HERBICIDAL PYRIDAZINONE DERIVATIVES
The present invention relates to novel pyridazinone derivatives, to processes
for their preparation, to herbicidal compositions which comprise the novel derivatives,
and to their use for controlling weeds, in particular in crops of useful plants, or for
inhibiting plant growth.
Thus, according to the present invention there is provided a compound of
Formula (I):
or an agronomically acceptable salt thereof,
wherein: -
R1 is selected from the group consisting of hydrogen, Ci-Cealkyl, C3-
C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, Ci-Cehaloalkyl, Ci-Cealkoxy-Ci
C3-alkyl, Cs-CecycloalkylCi-Q-alkyl-, tetrahydropyranyl- and benzyl-,
wherein the benzyl is optionally substituted by one or more R1 1
selected from the group consisting of Al, A2 and A3
wherein
X1 is N or CR7;
X2 is N or CR8;
X3 is N or CR9;
X4 is N or CR6;
R is selected from the group consisting of hydrogen, hydroxyl, halo, nitro,
amino, cyano, Ci-Cealkyl, Ci-C3alkoxy-, C3-C 6cycloalkyl, C 2-C6alkenyl, C -
C6alkynyl, Ci-Cehaloalkyl, Ci-Cealkoxy-Ci-Q-alkyl, Cs-Cecycloalkyl-Ci-Qalkyl,
Ci-C6alkyl-S(0) p-, Ci-C6alkyl-S(0) p- Ci-C3-alkyl, Ci-C6haloalkyl-
S(0)p-, Ci-Csalkylamino, Ci-Csdialkylamino and C1-C6haloalkyl-S(0) p-C1-
C3-alkyl;
R4 is selected from the group consisting of hydrogen, Ci-Cealkylcarbonyl-,
arylcarbonyl-, Ci-Cealkoxycarbonyl-, Ci-C6alkyl-S(0) p-, Ci-Cealkyl-
S(0) pcarbonyl- and aryl-S(0) p- , wherein said aryl groups may be optionally
substituted by one or more R1 1;
R5 is selected from the group consisting of hydroxyl, halogen, Ci-Cealkyl, Ci-
Cecycloalkyl, Ci-Cehaloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl,
Ci-C6 alkoxy-, C2-C6 alkenyloxy-, C3-C6cycloalkylCi-C 3-alkyl-, Ci-C6
alkoxyCi-C3alkyl-, Ci-C6 alkoxy-C2-C6alkoxy-, Ci-C6 alkoxy-C2-C6alkoxy-
Ci- alky Ci-C haloalkoxy-, Ci-C6 haloalkoxy-Ci-C 3alkyl-, Ci-Cealkyl-
S(0)p-, Ci-C6haloalkyl-S(0)p-, aryl, aryl-S(0) p-, heterocyclyl, heterocyclyl-
S(0)p-, aryloxy-, aryl-C2-C6alkyl-, aryl-Ci-Cealkoxy-, heterocyclyloxy-,
heterocyclyl-Ci-Qalkoxy-Ci-Qalkyl-, hydroxycarbonyl, hydroxycarbonyl-
Ci-C3 alkoxy-, Ci-C3 alkoxycarbonyl-, Ci-C3 alkoxycarbonyl-Ci-C3 alkoxy-,
Ci-C3alkylamino-, Ci-C3dialkylamino-, Ci-C3 alkylamino-S(0) p-, Ci-C3
alkylamino-S(0) p-C1-C3alkyl-, Ci-C3 dialkylamino-S(0) p-, Ci-C3
dialkylamino-S(0) p-C1-C3alkyl-, Ci-Csalkylaminocarbonyl-, C -
Csalkylaminocarbonyl-Ci-Csalkyl-, Ci-Csdialkylaminocarbonyl-, Ci-C3
dialkylaminocarbonyl-Ci-Csalkyl-, Ci-Csalkylcarbonylamino-, Ci-C3 alkyl-
S(0)p-amino-, C1-C3alkyl-S(0)p-C 1-C3alkylamino-, Ci-C3alkyl-S(0)paminoCi-
Qalkyl-, cyano and nitro, wherein said heterocyclyls are five or six
membered heterocyclyls containing from one to three heteroatoms each
independently selected from the group consisting of oxygen, nitrogen and
sulphur, and wherein the aryl or heterocyclyl components may be optionally
substituted by one or more substituents selected from the group consisting of
halo, Ci-C3alkyl, Ci-Qhaloalkyl, Ci-C3 alkoxy, Ci-C3 haloalkoxy, Ci-Cealkyl-
S(0) p-, phenyl, cyano and nitro;
R6 and R9 are independently selected from the group consisting of hydrogen,
hydroxyl, halogen, -C lkyl, Ci-Cecycloalkyl, Ci-Cehaloalkyl, C2-C6alkenyl,
C2-C6haloalkenyl, C2-C6alkynyl, Ci-Ce alkoxy-, C2-C6 alkenyloxy-, C3-
CecycloalkylCi-Cs-alkyl-, Ci-C alkoxyCi-Csalkyl-, Ci-C alkoxy-C2-
C6alkoxy-, -C alkoxy-C2-C6alkoxy-C1-C3alkyl-,C1-C6 haloalkoxy-, -C
haloalkoxy-CrQalkyl-, C1-C6alkyl-S(0) p-, C1-C6haloalkyl-S(0) p-, aryl, aryl-
S(0) p-, heterocyclyl, heterocyclyl-S(0) p-, aryloxy-, aryl-C2-C6alkyl-, aryl-Ci-
C6alkoxy-, heterocyclyloxy-, heterocyclyl-Ci-Csalkoxy-Ci-Csalkyl-,
hydroxycarbonyl, hydroxycarbonyl-Ci-Csalkoxy-, Ci-C3 alkoxycarbonyl-, Ci-
Csalkoxycarbonyl-Ci-Cs alkoxy-, Ci-Csalkylamino-, Ci-Qdialkylamino-, Ci-
C3alkylamino-S(0) p-, Ci-C3 alkylamino-S(0) p-C1-C3alkyl-, Ci-C3
dialkylamino-S(0) p-, Ci-C3 dialkylamino-S(0) p-C1-C3alkyl-, Ci-
C3alkylaminocarbonyl-, Ci-Qalkylaminocarbonyl-Ci-Qalkyl-, Ci-
C3dialkylaminocarbonyl-, Ci-C3 dialkylaminocarbonyl-Ci-Csalkyl-, C -
C3alkylcarbonylamino-, Ci-C3 alkyl-S(0) p-amino-, C1-C3alkyl-S(0) p-C1-
C3alkylamino-, C1-C3alkyl-S(0)p- aminoCi-Csalkyl-, cyano and nitro, wherein
said heterocyclyls are five or six membered heterocyclyls containing from one
to three heteroatoms each independently selected from the group consisting of
oxygen, nitrogen and sulphur, and wherein the aryl or heterocyclyl
components may be optionally substituted by one or more substituents
selected from the group consisting of halo, Ci-Csalkyl, Ci-Cshaloalkyl, Ci-C3
alkoxy, Ci-C3 haloalkoxy, C1-C6alkyl-S(0) p - , phenyl, cyano and nitro;
R7 and R8 are independently selected from the group consisting of hydrogen,
halogen, Ci-C3 alkyl-, Ci-C3 alkoxy-, C2-C3alkenyl-, C2-C3alkynyl-, Ci-C3
haloalkyl- and Ci-Cshaloalkoxy-;
and wherein R5 and R9 can together form a saturated or unsaturated 5- or 6-
membered carbocyclic or heterocyclic ring, said heterocyclic ring comprising
one or more nitrogen and/or oxygen heteroatoms, the 5- or 6-membered ring
12 being optionally substituted by one or more R ; or
R6 and R9 can together form a saturated or unsaturated 5- or 6-membered
carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more
heteroatoms selected from the group consisting of nitrogen, oxygen and S(0) 2 ,
12 the 5- or 6-membered ring being optionally substituted by one or more R ; or
R6 and R8 can together form a saturated or unsaturated 5- or 6-membered
carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more
nitrogen heteroatoms, the 5- or 6-membered ring being optionally substituted
13 by one or more R ; and
R1 1 is selected from the group consisting of halo-, Ci-Csalkyl, Ci-C3 haloalkyl
and Ci-C6alkoxy;
12 R is selected from the group of hydrogen, cyano, halo-, oxy-, Ci-
C3alkylS(0)p-, C1-C3 alkyl, C2-C3alkenyl, C2-C3alkynyl, C1-C3 alkoxy and -
C3 haloalkyl;
13 R is selected from the group of hydrogen, cyano, halo-, Ci-C3alkylS(0)p-,
Ci-C3 alkyl, C2-C3alkenyl, C2-C3alkynyl, morpholinyl- and Ci-C3 haloalkyl;
and
p = 0, 1 or 2.
Alkyl groups having a chain length of from 1 to 6 carbon atoms include, for
example, methyl (Me, CH3), ethyl (Et, C2H5) , n-propyl, isopropyl (z-Pr), n-butyl (nbu),
iso-butyl (z ' -bu), sec-butyl and tert-butyl (t-butyl).
Alkenyl groups having a chain length of from 2 to 6 carbon atoms include, for
example, -CH=CH2 (vinyl) and -CH2-CH=CH2 (allyl).
Alkynyl groups having a chain length of from 2 to 6 carbon atoms include, for
example, -CºCH (ethynyl) and -CH2-CºCH (propargyl).
Cycloalkyl groups include c-propyl (c-Pr), c-butyl (c-Bu), c-pentyl and chexyl.
Halogen (halo) encompasses fluorine, chlorine, bromine or iodine. The same
correspondingly applies to halogen in the context of other definitions, such as
haloalkyl or halophenyl.
Haloalkyl groups having a chain length of from 1 to 6 carbon atoms are, for
example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,
dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl,
pentafluoroethyl, l,l-difluoro-2,2,2-trichloroethyl, 2,2,3, 3-tetrafluoroethyl and 2,2,2-
trichloroethyl, heptafluoro-n-propyl and perfluoro-n-hexyl.
Haloalkenyl radicals include alkenyl groups substituted one or more times by
halogen, halogen being fluorine, chlorine, bromine or iodine and especially fluorine or
chlorine, for example 2,2-difluoro-l-methylvinyl, 3-fluoropropenyl, 3-chloropropenyl,
3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl and 4,4,4-
trifluorobut-2-en-l -yl. Preferred C2-C6alkenyl radicals substituted once, twice or three
times by halogen are those having a chain length of from 2 to 5 carbon atoms.
Alkoxy groups preferably have a chain length of from 1 to 6 carbon atoms.
Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy,
sec-butoxy or tert-butoxy or a pentyloxy or hexyloxy isomer, preferably methoxy and
ethoxy. Alkylcarbonyl is preferably acetyl or propionyl. Alkoxycarbonyl is, for
example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl,
n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxycarbonyl,
preferably methoxycarbonyl, ethoxycarbonyl or tert -butoxycarbonyl. It should also
be appreciated that two alkoxy substituents present on the same carbon atom may be
joined to form a spiro group. Thus, the methyl groups present in two methoxy
substituents may be joined to form a spiro 1,3 dioxolane substituent, for example.
Such a possibility is within the scope of the present invention.
Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy,
trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-
chloroethoxy, 2,2-difluoroethoxy or 2,2,2-trichloroethoxy, preferably
difluoromethoxy, 2-chloroethoxy or trifluoromethoxy.
Alkylthio (alky l - S-) groups preferably have a chain length of from 1 to 6
carbon atoms. Alkylthio is, for example, methylthio, ethylthio, propylthio,
isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably
methylthio or ethylthio.
Alkylsulfmyl (alkyl-SO-) is, for example, methylsulfmyl, ethylsulfmyl,
propylsulfinyl, isopropylsulfmyl, n-butylsulfinyl, isobutylsulfmyl, sec-butylsulfmyl or
tert-butylsulfinyl, preferably methylsulfmyl or ethylsulfmyl.
Alkylsulfonyl (alkyl-S(0) 2-) is, for example, methylsulfonyl, ethylsulfonyl,
propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl
or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.
Alkylamino (alkyl-NH-) is, for example, methylamino, ethylamino, npropylamino,
isopropylamino or a butylamino isomer. Dialkylamino ((alkyl)2-N-) is,
for example, dimethylamino, methylethylamino, diethylamino, n-propylmethylamino,
dibutylamino or diisopropylamino. Preference is given to alkylamino groups having a
chain length of from 1 to 4 carbon atoms.
Cycloalkylamino- or dicycloalkylamino- is for example cyclohexylamino or
dicyclopropylamino.
Alkoxyalkyl groups preferably have from 1 to 6 carbon atoms. Alkoxyalkyl is,
for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, npropoxymethyl,
n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
Alkylthioalkyl (alkyl-S-alkyl) groups preferably have from 1 to 6 carbon
atoms. Alkylthioalkyl is, for example, methylthiomethyl, methylthioethyl,
ethylthiomethyl, ethylthioethyl, n-propylthiomethyl, n-propylthioethyl,
isopropylthiomethyl, isopropylthioethyl, butylthiomethyl, butylthioethyl or
butylthiobutyl.
Cycloalkyl groups preferably have from 3 to 6 ring carbon atoms and may be
substituted by one or more methyl groups; they are preferably unsubstituted, for
example cyclopropyl (c-Pr), cyclobutyl (c-Bu), cyclopentyl (c-pentyl) or cyclohexyl
(c-hexyl).
Aryl includes benzyl, phenyl, including phenyl as part of a substituent such as
phenoxy, benzyl, benzyloxy, benzoyl, phenylthio, phenylalkyl, phenoxyalkyl or tosyl,
may be in mono- or poly-substituted form, in which case the substituents may, as
desired, be in the ortho-, meta- and/or para-position(s). The term also includes, for
example, naphthalenyl.
Heterocyclyl, includes, for example, morpholinyl, tetrahydrofuryl and
heteroaryl.
Heteroaryl, including heteroaryl as part of a substituent such as heteroaryloxy,
means, for example, a five to ten (preferably five or six) member heteroaryl
containing one to three heteroatoms, each independently selected from the group
consisting of oxygen, nitrogen and sulphur. The term heteroaryl thus includes, for
example, benzofuranyl, benzimidazolyl, indolyl, isobenzofuranyl, furanyl, thiophenyl,
thiazolyl, oxazolyl, isoxazolyl, thiazolyl, pyrazolyl, isothiazolyl, pyridyl, pyridazinyl,
pyrazinyl, pyrimidinyl, pyridonyl, triazolyl, napthyridinyl and napthyridinonyl. The
heteroaryl component may be optionally mono or poly substituted as previously
defined.
Preferably, R1 is selected from the group consisting of hydrogen, Ci-Cealkyl,
C2-C6alkenyl, C2-C6alkynyl, C 3-C6cycloalkyl, Ci-Cehaloalkyl Ci-Cealkoxy-Ci-
C3alkyl and Q-Cecycloalkyl-Ci-Qalkyl. In a more preferred embodiment R1 is
selected from the group consisting of C -C4alkyl, cyclopropyl, difluoromethyl,
cyclopropylmethyl-, vinyl and propargyl with methyl being particularly preferred.
Preferably R is selected from the group consisting of Ala, Alb, Ale, Aid,
Ale, Alf, Alg, Alh, A2a, A2b, A3a, A3b and A3b:
wherein R5, R6, R7, R8, R9 and R13 are as defined previously and n is 0, 1, 2 or
3.
More preferably, R is selected from the group consisting of phenyl (e.g. Ala),
3-pyridyl (e.g. Ale), N-pyridonyl (e.g. A2a) and 3-linked [l,8]naphthyridinyl (e.g.
Aid). Even more preferably R is phenyl (e.g. Ala).
Preferably, R is selected from the group consisting of hydrogen, halo, cyano,
Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Ci-C6haloalkyl and C1-C6alkyl-S(0) p- . More
preferably, R is selected from the group consisting of hydrogen, halo and C -C lkyl,
most preferred being hydrogen or methyl.
R4 is preferably hydrogen.
R3 and R4 are both preferably hydrogen.
R5 is preferably selected from the group consisting of hydroxyl, halo, Ci-
C6alkyl, Ci-Cecycloalkyl, Ci-Cehaloalkyl, Ci-Cealkenyl, Ci-Cealkynyl, C -C alkoxy,
C -C alkoxyCi-Csalkyl, Ci-C alkoxy-C2-C6alkoxy, C -C alkoxy-C2-C6alkoxy-Ci-
C3alkyl, Ci-C6 haloalkoxy, Ci-C6 haloalkoxy-Ci-C 3alkyl, Ci-C6alkyl-S(0)p-, Ci-
C6haloalkyl-S(0) p-, aryl, aryloxy, heterocyclyl, heterocyclyl-Ci-Qalkoxy-Ci-Qalkyl,
Ci-Qalkylamino-, Ci-Csdialkylamino-, Ci-C3 alkylamino-S(0) p-, Ci-C3 alkylamino-
S(0) p-C1-C3alkyl-, Ci-C3 dialkylamino-S(0) p-, Ci-C3 dialkylamino-S(0) p-C1-C3alkyl-,
Ci-Csalkylaminocarbonyl-, Ci-Csdialkylaminocarbonyl-, Ci-C3
dialkylaminocarbonyl-Ci-Csalkyl-, Ci-Qalkylcarbonylamino-, Ci-C3 alkyl-S(0) p-
amino-, cyano and nitro, wherein said heterocyclyls are five or six membered
heterocyclyls containing from one to three heteroatoms each independently selected
from the group consisting of oxygen, nitrogen and sulphur, and wherein the aryl or
heterocyclyl components may be optionally substituted by one or more substituents
selected from the group consisting of halo, Ci-C3alkyl, CrCshaloalkyl, Ci-C3 alkoxy,
Ci-C3 haloalkoxy, cyano and nitro.
