optionally substituted with R38, -C(0)R39, -C(0)C(0)R40, -C(0)OR40, -
C(0)C(0)OR40, -C(0)SR40, -C(0)N(R42)R41, -C(S)R39, -C(S)OR40, -C(S)SR4°, -
C(S)N(R42)R41, -S(0)2R4°, -S(0)2N(R42)R41, -Si(R14a)(R14b)R14, -P(0)(OR43)2 or-
P(S)(OR43)2,
R37 is Ci-Ce alkyl, (Ci-C8)alkyl optionally substituted with R38, Cs-Ce cycloalkyi,
(C3-C8)cycloalkyl optionally substituted with R38, E-2 to E-6, E-8, E-14 to E-21, C3-C8
alkenyl, (C3-Ce)alkenyl optionally substituted with R38, C3-C8 alkynyl, (C3-Ce)alkynyl
optionally substituted with R38, -C(0)R39, -C(0)C(0)R4°, -C(0)OR40, -C(0)C(0)OR40, -
C(0)SR40, -C(0)N(R42)R41, -C(S)R39, -C(S)OR40, -C(S)SR40, -C(S)N(R42)R41, -SH, Ci-
Ce alkylthio, Ci-Ce haloalkylthio, phenylthio, phenylthio substituted with (Z)m, -
P(0)(OR43)2 or -P(S)(OR43)2,
R38 is a halogen atom, cyano, nitro, C3-C8 cycloalkyi, C3-C8 halocycloalkyl, E-5,
E-6, E-9, E-10, E-12, E-14, E-15, E-18, E-19, E-21, -OH, -OR40, -OC(0)R39, -
OC(0)OR40, -OC(0)N(R42)R41, -OC(S)N(R42)R41, -SH, -S(0)rR4°, -SC(0)R39, -
SC(0)0R4°, -SC(0)N(R42)R41, -SC(S)N(R42)R41, -N(R42)R41, -N(R42)C(0)R39, -
N(R42)C(0)OR4°, -N(R42)C(0)SR40, -N(R42)C(0)N(R42)R41, -N(R42)C(S)N(R42)R41, -
N(R42)S(0)2R4°, -C(0)R39, -C(0)OH, -C(0)OR40, -C(0)SR40, -C(0)N(R42)R41, -
C(0)C(0)OR40, -C(S)SR40, -C(S)N(R42)R41, -Si(R14a)(R14b)R14, -P(0)(OR43)2, -
P(S)(OR43)2, -P(phenyl)2, -P(0)(phenyl)2, phenyl, phenyl substituted with (Z)m, or D-1
to D-38,
R39 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, (Ci-C4)alkyl optionally
substituted with R44, C3-C6 cycloalkyi, C3-Ce halocycloalkyl, E-5, E-6, E-14, E-15, C2-C8
alkenyl, C2-C8 haloalkenyl, C5-C10 cycloalkenyl, C5-C10 halocycloalkenyl, C2-C8 alkynyl,
C2-C8 haloalkynyl, phenyl, phenyl substituted with (Z)m, or D-1 to D-38,
R40 is Ci-Ce alkyl, Ci-Ce haloalkyl, (Ci-C4)alkyl optionally substituted with R44, C3-
Ce cycloalkyi, E-5, E-6, C2-C8 alkenyl, C2-C8 haloalkenyl, C3-C8 alkynyl or phenyl,
R41 is a hydrogen atom, Ci-Ce alkyl, Ci-Ce haloalkyl, (Ci-C4)alkyl optionally
substituted with R44, C3-C6 cycloalkyi, E-5, E-6, E-14, C2-C8 alkenyl, C2-C8 haloalkenyl,
C3-C8 alkynyl, phenyl, phenyl substituted with (Z)m, D-1 to D-25 or D-27 to D-38, or
297
may form the after-mentioned ring together with R42,
R42 is a hydrogen atom, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C3-C6
alkenyl or C3-C6 alkynyl,
or R42 may form, together with R41, a C2-C5 alkylene chain to form a 3- to 6-
membered ring together with the nitrogen atom attached to R41 and R42, wherein the
alkylene chain may contain an oxygen atom, sulfur atom or nitrogen atom, and may
optionally be substituted with a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy
group, a -CHO group, a C1-C4 alkylcarbonyl group, a C1-C4 alkoxycarbonyl group, a
phenyl group or a phenyl group substituted with (Z)m,
R43 is Ci-Ce alkyl or Ci-Ce haloalkyl,
R44 is cyano, Ca-Ce cycloalkyl, Ca-Ce halocycloalkyl, E-5, E-6, E-14, E-15, C1-C4
alkoxy, C1-C4 haloalkoxy, phenoxy, phenoxy substituted with (Z)m, C1-C4 alkylthio, C1-
C4 haloalkylthio, phenylthio, phenylthio substituted with (Z)m, C1-C4 alkylsulfonyl, C1-C4
haloalkylsulfonyl, phenylsulfonyl, phenylsulfonyl substituted with (Z)m, -N(R46)R45, C1-
C4 alkylcarbonyl, C1-C4 haloalkylcarbonyl, C1-C4 alkoxycarbonyl, C1-C4
alkylaminocarbonyl, di(Ci-C4 alkyl)aminocarbonyl, tri(Ci-C4 alkyl)silyl, phenyl, phenyl
substituted with (Z)m, or D-1 to D-38,
R45 is a hydrogen atom, C1-C4 alkyl, C1-C4 alkylcarbonyl, C1-C4
haloalkylcarbonyl, C1-C4 alkoxycarbonyl, phenylcarbonyl or phenylcarbonyl substituted
with (Z)m,
R46 is a hydrogen atom or C1-C4 alkyl,
m is an integer of 1, 2, 3, 4 or 5,
n is an integer of 0, 1, 2, 3 or 4,
p is an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9,
r is an integer of 0, 1 or 2, and
t is an integer of 0 or 1.
2. The oxime-substituted amide compound according to Claim 1, wherein G1 is a
structure represented by any one of G1-1 to G1-5, G1-7 to G1-13, G1-16, G1-19, G1-20,
G1-23, G1-27, G1-30 to G1-33, GM1, GM3 to GM6 and G1-49 to G1-51,
G2 is a structure represented by any one of G2-1 to G2-7, G2-9 to G2-12, G2-14,
G2-16andG2-17,
X1 is a halogen atom, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C3-C6 cycloalkyl,
C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, -NH2, phenyl or D-
3,
X2 is a hydrogen atom or a halogen atom, provided that when G1 is a structure
represented by G1-27 and X1 is dihalomethyl, X2 is a hydrogen atom,
X3 is a hydrogen atom, a halogen atom, C1-C4 alkyl, C1-C4 haloalkyl, C3-C6
cycloalkyl, C1-C4 alkoxy, -NH2 or phenyl,
X4 is a hydrogen atom, a halogen atom ortrifluoromethyl,
X5 is a hydrogen atom or a halogen atom,
Y1 is a hydrogen atom, a halogen atom, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl,
C1-C4 alkoxymethyl, E-9, C1-C4 alkoxy, C1-C4 haloalkoxy, phenoxy, C1-C4 alkylthio or
-C(R10)=NOR11, or may form the after-mentioned ring together with Y2,
Y2 is a hydrogen atom, a halogen atom, cyano, methyl, trifluoromethyl, C1-C4
alkoxy, C1-C4 haloalkoxy, phenoxy or C1-C4 alkyothio, or may form the after-mentioned
ring together with Y3,
or Y2 may form, together with Y\ -OCH2O-, -CH2CH2CH2CH2-, -OCH2CH2O- or -
CH=CHCH=CH- to form a 5-membered ring or a 6-membered ring together with the
298
carbon atoms attached to Y1 and Y2, wherein hydrogen atoms on the respective ringconstituting
carbon atoms may optionally be substituted with a halogen atom or methyl,
Y3 is a hydrogen atom, a halogen atom, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl,
C1-C4 alkoxymethyl, C3-C6 cycloalkyl, -OR7, -S(0)rR7, -N(R9)R8, -C(0)R10,
-C(R10)=NOR11, M-3, -C(0)NH2, M-7, -C(S)NH2, -S02N(CH3)2, C2-C4 alkenyl, C2-C6
alkynyl, (C2-Ce)alkynyl substituted with R6, phenyl, phenyl substituted with (Z)m, D-3, D-
7, D-11, D-22, D-28 or D-29, or may form the after-mentioned ring together with Y4,
or Y3 may form, together with Y2, -OCH2O-, -OCH2CH2O- or -CH=CHCH=CH- to