The terms "aryl" and "heterocyclyl" are further defined above. However, in
the context of R5 phenyl, benzyl, isoxazolinyl, pyrimidinyl, morpholinyl, furyl and
thiophenyl are particularly preferred.
More preferably, R5 is selected from the group consisting of chloro, fluoro,
methyl, trifluoromethyl, 2-fluoroethyl-, methoxyethoxymethyl-,
trifluoromethoxymethyl-, methylS(0) p-, aryl, isoxazolinyl, morpholinyl, methyl-
S(0) p-dimethylamino-, cyano and nitro, wherein the aryl or heterocyclyl components
may be optionally substituted by one or more substituents selected from the group
consisting of chloro, methyl and trifluoromethyl. Most preferably, R5 is selected from
the group consisting of methyl, methyl-S(0) 2- and trifluoromethyl.
Preferably, R6 is selected from the group consisting of hydrogen, halogen, Ci-
Cealkyl, Ci-C6haloalkyl, Ci-C6alkyl-S(0) p-, Ci-C6cycloalkyl, C2-C6alkenyl, C2-
Cehaloalkenyl, C2-C6alkynyl, Ci-C6 alkoxy-, Ci-Cehaloalkoxy, C2-C6alkenyloxy-, C3-
CecycloalkylCi-Cs-alkyl-, Ci-C6 alkoxyCi-C 3alkyl-, Ci-C6 alkoxy-C2-C6alkoxy-, nitro
and phenyl wherein the phenyl may be optionally substituted by one or more
substituents selected from the group consisting of halo, Ci-C3alkyl, Ci-Cshaloalkyl,
Ci-C3 alkoxy, Ci-C3 haloalkoxy, C1-C6alkyl-S(0) p-, phenyl, cyano and nitro. More
preferably, R6 is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl,
Ci-Cehaloalkyl, Ci-C6alkyl-S(0) p-, C2-C6alkenyl and C2-C6alkynyl.
Preferably, R is selected from the group consisting of hydrogen, halogen and
Ci-C3 alkyl-.
Preferably, R is selected from the group consisting of hydrogen, halogen and
Ci-C3 alkyl-.
Preferably, R9 is selected from the group consisting of hydrogen, halogen, Ci-
C6alkyl, Ci-Cehaloalkyl, C1-C6alkyl-S(0) p-, Ci-C6cycloalkyl, C2-C6alkenyl, C2-
Cehaloalkenyl, C2-C6alkynyl, Ci-C6 alkoxy-, Ci-Cehaloalkoxy, C2-C6alkenyloxy-, C3-
C6cycloalkylCi-C 3-alkyl-, Ci-C6 alkoxyCi-C 3alkyl-, Ci-C6 alkoxy-C2-C6alkoxy-, nitro
and phenyl wherein the phenyl may be optionally substituted by one or more
substituents selected from the group consisting of halo, Ci-C3alkyl, Ci-C3haloalkyl,
Ci-C3 alkoxy, Ci-C3 haloalkoxy, C1-C6alkyl-S(0) p-, phenyl, cyano and nitro. More
preferably, R9 is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl,
Ci-Cehaloalkyl, Ci-C6alkyl-S(0) p-, C2-C6alkenyl and C2-C6alkynyl.
Compounds of Formula I may contain asymmetric centres and may be present
as a single enantiomer, pairs of enantiomers in any proportion or, where more than
one asymmetric centre are present, contain diastereoisomers in all possible ratios.
Typically one of the enantiomers has enhanced biological activity compared to the
other possibilities.
Similarly, where there are disubstituted alkenes, these may be present in E or
Z form or as mixtures of both in any proportion.
Furthermore, compounds of Formula I may be in equilibrium with alternative
hydroxyl tautomeric forms. It should be appreciated that all tautomeric forms (single
tautomer or mixtures thereof), racemic mixtures and single isomers are included
within the scope of the present invention.
The present invention also includes agronomically acceptable salts that the
compounds of Formula I may form with amines (for example ammonia,
dimethylamine and triethylamine), alkali metal and alkaline earth metal bases or
quaternary ammonium bases. Among the alkali metal and alkaline earth metal
hydroxides, oxides, alkoxides and hydrogen carbonates and carbonates used as salt
formers, emphasis is to be given to the hydroxides, alkoxides, oxides and carbonates
of lithium, sodium, potassium, magnesium and calcium, but especially those of
sodium, magnesium and calcium. The corresponding trimethylsulfonium salt may also
be used.
The compounds of Formula (I) according to the invention can be used as
herbicides by themselves, but they are generally formulated into herbicidal
compositions using formulation adjuvants, such as carriers, solvents and surfaceactive
agents (SFAs). Thus, the present invention further provides a herbicidal
composition comprising a herbicidal compound according to any one of the previous
claims and an agriculturally acceptable formulation adjuvant. The composition can be
in the form of concentrates which are diluted prior to use, although ready-to-use
compositions can also be made. The final dilution is usually made with water, but can
be made instead of, or in addition to, water, with, for example, liquid fertilisers,
micronutrients, biological organisms, oil or solvents.
The herbicidal compositions generally comprise from 0.1 to 99 % by weight,
especially from 0.1 to 95 %by weight, compounds of Formula I and from 1 to 99.9 %
by weight of a formulation adjuvant which preferably includes from 0 to 25 % by
weight of a surface-active substance.
The compositions can be chosen from a number of formulation types, many of
which are known from the Manual on Development and Use of FAO Specifications
for Plant Protection Products, 5th Edition, 1999. These include dustable powders
(DP), soluble powders (SP), water soluble granules (SG), water dispersible granules
(WG), wettable powders (WP), granules (GR) (slow or fast release), soluble
concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL),
emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in
water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates
(SC), aerosols, capsule suspensions (CS) and seed treatment formulations. The
formulation type chosen in any instance will depend upon the particular purpose
envisaged and the physical, chemical and biological properties of the compound of
Formula (I).
Dustable powders (DP) may be prepared by mixing a compound of Formula (I)
with one or more solid diluents (for example natural clays, kaolin, pyrophyllite,
bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium
phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other
organic and inorganic solid carriers) and mechanically grinding the mixture to a fine
powder.
Soluble powders (SP) may be prepared by mixing a compound of Formula (I)
with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium
carbonate or magnesium sulphate) or one or more water-soluble organic solids (such
as a polysaccharide) and, optionally, one or more wetting agents, one or more
dispersing agents or a mixture of said agents to improve water dispersibility/solubility.
The mixture is then ground to a fine powder. Similar compositions may also be
granulated to form water soluble granules (SG).
Wettable powders (WP) may be prepared by mixing a compound of Formula
(I) with one or more solid diluents or carriers, one or more wetting agents and,
preferably, one or more dispersing agents and, optionally, one or more suspending
agents to facilitate the dispersion in liquids. The mixture is then ground to a fine
powder. Similar compositions may also be granulated to form water dispersible
granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound
of Formula (I) and one or more powdered solid diluents or carriers, or from pr e
formed blank granules by absorbing a compound of Formula (I) (or a solution thereof,
in a suitable agent) in a porous granular material (such as pumice, attapulgite clays,
fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a
compound of Formula (I) (or a solution thereof, in a suitable agent) on to a hard core
material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and
drying if necessary. Agents which are commonly used to aid absorption or adsorption
include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers,
ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols,
dextrins, sugars and vegetable oils). One or more other additives may also be
included in granules (for example an emulsifying agent, wetting agent or dispersing
agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of
Formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether.
These solutions may contain a surface active agent (for example to improve water
dilution or prevent crystallisation in a spray tank).
Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be
prepared by dissolving a compound of Formula (I) in an organic solvent (optionally
containing one or more wetting agents, one or more emulsifying agents or a mixture
of said agents). Suitable organic solvents for use in ECs include aromatic
hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by
SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered
Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols
(such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as Nmethylpyrrolidone
or N-octylpyrrolidone), dimethyl amides of fatty acids (such as C -
Cio fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may
spontaneously emulsify on addition to water, to produce an emulsion with sufficient
stability to allow spray application through appropriate equipment.
Preparation of an EW involves obtaining a compound of Formula (I) either as
a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable
temperature, typically below 70°C) or in solution (by dissolving it in an appropriate
solvent) and then emulsifying the resultant liquid or solution into water containing
one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for
use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes),
aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate
organic solvents which have a low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one
or more solvents with one or more SFAs, to produce spontaneously a
thermodynamically stable isotropic liquid formulation. A compound of Formula (I) is
present initially in either the water or the solvent/SFA blend. Suitable solvents for use
in MEs include those hereinbefore described for use in in ECs or in EWs. An ME
may be either an oil-in-water or a water-in-oil system (which system is present may
be determined by conductivity measurements) and may be suitable for mixing watersoluble
and oil-soluble pesticides in the same formulation. An ME is suitable for
dilution into water, either remaining as a microemulsion or forming a conventional
oil-in-water emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous
suspensions of finely divided insoluble solid particles of a compound of Formula (I).
SCs may be prepared by ball or bead milling the solid compound of Formula (I) in a
suitable medium, optionally with one or more dispersing agents, to produce a fine
particle suspension of the compound. One or more wetting agents may be included in
the composition and a suspending agent may be included to reduce the rate at which
the particles settle. Alternatively, a compound of Formula (I) may be dry milled and
added to water, containing agents hereinbefore described, to produce the desired end
product.
Aerosol formulations comprise a compound of Formula (I) and a suitable
propellant (for example n-butane). A compound of Formula (I) may also be dissolved
or dispersed in a suitable medium (for example water or a water miscible liquid, such
as n-propanol) to provide compositions for use in non-pressurised, hand-actuated
spray pumps.
Capsule suspensions (CS) may be prepared in a manner similar to the
preparation of EW formulations but with an additional polymerisation stage such that
an aqueous dispersion of oil droplets is obtained, in which each oil droplet is
encapsulated by a polymeric shell and contains a compound of Formula (I) and,
optionally, a carrier or diluent therefor. The polymeric shell may be produced by
either an interfacial polycondensation reaction or by a coacervation procedure. The
compositions may provide for controlled release of the compound of Formula (I) and
they may be used for seed treatment. A compound of Formula (I) may also be
formulated in a biodegradable polymeric matrix to provide a slow, controlled release
of the compound.
The composition may include one or more additives to improve the biological
performance of the composition, for example by improving wetting, retention or
distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of
a compound of Formula (I). Such additives include surface active agents (SFAs),
spray additives based on oils, for example certain mineral oils or natural plant oils
(such as soy bean and rape seed oil), and blends of these with other bio-enhancing
adjuvants (ingredients which may aid or modify the action of a compound of Formula
(I)).
Wetting agents, dispersing agents and emulsifying agents may be SFAs of the
cationic, anionic, amphoteric or non-ionic type.
Suitable SFAs of the cationic type include quaternary ammonium compounds
(for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of
aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of
sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate,
calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of
sodium di-z propyl- and tri-zsopropyl-naphthalene sulphonates), ether sulphates,
alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates
(for example sodium laureth-3-carboxylate), phosphate esters (products from the
reaction between one or more fatty alcohols and phosphoric acid (predominately
mono-esters) or phosphorus pentoxide (predominately di-esters), for example the
reaction between lauryl alcohol and tetraphosphoric acid; additionally these products
may be ethoxylated), sulphosuccinamates, paraffin or olefme sulphonates, taurates
and lignosulphonates.
Suitable SFAs of the amphoteric type include betaines, propionates and
glycinates.
Suitable SFAs of the non-ionic type include condensation products of alkylene
oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof,
with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such
as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain
fatty acids or hexitol anhydrides; condensation products of said partial esters with
ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide);
alkanolamides; simple esters (for example fatty acid polyethylene glycol esters);
amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
Suitable suspending agents include hydrophilic colloids (such as
polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and
swelling clays (such as bentonite or attapulgite).
The composition of the present may further comprise at least one additional
pesticide. For example, the compounds according to the invention can also be used in
combination with other herbicides or plant growth regulators. In a preferred
embodiment the additional pesticide is a herbicide and/or herbicide safener. Examples
of such mixtures are (in which T represents a compound of Formula I). I + acetochlor,
I + acifluorfen, I + acifluorfen-sodium, I + aclonifen, I + acrolein, I + alachlor, I +
alloxydim, I + ametryn, I + amicarbazone, I + amidosulfuron, I + aminopyralid, I +
amitrole, I + anilofos, I + asulam, I + atrazine, I + azafenidin, I + azimsulfuron, I +
BCPC, I + beflubutamid, I + benazolin, I + bencarbazone, I + benfluralin, I +
benfuresate, I + bensulfuron, I + bensulfuron-methyl, I + bensulide, I + bentazone, I +
benzfendizone, I + benzobicyclon, I + benzofenap, I + bicyclopyrone, I + bifenox, I +
bilanafos, I + bispyribac, I + bispyribac-sodium, I + borax, I + bromacil, I +
bromobutide, I + bromoxynil, I + butachlor, I + butamifos, I + butralin, I +
butroxydim, I + butylate, I + cacodylic acid, I + calcium chlorate, I + cafenstrole, I +
carbetamide, I + carfentrazone, I + carfentrazone-ethyl, I + chlorflurenol, I +
chlorflurenol-methyl, I + chloridazon, I + chlorimuron, I + chlorimuron-ethyl, I +
chloroacetic acid, I + chlorotoluron, I + chlorpropham, I + chlorsulfuron, I + chlorthal,
I + chlorthal-dimethyl, I + cinidon-ethyl, I + cinmethylin, I + cinosulfuron, I +
cisanilide, I + clethodim, I + clodinafop, I + clodinafop-propargyl, I + clomazone, I +
clomeprop, I + clopyralid, I + cloransulam, I + cloransulam-methyl, I + cyanazine, I +
cycloate, I + cyclosulfamuron, I + cycloxydim, I + cyhalofop, I + cyhalofop-butyl,, I
+ 2,4-D, I + daimuron, I + dalapon, I + dazomet, I + 2,4-DB, I + I + desmedipham, I +
dicamba, I + dichlobenil, I + dichlorprop, I + dichlorprop-P, I + diclofop, I + diclofopmethyl,
I + diclosulam, I + difenzoquat, I + difenzoquat metilsulfate, I + diflufenican,
I + diflufenzopyr, I + dimefuron, I + dimepiperate, I + dimethachlor, I +
dimethametryn, I + dimethenamid, I + dimethenamid-P, I + dimethipin, I +
dimethylarsinic acid, I + dinitramine, I + dinoterb, I + diphenamid, I + dipropetryn, I
+ diquat, I + diquat dibromide, I + dithiopyr, I + diuron, I + endothal, I + EPTC, I +
esprocarb, I + ethalfluralin, I + ethametsulfuron, I + ethametsulfuron-methyl, I +
ethephon, I + ethofumesate, I + ethoxyfen, I + ethoxysulfuron, I + etobenzanid, I +
fenoxaprop-P, I + fenoxaprop-P-ethyl, I + fentrazamide, I + ferrous sulfate, I +
flamprop-M, I + flazasulfuron, I + florasulam, I + fluazifop, I + fluazifop-butyl, I +
fluazifop-P, I + fluazifop-P-butyl, I + fluazolate, I + flucarbazone, I + flucarbazonesodium,
I + flucetosulfuron, I + fluchloralin, I + flufenacet, I + flufenpyr, I +
flufenpyr-ethyl, I + flumetralin, I + flumetsulam, I + flumiclorac, I + flumicloracpentyl,
I + flumioxazin, I + flumipropin, I + fluometuron, I + fluoroglycofen, I +
fluoroglycofen-ethyl, I + fluoxaprop, I + flupoxam, I + flupropacil, I + flupropanate, I
+ flupyrsulfuron, I + flupyrsulfuron-methyl-sodium, I + flurenol, I + fluridone, I +
flurochloridone, I + fluroxypyr, I + flurtamone, I + fluthiacet, I + fluthiacet-methyl, I
+ fomesafen, I + foramsulfuron, I + fosamine, I + glufosinate, I + glufosinateammonium,
I + glyphosate, I + halosulfuron, I + halosulfuron-methyl, I + haloxyfop, I
+ haloxyfop-P, I + hexazinone, I + imazamethabenz, I + imazamethabenz-methyl, I +
imazamox, I + imazapic, I + imazapyr, I + imazaquin, I + imazethapyr, I +
imazosulfuron, I + indanofan, I + indaziflam, I + iodomethane, I + iodosulfuron, I +
iodosulfuron-methyl-sodium, I + ioxynil, I + isoproturon, I + isouron, I + isoxaben, I
+ isoxachlortole, I + isoxaflutole, I + isoxapyrifop, I + karbutilate, I + lactofen, I +
lenacil, I + linuron, I + mecoprop, I + mecoprop-P, I + mefenacet, I + mefluidide, I +
mesosulfuron, I + mesosulfuron-methyl, I + mesotrione, I + metam, I + metamifop, I
+ metamitron, I + metazachlor, I + methabenzthiazuron, I + methazole, I +
methylarsonic acid, I + methyldymron, I + methyl isothiocyanate, I + metolachlor, I +
S-metolachlor, I + metosulam, I + metoxuron, I + metribuzin, I + metsulfuron, I +
metsulfuron-methyl, I + molinate, I + monolinuron, I + naproanilide, I + napropamide,
I + naptalam, I + neburon, I + nicosulfuron, I + n-methyl glyphosate, I + nonanoic
acid, I + norflurazon, I + oleic acid (fatty acids), I + orbencarb, I + orthosulfamuron, I
+ oryzalin, I + oxadiargyl, I + oxadiazon, I + oxasulfuron, I + oxaziclomefone, I +
oxyfluorfen, I + paraquat, I + paraquat dichloride, I + pebulate, I + pendimethalin, I +
penoxsulam, I + pentachlorophenol, I + pentanochlor, I + pentoxazone, I +
pethoxamid, I + phenmedipham, I + picloram, I + picolinafen, I + pinoxaden, I +
piperophos, I + pretilachlor, I + primisulfuron, I + primisulfuron-methyl, I +
prodiamine, I + profoxydim, I + prohexadione-calcium, I + prometon, I + prometryn,
I + propachlor, I + propanil, I + propaquizafop, I + propazine, I + propham, I +
propisochlor, I + propoxycarbazone, I + propoxycarbazone-sodium, I + propyzamide,
I + prosulfocarb, I + prosulfuron, I + pyraclonil, I + pyraflufen, I + pyraflufen-ethyl, I
+ pyrasulfotole, I + pyrazolynate, I + pyrazosulfuron, I + pyrazosulfuron-ethyl, I +
pyrazoxyfen, I + pyribenzoxim, I + pyributicarb, I + pyridafol, I + pyridate, I +
pyriftalid, I + pyriminobac, I + pyriminobac-methyl, I + pyrimisulfan, I + pyrithiobac,
I + pyrithiobac-sodium, I + pyroxasulfone, I + pyroxsulam, I + quinclorac, I +
quinmerac, I + quinoclamine, I + quizalofop, I + quizalofop-P, I + rimsulfuron, I +
saflufenacil, I + sethoxydim, I + siduron, I + simazine, I + simetryn, I + sodium
chlorate, I + sulcotrione, I + sulfentrazone, I + sulfometuron, I + sulfometuron-methyl,
I + sulfosate, I + sulfosulfuron, I + sulfuric acid, I + tebuthiuron, I + tefuryltrione, I +
tembotrione, I + tepraloxydim, I + terbacil, I + terbumeton, I + terbuthylazine, I +
terbutryn, I + thenylchlor, I + thiazopyr, I + thifensulfuron, I + thiencarbazone, I +
thifensulfuron-methyl, I + thiobencarb, I + topramezone, I + tralkoxydim, I + tri-allate,
I + triasulfuron, I + triaziflam, I + tribenuron, I + tribenuron-methyl, I + triclopyr, I +
trietazine, I + trifloxysulfuron, I + trifloxysulfuron-sodium, I + trifluralin, I +
triflusulfuron, I + triflusulfuron-methyl, I + trihydroxytriazine, I + trinexapac-ethyl, I
+ tritosulfuron, I + [3-[2-chloro-4-fluoro-5-(l-methyl-6-trifluoromethyl-2,4-dioxol,
2,3,4-tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]acetic acid ethyl ester (CAS
RN 353292-31-6). The compounds of the present invention may also be combined
with herbicidal compounds disclosed in WO06/024820 and/or WO07/096576.