form a 5-membered ring or a 6-membered ring together with the carbon atoms
attached to Y2 and Y3, wherein hydrogen atoms on the respective ring-constituting
carbon atoms may optionally be substituted with a halogen atom or methyl,
Y4 is a hydrogen atom, a halogen atom, cyano, methyl, trifluoromethyl or methoxy,
or Y4 may form, together with Y3, -OCH2O-, -OCH2CH2O- or -CH=CHCH=CH- to
form a 5-membered ring or a 6-membered ring together with the carbon atoms
attached to Y3 and Y4, wherein hydrogen atoms on the respective ring-constituting
carbon atoms may optionally be substituted with a halogen atom or methyl,
Y5 is a hydrogen atom, a halogen atom or methyl,
Z is a halogen atom, cyano, nitro, C1-C4 alkyl, trifluoromethyl, methoxy,
difluoromethoxy, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl,
trifluoromethylthio, trifluoromethylsulfinyl, trifluoromethylsulfonyl or phenyl,
when m or n is an integer of at least 2, the respective Z's may be identical with or
different from one another, and when there are two neighboring Z's, the two
neighboring Z's may form -CH=CH-CH=CH-, to form a 6-membered ring together with
the carbon atoms attached to the two Z's,
R1 is C1-C6 alkyl, C1-C4 haloalkyl, (Ci-C4)alkyl optionally substituted with R18, C3-
C6 cycloalkyl, Ca-Ce halocycloalkyl, E-2 to E-6, E-8, E-14, E-15, E-17, Ca-Ce alkenyl,
C3-C4 haloalkenyl, C3-C6 alkynyl, C3-C4 haloalkynyl or phenyl,
R2 is a hydrogen atom, C1-C4 alkyl, fluoromethyl, trifluoromethyl, methoxymethyl,
methylthiomethyl, methylsulfinylmethyl, methylsulfonylmethyl, cyclopropyl, cyclobutyl
or phenyl, or may form the after-mentioned ring together with R3,
provided that when G1 is a structure represented by G1-1, X1 is a chlorine atom,
X2, X3 and X5 are hydrogen atoms, X4 is a hydrogen atom or a chlorine atom, G2 is a
structure represented by G2-1, Y3 is a chlorine atom, and Y1, Y2, Y4 and Y5 are
hydrogen atoms, R2 is C1-C4 alkyl, fluoromethyl, trifluoromethyl, methoxymethyl,
methylthiomethyl, methylsulfinylmethyl, methylsulfonylmethyl, cyclopropyl, cyclobutyl
or phenyl,
R3 is a hydrogen atom or C1-C4 alkyl,
or R3 may form, together with R2, a C2-C5 alkylene chain to form a 3- to 6-
membered ring together with the carbon atom attached to R2 and R3, wherein the
alkylene chain may contain an oxygen atom or sulfur atom,
R4 is a hydrogen atom, C1-C4 alkyl, (Ci-C2)alkyl substituted with R19, C3-C6
cycloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, -C(0)R20, -C(0)OR2\ C1-C4 alkoxy or C1-C4
haloalkylthio,
R5 is C1-C4 alkyl, C1-C4 haloalkyl or Cs-Ce cycloalkyl,
R6 is a halogen atom, C3-C6 cycloalkyl, hydroxy(C3-C6)cycloalkyl, C3-C4 alkenyl,
Cs-Ce cycloalkenyl, -OH, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4
alkylsulfinyl, C1-C4 alkylsulfonyl, -Si(R14a)(R14b)R14, phenyl, phenyl substituted with (Z)m,
D-1.D-2, D-4, D-12orD-32,
299
R7 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C3-C4 haloalkynyl, phenyl or