The mixing partners of the compound of Formula I may also be in the form of
esters or salts, as mentioned e.g. in The Pesticide Manual, Fourteenth Edition, British
Crop Protection Council, 2006.
The compound of Formula I can also be used in mixtures with other
agrochemicals such as fungicides, nematicides or insecticides, examples of which are
given in The Pesticide Manual.
The mixing ratio of the compound of Formula I to the mixing partner is
preferably from 1: 100 to 1000:1.
The mixtures can advantageously b e used in the above-mentioned
formulations (in which case "active ingredient" relates to the respective mixture of
compound of Formula I with the mixing partner).
The compounds of Formula I according to the invention can also be used in
combination with one or more safeners. Likewise, mixtures of a compound of
Formula I according to the invention with one or more further herbicides can also be
used in combination with one or more safeners. The safeners can be AD 67 (MON
4660), benoxacor, cloquintocet-mexyl, cyprosulfamide (CAS RN 22 1667-31-8),
dichlormid, fenchlorazole-ethyl, fenclorim, fluxofenim, furilazole and the
corresponding R isomer, isoxadifen-ethyl, mefenpyr-diethyl, oxabetrinil, N-isopropyl-
4-(2-methoxy-benzoylsulfamoyl)-benzamide (CAS RN 221668-34-4). Other
possibilities include safener compounds disclosed in, for example, EP0365484 e.g N-
(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide.
Particularly preferred are mixtures of a compound of Formula I with cyprosulfamide,
isoxadifen-ethyl, cloquintocet-mexyl and/or N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)
amino]benzenesulfonamide.
The safeners of the compound of Formula I may also be in the form of esters
or salts, as mentioned e.g. in The Pesticide Manual, 14th Edition (BCPC), 2006. The
reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium,
magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium
salt thereof as disclosed in WO 02/34048, and the reference to
fenchlorazole-ethyl also applies to fenchlorazole, etc.
Preferably the mixing ratio of compound of Formula I to safener is from 100:1
to 1:10, especially from 20: 1 to 1:1.
The mixtures can advantageously be used in the above-mentioned
formulations (in which case "active ingredient" relates to the respective mixture of
compound of Formula I with the safener).
The present invention still further provides a method of selectively controlling
weeds at a locus comprising crop plants and weeds, wherein the method comprises
application to the locus of a weed controlling amount of a composition according to
the present invention. 'Controlling' means killing, reducing or retarding growth or
preventing or reducing germination. Generally the plants to be controlled are
unwanted plants (weeds). 'Locus' means the area in which the plants are growing or
will grow.
The rates of application of compounds of Formula I may vary within wide
limits and depend on the nature of the soil, the method of application (pre- or postemergence;
seed dressing; application to the seed furrow; no tillage application etc.),
the crop plant, the weed(s) to be controlled, the prevailing climatic conditions, and
other factors governed by the method of application, the time of application and the
target crop. The compounds of Formula I according to the invention are generally
applied at a rate of from 10 to 2000 g/ha, especially from 50 to 1000 g/ha.
The application is generally made by spraying the composition, typically by
tractor mounted sprayer for large areas, but other methods such as dusting (for
powders), drip or drench can also be used.
Useful plants in which the composition according to the invention can be used
include crops such as cereals, for example barley and wheat, cotton, oilseed rape,
sunflower, maize, rice, soybeans, sugar beet, sugar cane and turf. Maize is particularly
preferred.
Crop plants can also include trees, such as fruit trees, palm trees, coconut trees
or other nuts. Also included are vines such as grapes, fruit bushes, fruit plants and
vegetables.
Crops are to be understood as also including those crops which have been
rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-,
PPO-, ACCase- and HPPD-inhibitors) by conventional methods of breeding or by
genetic engineering. An example of a crop that has been rendered tolerant to
imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield®
summer rape (canola). Examples of crops that have been rendered tolerant to
herbicides by genetic engineering methods include e.g. glyphosate- and glufosinateresistant
maize varieties commercially available under the trade names
RoundupReady® and LibertyLink®.
In a preferred embodiment the crop plant is rendered tolerant to HPPDinhibitors
via genetic engineering. Methods of rending crop plants tolerant to HPPDinhibitors
are known, for example from WO0246387. Thus in an even more preferred
embodiment the crop plant is transgenic in respect of a polynucleotide comprising a
DNA sequence which encodes an HPPD-inhibitor resistant HPPD enzyme derived
from a bacterium, more particularly from Pseudomonas fluorescens or Shewanella
colwelliana, or from a plant, more particularly, derived from a monocot plant or, yet
more particularly, from a barley, maize, wheat, rice, Brachiaria, Chenchrus, Lolium,
Festuca, Setaria, Eleusine, Sorghum or Avena species.
Crops are also to be understood as being those which have been rendered
resistant to harmful insects by genetic engineering methods, for example Bt maize
(resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also
Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize
hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally
by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic plants able to
synthesise such toxins, are described in EP-A-451 878, EP-A-374 753, WO 93/07278,
WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants
comprising one or more genes that code for an insecticidal resistance and express one
or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B®
(cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.
Plant crops or seed material thereof can be both resistant to herbicides and, at the
same time, resistant to insect feeding ("stacked" transgenic events). For example, seed
can have the ability to express an insecticidal Cry3 protein while at the same time
being tolerant to glyphosate.
Crops are also to be understood to include those which are obtained by
conventional methods of breeding or genetic engineering and contain so-called output
traits (e.g. improved storage stability, higher nutritional value and improved flavour).
Other useful plants include turf grass for example in golf-courses, lawns, parks
and roadsides, or grown commercially for sod, and ornamental plants such as flowers
or bushes.
The compositions can be used to control unwanted plants (collectively,
'weeds'). The weeds to be controlled may be both monocotyledonous species, for
example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus,
Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus,
Setaria and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus,
Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium,
Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium. Weeds can also
include plants which may be considered crop plants but which are growing outside a
crop area ('escapes'), or which grow from seed left over from a previous planting of a
different crop ('volunteers'). Such volunteers or escapes may be tolerant to certain
other herbicides.
The compounds of the present invention can be prepared using the following methods.
Compounds of formula (la) may be prepared from compounds of formula (I) as
shown in reaction scheme 1.
Reaction scheme 1
(I) (la)
Compounds of formula (la), in which R4 is hydrogen, may be prepared from
compounds of formula I in which R4 is lower alkyl, for example methyl, by heating
with morpholine (Nagashima, Hiromu et al. Heterocycles, 26(1), 1-4; 1987);
Compounds of formula (I) may be prepared from compounds of formula (2) as shown
in reaction scheme 2.
Reaction scheme 2
(2)
Compounds of formula (I) in which R4 is lower alkyl, for example methyl, and in
which R is aryl or heteroaryl, may be prepared from compounds of formula (2) by
reaction with a suitable metal or metalloid derivative Y-M (e.g. a boronic acid or ester,
a trialkyltin derivative, a zinc derivative or a Grignard reagent) in the presence of a
suitable base (e.g. an inorganic base, such as potassium phosphate or caesium
fluoride), a metal source (e.g. a palladium source, such as Pd (OAc)2) and optionally
a ligand for the metal (e.g. a phosphine ligand) in a suitable solvent (e.g. a single
solvent, such as dimethylformamide, or a mixed solvent system such as a mixture of
dimethoxyethane and water or toluene and water). The metal catalyst and ligands may
also be added as a single, pre-formed complex (e.g. a palladium/phosphine complex,
such as bis(triphenylphosphine)palladium dichloride or [I , -
bis(diphenylphosphino)ferrocene] palladium dichloride dichloromethane adduct).
Compounds of formula (2) may be prepared from compounds of formula (3) as shown
in reaction scheme 3.
Reaction scheme 3
(3) (2)
Compounds of formula (2) in which R4 is lower alkyl, for example methyl, may be
prepared from compounds of formula (3) by reaction with a suitable metal alkoxide,
for example sodium methoxide, in a suitable solvent such as dioxane;
Compounds of formula (3) may be prepared from compounds of formula (4) as shown
in reaction scheme 4.
Reaction scheme 4
(4) (3)
Compounds of formula (3) may be prepared from the compound of formula (4) (4,5-
dichloro-lH-pyridazin-6-one - available commercially) by reaction with a suitable
alkylating agent R^-X, where X is a leaving group such as halide, for example methyl
iodide, in the presence of a suitable base (e.g. an inorganic base, such as potassium
carbonate) in a suitable solvent such as N,N-dimethylformamide.
Alternatively, compounds of formula (1) may be prepared from compounds of
formula (5) as shown in reaction scheme 5.
Reaction scheme 5
(5) (1 )
Compounds of formula (1) in which R4 is lower alkyl, for example methyl, and in
which R is aryl or heteroaryl, may be prepared from compounds of formula (5) by
reaction with a suitable alkylating agent R -X in the presence of a suitable base (e.g.
an inorganic base, such as potassium phosphate or caesium fluoride), a metal source
(e.g. a palladium source, such as Pd (OAc)2) and optionally a ligand for the metal (e.g.
a phosphine ligand) in a suitable solvent (e.g. a single solvent, such as
dimethylformamide, or a mixed solvent system such as a mixture of dimethoxyethane
and water or toluene and water). The metal catalyst and ligands may also be added as
a single, pre-formed complex (e.g. a palladium/phosphine complex, such as
bis(triphenylphosphine)palladium dichloride or [I , -
bis(diphenylphosphino)ferrocene] palladium dichloride dichloromethane adduct).
Compounds of formula (5) may be prepared from compounds of formula (6) as shown
in reaction scheme 6.
(5)
(6)
Compounds of formula (5) in which R4 is lower alkyl, for example methyl, may be
prepared from compounds of formula (6) by reaction with a suitable boronic acid or
ester for example bis(pinacolato)diboron in the presence of a suitable base (e.g. an
inorganic base, such as potassium phosphate or caesium fluoride), a metal source (e.g.
a palladium source, such as Pd2(dba)3 or Pd(OAc)2) and optionally a ligand for the
metal (e.g. a phosphine ligand such as tricyclohexylphosphine) in a suitable solvent
(e.g. a single solvent, such as dioxane, or a mixed solvent system such as a mixture of
dimethoxy ethane and water or toluene and water). The metal catalyst and ligands may
also be added as a single, pre-formed complex (e.g. a palladium/phosphine complex,
such as bis(triphenylphosphine)palladium dichloride or [1,1'-
bis(diphenylphosphino)ferrocene] palladium dichloride dichloromethane adduct).
Analogous reactions are known in the art e.g. Tetrahedron, 57(49), 9813-9816; 2001
Alternatively, compounds of formula (lc) in which R is a nitrogen-linked heterocycle,
for example indole or pyridone, may be prepared from compounds of formula (3) or
(4) as shown in reaction scheme 7.
(1c)
Compounds of formula (7) and (lb) may be prepared from compounds of formula (3)
and (4) respectively by reaction with a nitrogen-containing heterocycle such as an
indole or pyridone in the presence of a suitable base such in a suitable solvent.
Compounds of formula (lb) in which R4 is lower alkyl, for example methyl, may be
prepared from compounds of formula (7) as described in reaction scheme 3, and
compounds of formula (lc) may be prepared from compounds of formula (lb) as
described in reaction scheme 1. Alternatively compounds of formula (lc) may be
prepared directly from compounds of formula (7) by reaction with a suitable metal
hydroxide such as potassium hydroxide, in a suitable solvent such as aqueous
methanol.
Compounds of formula (1) may also be prepared from compounds of formula (8) as
shown in reaction scheme 8.
Reaction scheme 8
Compounds of formula (1) in which R4 is lower alkyl, for example methyl, may be
prepared from compounds of formula (8) by reaction with a suitable alcohol R^H, in
a suitable solvent such as tetrahydrofuran, in the presence of a suitable additive such
as triphenylphosphine and an azodicarboxylate such as diethyl azodicarboxylate
(DEAD) or diisopropyl azodicarboxylate (DIAD).
Compounds of formula (8) may be prepared from compounds of formula (Id) as
shown in reaction scheme 9.
Reaction scheme 9.
( 1d)
Compounds of formula (8) may be prepared from compounds of formula (Id), in
which R1 is a removable protecting group such as /?-methoxybenzyl, by reaction with
a suitable oxidising agent such as cerium ammonium nitrate in a suitable solvent such
as aqueous acetonitrile.
Compounds of formula (Id), in which R1 is a removable protecting group such as p -
methoxybenzyl , may be prepared from commercially available compound (4) (4,5-
dichloro-lH-pyridazin-6-one ) in a method analogous to that in schemes 2-4.
Compounds of formula (3) may also be prepared from compounds (9) as shown in
reaction scheme 10
Reaction scheme 10
Compounds of formula (3), in which R is for example alkyl, alkenyl or alkynyl, may
also be prepared from compounds (9), in which X is a suitable leaving group such as
bromide, by reaction with a suitable metal or metalloid derivative Y-M (e.g. a boronic
acid or ester, a trialkyltin derivative, a zinc derivative or a Grignard reagent) in the
presence of a suitable base (e.g. an inorganic base, such as potassium phosphate or
caesium fluoride), a metal source (e.g. a palladium source, such as Pd (OAc)2) and
optionally a ligand for the metal (e.g. a phosphine ligand ) in a suitable solvent (e.g. a
single solvent, such as dioxane, or a mixed solvent system such as a mixture of
dimethoxyethane and water or toluene and water). The metal catalyst and ligands may
also be added as a single, pre-formed complex (e.g. a palladium/phosphine complex,
such as bis(triphenylphosphine)palladium dichloride or [I , -
bis(diphenylphosphino)ferrocene] palladium dichloride dichloromethane adduct).
Compounds of formula (9) can be prepared via known methods.
Compounds of formula (3) may also be prepared as shown in reaction scheme 11.
Reaction scheme 11
Compounds of formula (3) in which R is hydrogen may be prepared by reaction of
3,4-dichloro-2,5-furandione or 3,4-dibromo-2,5-furandione with a suitably protected
hydrazine in a suitable solvent such as aqueous hydrochloric acid.
Analogous reactions are known e.g. Angewandte Chemie (1965), 77(7), 282-90;
Synthetic Communications (2006), 36(18), 2719-2726
Compounds of formula (I) in which R is a C-linked pyridone may be prepared from
compounds of formula 2 as shown in scheme 12.