phenyl substituted with (Z)m,
R8 and R9 together form a C4-C5 alkylene chain to form a 5- to 6-membered ring
together with the nitrogen atom attached to R8 and R9, and the alkylene chain may
contain an oxygen atom or sulfur atom,
R10 is a hydrogen atom, C1-C4 alkyl or cyclopropyl,
R11 is C1-C4 alkyl or C1-C4 haloalkyl,
R14 is C1-C4 alkyl or phenyl,
each of R14a and R14b is independently C1-C4 alkyl,
R16is-C(O)R10or-C(O)OR11,
R17 is C1-C4 alkyl, and when p is 2, the respective R17's may be identical with or
different from one another,
R18 is a halogen atom, cyano, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, E-2 to E-6,
E-8, E-9, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, -C(R32)=NOR33, M-3, M-4,
C1-C4 alkoxycarbonyl, -C(0)NH2, C1-C4 haloalkylaminocarbonyl, -C(S)NH2,
trimethylsilyl, phenyl, phenyl substituted with (Z)m, D-1, D-2, D-4 to D-6, D-8 to D-10,
D-12, D-14, D-15, D-17 or D-32,
R19 is cyano, -OR36, -C(0)NH2 or -C(S)NH2,
R20 is a hydrogen atom, C1-C4 alkyl, C1-C4 alkoxymethyl, C1-C4 alkylthiomethyl,
C1-C4 alkylsulfonylmethyl, C3-C4 cycloalkyl or C2-C4 alkenyl,
R21 is C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy(Ci-C2)alkyl, allyl or propargyl,
R32 is a hydrogen atom, C1-C4 alkyl or C3-C6 cycloalkyl,
R33 is C1-C4 alkyl or C1-C4 haloalkyl,
R36 is C1-C4 alkyl, C2-C4 haloalkyl, C1-C4 alkylcarbonyl, C3-C6 cycloalkylcarbonyl
or C1-C4 alkoxycarbonyl,
m is an integer of 1, 2 or 3,
n is an integer of 0,1 or 2, and
p is an integer of 0, 1 or 2.
3. The oxime-substituted amide compound according to Claim 2, wherein G1 is a
structure represented by any one of G1-1 to G1-4, G1-7to G1-9, G1-11 to G1-13, G1-16,
G1-20, G1-27, G1-30, G1-32, G1-33, G1-44 and G1-50,
G2 is a structure represented by any one of G2-1 to G2-3, G2-6, G2-9 to G2-12
and G2-17,
X1 is a halogen atom, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-
C4 haloalkoxy, C1-C4 alkylthio or phenyl,
X3 is a hydrogen atom, methyl, trifluoromethyl or phenyl,
Y1 is a hydrogen atom, a halogen atom, methyl, trifluoromethyl, E-9, methoxy or
-C(R10)=NOR11, or may form the after-mentioned ring together with Y2,
Y2 is a hydrogen atom, a halogen atom, cyano or C1-C4 alkoxy, or may form the
after-mentioned ring together with Y3,
or Y2 may form, together with Y1, -CH=CHCH=CH- to form a 6-membered ring
together with the carbon atoms attached to Y1 and Y2,
Y3 is a hydrogen atom, a halogen atom, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-
C4 alkoxymethyl, -OR7, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, -
C(0)R10, -C(R10)=NOR11, M-7, C2-C4 alkenyl, C2-C6 alkynyl, (C2-C6)alkynyl substituted
with R6, phenyl, phenyl substituted with (Z)m, D-3, D-7 or D-22,
or Y3 may form, together with Y2, -CH=CHCH=CH- to form a 6-membered ring
together with the carbon atoms attached to Y2 and Y3,
300
Y4 is a hydrogen atom, a halogen atom, trifluoromethyl or methoxy,
Y5 is a hydrogen atom or a halogen atom,
Z is a halogen atom, cyano, nitro, C1-C4 alkyl, trifluoromethyl, methoxy,
trifluoromethoxy, trifluoromethylthio or phenyl,
when m or n is an integer of at least 2, the respective Z's may be identical with or
different from one another, and when there are two neighboring Z's, the two
neighboring Z's may form -CH=CH-CH=CH- to form a 6-membered ring together with
the carbon atoms attached to the two Z's,
R1 is C1-C6 alkyl, C1-C4 haloalkyl, (Ci-C4)alkyl substituted with R18, Ca-Ce
cycloalkyl, E-2, E-14, C3-C6 alkenyl, C3-C4 haloalkenyl, C3-C6 alkynyl or phenyl,
R2 is a hydrogen atom, C1-C4 alkyl or phenyl, or may form the after-mentioned
ring together with R3,
provided that when G1 is a structure represented by G1-1, X1 is a chlorine atom,
X2, X3 and X5 are hydrogen atoms, X4 is a hydrogen atom or a chlorine atom, G2 is a
structure represented by G2-1, Y3 is a chlorine atom, and Y1, Y2, Y4 and Y5 are
hydrogen atoms, R2 is C1-C4 alkyl or phenyl,
R3 is a hydrogen atom or methyl, or R3 may form, together with R2, a C2-C5
alkylene chain to form a 3- to 6-membered ring together with the carbon atom attached
to R2 and R3,
R4 is a hydrogen atom, C1-C4 alkyl, (Ci-C2)alkyl substituted with R19, cyclopropyl,
allyl, propargyl, C1-C4 alkylcarbonyl, C1-C4 alkoxycarbonyl or C1-C4 haloalkylthio,
R5 is C1-C4 alkyl,
R6 is a halogen atom, C3-C6 cycloalkyl, hydroxy(C3-C6)cycloalkyl, Cs-Ce
cycloalkenyl, -OH, tri(Ci-C4 alkyl)silyl, phenyl, phenyl substituted with (Z)m or D-32,
R7 is C1-C4 alkyl, C1-C4 haloalkyl, phenyl or phenyl substituted with (Z)m,
R10 is a hydrogen atom or C1-C4 alkyl,
R11 is C1-C4 alkyl,
R17 is methyl,
R18 is cyano, C3-C6 cycloalkyl, E-5, E-9, C1-C4 alkoxy, C1-C4 alkylthio,
-C(R32)=NOR33, M-4, C1-C4 alkoxycarbonyl, C1-C4 haloalkylaminocarbonyl,
trimethylsilyl, phenyl, phenyl substituted with (Z)m, D-1, D-5, D-10 or D-32,
R19 is C1-C4 alkoxy,
R32 is a hydrogen atom or C1-C4 alkyl,
R33 is C1-C4 alkyl, and
risO.
4. The oxime-substituted amide compound according to Claim 3, wherein G1 is a
structure represented by any one of G1-1 to G1-3, G1-7, G1-9, G1-11, G1-12, G1-16, G1-
27, G1-32, G1-33 and G1-50,
G2 is a structure represented by any one of G2-1, G2-2, G2-6, G2-9 and G2-10,
W is an oxygen atom,
X1 is a halogen atom, nitro, methyl, difluoromethyl or trifluoromethyl,
X2 is a hydrogen atom, and when G1 is a structure represented by G1-27 and X1
is trifluoromethyl, X2 may be a halogen atom,
X3 is a hydrogen atom or methyl,
X4 is a hydrogen atom or a halogen atom,
X5 is a hydrogen atom,
Y1 is a hydrogen atom, a halogen atom, methyl, trifluoromethyl or methoxy,
Y2 is a hydrogen atom, a halogen atom or cyano, or may form the after301
mentioned ring together with Y3,
Y3 is a hydrogen atom, a halogen atom, cyano, methyl, trifluoromethyl, C1-C4
alkoxy, C1-C4 haloalkoxy, -C(R10)=NOR11, C2-C4 alkenyl, C2-C6 alkynyl, (C2-Ce)alkynyl
substituted with R6, phenyl, D-3 or D-7,
or Y3 may form, together with Y2, -CH=CHCH=CH- to form a 6-membered ring