Reaction Scheme 12
Compounds of formula l h in which R4 is lower alkyl, for example methyl, may be
prepared from compounds of formula 2 by reaction with a suitable metal or metalloid
derivative of 2-methoxypyridine (e.g. a boronic acid or ester, a trialkyltin derivative, a
zinc derivative or a Grignard reagent) in the presence of a suitable base (e.g. an
inorganic base, such as potassium phosphate or caesium fluoride), a metal source (e.g.
a palladium source, such as Pd (OAc)2) and optionally a ligand for the metal (e.g. a
phosphine ligand) in a suitable solvent (e.g. a single solvent, such as
dimethylformamide, or a mixed solvent system such as a mixture of dimethoxyethane
and water or toluene and water). The metal catalyst and ligands may also be added as
a single, pre-formed complex (e.g. a palladium/phosphine complex, such as
bis(triphenylphosphine)palladium dichloride or [I , -
bis(diphenylphosphino)ferrocene] palladium dichloride dichloromethane adduct).
Compound l g may be prepared from compound l h by reaction with a dilute aqueous
acid such as hydrochloric acid, optionally with heating or reaction in the microwave,
analogous to known methods such as disclosed in Bioorganic & Medicinal
Chemistry Letters, 18(9), 2967-2971; 2008.
Compounds of formula I f may be prepared from compounds of formula l g by
reaction with a suitable aryl iodide, in the presence of copper iodide, a suitable base
such as potassium triphosphate, in the presence of a suitable catalyst such as
tetrabutylammonium chloride in a suitable solvent such as N,N-dimethylformamide,
optionally with heating or reaction in the microwave. Analogous reactions are known
e.g. Tet. Lett. 45 (2004) 4257-4260.
Compounds of formula l e may be prepared from compounds of Formula (lg) as
described in Reaction Scheme 1.
Reaction scheme 13
(laa)
(la)
Compounds of formula (laa) in which R4 is for example is alkylcarbonyl,
arylcarbonyl, alkoxycarbonyl, alkoxysulphonyl or arylsulphonyl may be prepared
from compounds of general formula (la) in which R4 is hydrogen by reaction with a
suitable halide such as acetyl chloride, methyl chloroformate, ethyl thiochloroformate
or p-toluenesulphonyl chloride, in the presence of a suitable base such as
triethylamine or pyridine, in the presence of a suitable solvent such as
dichloromethane or toluene.
Reaction Scheme 14
Compounds of Formula (li) in which R is a substituted pyrimidine, or Formula (11),
in which R is a substituted pyrimidinone may be prepared according to reaction
scheme 14. Compounds of Formula ( 11) may be prepared from compounds of
Formula 10 by reaction of the corresponding Grignard reagent with tributyltin
chloride in the presence of a suitable solvent such as tetrahydrofuran, the reaction
being cooled during addition of the reagents. Analogous reactions are known e.g J .
Org. Chem., 201 1, 76, 6670-6677 (Grignard formation), WO2010/59943 (p.32) and
Journal of Organometallic Chemistry, 1973, (63), 133 - 138.
Compounds of Formula (12) may be prepared from compounds of Formula ( 11) by
reaction with methyl (Z)-2-iodo-3-methoxy-prop-2-enoate in the presence of a
suitable base (e.g. an inorganic base, such as potassium phosphate or caesium
fluoride), a metal source (e.g. a palladium source, such as palladium (0)
tetrakis(triphenylphosphine)) and a catalyst such as copper iodide, optionally with
heating, according to analogous processes e.g. Angew. Chem. Int. Ed., 2004, 43,
1132-1 136.
Compounds of general Formula (lk) may be prepared from compounds of general
Formula (12) by reaction with a suitable amidine in the presence of a suitable metal
alkoxide, for example sodium methoxide, in a suitable solvent such as methanol, the
reaction mixture being heated.
Compounds of general Formula (lj) may be prepared from compounds of general
Formula (lk) by reaction with a suitable chlorinating reagent, such as phosphorus
oxychloride, optionally in the presence of a suitable solvent, according to procedures
known e.g. Journal of Organic Chemistry, 76(10), 4149-4153; 201 1.
Compounds of general Formulas (li) and (11) may be prepared from compounds of
general Formulas (lj) and (lk) respectively as described in Reaction Scheme 1
Examples
Examples of the synthesis of specific compounds of the present invention are
provided below.
Example 1.
5-[2-chloro-3-f4,5-dihvdroisoxazol-3-yl)-4-methylsulfonyl-phenyll-4-hydroxy-2-
propyl-pyridazin-3-one
A mixture of 5-[2-chloro-3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-phenyl]-4-
methoxy-2-propyl-pyridazin-3-one (692 mg, 1.62mmol) in morpholine (1.42 ml) was
heated to 100 °C for 1 h. The reaction mixture was cooled then dichloromethane
(20ml) and 2M hydrochloric acid (20ml) were added and the mixture stirred for 30
mins. The dichloromethane layer was separated then the aqueous layer extracted twice
with dichloromethane. The combined organic extracts were passed through a phase
separation cartridge then concentrated in vacuo. The crude product was dissolved in
ethyl acetate then precipitated with hexane, concentrated in vacuo and triturated with
acetonitrile to give the product as an off-white solid (224.6mg).
5-[2-chloro-3-f4,5-dihvdroisoxazol-3-yl)-4-methylsulfonyl-phenyll-4-methoxy-2-
propyl-pyridazin-3-one
A mixture of 5-chloro-4-methoxy-2-propyl-pyridazin-3-one (81 1 mg, 4mmol),
potassium acetate (589mg, 6mmol), bis(pinicolato)diboron (1.52g, 6mmol),
tris(dibenzylideneacetone)dipalladium(0) (148mg, 0.16mmol) and
tricyclohexylphosphine (180mg, 0.64mmol) in degassed dioxane (12ml) was heated at
150°C for 15 minutes under microwave irradiation. The mixture was allowed to cool
to room temperature then filtered through Celite, eluting with ethyl acetate. The
filtrate was evaporated under reduced pressure then used directly in the next step.
The crude boronate ester was dissolved in degassed dimethoxyethane (12ml); to the
mixture were added 3-(3-bromo-2-chloro-6-methylsulfonyl-phenyl)-4,5-
dihydroisoxazole (2.7 lg, 8mmol), caesium fluoride (2.43g, 16mmol) and [I ,G-
bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct
(260mg, 0.32mmol). The resulting mixture was heated at 150°C for 20 minutes under
microwave irradiation then allowed to cool to room temperature and filtered through
Celite, eluting with ethyl acetate. The filtrate was concentrated under reduced pressure
then purified by chromatography on silica eluting with 0-100% ethyl acetate in
isohexane to give the product as a brown oil (692mg).
8.06 (1H, d, J 8.1), 7.59 (1H, s), 7.56 (1H, d, J 8.1), 4.63 (3H, t, J 10.2), 4.19 (3H, s),
4.12 (2H, dd, J 7.3, 7.3), 3.47 (3H, t, J 10.2), 3.28 (3H, s), 1.90 (2H, m), 1.02 (3H, t, J
7.2)
5-chloro-4-methoxy-2-propyl-pyridazin-3-one
To a stirred solution of 4,5-dichloro-2 -propyl-pyridazin-3-one (7.3 lg, 35.3mmol)
in dioxane (150ml) was added a solution of sodium methoxide in methanol (25% wt
in methanol, 8.6ml, 38.8mmol) dropwise and the mixture stirred at room temperature
for 60 mins. Water (150ml) was added and the mixture extracted with diethyl ether (3
x 100ml). The combined organics were dried, filtered and concentrated in vacuo.
The crude product was purified by chromatography on silica eluting with ethyl
acetate/hexanes to give the desired product as a colourless oil (5.44g).
4,5-dichloro-2-propyl-pyridazin-3-one
To a stirred solution of 4,5-dichloro-lH-pyridazin-6-one (8.25g, 50mmol)
in N,N-dimethylformamide (25ml) at room temperature was added potassium
carbonate (1.2g, 60mmol) and 1-iodopropane (5.85ml, 60mmol). The mixture was
stirred at 70C for 2hrs then water (75 ml) was added and the mixture extracted with
dichloromethane (3 x 100ml). The combined organic extracts were dried, filtered and
concentrated in vacuo then partitioned between brine (200ml) and diethylether
(200ml). The organic layer was dried, filtered and concentrated in vacuo to give a
brown oil. The crude product was purified by chromatography on silica eluting with
ethyl acetate/hexanes to give the desired product as a colourless oil (7.3 lg).
7.78 (1H, s), 4.20-4.1 1 (2H, m), 1.90-1.74 (2H, m), 0.96 (3H, t, J 7.2)
Example 2
4-hvdroxy-2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyllpyridazin-3-
one
A mixture of 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (48mg, 0.132mmol) in morpholine (2ml)
was heated to 100 °C for 3 hours. The reaction was then allowed to cool to room
temperature and evaporated under reduced pressure. The resulting residue was
dissolved in ethyl acetate and washed with 2M hydrochloric acid. The organic layer
was then dried over sodium sulphate and evaporated. The resulting solid was
triturated with dichloromethane/hexane to give the desired product as a pale pink solid
(25 mg).
4-methoxy-2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyllpyridazin-3-
one
To a solution of 4-methoxy-2-methyl-5-[2-methylsulfanyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (90 mg. 0.27mmol) in acetic acid (4ml) was
added hydrogen peroxide (50% wt in water, 56mg, 0.82mmol) at room temperature.
The reaction mixture was slowly heated to 55°C and maintained at that temperature
overnight. The reaction mixture was diluted with dichloromethane and quenched with
sat. aq. sodium hydrogen carbonate and solid sodium hydrogen carbonate slowly
until the pH was -6-7. The organic layer was separated and the aqueous phase
extracted with dichloromethane. The combined organics were dried over sodium
sulphate and evaporated to give the desired product (78 mg) as a pale yellow oil. This
was used without further purification.
dH (CDC13) 8.46 (IH, d), 7.98 (IH, dd), 7.60 (IH, s), 7.46 (IH, d), 4.14 (3H, s), 3.85
(3H, s), 3.02 (3H, s)
4-methoxy-2-methyl-5-[2-methylsulfanyl-4-ftrifluoromethyl)phenyllpyridazin-3-
one
A mixture of 5-chloro-4-methoxy-2-methyl-pyridazin-3-one (100 mg, 0.573mmol),
potassium acetate (84mg, 0.86mmol), bis(pinacolato)diboron (218 mg, 0.86mmol),
tris(dibenzylideneacetone)dipalladium(0) (4%, 2 1 mg, 0.023mmol) and
tricyclohexylphosphine (16%, 26mg,0.092mmol) in degassed dioxane (2.5ml) was
heated at 150 °C for 15 min under microwave irradiation. The mixture was filtered
through celite, washing with ethyl acetate and the filtrate evaporated under reduced
pressure. The residue was dissolved in degassed 1,2-dimethoxyethane (2.5ml) and 1-
bromo-2-methylsulfanyl-4-(trifluoromethyl)benzene (233 mg, 0.86mmol), caesium
fluoride (348 mg, 2.29 mmol) and [l,l'-bis(diphenylphosphino)-
ferrocene]palladium(II)chloride, dichloromethane complex (8%, 38 mg, 0.046mmol)
were then added. The resulting mixture was heated at 160°C for 15 min under
microwave irradiation. The reaction mixture was filtered through celite, washing with
ethyl acetate. The filtrate was evaporated under reduced pressure and the residue
purified by chromatography on silica, eluting with 0-40% ethyl acetate in hexanes, to
give the desired product (190mg, containing some residual pinacol impurity) as a red
oil. This was used without further purification.
dH (CDC13) 7.52 (IH, s), 7.50 (IH, br s), 7.47 (IH, br d), 7.26 (IH, br d), 4.05 (3H, s),
3.84 (3H, s), 2.49 (3H, s)
5-chloro-4-methoxy-2-methyl-pyridazin-3-one
To a stirred solution of 4,5-dichloro-2-methyl-pyridazin-3-one (19.7 g, 110 mmol) in
1.4-dioxane (550ml) was added sodium methoxide (28.5 g, 132 mmol, 30.2 ml)
dropwise and the resulting mixture stirred at room temperature for lhr. The reaction
was quenched with water (~500ml) then extracted with diethyl ether (500ml then
250ml). The combined organics were dried, filtered and concentrated in vacuo to give
15.83 g of a white solid.
dH (CDC13) 7.68 (1H, s), 4.28 (3H, s), 3.75 (3H, s)
4.5-dichloro-2-methyl-pyridazin-3-one
To a stirred solution of 4,5-dichloro-lH-pyridazin-6-one (25.0 g, 152 mmol) in N,Ndimethylformamide
(152 ml) was added potassium carbonate (25.4 g, 182 mmol) and
iodomethane (25.8 g, 182 mmol, 11.3 ml). The resulting mixture was stirred at room
temperature overnight. The reaction mixture was then poured onto ice-water (300ml)
and the mixture stirred for 15 mins. The resulting precipitate was collected by
filtration, then dissolved in dichloromethane and passed through a phase separation
cartridge. The organics were concentrated in vacuo to give 19.7 g of a pale brown
solid.
1H NMR (400 MHz, Chloroform) d ppm 3.83 (s, 3 H) 7.77 (s, 1H)
Example 3
4-hvdroxy-2-methyl-5-[3-fm-tolyl)-2-oxo-4-ftrifluoromethyl)-lpyridyllpyridazin-
3-one
A mixture of 4-chloro-2-methyl-5-[3-(m-tolyl)-2-oxo-4-(trifluoromethyl)-lpyridyl]
pyridazin-3-one (74 mg, 0.19mmol) in aqueous potassium hydroxide (0.5M,
3ml, 0.606mmol) and methanol (2.5ml) was heated at 55 °C for 90 minutes.
Morpholine ( 1 ml) was added and reaction heated at 90°C for 2 hours. The reaction
mixture was concentrated under reduced pressure. 2M hydrochloric acid was then
carefully added to the residue with rapid stirring for 5-10 min. The resulting cream
precipitate was filtered, washed with 2M hydrochloric acid and water and then dried
in a vacuum oven at 55 °C overnight to give the desired product (37mg).
4-chloro-2-methyl-5-[3-fm-tolyl)-2-oxo-4-ftrifluoromethyl)-l-pyridyllpyridazin-
3-one
A mixture of 3-(m-tolyl)-4-(trifluoromethyl)-lH-pyridin-2-one (68mg, 0.269mmol),
4,5-dichloro-2-methyl-pyridazin-3-one (58 mg, 0.323mmol) and potassium carbonate
( 112 mg, 0.807mmol) in N,N-dimethylformamide (1ml) was heated in the microwave
at 150 °C for 25 min. The reaction mixture was then poured into 2M hydrochloric acid
and extracted with ethyl acetate. The organic extracts were combined, dried over
sodium sulphate and evaporated under reduced pressure. The crude mixture was
purified by chromatography on silica, eluting with ethyl acetate in hexanes to give the
desired product as a yellow oil (74 mg).
dH (CDC13) 7.84 (1H, s), 7.34-7.22 (3H, m), 7.1 1 (2H, m), 6.63 (1H, d), 3.88 (3H, s),
2.38 (3H, s)
3-fm-tolyl)-4-ftrifluoromethyl)-lH-pyridin-2-one
A mixture of 2-chloro-3-(m-tolyl)-4-(trifluoromethyl)pyridine (96mg, 0.353mmol)
and sodium hydroxide in dimethylsulphoxide (0.6ml) and water (0.6ml) was heated at
150 °C under microwave irradiation for 60 minutes. The liquid mixture was separated
from the glassy residue and acidified to pH 1 with 2M hydrochloric acid. The
resulting white precipitate was filtered, washed with a few drops of water and dried in
a vacuum oven at 55 °C overnight to give the product as a white solid (68 mg).
dH (CD30D) 7.62 (1H, d), 7.34-7.30 (1H, m), 7.25-7.23 (1H, m), 7.06 (1H, s), 7.02
(1H, d), 6.66 (1H, d), 2.40 (3H, s)
2-chloro-3-fm-tolyl)-4-ftrifluoromethyl)pyridine
A mixture o f 2-chloro-3-iodo-4-methyl-pyridine (200 mg, 0.652mmol), mtolylboronic
acid (132mg, 0.976mmol), tetrakis(triphenylphosphine) palladium(O)
(8%,60mg, 0.052mmol) and potassium carbonate (136 mg, 0.976mmol) in 1,2-
dimethoxyethane (2.8ml) was heated at 150 °C for 30 min under microwave
irradiation. The reaction mixture was poured into brine and extracted with ethyl
acetate. The organic extracts were dried over sodium sulphate and evaporated.
The crude mixture was purified by chromatography on silica, eluting with ethyl
acetate in hexanes, to give the product as a colourless oil (96 mg).
2-chloro-3-iodo-4-methyl-pyridine
n-Butyllithium (1.6M in hexanes, 13.3ml, 21.3mmol) was added dropwise to a
solution of diisopropylamine (33ml, 23.3mmol) in tetrahydrofuran (7 ml) at -70 °C
(internal temp) and the resulting mixture was stirred for 30 min. 2-Chloro-4-
trifluoromethyl-pyridine (2.5 ml, 3.52 g, 19.4mmol) was then added dropwise over 20
minutes and the mixture stirred for 2 hours at -70 °C. This was then cannulated
rapidly into a solution of iodine (5.2g, 20.4mmol) in tetrahydrofuran (3 ml) held at 0
°C. The resulting mixture was stirred for 10 min, quenched with aqueous sodium
metabisulfite and extracted with ethyl acetate. The organic layer was collected,
washed with brine, dried over magnesium sulphate and evaporated. The crude mixture
was purified by chromatography on silica, eluting with ethyl acetate in hexane, to give
the desired compound (4.87 g, -82%) as a pale yellow solid contaminated with traces
of starting material.
dH (CDC13) 8.50 (lH,d), 7.44 (1H, d)
Example 4
2-cvclopentyl-5-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-
4-methoxy-pyridazin-3-one
To a stirred solution of 4-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyl]-
5-methoxy-lH-pyridazin-6-one (126mg, 0.35mmol), triphenylphosphine
(184mg, 0.70mmol) and cyclopentanol (0.06ml, 0.70mmol) in dry THF (3.5ml) under
a nitrogen atmosphere was added diisopropyl azodicarboxylate (0.14ml, 0.7mmol)
dropwise. The resulting mixture was stirred at room temperature for 3 hours then
concentrated in vacuo. The crude product was purified by column chromatography on
silica, eluting with isohexane/ethyl acetate, to give 2-cyclopentyl-5-[3-(4,5-
dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-pyridazin-3-
one (94mg).
8.06 (1H, d, J 8.1), 7.56 (1H, s), 7.43 (1H, d, J 8.1), 5.50-5.41 (1H, m), 4.61 (2H, t, J
9.9), 4.10 (3H, s), 3.41 (2H, br s), 3.22 (3H, s), 2.17-2.02 (2H, m), 2.04 (3H, s), 2.00-
1.86 (4H, m), 1.74-1 .67 (2H, m)
4-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-5-methoxylH-
pyridazin-6-one
To a stirred solution of 5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyl]
-2-[(4-hydroxyphenyl)methyl] -4-methoxy-pyridazin-3 -one (281mg,
0.58mmol) in acetonitrile(5ml) and water (1ml) at room temperature was added eerie
ammonium nitrate and the mixture was stirred at room temperature. The reaction was
monitored by LCMS.
After 90 minutes, brine (25 ml) and ethyl acetate (25 ml) were added. The layers were
separated and the aqueous layer extracted with ethyl acetate a further two times. The
combined organics were washed with sat aqueous sodium bicarbonate (25 ml), then
dried and concentrated in vacuo. The crude product was triturated with hexane (~20
ml) and filtered to give 126mg pale yellow solid.
8.08 (1H, d, J 8.1), 7.56 (1H, s), 7.44 (1H, d, J 8.1), 4.61 (2H, t, J 10.2), 4.19 (3H, s),
3.43 (2H, br s), 3.22 (3H, s), 2.19 (3H, s)
5- [3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll-2-[f4-
hvdroxyphenyl)methyll-4-methoxy-pyridazin-3-one
A mixture of 5-chloro-4-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one
(281mg, lmmol), palladium acetate (18mg, 0.08mmol), 3-[2-methyl-6-
methylsulfonyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]-4,5-
dihydroisoxazole (548mg, 1.5mmol), aqueous tripotassium phosphate (0.4ml. 2mmol)
and SPhos (66mg, 0.16mmol) in degassed toluene was heated at 150°C for 30 minutes
under microwave irradiation. The mixture was allowed to cool to room temperature
then filtered through Celite, eluting with ethyl acetate. The filtrate was evaporated
under reduced pressure, and then purified by column chromatography to give the
desired product as a pink oil (281mg).
8.00 (IH, d), 7.49 (IH, s), 7.41 (2H, d), 7.35 (IH, d), 6.86 (2H, d), 5.36-5.14 (2H, br
d), 4.54 (2H, t), 4.07 (3H, s), 3.77 (3H, s), 3.34 (2H, br s), 3.18 (3H, s), 2.1 1 (3H, s)
3-[2-methyl-6-methylsulfonyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-
yl)phenyl]-4,5-dihydroisoxazole is prepared as described in example 7 below.
5-chloro-4-methoxy-2-\(4-methoxyphenyl)methyllpyridazin-3-one
To a stirred solution of 4,5-dichloro-2-[(4-methoxyphenyl)methyl]pyridazin-3-one
(5.70 g, 20mmol) in dry dioxane (50ml) was added the sodium methoxide solution
(30 wt% soln. in methanol (~5.4 M), 4.07ml, 22mmol) at room temperature. The
resulting mixture was stirred at room temperature, monitoring by LCMS, and then
poured into water (50 ml)/dichloromethane (50ml). The organic layer was separated
and the aqueous layer extracted with dichloromethane (2 x 50 ml). The combined
organics were dried over magnesium sulphate and evaporated. The crude product was
purified by column chromatography on silica, eluting with ethyl acetate/hexane, to
give the desired product 5-chloro-4-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-
3-one as a white solid (4.53g) together with the isomeric compound, 4-chloro-5-
methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one (650mg).
Nmr data:
5-chloro-4-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one : 7.70 (IH, s), 7.39
(2H, d), 6.84 (2H, d), 5.20 (2H, s), 4.24 (3H, s), 3.79 (3H, s)
4-chloro-5-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one: 7.80 (IH, s), 7.40
(2H, d), 6.86 (2H, d), 5.29 (2H, s), 4.02 (3H, s), 3.79 (3H, s)
4,5-dichloro-2-[(4-methoxyphenyl)methyl]pyridazin-3-one is prepared from 4,5-
dichloro-lH-pyridazin-6-one by a procedure analogous to that described in example 1
above.
Example 5
5-[6-fluoro-2-ftrifluoromethyl)-l,8-naphthyridin-3-yll-4-hvdroxy-2-methylpyridazin-
3-one
5-[6-fluoro-2-(trifluoromethyl)-l,8-naphthyridin-3-yl]-4-methoxy-2-methylpyridazin-
3-one (70 mg, 0.1976 mmol) was dissolved in acetonitrile (5 ml) and
sodium iodide (50 mg, 0.33 mmol) was added in a 20ml microwave tube.
Chloro(trimethyl)silane (0.043 ml, 0.34 mmol) was added and the yellow reaction
mixture immediately went purple. The mixture was stirred in a microwave vial at
100°C for 30minutes. LCMS showed only partial conversion to the desired product.
More chloro(trimethyl)silane and sodium iodide were added and the reaction remicrowaved
at 100°C for 30mins. LCMS showed an increase in the desired product
but suggested the starting material was still the major component (-60%). The
mixture was poured into water, basified with 2M sodium hydroxide and extracted into
dichloromethane. The organic extracts were passed through a phase separation
cartridge and evaporated to yield the un-reacted starting material. The basic aqueous
layer was acidified with 2M hydrochloric acid and extracted with dichloromethane.
The organic extracts were passed through a second phase separation cartridge and
evaporated to yield the desired product, 5-[6-fluoro-2-(trifluoromethyl)-l,8-
naphthyridin-3-yl]-4-hydroxy-2-methyl-pyridazin-3-one (21 mg, 0.062 mmol) as a
pink solid.
IH NMR (400 MHz, Chloroform) d ppm d IH 9.18, s IH 8.35, dd IH 7.98, s IH 7.69,
S3H 3.90
5-[6-fluoro-2-ftrifluoromethyl)-l,8-naphthyridin-3-yll-4-methoxy-2-methylpyridazin-
3-one
[6-fluoro-2-(trifluoromethyl)-l,8-naphthyridin-3-yl]-trimethyl-stannane (200 mg,
0.528 mmol), 5-chloro-4-methoxy-2-methyl-pyridazin-3-one (105 mg, 0.60144
mmol), l,4-bis(diphenylphosphinobutane)palladium dichloride (33 mg), copper(II)
oxide (45 mg, 0.566mmol) and N,N-dimethylformamide (5 ml, 64.4 mmol) were
stirred in a microwave vial at 140°C for 30 minutes. LCMS showed good conversion
to the desired product with a minor amount of the 'homo-coupled' by-product as well
and several other small impurities. The reaction mixture was filtered through a very
small silica plug. The filtrate was partitioned between ether and water. The organic
extracts were separated, washed, dried over anhydrous magnesium sulphate and
evaporated. The crude product was dissolved in dichloromethane and purified by
column chromatography, eluting with ethyl acetate/ iso-hexane) to give 5-[6-fluoro-
2-(trifluoromethyl)-l,8-naphthyridin-3-yl]-4-methoxy-2-methyl-pyridazin-3-one (75
mg, 0.21 17 mmol) as a yellow solid.
IH NMR (400 MHz, Chloroform) d ppm d IH 9.20, s IH 8.20, dd IH 7.92, s IH 7.61,
s 3H 4.14, s 3H 3.88
5-chloro-4-methoxy-2-methyl-pyridazin-3-one is prepared from 4,5-dichloro-lHpyridazin-
6-one as described in example 2.
r6-fluoro-2-( trifluoromethyl)-1,8-naphthyridin-3-yll-trimethyl-stannane
A mixture of 6-fluoro-3-iodo-2-(trifluoromethyl)-l,8-naphthyridine (400 mg,
1.17mmol), hexamethyl ditin (1.15 g, 3.40 mmol) and
bis(triphenylphosphine)palladium(II)dichloride (100 mg, 0.141mmol) catalyst, in degassed
1,4-dioxane (6 mL, 70.3 mmol) was heated at 110°C for 60 minutes under
microwave irradiation. LCMS showed excellent conversion to the desired product.
The reaction mixture was adsorbed on silica and purified by column chromatography,
eluting with ethyl acetate/isohexane, to give [6-fluoro-2-(trifluoromethyl)-l,8-
naphthyridin-3-yl] -trimethyl-stannane as a pale orange solid (300 mg, 0.7918 mmol).
IH NMR (400 MHz, Chloroform) d ppm d IH 9.10, s IH 8.48, dd IH 7.85, s 9H 0.47
6-fluoro-3-iodo-2-(trifluoromethyl)-l,8-naphthyridine can be prepared from 6-fluoro-
2-(trifluoromethyl)-l,8-naphthyridin-3-amine by known procedures e.g. in J. Org.
Chem. 1977, 42 (14), 2426-2431.
Example 6
4- [3-(4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyll -1,3-dimethyl-
4H-pyridazine-5.,6-dione
4-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-l,3-dimethyl-4Hpyridazine-
5,6-dione is prepared from 4,5-dichloro-2,6-dimethyl-pyridazin-3-one by a
reaction sequence analogous to that in Example 1.
4,5-dichloro-2,6-dimethyl-pyridazin-3-one
To a 20 ml microwave vial was added 6-bromo-4,5-dichloro-2-methyl-pyridazin-3-
one (1.00 g, 3.88 mmol), [ l ,r-bis(diphenylphosphino)ferrocene]palladium(II)
dichloride dichloromethane adduct (0.032 g, 0.039 mmol), caesium carbonate (2.02 g,
6.20 mmol), trimethylboroxine (0.787 g, 6.20 mmol, 0.876 mL) and 1,4-dioxane (9
mL) and heated in the microwave at 100 °C for lhour then for a further 30 minutes at
150 C .
The reaction mixture was filtered through celite, silica added and reduced under
vacuum. The residue was purified by chromatography on silica, eluting with 0-30%
ethyl acetate/hexane to give a white solid containing a 9:1 ratio of the desired product,
4,5-dichloro-2,6-dimethyl-pyridazin-3-one, together with a byproduct, 5-chloro-2,4,6-
trimethyl-pyridazin-3-one (502 mg in total). This mixture was used directly in the
next step to form 5-chloro-4-methoxy-2,6-dimethyl-pyridazin-3-one, as the by
product does not react.
1H NMR (CDC1 3) :
4,5-dichloro-2,6-dimethyl-pyridazin-3-one d 3.79 (s, 3H), 2.44 (s, 3H)
5-chloro-2,4,6-trimethyl-pyridazin-3-one d 3.73 (s, 3H), 2.38 (s, 3H), 2.29 (s, 3H)
Example 7
2-cvclopropyl-5-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyll-
4-hvdroxy-pyridazin-3-one
A solution of 2-cyclopropyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-
methylsulfonyl-phenyl]-4-methoxy-pyridazin-3-one (0.203 g, 0.5032 mmol) in
morpholine (0.4384 g, 5.032 mmol, 0.440 ml) was heated at 100°C for 1 hour.
The reaction mixture was allowed to cool to room temperature then diluted with
dichloromethane (5ml) and 2M hydrochloric acid (5ml). The mixture was then stirred
for 30mins.
The organic layer was separated and the aqueous layer extracted with
dichloromethane (2 x 5ml). The combined organics were dried and concentrated in
vacuo to give a pink solid.
The crude solid was triturated with acetonitrile (3 x 2ml portions) and collected by
filtration to give 2-cyclopropyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-
methylsulfonyl-phenyl]-4-hydroxy-pyridazin-3-one as a white solid (0.0883 g).
1H NMR (400 MHz, Chloroform) d ppm 1.05 - 1.12 (m, 2 H) 1.22 - 1.29 (m, 2 H)
2.23 (s, 3 H) 3.21 (s, 3 H) 3.39 (br. s., 2 H) 4.19 (dt, J=7.65, 3.69 Hz, 1 H)
4.60 (t, J=10.07 Hz, 2 H) 7.49 (d, J=8.19 Hz, 1 H) 7.60 (s, 1 H) 8.08 (d, J=8.19 Hz, 1
H)
2-cvclopropyl-5-[3-f4,5-dihvdroisoxazol-3-yl)-2-methyl-4-methylsulfonylphenyll-
4-methoxy-pyridazin-3-one
A mixture of 5-chloro-2-cyclopropyl-4-methoxy-pyridazin-3-one (0.20 g, 1 mmol) ,
3-[2-methyl-6-methylsulfonyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-
yl)phenyl]-4,5-dihydroisoxazole (0.438 g, 1.2 mmol), palladium (II) acetate (0.018 g,
0.08 mmol), tripotassium phosphate (1.026 g, 2 mmol, 0.4 ml, 5 mol/1) and SPhos
(0.0670 g, 0.16 mmol) in toluene (3.46 g, 37.4 mmol, 4.0 ml) was heated at 150°C for
30minutes under microwave irradiation.
The reaction mixture was filtered through celite, eluting with ethyl acetate. The
filtrate was concentrated in vacuo to give the crude product. The crude product was
dryloaded onto silica and purified by chromatography to give 2-cyclopropyl-5-[3-
(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-pyridazin-
3-one as a colourless oil (0.203 g, 0.503mmol).
1H NMR (400 MHz, Chloroform) d ppm 1.03 - 1.1 1 (m, 2 H) 1.19 (br. s., 2 H) 2.18
(s, 3 H) 3.22 (s, 3 H) 3.40 (br. s., 2 H) 4.14 (s, 4 H) 4.60 (t, J=10.07 Hz, 3
H) 7.41 (d, J=8.19 Hz, 1 H) 7.48 (s, 1 H) 8.06 (d, J=8.19 Hz, 1 H)
3-[2-methyl-6-methylsulfonyl-3- 4,4,5.,5-tetramethyl-l ,3 2-(iioxaborolan-2-
vDphenyll -4,5- ih roisoxazole
A mixture of 3-(3-bromo-2-methyl-6-methylsulfonyl-phenyl)-4,5-dihydroisoxazole
(A, 3.182 g, 10 mmol), bis(pinacolato)diboron (3.8476 g, 15 mmol),
tris(dibenzylideneacetone)dipalladium(0) (0.092 g, 0.1 mmol), S-Phos (0.168 g, 0.4
mmol) and potassium acetate (1.487g, 15 mmol) in 1,4-dioxane (15.51 g, 176 mmol,
15 ml) was heated at 150C for 30mins under microwave irradiation. The crude
mixture was filtered through a pad of celite eluting with ethyl acetate. The crude
product was dry loaded onto silica and purified by chromatography to give 3-[2-
methyl-6-methylsulfonyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]-4,5-
dihydroisoxazole as a pale yellow solid. (2.06 g, 5.64 mmol)
1H NMR (400 MHz, Chloroform) d ppm 1.37 (s, 13 H) 2.52 (s, 3 H) 3.16 (s, 4 H)
3.33 (br. s., 2 H) 4.57 (t, J=10.00 Hz, 2 H) 7.94 (d, J=8.06 Hz, 1 H) 7.99 (d,
J=7.92 Hz, 1 H)
3-(3-bromo-2-chloro-6-methylsulfonyl-phenyl)-4,5-dihydroisoxazole can be prepared
as reported for example in DE 19820722.
5-chloro-2-cvclopropyl-4-methoxy-pyridazin-3-one
To a stirred solution of 4,5-dichloro-2-cyclopropyl-pyridazin-3-one (A, 0.599 g,
2.9214 mmol, 100 mass%) in 1,4-dioxane (100 mL, 100 mass%) was added sodium
methoxide (0.69443 g, 3.2135 mmol, 0.735 mL, 25 mass%) dropwise and the
resulting mixture stirred at room temperature for lhour. The reaction mixture was
concentrated in vacuo to give a crude brown oil then dry loaded onto silica and
purified by chromatography to give 5-chloro-2-cyclopropyl-4-methoxy-pyridazin-3-
one as a white solid (0.498 g).
1H NMR (400 MHz, Chloroform) d ppm 0.96 - 1.14 (m, 4 H) 3.95 - 4.07 (m, 1H)
4.28 (s, 3 H) 7.64 (s, 1 H)
4,5-dichloro-2-cvclopropyl-pyridazin-3-one
A mixture of tert-butyl N-(tert-butoxycarbonylamino)-N-cyclopropyl-carbamate (0.68
g, 2.5 mmol) and mucochloric acid (0.43 g, 2.5 mmol) in hydrochloric acid (4 mol/1)
in water (25 mmol, 6.3 ml) was heated at reflux for 6 hours. The reaction mixture was
allowed to cool to room temperature then extracted with dichloromethane (3 x 10ml).