together with the carbon atoms attached to Y2 and Y3,
Y4 is a hydrogen atom or a halogen atom,
R1 is Ci-Ce alkyl, C1-C4 haloalkyl, (Ci-C4)alkyl substituted with R18, Cs-Ce
cycloalkyl, C3-C6 alkenyl, C3-C4 haloalkenyl, C3-C6 alkynyl or phenyl,
R2 is a hydrogen atom, methyl or ethyl, or may form a cyclopropyl ring together
with R3,
provided that when G1 is a structure represented by G1-1, X1 is a chlorine atom,
X2, X3 and X5 are hydrogen atoms, X4 is a hydrogen atom or a chlorine atom, G2 is a
structure represented by G2-1, Y3 is a chlorine atom, and Y1, Y2, Y4 and Y5 are
hydrogen atoms, R2 is methyl or ethyl,
R3 is a hydrogen atom or methyl, or R3 may form a cyclopropyl ring together with
R2,
R4 is a hydrogen atom, C1-C4 alkylcarbonyl, C1-C4 alkoxycarbonyl or C1-C4
haloalkylthio,
R5 is methyl,
R6 is a halogen atom, C3-C6 cycloalkyl, -OH, trimethylsilyl or phenyl,
R10 is methyl,
R11 is methyl or ethyl,
R18 is cyano, C3-C6 cycloalkyl, E-5, C1-C4 alkoxy, C1-C4 alkylthio, -C(R32)=NOR33,
trimethylsilyl, phenyl, phenyl substituted with (Z)m, D-5, D-10 or D-32,
R32 is methyl,
R33 is methyl or ethyl, and
p isO.
5. The oxime-substituted amide compound according to Claim 4, wherein G1 is a
structure represented by any one of G1-1 to G1-3, G1-7, G1-11, G1-12, G1-16, G1-27
and G1-33,
G2 is a structure represented by G2-1 or G2-2,
X1 is a halogen atom, methyl, difluoromethyl or trifluoromethyl,
X2 is a hydrogen atom,
X4 is a hydrogen atom,
Y1 is a halogen atom,
Y2 is a hydrogen atom or a halogen atom,
Y3 is a halogen atom, cyano, methyl, trifluoromethyl, C1-C4 haloalkoxy, -
C(R10)=NOR11, C2-C6 alkynyl, cyclopropylethynyl, trimethylsilylethynyl or phenylethynyl,
Y5 is a hydrogen atom,
R1 is Ci-Ce alkyl, C1-C4 haloalkyl, (Ci-C4)alkyl substituted with R18, Cs-Ce
cycloalkyl, C3-C6 alkenyl, C3-C4 haloalkenyl or C3-C6 alkynyl,
R2 is a hydrogen atom or methyl, provided that when G2 is a structure
represented by G2-1, R2 is methyl,
R3 is a hydrogen atom,
R4 is a hydrogen atom,
R18 is C3-C6 cycloalkyl, trimethylsilyl, phenyl, phenyl substituted with (Z)m or D-32,
Z is a halogen atom, cyano, nitro, methyl, trifluoromethyl or trifluoromethoxy, and
302
when m is an integer of at least 2, the respective Z's may be identical with or different
from one another, and
n is 1.
6. The oxime-substituted amide compound according to any one of Claims 1 to 5,
wherein G1 is a structure represented by G1-1,
X1 is a halogen atom, methyl, difluoromethyl ortrifluoromethyl, and
X2, X3, X4 and X5 are hydrogen atoms.
7 The oxime-substituted amide compound according to any one of Claims 1 to 5,
wherein G1 is a structure represented by G1-2 or G1-3,
X1 is a halogen atom, methyl ortrifluoromethyl, and
X2, X3, X4 and X5 are hydrogen atoms.
8 The oxime-substituted amide compound according to any one of Claims 1 to 5,
wherein G1 is a structure represented by G1-7,
X1 is trifluoromethyl, and
X3 and X4 are hydrogen atoms.