The combined organic extracts were dried and concentrated in vacuo. The crude
product was purified by chromatography to give 4,5-dichloro-2-cyclopropylpyridazin-
3-one as a white solid (0.353 g).
1H NMR (400 MHz, Chloroform) d ppm 1.02 - 1.17 (m, 4 H) 4.09 - 4.16 (m, 1H)
7.72 (s, 1 H)
Tert-butyl N-ftert-butoxycarbonylamino)-N-cvclopropyl-carbamate
To a stirred suspension of magnesium ( 1.34g, 55mmol) and catalytic iodine in
tetrahydrofuran (5ml)was added 5ml of a 45ml solution of cyclopropyl bromide
(4.0ml) in tetrahydrofuran (50ml). The mixture was heated to initiate Grignard
formation then the remaining solution of cyclopropyl bromide was added dropwise
over 30mins with heating (70C). The Grignard solution was heated at reflux for a
further 30 minutes then cooled to 0°C.
To a stirred solution of di-tert-butyl azodicarboxylate in THF (50ml) at -78°C was
added the solution of cyclopropylmagnesium bromide dropwise via cannula. The
resulting solution was stirred at -78°C for 30mins then quenched with acetic acid. The
mixture was allowed to warm to room temperature then water (150 ml) was added and
the mixture extracted three times with diethyl ether. The combined organic extracts
were dried, filtered and concentrated in vacuo. The crude product was purified by
column chromatography on silica, eluting with ethyl acetate/hexane, to give the
product as a white solid (6.68g).
IH NMR (400 MHz, Chloroform) d ppm 0.7 (4H, br s), 1.5 (18H, s), 2.9-3.0 (IH, br
m), 6.1 and 6.4 (IH, br s)
Example 8
[2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]
acetate
To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.29 mmol) in dry dichloromethane ( 1
ml) at room temperature was added pyridine (0.03 g, 0.03 ml, 0.37 mmol) and 4-
(dimethylamino)pyridine (0.35mg, 0.0029 mmol). The mixture was stirred for 2 min
and acetyl chloride (0.027 g, 0.025 ml, 0.345 mmol) was added dropwise. The
resulting suspension was stirred at room temperature for 2 hours, then diluted with
dichloromethane and washed successively with 2M hydrochloric acid and saturated
aqueous sodium hydrogen carbonate. The organic layer was collected, passed through
a phase-separation cartridge and the filtrate evaporated.
The crude residue was purified by flash chromatography (10-55% ethyl acetate in
hexanes, 13 min, then 3 min at 55%, 4g silica GOLD) to give [2-methyl-5-[2-
methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl] acetate (0.095 g,
0.2434 mmol, 84.78% yield) as a white solid.
4-hydroxy-2-methyl-5 -[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3 -
was prepared as described in Example 2.
Example 9
Methyl [2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethvDphenyll-3-oxopyridazin-
4-yll carbonate
To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.29 mmol) in dry toluene (1.99 g, 2.3
ml, 21.5 mmol) at room temperature was added triethylamine (0.032 g, 0.044 ml, 0.31
mmol), followed by methyl chloroformate (0.03 g, 0.024 ml, 0.31 mmol). The
resulting mixture was stirred overnight.
Water was added and the mixture extracted with ethyl acetate. The organic extracts
were passed through a phase-separation cartridge and the filtrate concentrated under
reduced pressure. The residue was purified by flash chromatography (0-50% Ethyl
acetate in hexanes, 12 min, then 3 minutes at 50%, 4g silica) to give methyl [2-
methyl-5 -[2-methylsulfonyl-4-(trifluoromethyl)phenyl] -3-oxo-pyridazin-4-yl]
carbonate (0.1 13 g, 0.2781 mmol, 96.87% yield) as a white solid.
4-hydroxy-2-methyl-5 -[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3 -one
was prepared as described in Example 2.
Example 10
[2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-3-oxo-pyridazin-4-yll
ethylsulfanylformate
To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulphonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.29 mmol) in dry tetrahydrofuran
(4.6 g, 5.17 ml, 63.7 mmol) at room temperature was added triethylamine (0.059 g,
0.08 ml, 0.57 mmol) followed by ethyl chlorothioformate (0.047 g, 0.039 ml,
0.36mmol). The resulting suspension was stirred at room temperature for 90 minutes
and then diluted with ethyl acetate and washed with brine. The organic phase was
collected and passed through a phase-separation cartridge. The filtrate was evaporated
and the residue was purified by flash chromatography (0-40% ethyl acetate in
hexanes, 13 min, then 3 min at 40%, 4g silica) to give [2-methyl-5-[2-methylsulfonyl4-(
trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl] ethylsulfanylformate (0.126 g, 0.289
mmol, 100% yield) as a white solid.
4-hydroxy-2-methyl-5 -[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3 -one
was prepared as described in Example 2.
Example 11
[2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-3-oxo-pyridazin-4-yll
propane-l-sulfonate
To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.29 mmol) in dichloromethane (1.14
g, 0.86 ml, 13.4 mmol) at room temperature was added a solution of potassium
carbonate (0.06 g, 0.43 mmol) in water (0.86g, 0.86ml, 47.81 mmol) followed by a
solution of 1-propanesulphonyl chloride (0.063 g, 0.05 ml, 0.43 mmol) in
dichloromethane (0.2 ml). Benzyltrimethylammonium chloride (0.0027 g, 0.0025ml,
0.014mmol) was then added and the biphasic mixture stirred vigorously at room
temperature overnight.
The reaction mixture was diluted with water/dichloromethane and the organic phase
separated. The aqueous layer was extracted with dichloromethane. The combined
organic extracts were washed with aqueous 2M hydrochloric acid and brine and then
passed through a phase-separation cartridge. The filtrate was evaporated and the
residue purified by flash chromatography (0-50% ethyl acetate in hexanes, 13 min, 4g
silica) to afford [2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxopyridazin-
4-yl] propane-l-sulfonate (0.1 g, 0.22 mmol, 76.7% yield) as a white solid.
4-hydroxy-2-methyl-5 -[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3 -one
was prepared as described in Example 2.
Example 12
[2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-3-oxo-pyridazin-4-yll
propane-l-sulfonate
To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.2871 mmol) and -toluene
sulphonyl chloride (0.061 g, 0.32 mmol) in dry acetonitrile (4.51 g, 5.7 ml, 110
mmol) at room temperature was added potassium carbonate (0.071 g, 0.52 mmol).
The resulting suspension was stirred at room temperature overnight.
The reaction mixture was diluted with water and extracted with ethyl acetate. The
organic extracts were passed through a phase-separation cartridge and the filtrate
evaporated. The resulting solid was dissolved in minimum amount of
dichloromethane and hexane was added dropwise with rapid stirring until
precipitation. The precipitate was collected by filtration and dried under suction to
afford [2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl] -3-oxo-pyridazin-4-
yl] 4-methylbenzenesulfonate (0.10 g, 0.2 mmol, 70.0% yield) as a white solid.
4-hydroxy-2-methyl-5 -[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3 -one
was prepared as described in Example 2.
Example 13
4-hvdroxy-2-methyl-5-[4-morpholino-2-ftrifluoromethyl)pyrimidin-5-
llpyridazin-3-one
5-[4-chloro-2-(trifluoromethyl)pyrimidin-5 -yl]-4-methoxy-2-methyl-pyridazin-3 -one
(240.0 mg, 0.22 mmol) was dissolved in morpholine (2.5 ml, 28.6 mmol). The
reaction was stirred at 100°C for 45 minutes. The reaction mixture was carefully
added to 30.0ml water and stirred for 10 minutes. The aqueous layer was extracted
with dichloromethane (2x20m). The aqueous layer was then acidified with aqueous
hydrochloric acid (2.0M) and then washed with dichloromethane, which was collected
using a phase-separation cartridge. The solvent was concentrated in vacuo and the
crude was triturated with 5.0ml acetonitrile then sonicated and the resulting solid
(40.0mg) was collected by filtration. TLC showed some impurity so it was triturated
once more using 5.0ml methanol and the resulting precipitate was isolated to yield 4-
hydroxy-2-methyl-5 -[4-morpholino-2-(trifluoromethyl)pyrimidin-5 -yl]pyridazin-3 -
one (25.0 mg, 0.07 mmol, 31.2% yield) as a white solid.
5-[4-chloro-2-ftrifluoromethyl)pyrimidin-5-yll-4-methoxy-2-methyl-pyridazin-3-
one
4-methoxy-2-methyl-5 -[6-oxo-2-(trifluoromethyl)- 1H-pyrimidin-5 -yl]pyridazin-3 -one
515.0 mg, 1.7 mmol) was dissolved in phosphorus (V) oxychloride (5.0 ml, 53
mmol). The mixture stirred at 85°C for 90 minutes. The reaction was then stopped,
and let to cool to room temperature and was then concentrated in vacuo. The crude
product was dropped into ice cold water and the aqueous layer extracted with
dichloromethane. The organic layers were combined, dried over sodium sulphate,
filtrate and concentrated in vacuo, then was purified using a 24g silica cartridge
eluting with iso-hexane: ethyl acetate (100:0 —> 60:40 over 12 minutes then keeping
the gradient for 6 minutes). The fractions containing product were concentrated in
vacuo to yield 5-[4-chloro-2-(trifluoromethyl)pyrimidin-5-yl]-4-methoxy-2-methylpyridazin-
3-one (240.0 mg, 0.22 mmol, 13.18% yield) as a translucent oil.
1H MR (400 MHz, Chloroform) d ppm = 3.86 (3 H, s) 4.29 (3 H, s) 7.63 ( 1 H, s)
8.76 ( 1 H, s)
4-methoxy-2-methyl-5-[6-oxo-2-ftrifluoromethyl)-lH-pyrimidin-5-yllpyridazin-
3-one
2,2,2-Trifluoroacetamidine (450mg, 11.8 mmol) was suspended in methanol (3.0 ml).
Then methyl (E)-3-methoxy-2-(5-methoxy-l-methyl-6-oxo-pyridazin-4-yl)prop-2-
enoate (1.00 g, 3.93 mmol) was added, followed by sodium methoxide (1.35ml, 5.90
mmol). The mixture was heated to 65°C for 2 hours.
More 2,2,2-trifluoroacetamidine (450.0mg,l 1.8 mmol) and sodium methoxide
( 1.35ml, 5.90 mmol) were added and the mixture stirred for another 2 hours. The
reaction was stopped and let to cool to room temperature. 2M aqueous hydrochloric
acid was added and the mixture was concentrated in vacuo.
The crude product was purified by chromatography on silica, eluting with isohexane:
ethyl acetate then with dichloromethane:methanol. The fractions containing
product were combined and concentrated in vacuo to yield 4-methoxy-2-methyl-5-[6-
oxo-2-(trifluoromethyl)-lH-pyrimidin-5-yl]pyridazin-3-one (520.0 mg, 1.72mmol,
43.7% yield) as a pale yellow solid.
H NMR (400 MHz, ^-Methanol) d ppm = 3.80 (3 H, s) 4.01 (3 H, s) 7.94 ( 1 H, s)
8.13 ( 1 H, s)
Methyl fE)-3-methoxy-2-f5-methoxy-l-methyl-6-oxo-pyridazin-4-yl)prop-2-
enoate
4-methoxy-2-methyl-5-tributylstannyl-pyridazin-3-one (2.9g, 6.8 mmol) and methyl
(Z)-2-iodo-3-methoxy-prop-2-enoate (1.5 g, 6.2 mmol) were dissolved in N,Ndimethylformamide
(15.0 ml, 193 mmol,). Caesium fluoride (1.9g, 2.0 equiv., 12
mmol) was added and the mixture degassed with nitrogen. Copper iodide (0.12g, 0.62
mmol) and palladium (0) tetrakis(triphenylphosphine) (0.36g, 0.31 mmol) were then
added and the mixture degassed another time with nitrogen before being put in a 55°C
pre-heated heating block for 2 hours.
Water (50ml) and dichloromethane (50ml) were added and the reaction shaken
vigorously. 50.0ml Saturated aqueous sodium hydrogen carbonate was added and the
mixture shaken again. The dichloromethane layer was collected and concentrated in
vacuo.. The crude product was dry-loaded onto a 120g silica cartridge eluting with
dichloromethane: ethyl acetate (100:0 —> 40:60 over 20 minutes, then keeping the
gradient for another 10 minutes). The fractions containing product were combined and
concentrated in vacuo to yield a 1.12g brown oil that solidified upon standing.
The crude product was further purified by column chromatography on silica, eluting
with iso-hexane: ethyl acetate (60:40 —> 30:70 over 8 minutes then keeping the
gradient for 5 minutes then going to 100% ethyl acetate). The fractions containing
product were combined and concentrated in vacuo to yield the product as a pale
yellow solid (882.0mg, 56% yield).
H NMR (400 MHz, Chloroform, (12wql61h2)) d ppm = 3.74 (3 H, s) 3.77 (3 H, s)
3.90 (3 H, s) 4.1 1 (3 H, s) 7.52 ( 1 H, s) 7.56 ( 1 H, s)
4-methoxy-2-methyl-5-tributylstannyl-pyridazin-3-one
To a stirred solution of 5-bromo-4-methoxy-2-methyl-pyridazin-3-one (5.00 g, 22.8
mmol) in tetrahydrofuran (40.6 g, 560 mmol, 45.7 ml) at -40C was added 2-
mesitylmagnesium bromide (1.0 mol/) in tetrahydrofuran (46 g, 45.7 mmol, 46 ml, 1.0
mol/L) dropwise via a dropping funnel (maintaining the internal temperature below -
30C at all times) and the mixture stirred at -40C for 30 minutes. Tri-n-butyltin
chloride (23.2 g, 68.5 mmol, 19.3 ml) was then added dropwise as a solution in
tetrahydrofuran (20ml) and the mixture allowed to warm to 0C over ~lhr.
The reaction mixture was then quenched with saturated aqueous ammonium chloride
solution (100ml) and extracted with ethyl acetate (3 x lOOmL). The combined organic
extracts were dried, filtered and concentrated in vacuo to give the crude product.
The crude product was dry loaded onto silica and purified by chromatography to give
4-methoxy-2-methyl-5-tributylstannyl-pyridazin-3-one as a reddish oil (5.21 g, 12.1
mmol, 53.2% yield)
H NMR (400 MHz, Chloroform) d ppm 7.56 ( 1 H, s) 4.14 (3 H, s) 3.78 (3 H, s) 1.44
- 1.62 (6 H, m) 1.27 - 1.38 (6 H, m) 1.00 - 1.21 (6 H, m) 0.89 (9 H, t, J=7.3 Hz)
5-bromo-4-methoxy-2-methyl-pyridazin-3-one may be prepared by a route analogous
to that in Reaction Scheme 3.
Example 14
3-cvclohexyl-2-f3-fluorophenyl)-5-f5-hvdroxy-l-methyl-6-oxo-pyridazin-4-
yl)pyrimidin-4-one
3-cyclohexyl-2-(3-fluorophenyl)-5-(5-methoxy-l-methyl-6-oxo-pyridazin-4-
yl)pyrimidin-4-one (51.0 mg, 0.1 18 mmol) was dissolved in morpholine (2.0 ml, 23
mmol. The reaction was stirred at 95°C for 2 hours. LC indicated no reaction, so
temperature was increased to 105°C and the reaction stirred for a further 2 hours. This
time, reaction had gone to completion so it the mixture was allowed to cool to room
temperature. Aqueous hydrochloric acid was then added carefully to the reaction
mixture until the mixture was acidic. The aqueous layer was washed with
dichloromethane and the organic layers were combined and passed through a phase
separation cartridge. The solvent was concentrated in vacuo and the crude triturated
with 3.0ml acetonitrile, sonicating the solution for about 1 minute.
The solid was collected by filtration to yield the product as a pale pink solid (25.0mg,
53.4% yield).
3-cvclohexyl-2-f3-fluorophenyl)-5-f5-methoxy-l-methyl-6-oxo-pyridazin-4-
yl)pyrimidin-4-one
Ethyl 3-fluorobenzenecarboximidate hydrochloride (135.0 mg, 0.6629 mmol,) was
suspended in methanol (3.0 ml). Then cyclohexanamine (0.066 g, 0.6629 mmol,) was
added and the mixture stirred for 2 hours at for 18 hours. The reaction was heated
gradually to reflux and stirred for another 2 hours. More cyclohexylamine (0.066 g,
0.6629 mmol) was added and the mixture stirred at reflux for 2 hours. The reaction
was stopped and concentrated in vacuo to yield an oil.
The crude product was re-dissolved in methanol (3.0 ml), then sodium methoxide
(0.12 g, 0.57 mmol) was added and the mixture stirred for 5 minutes before methyl
(E)-3-methoxy-2-(5-methoxy-l-methyl-6-oxo-pyridazin-4-yl)prop-2-enoate (145.0
mg, 0.57 mmol) was then added and the mixture stirred at 65°C for 3 hours.
The reaction was cooled and the solvent was concentrated in vacuo, then the crude
product was taken up in diethyl ether. The organic layer was washed with saturated
sodium hydrogen carbonate, and the aqueous washed with diethyl ether. The organic
phases were combined, dried over sodium sulphate, filtered and concentrated in
vacuo, then was purified by chromatography on silica, eluting with iso-hexane: ethyl
acetate to give the product (95mg) as a pale yellow gum. This was further purified
by preparative HPLC and concentrated in vacuo to give the product as a translucent
oil (51.0mg, 21.8% yield).
H MR (400 MHz, Chloroform) d ppm = 0.93 - 1.1 1 (2 H, m) 1.14 - 1.30 ( 1 H, m)
1.57 ( 1 H, d, J=12.9 Hz) 1.72 (2 H, d, J= 11.3 Hz) 1.81 (2 H, d, J=13.4 Hz) 2.63 - 2.79
(2 H, m) 3.81 (3 H, s) 3.87 - 3.97 ( 1 H, m) 4.21 (3 H, s) 7.21 - 7.26 ( 1 H, m) 7.27 -
7.30 ( 1 H, m) 7.52 ( 1 H, td, J=7.9, 5.6 Hz) 7.88 ( 1 H, s) 8.07 ( 1 H, s)
Methyl (E)-3-methoxy-2-(5-methoxy-l-methyl-6-oxo-pyridazin-4-yl)prop-2-enoate
was prepared as described in Example 13 above.
Example 15
4-hvdroxy-2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-6-propoxypyridazin-
3-one
4-hydroxy-2-methyl-5 -[2-methylsulfonyl-4-(trifluoromethyl)phenyl] -6-propoxypyridazin-
3-one can be prepared from 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-
(trifluoromethyl)phenyl]-6-propoxy-pyridazin-3-one was prepared by a method
analogous to that described in, for example, Example 1, step 1.
4-methoxy-2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-6-propoxypyridazin-
3-one
To a mixture of 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-
lH-pyridazine-3,6-dione (0.09 g, 0.24 mmol) and potassium carbonate (0.17 g, 1.19
mmol) in N, N-dimethylformamide (1.4 g, 1.5 ml, 19 mmol) at room temperature was
added 1-iodopropane (0.045 g, 0.026 ml, 0.26 mmol). The resulting yellow mixture
was stirred for 3hours and then poured into water and extracted with ethyl acetate.
The organic extracts were washed with brine, filtered through a phase-separation
cartridge and the filtrate evaporated. The crude residue was purified by flash
chromatography (30-80% ethyl acetate in hexanes, 13 min, 4g silica) to give 4-
methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-propoxypyridazin-
3-one as a pale yellow oil (0.099 g, 0.236 mmol, 99.0% yield).
1H NMR (400 MHz, CDC13): d 8.41 (1H, br d), 7.94 (1H, br dd), 7.39 (1H, d), 4.10
(3H, s), 4.04-4.00 (2H, m), 3.72 (3H, s), 2.99 (3H, s), 1.57-1.52 (2H, m), 0.76 (3H, t).
4-methoxy-2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-lHpyridazine-
3.,6-dione
To a solution of sodium nitrite (0.1 1 g, 1.6 mmol) in concentrated sulphuric acid (3
ml) at 0°C was added dropwise a suspension of 6-amino-4-methoxy-2-methyl-5-[2-
methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (0.51 g, 1.352 mmol) in
glacial acetic acid(6.294 g, 6 ml, 105 mmol). The resulting mixture was allowed to
warm to room temperature and stirred for 40 min. It was then cooled to 0°C and water
(9 ml) was added dropwise. The resulting suspension was stirred for 60minutes at
room temperature, then diluted with water (10 ml) and the precipitate collected by
filtration, washed with water and dried in a vacuum oven at 55°C overnight to afford
4-methoxy-2-methyl-5 -[2-methylsulfonyl-4-(trifluoromethyl)phenyl] -1H-pyridazine-
3,6-dione as an off-white solid (0.35 g, 0.92 mmol, 68.25% yield).
1H NMR (400 MHz, MeOD): d 8.38 (1H, br d), 8.08 (1H, br dd), 7.62 (1H, d), 3.95
(3H, s), 3.67 (3H, s), 3.14 (3H, s)
6-amino-4-methoxy-2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyllpyridazin-
3-one
To a solution of 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-
6-nitro-pyridazin-3-one (0.8 g, 1.964 mmol) in ethanol (19.7 g, 25 ml, 4 11 mmol) at
80°C was added ammonium formate (2.502 g, 39.28 mmol) and palladium hydroxide
on carbon (0.5517 g, 3.928 mmol). The resulting black mixture was maintained at
80°C for l h (NB Sublimation of ammonium formate observed) and then hot-filtered
through a short pad of celite, washing with hot ethanol, ethyl acetate and methanol.
The filtrate was evaporated and the resulting residue rapidly stirred with water for 10
min and then collected by filtration and dried in a vacuum oven at 55°C over 2d
(weekend).
Yield: 510 mg (69%, yellow solid)
IH NMR (400 MHz, MeOD): d 8.42 (IH, br s), 8.14 (IH, br d), 7.65 (IH, d), 3.94
(3H, s), 3.66 (3H, s), 3.16 (3H, s)
4-methoxy-2-methyl-5-[2-methylsulfonyl-4-ftrifluoromethyl)phenyll-6-nitropyridazin-
3-one
To a solution of 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-
pyridazin-3-one (1.81 g, 5.00 mmol) in sulphuric acid (14.7 g, 8 ml, 138 mmol) at
0°C was added dropwise nitric acid (1.26 g, 0.891 ml, 20.0 mmol). The resulting
solution was stirred at 0°C for 5 min, then allowed to warm to room temperature for
15 min and then heated to 50°C for a further 2.5 hours. More nitric acid (1.26 g, 0.891
ml, 20.0 mmol) was added and heating continued for a further 2h. LC-MS still
showed presence of starting material. More nitric acid (1.26 g, 0.891 ml, 20.0 mmol)
was added and heating continued for a further lhour. The reaction mixture was
allowed to cool to room temperature and then carefully poured into ice-cold water
with rapid stirring. The resulting pale yellow precipitate was filtered, washed with icecold
water and then dried in a vacuum oven overnight at 55°C.
It was found that the crude product had some acid contaminant. The orange solid was
dissolved in dichloromethane and the organic phase washed with water (with a few
drops of aqueous sodium hydroxide added - pH 14) and then passed through a phaseseparation
cartridge. The filtrate was evaporated under reduced pressure to give 4-
methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-nitro-pyridazin-
3-one (0.8 g, 1.96 mmol, 39.3% Yield) as a pale pink solid.
IH NMR (400 MHz, CDC13): d 8.38 (IH, br s), 7.98 (IH, dd), 7.41 (IH, d), 4.20 (3H,
s), 3.92 (3H, s), 3.00 (3H, s)
Example 16
4-hvdroxy-2-methyl-5-[l-methyl-2-oxo-6-ftrifluoromethyl)-3-pyridyllpyridazin-
3-one
2-methoxy-6-ftrifluoromethyl)pyridine
To a solution of 6-(trifluoromethyl)pyridin-2-ol (10.0 g, 10.0 g, 61.3 mmol) in
dichloromethane (3 ml/mmol, 184 ml) was added silver carbonate (22.8 g, 82.8 mmol,
3.75 mL) and iodomethane (87.0 g, 613 mmol, 38.2 mL) and stirred in the dark for 24
hours. The reaction mixture was then filtered through Celite and washed with
dichloromethane. The filtrate was concentrated at 30 oC at 250 mbar, silica added and
the residue was purified by chromatography eluting with 0-10% ethyl acetate/hexane.
Fractions containing product were combined to give 2-methoxy-6-
(trifluoromethyl)pyridine (6.49 g, 36.6 mmol, 59.8% yield).
IHNMR (CDC13): d 7.69 ft, =8.1 Hz, IH) 7.25 (d, J=7.5 Hz, 1 H) 6.91 (d, J=8.6 Hz,
1 H) 3.98 (s, 3 H);
[2-methoxy-6-ftrifluoromethyl)-3-pyridyllboronic acid
To a solution of 2-methoxy-6-(trifluoromethyl)pyridine (1.0 g, 5.6 mmol) and in
diethyl ether (1.2 mL/mmol, 6.8 mL) at -78 C under nitrogen was added nBuLi (2.5
mol/L) in hexanes (4.7 g, 17 mmol, 6.8 mL) over 5 min and allowed to warm up to
room temperature over 30 minutes. Boric acid triisopropyl ester (2.1 g, 11 mmol, 2.6
mL) in diethyl ether (1.2 mL/mmol, 6.8 mL) was cooled to -78 C and [2-methoxy-6-
(trifluoromethyl)-3-pyridyl]lithium was added to this solution over 15 minutes and
then warmed up to room temperature over 30 mins.
Hydrogen chloride (aqueous 25%>) (10 mL, 10 mmol) was added and the reaction
mixture diluted with water and extracted twice with dichloromethane, passed through
a phase separator and reduced under vacuum to give a yellow oil which solidified
overnight.
The reaction mixture was adsorbed onto silica and purified by chromatography on
silica, eluting with 0-25% ethyl acetate/hexane. Fractions containing product were
combined to give [2-methoxy-6-(trifluoromethyl)-3-pyridyl]boronic acid as a yellow
solid (707 mg, 3.20 mmol, 59% yield).
IHNMR (llvu941hl, CDC13): d 8.29 (d, J=7.5 Hz, 1H) 7.34 (d, J=7.5 Hz, 1H) 5.92
(s, 2 H) 4.10 (s, 3 H);
4-methoxy-5-[2-methoxy-6-ftrifluoromethyl)-3-pyridyll-2-methyl-pyridazin-3-
one
To a mixture of 5-chloro-4-methoxy-2-methyl-pyridazin-3-one (400 mg, 2.29 mmol),
prepared as described in Example 2, [2-methoxy-6-(trifluoromethyl)-3-
pyridyl]boronic acid (0.71 g, 3.20 mmol) sPhos (0.19 g, 0.46 mmol)
tris(dibenzylidineacetonyl)bispalladium (0.1 1 g, 0.11 mmol), potassium phosphate
( 1.00 g, 4.58 mmol, 0.39 mL) and the reaction mixture diluted with tert-butanol ( 1.6
mL/mmol, 2.88 g, 38.5 mmol, 3.67mL). The reaction mixture was heated to 80 C for
50 min. The reaction mixture was diluted with brine and extracted with ethyl acetate
(3x). The orange solution was passed through a phase separator, silica added and
reduced under vacuum. This was then purified by chromatography, eluting with 0-
50% ethyl acetate/hexane. Fractions containing product were combined to give 4-
methoxy-5-[2-methoxy-6-(trifluoromethyl)-3-pyridyl]-2 -methyl -pyridazin-3-one (545
mg, 0.54g, 1.73 mmol, 75.46% yield)
5-[2-hvdroxy-6-ftrifluoromethyl)-3-pyridyll-4-methoxy-2-methyl-pyridazin-3-
one
To 4 microwave vials was added in each 1 g of 4-methoxy-5-[2-methoxy-6-
(trifluoromethyl)-3-pyridyl]-2 -methyl-pyridazin-3-one (4.0 g, 13 mmol) followed by
15 ml of hydrogen bromide (48%> aqueous solution) (60 ml) and heated sequentially
at 40 C in the microwave for 45 minutes. The reaction mixtures were combined and
ethyl acetate was added followed by brine and then extracted with ethyl acetate (3 x
10 ml), the combined organics passed through a phase separator and reduced under
vacuum to give a white solid. This was then purified by chromatography, eluting with
0-50% ethyl acetate/hexane.
Fractions containing product were combined to give 5-[2-hydroxy-6-
(trifluoromethyl)-3-pyridyl]-4-methoxy-2-methyl-pyridazin-3-one as a pink solid (1.6
g, 5.3 mmol, 42% yield)
IHNMR (llvz747hl, CDC13): d 7.83 (s, 1H) 7. 75 (d, J=7.6Hz, 1H) 6.96 (d, J=7.4
Hz, 1H) 4.18 (s, 3 H) 3.82 (s, 3 H);
4-methoxy-2-methyl-5-[l-methyl-2-oxo-6-ftrifluoromethyl)-3-pyridyllpyridazin-
3-one
To a solution of 5-[2-hydroxy-6-(trifluoromethyl)-3-pyridyl]-4-methoxy-2-methylpyridazin-
3-one (150 mg, 0.49797 mmol) in 1,2-dimethoxyethane (12 ml/mmol, 5.98
mL) was added dipotassium carbonic acid (0.21 g, 1.49 mmol) followed by
iodomethane (0.64 g, 4.48 mmol, 0.28 ml) and the reaction mixture heated to reflux
(75 C) for 30 min. The reaction mixture was cooled to room temperature and the
inorganic solids were filtered and washed with ethyl acetate and the solvent; silica
was added and the reaction mixture concentrated under vacuum and purified by
chromatography, eluting with 0-35-50% ethyl acetate/hexane.
Fractions containing product were combined to give 4-methoxy-2-methyl-5-[lmethyl-
2-oxo-6-(trifluoromethyl)-3-pyridyl]pyridazin-3-one as a white solid (88 mg,
0.28 mmol, 56.06% Yield)
IHNMR (12wk938hl, CDC13): d 7.82 (s, 1H) 7.55 (d, J=7.5 Hz, 1H) 6. 78 (d, J=7.0
Hz, 1 H) 4.16 (s, 3 H) 3.80 (s, 3 H) 3. 70 (d, J=l.l Hz, 3 H)
4-hvdroxy-2-methyl-5-[l-methyl-2-oxo-6-ftrifluoromethyl)-3-pyridyllpyridazin-
3-one
A solution of 4-methoxy-2-methyl-5-[l-methyl-2-oxo-6-(trifluoromethyl)-3-
pyridyl]pyridazin-3-one (88 mg, 0.2792 mmol) in morpholine ( 1 ml, 11.4 mmol,) was
heated to 100 C for 1.5h. The reaction mixture was reduced under vacuum, diluted
with ethyl acetate, washed with 1M HCl 3 times, reduced under vacuum and triturated
with TBME to give 4-hydroxy-2-methyl-5-[l-methyl-2-oxo-6-(trifluoromethyl)-3-
pyridyl]pyridazin-3-one as a white solid (48 mg, 0.16 mmol, 57.08% yield)
TABLE CI - Examples of herbicidal compounds of the present invention.

s);
s);
t);
s);
t);
d);
s);
d)
s);
s);
s);
s);
d);
d)
3.89
s)
(IH,
(IH,
d),
s)
8.64
s),
2.99
s)

Compound R1 R2 R3 NMR
3.88 ppm (3H, s);
4.02 ppm (3H, d);
7.19 ppm (lH, dd); 1.063 Me H 7.28 ppm (1H, dd);
7.81 ppm (lH, d)
2.92 ppm (6H, 2s);
3.88 ppm (3H, s);
7.15 ppm (lH, dd); 1.064 Me H 7.26 ppm (1H, dd);
7.80 ppm (1H, d)
2.18(3H,s);
3.70(3H,s); 6.18-
6.20(lH,dd);
6.30(lH,s); 7.40- 1.065 Me H 7.42(lH,d);
7.82(lH,s); 11.7-
11.9 (lH b s).
0
3.70(3H,s); 6.17-
6.19(lH,d); 7.70- 1.066 Me H 7.72(lH,d);
7.87(lH,s).
7.74 (1H, d), 7.66
(1H, s), 7.62 (lH,
1.067 Me H d), 3.90 (3H, s),
2.58 (3H, s)
7.83 (1H, d), 7.67
(1H, s), 7.59 (lH,
d), 5.90 (1H, dq),
1.068 Me H 3.90 (3H, s), 2.59
(3H, s), 1.76 (3H,
dd)
3.72(3H,s); 6.70-
6.72(lH,d); 7.30-
7.32(lH,d); 7.53-
7.57(lH,t); 7.70-
1.069 Me H 7.72(lH,d); 7.76-
7.80(lH,t);
7.92(lH,s); 8.21-
8.23(lH,d).

Compound R1 R2 R3 NMR
d7.86 (br. s, 1 H)
7.65 (d, J=5.9 Hz, 1
H) 7.58 (br. s., 1 H)
7.49 (br. s., 1 H) 1.143 Me H 7.40 (br. s., 1 H)
6.40 (t, J=7.0 Hz, 1
H) 3.58 (br. s., 3 H);
8.21 (1H, dd), 7.77-
7.74 (1H, m), 7.75
(1H, s), 7.71-7.67
(1H, m), 7.38 (lH, 1.144 CH3-0-CH 2- H dd), 5.57-5.47 (2H,
br m), 3.53 (3H, s),
3.00 (3H, s)
8.19 (lH, dd), 7.75
(1H, s), 7.72 (lH,
dd), 7.62 (1H, td),
1.145 CH3-0-CH 2- 0 0 H 7.34 (1H, dd), 5.55-
5.50 (2H, m), 3.54
(3H, s), 2.69 (3H, s)
8.47 (1H, d), 7.87
(1H, dd), 7.74 (1H,
s), 7.49 (1H, d),
1.146 CH3-0-CH - H 5.54 (lH, d), 5.51
(1H, d), 3.55 (3H,
s), 2.69 (3H, s)
d8.39 - 8.43 (m, 1
H) 8.30 - 8.36 (m, 1
H) 7.97 - 8.02 (m, 1
1.147 Me H H) 7.93 (s, 1 H)
7.81 - 7.89 (m, 3 H)
6.53 (t, J=7.0 Hz, 1
H) 3.67 (s, 3 H);
8.1 1 (s, 1 H) 7.90
(dd, J=5.9, 1.1 Hz, 1
H) 7.49 (m, J=5.9
1.148 Hz, 2 H) 7.17 - 7.24 Me H (m, 2 H) 6.49 (t,
J=7.0 Hz, 1 H) 3.84
(s, 2 H);
3.90 (2 H, s) 7.73 ( 1
H, d, J=1.074 Hz)
1.149 Me H 8.02 ( 1 H, dd,
J=2.149, 1.074 Hz)
C I
3.88 (2 H, s) 4.07 (2
H, s) 6.93 ( 1 H, d,
J=5.37 Hz) 7.73 ( 1 1.150 Me H H, s) 8.14 ( 1 H, d,
J=5.37 Hz) 8.15 -
8.16 ( 1 H, m)

TABLE C2 - Examples of herbicidal compounds of the present invention.