9. The oxime-substituted amide compound according to any one of Claims 1 to 5,
wherein G1 is a structure represented by G1-11 or G1-12,
X1 is a halogen atom, methyl or trifluoromethyl, and
X2, X3 and X4 are hydrogen atoms.
10. The oxime-substituted amide compound according to any one of Claims 1 to 5,
wherein G1 is a structure represented by G1-16,
X1 is trifluoromethyl,
X2 and X4 are hydrogen atoms, and
R5 is methyl.
11. The oxime-substituted amide compound according to any one of Claims 1 to 5,
wherein G1 is a structure represented by G1-27,
X1 is difluoromethyl or trifluoromethyl,
X2 is a hydrogen atom, and
R5 is methyl.
12. The oxime-substituted amide compound according to any one of Claims 1 to 5,
wherein G1 is a structure represented by G1-33,
X1 is difluoromethyl ortrifluoromethyl, and
X3 is methyl.
13. The oxime-substituted amide compound according to any one of Claims 1 to 5,
wherein G2 is a structure represented by G2-2,
Y1 is a halogen atom,
Y2 is a hydrogen atom or a halogen atom,
Y3 is a halogen atom, cyano, methyl, trifluoromethyl, C1-C4 haloalkoxy,
-C(R10)=NOR11, C2-C6 alkynyl, cyclopropylethynyl, trimethylsilylethynyl or
phenylethynyl,
Y4 is a hydrogen atom or a halogen atom,
R10 is methyl, and
R11 is methyl or ethyl.
14. An intermediate of the oxime-substituted amide compound as defined in any
one of Claims 1 to 13, which is represented by the formula (Ma):
303
Y!
R2 R3
H2N II
N
*N'
"h.
i
R1
(Ha)
wherein Y1 is a halogen atom,
Y2 is a hydrogen atom, a halogen atom or cyano,
Y3 is a halogen atom, cyano, methyl, trifluoromethyl, C1-C4 alkoxy, C1-C4
haloalkoxy, -C(R10)=NOR11, C2-C4 alkenyl, C2-C6 alkynyl, (C2-Ce)alkynyl substituted
with R6, D-3 or D-7,
Y4 is a hydrogen atom or a halogen atom,
R1 is Ci-Ce alkyl, C1-C4 haloalkyl, (Ci-C4)alkyl substituted with R18, Ca-Ce
cycloalkyl, C3-C6 alkenyl, C3-C4 haloalkenyl, C3-C6 alkynyl or phenyl,
R2 is a hydrogen atom, methyl or ethyl,
R3 is a hydrogen atom or methyl, or R3 may form a cyclopropyl ring together with
R2,
R6 is a halogen atom, C3-C6 cycloalkyl, -OH, trimethylsilyl or phenyl,
R10 is methyl,
R11 is methyl or ethyl,
R18 is cyano, Ca-Ce cycloalkyl, E-5, C1-C4 alkoxy, C1-C4 alkylthio, -C(R32)=NOR33,
trimethylsilyl, phenyl, phenyl substituted with (Z)m, D-5, D-10 or D-32,
R32 is methyl,
R33 is methyl or ethyl,
Z is a halogen atom, cyano, nitro, C1-C4 alkyl, trifluoromethyl, methoxy,
trifluoromethoxy, trifluoromethylthio or phenyl,
when m or n is an integer of at least 2, the respective Z's may be identical with or
different from one another, and when there are two neighboring Z's, the two
neighboring Z's may form -CH=CH-CH=CH- to form a 6-membered ring together with
the carbon atoms attached to the two Z's,
m is 1, 2 or 3,
n is an integer of 0, 1 or 2, and
p is 0.
15. An intermediate of the oxime-substituted amide compound as defined in any one
of Claims 1 to 7 and 13, which is represented by the formula (IVa):
Y2
/3
(IVa)
wherein G1 is a structure represented by any one of G1-1, G1-2 and G1-3:
304
IS
xz xA N
G1-! G1-! G*-3
X1 is a halogen atom, nitro, methyl, difluoromethyl or trifluoromethyl,
X2, X3 and X5 are hydrogen atoms,
X4 is a hydrogen atom, and when G1 is G1-1, X4 may be a halogen atom,
Y1 is a halogen atom,
Y2 is a hydrogen atom, a halogen atom or cyano,
Y3 is a halogen atom, cyano, methyl, trifluoromethyl, C1-C4 alkoxy, C1-C4
haloalkoxy, -C(R10)=NOR11, C2-C4 alkenyl, C2-C6 alkynyl, (C2-Ce)alkynyl substituted
with R6, D-3 or D-7,
Y4 is a hydrogen atom or a halogen atom,
R2 is a hydrogen atom or methyl,
R6 is a halogen atom, C3-C6 cycloalkyl, -OH, trimethylsilyl or phenyl,
R10 is methyl,
R11 is methyl or ethyl, and
n is 0.
16. An intermediate of the oxime-substituted amide compound as defined in any one
of Claims 1 to 13, which is represented by the formula (Via) or (Villa):
1
Y1 JL Y3
(Via)
wherein A is C-H or N,
G1 is a structure represented by any one of G1 -1 to G1 -3, G1 -7, G1 -9, G1 -11,
G1 -12, G1 -16, G1 -27, G1 -32, G1 -33 and G1 -50:
N02
(Villa)
X1 is a halogen atom, nitro, methyl, difluoromethyl or trifluoromethyl,
X2 is a hydrogen atom, and when G1 is a structure represented by G1-27 and X1
is trifluoromethyl, X2 may be a halogen atom,
X3 is a hydrogen atom or methyl,
X4 is a hydrogen atom or a halogen atom,
X5 is a hydrogen atom,
Y1 is a halogen atom,
Y2 is a hydrogen atom, a halogen atom or cyano,
Y3 is a halogen atom, cyano, methyl, trifluoromethyl, C1-C4 alkoxy, C1-C4
haloalkoxy, -C(R10)=NOR11, C2-C4 alkenyl, C2-C6 alkynyl, (C2-Ce)alkynyl substituted
with R6, D-3 or D-7,
Y4 is a hydrogen atom or a halogen atom,
R2 is a hydrogen atom, methyl or ethyl, provided that when G1 is a structure
represented by G1-1, X1 is a chlorine atom, X2, X3 and X5 are hydrogen atoms, X4 is a
hydrogen atom or a chlorine atom, A is C-H, Y3 is a chlorine atom, and Y1, Y2 and Y4
are hydrogen atoms, R2 is methyl or ethyl,
R3 is a hydrogen atom or methyl, or R3 may form a cyclopropyl ring together with
R2,
R5 is methyl,
R6 is a halogen atom, C3-C6 cycloalkyl, -OH, trimethylsilyl or phenyl,
R10 is methyl,
R11 is methyl or ethyl,
n is 0, and
risO.
17. A pesticidal composition containing at least one member selected from the
306
oxime-substituted amide compounds as defined in Claims 1 to 13, as active
ingredient(s).
18. An agricultural fungicidal or nematocidal composition containing at least one
member selected from the oxime-substituted amide compounds as defined in Claims 1
to 13, as active ingredient(s).
19. The agricultural fungicidal or nematocidal composition according to Claim 1 &,
which is applied to plants by foliar treatment.
20. The agricultural fungicidal or nematocidal composition according to Claim 18,
which is used to treat soil in which plants grow.
21. The agricultural fungicidal or nematocidal composition according to Claim 18,
which is used to treat seeds, tuberous roots or rhizomes of plants.
22. An antifungal or parasrticidal composition for a mammal or bird, which contains at
least one member selected from the oxime-substituted amide compounds as defined in
Claims 1 to 13, as active ingredient(s).
23. The parasiticidal composition according to Claim 22, which is against internal
parasites in a mammal or bird by oral administration.
24. The parasiticidal composition according to Claim 22, which is against internal
parasites in a mammal or bird by parenteral administration.
25. The parasiticidal composition according to Claim 22, which is against internal
parasites in a mammal or bird by percutaneous administration.