CMP R R3 R5 R6 R7 R8 R9 NMR
8.48 ( 1 H, s), 7.96 - 8.01 ( 1
H, m), 7.65 ( 1 H, s), 7.53 ( 1
H, d, J=7. Hz), 4.16 ( 1 H,
2.015 c-Propyl H -S(0) 2Me -CF 3 H H H dt, J=7.8, 3.7 Hz), 3.03 (3
H, s), 1.27 (2 H, br. s.), 1.07
(2 H, dd, J=7.5, 1.6 Hz)
8.5 (1H, s), 8.0 (1H, d), 7.7
-S(0) 2Me (1H, s), 7.5 (1H, d), 4.3
2.016 Ethyl H -CF 3 H H H
e (2H, b ), 3.0 (3H, s), 1.5
(3H, t)
8.2 (lH, b s), 7.8 (lH, dd),
7.6 (1H, s), 7.4 (1H, d), 4.3
2.017 Ethyl H -S(0) 2Me CI H H H (2H, b m), 3.1 (3H, s), 1.4
(3H, t)
2.01 8 /-propyl H CI H CI H H
0.71 - 0.82 (2 H, m) 0.87 -
1.07 (2 H, m) 1.21 - 1.32 ( 1
H, m) 2.18 (3 H, s) 3.23 (3
2.019 Methyl cPr -S(0) Me H H H H, s) 3.41 (2 H, br. s.) 3.81
(3 H, s) 4.60 (2 H, t, J=9.9
Hz) 7.48 ( 1 H, d, J=8.1 Hz)
8.09 ( 1 H, d, J=8.1 Hz)
2.13 (3 H, s) 3.24 (3 H, s)
3.40 (2 H, br. s.) 3.93 (3 H,
s) 4.60 (2 H, t, J=9.9 Hz)
2.020 Methyl vinyl -S(0) Me H H H 5.29 - 5.34 ( 1 H, m) 5.95 -
6.10 (2 H, m) 7.41 ( 1 H, d,
J=8.1 Hz) 8.09 ( 1 H, d,
J=8.1 Hz)
1.40 (3 H, t, J=7.3 Hz) 2.17
(3 H, s) 3.22 (3 H, s) 3.30 -
3.61 (2 H, m and 2 H, br s)
2.021 Methyl S(0) Me -S(0) 2Me H H 3.95 (3 H, s) 4.58 (2 H, t,
Et J=9.9 Hz) 7.51 ( 1 H, d,
J=8.1 Hz) 8.06 ( 1 H, d,
J=8.1 Hz)
8.40 (lH, b d), 8.02 (1H,
2.022 Methyl -N0 2 -S(0) 2Me -CF 3 H H H dd), 7.53 (1H, d), 3.99 (3H,
s), 2.98 (3H, s)
CMP R R3 R5 R6 R7 R8 R9 NMR
1.83 (3 H, d, J=1.6 Hz) 2.16
(3 H, s) 3.23 (3 H, s) 3.29 -
CH2= 3.48 (2 H, br s) 3.91 (3 H, s)
2.023 Methyl C(CH Me H H H 4.60 (2 H, t, J=9.9 Hz) 4.76
( 1 H, s) 5.13 ( 1 H, s) 7.38 ( 1 3)- H, d, J=8. 1 Hz) 8.03 ( 1 H,
d, J=8.1 Hz)
1.07 (3 H, d, J=7.0 Hz) 1.10
(3 H, d, J=7.0 Hz) 2.13 (3
H, s) 2.42 - 2.54 ( 1 H, m)
3.24 (3 H, s) 3.33 - 3.50 (2
2.024 Methyl z'-Pr Me -S(0) 2Me H H H, br s) 3.88 (3 H, s) 4.60 (2
H, t, J=10.2 Hz) 7.40 ( 1 H,
d, J=8.1 Hz) 8.08 ( 1 H, d,
J=8.6 Hz)003
9
2.23 (3 H, s) 3.24 (3 H, s)
3.30 - 3.51 (2 H, b s) 3.98
2.025 Methyl -CN Me -S(0) 2Me H H (3 H, s) 4.61 (2 H, t, J=10.2
Hz) 7.52 ( 1 H, d, J=8.1 Hz)
8.14 ( 1 H, d, J=8.6 Hz)
7.98 (lH, d), 7.56 (1H, s),
7.45 (1H, d), 3.88 (7H, s
2.026 Methyl H -S(0) 2Me H Br H overlapping with br s), 3.36
(3H, s), 3.17 (2H, br m),
2.96 (2H, b m)
8.18 (1H, s), 7.55 (lH, s),
4.22-4.17 (1H, m), 3.97-
3.95 (1H, m), 3.91-3.83
2.027 Methyl H -S(0) 2Me Br Br H (3H, m), 3.87 (3H, s), 3.79-
3.74 (1H, m), 3.34 (3H, s),
2.99-2.97 (1H, m), 2.73-
2.71 (lH, m)
8.31 (1H, d), 7.80 (1H, dd),
7.68 (1H, s), 7.33 (1H, d),
2.028 Methyl H -S(0) 2Me -CºC H H H 3.88 (3H, s), 3.28 (1H, s),
2.99 (3H, s)
8.20 (1H, d), 7.69 (1H, dd),
-CºC- 7.68 (1H, s), 7.27 (1H, d),
2.029 Methyl H -S(0) 2Me H H H
CH3
3.87 (3H, s), 2.98 (3H, s),
2.10 (3H, s)
7.75 (1H, d), 7.68 (1H, s),
CF3CH - 7.35-7.29 (2H, m), 4.50
2.030 Methyl H -S(0) 2Me H H H
O- (1H, d), 4.46 (1H, d), 3.88
(3H, s), 2.98 (3H, s)
CMP R R3 R5 R6 R7 R8 R9 NMR
8.01 (IH, m), 7.69 (lH, s),
7.54-7.52 (IH, m), 7.25 2.03 1 Methyl H -S(0) 2Me Me H H H (IH, d), 3.88 (3H, s), 2.97
(3H, s), 2.51 (3H, s)
9.06 (IH, d), 8.57 (IH, dd),
2.032 Methyl H -S(0) 2Me -N0 2 H H H 7.69 (IH, s), 7.61 (IH, d),
3.90 (3H, s), 3.06 (3H, s)
8.42 (IH, d), 7.94 (IH, dd),
7.75 (IH, s), 7.68-7.66 (2H, 2.033 Methyl H -S(0) 2Me -phenyl H H H m), 7.53-7.43 (4H, m), 3.90
(3H, s), 3.03 (3H, s)
2.034 Methyl H -S(0) 2Me NH C(0)- H H H
8.05 (IH, d), 7.66 (IH, s),
7.55 (IH, dd), 7.40-7.28
2.035 Methyl H -S(0) Me Benzyl-5- H H H (5H, m), 7.21 (lH, d), 4.25
(2H, s), 3.87 (3H, s), 2.92
(3H, s)
8.39 (IH, d), 7.94 (IH, dd),
Benzyl- 7.65 (IH, s), 7.45 (IH, d),
2.036 Methyl H -S(0) Me H H H 7.38-7.30 (3H, m), 7.16-
S(0) - 7.15 (2H, m), 4.42 (2H, s),
3.89 (3H, s), 2.94 (3H, s)
8.55 (lH, d), 8.10 (lH, dd),
7.71 (IH, s), 7.58 (lH, d),
2.037 Methyl H -S(0) 2Me H H H 3.90 (3H, s), 3.80 (4H, m),
3.12 (4H, m), 3.04 (3H, s)
8.59 (lH, d), 8.15 (lH, dd),
(CH 3) CH 7.69 (IH, s), 7.52 (IH, d),
2.038 Methyl H -S(0) 2Me N(CH 3)S( H H H 4.31 (IH, pent), 3.89 (3H,
o) - s), 3.03 (3H, s), 2.80 (3H,
s), 1.10 (6H, d)
CMP R R3 R5 R6 R7 R8 R9 NMR
2.039 Methyl -NH 2 -S(0) 2Me -CF 3 H H H
8.16 (lH, br d), 7.71 (lH, br
CH3O - dd), 7.69 (1H, s), 7.35 (1H, 2.040 Methyl H -S(0) 2Me H H H
CH - d), 4.58 (2H, s), 3.88 (3H,
s), 3.48 (3H, s), 2.99 (3H, s)
CH3- 8.43 (lH, br d), 7.97 (lH, br
2.041 Methyl -S(0) 2Me -CF 3 H H H dd), 7.47 (1H, d), 3.78 (3H,
O- s), 3.75 (3H, s), 3.01 (3H, s)
2.042 Methyl H -S(0) Me -C(0)OH H H H
8.16 (1H, d), 7.73 (lH, dd),
i-Pr-O- 7.69 (1H, s), 7.34 (1H, d),
2.043 Methyl H -S(0)2Me H H H 4.62 (2H, s), 3.86 (3H, s),
CH - 3.76 (1H, pent), 2.99 (3H,
s), 1.27 (6H, d)
c-hexyl-
2.044 Methyl H -S(0)2Me CH -0- H H H
CH -
2.045 Methyl H -S(0) 2Me H H H
2.046 Methyl H -S(0) 2Me H H H
CMP R R3 R5 R6 R7 R8 R9 NMR
7.90 (lH, dd), 7.69 (lH, br
d), 7.64 (1H, s), 7.53 (1H,
d), 7.34-7.31 (1H, m), 7.26-
2.047 Methyl H S(0) 2benz -CF 3 H H H 7.22 (2H, m), 7.08-7.07
y i (2H, m), 4.28 (2H, s), 3.91
(3H, s)
2.048 Methyl H S(0) N(C -CF 3 H H H
¾ ) -Pr)
8.30 (1H, d), 7.94 (1H, dd),
7.73 (1H, s), 7.56 (1H, d),
2.049 Methyl H -CF 3 H H H
— □ 3.88 (3H, s), 3.65-3.62 (4H,
m), 2.98 (4H, br s)
8.43 (lH, br d), 7.96 (lH,
dd), 7.47 (1H, d), 4.17 (2H,
2.050 Methyl EtO- -S(0) 2Me -CF 3 H H H q), 3.76 (3H, s), 3.01 (3H,
s), 1.19 (3H, t)
8.43 (lH, br d), 7.96 (lH,
dd), 7.47 (1H, d), 4.05 (2H,
2.05 1 Methyl nPr-O- -S(0) 2Me -CF 3 H H H t), 3.76 (3H, s), 3.01 (3H, s),
1.61-1.52 (2H, m), 0.78
(3H, t)
8.42 (lH, b d), 7.96 (1H,
dd), 7.44 (1H, d), 5.01 (1H,
2.052 Methyl iPr-O- -S(0) Me -CF 3 H H H pent), 3.76 (3H, s), 3.01
(3H, s), 1.19 (3H, d), 1.16
(3H, d)
8.16 (lH, d), 7.75 (lH, dd),
CF3CH 0 7.69 (1H, s), 7.39 (1H, d),
2.053 Methyl H -S(0) 2Me H H H
CH - 4.82 (2H, s), 3.97 (2H, q),
3.88 (3H, s), 2.99 (3H, s)
8.20 ( 1 H, dd, J=7.9, 1.1
Hz) 7.81 ( 1 H, td, J=7.6, 1.4
Hz) 7.74 ( 1 H, td, J=7.7, 1.3
Hz) 7.70 ( 1 H, s) 7.40 ( 1 H,
2.054 Vinyl H -S(0) 2Me H H H H dd, J=7.5, 1.2 Hz) 5.18 ( 1
H, d, J=16.5 Hz) 4.82 ( 1 H,
d, J=16.5 Hz) 3.83 (3 H, s)
3.00 (3 H, s)
CMP R R3 R5 R6 R7 R8 R9 NMR
8.17 ( 1 H, d, J=8.1 Hz),
7.76 ( 1 H, s), 7.69 ( 1 H, d,
2.055 H H CI -S(0) 2Me H H J=8.6 Hz), 4.64 (2 H, t,
J=10.2 Hz), 3.47 (2 H, t,
J=10.2 Hz), 3.28 (3 H, s)
8.37 (lH, b d), 8.06 (lH, br
2.056 Me -OH -S(0) 2Me -CF 3 H H H dd), 7.61 (1H, d), 3.66 (3H,
s), 3.14 (3H, s)
8.17 (lH, d), 7.74 (lH, dd),
C H 3O - 7.69 (1H, s), 7.34 (1H, d),
4.70 (2H, s), 3.88 (3H, s),
2.057 Me H -S(0) 2Me c ¾-o- H H H 3.74-3.72 (2H, m), 3.64-
CH - 3.62 (2H, m), 3.42 (3H, s),
2.99 (3H, s)
TABLE C3 - Examples o f herbicidal compounds o f the present invention.
Cmp R1 R4 R5 R6 NMR
8.49 (IH, br d), 7.98 (IH, dd), 7.77
3.001 Methyl CH3C(0)- -S(0) 2Me -CF3
(IH, s), 7.52 (IH, d), 3.88 (3H, s),
3.02 (3H, s), 2.21 (3H, s)
8.46 (IH, br d), 7.97-7.94 (3H, m),
7.83 (IH, s), 7.64-7.60 (2H, m), 7.46- 3.002 Methyl Phenyl-C(O)- -S(0) Me -CF3 7.42 (2H, m), 3.91 (3H, s), 3.09 (3H,
s)
8.48 (IH, br d), 8.00 (IH, dd), 7.78
3.003 Methyl CH3OC(0)- -S(0) Me -CF3 (IH, s), 7.54 (IH, d), 3.90 (3H, s),
3.88 (3H, s), 3.03 (3H, s)
8.48 (IH, br d), 7.99 (IH, dd), 7.76
3.004 Methyl C ¾SC(0)- -S(0) 2Me -CF3 (IH, s), 7.53 (IH, d), 3.89 (3H, s),
3.02 (3H, s), 2.91 (2H, q), 1.30 (3H, t)
8.44 (IH, br d), 8.03 (IH, br dd), 7.78
(IH, s), 7.64 (IH, d), 3.90 (3H, s),
3.005 Methyl «Pr-S(0) 2- -S(0) 2Me -CF3 3.91-3.85 (IH, m), 3.79-3.73 (IH, m),
3.07 (3H, s), 2.01-1.95 (2H, m), 1.10
(3H, t)
8.43 (IH, br d), 8.00 (IH, br dd), 7.87
4-Me-phenyl- (2H, d), 7.77 (IH, s), 7.65 (IH, d), 3.006 Methyl -S(0) 2Me S(0) - -CF3 7.33 (2H, d), 3.87 (3H, s), 3.06 (3H,
s), 2.45 (3H, s)
TABLE C4 - Examples of herbicidal compounds of the present invention.
Compound R R5 R6 NMR
8.1 (1H, d), 8.0 (1H, d), 7.9 (1H, br s), 4.3 (2H,
4.001 Ethyl- -S0 2Me -CF 3 q), 3.4 (3H, s), 1.4 (3H, t)
4.002 Methyl- -CF 3
3.41 (3 H, s) 3.86 (3 H, s) 7.85 ( 1 H, s) 8.00 ( 1 H,
4.003 Methyl- -S0 2Me -CF 3 d, J=8.1 Hz) 8.13 ( 1 H, d, J=8.1 Hz)
1.14 (6 H, d, J=5.9 Hz) 2.58 - 2.69 (21 H, m) 3.41
(2 H, d, J=10.7 Hz) 3.64 - 3.76 (2 H, m) 3.88 (3
4.004 Methyl- 0 N-M- -CF 3 H, s) 7.31 ( 1 H, d, J=8.1 Hz) 7.86 ( 1 H, d, J=7.0
Hz) 7.95 ( 1 H, s)
d 11.28 (br s, 1 H) 7.97 (d, J=7.5 Hz, 1 H) 7.77 (s,
4.005 Methyl- C H 3-O- -CF 3 1 H) 7.53 (d, J=7.5 Hz, 1 H) 3.85 (s, 3 H) 3.65 (s,
3 H);
d 12.21 (br. s., 1 H) 7.90 (d, J=8.1 Hz, 1 H) 7.77
4.006 Methyl- -OH -CF 3 (s, 1 H) 7.35 (d, J=7.0 Hz, 1 H) 3.65 (s, 3 H);
Compound R R5 R6 NMR
4.007 Methyl- HOC(0)CH -CF 3
3.88 (3 H, s) 7.14 - 7.19 (2 H, m) 7.19 - 7.24 ( 1 H,
4.008 Methyl- Ph-O- -CF 3
m) 7.36 - 7.42 (2 H, m) 7.49 ( 1 H, d, J=8.1 Hz)
8.01 ( 1 H, s) 8.07 ( 1 H, d, J=8.6 Hz)
3.87 (3 H, s) 5.46 (2 H, s) 7.27 - 7.35 (3 H, m)
4.009 Methyl 3-Cl-benzyl-O- -CF 3
7.40 ( 1 H, d, J=7.5 Hz) 7.45 ( 1 H, s) 7.89 ( 1 H, s)
7.97 ( 1 H, d, J=7.5 Hz)
3.88 (3 H, s) 7.63 ( 1 H, s) 7.85 ( 1 H, d, J=7.5 Hz)
4.010 Methyl jri -CF 3 7.95 ( 1 H, s) 8.11 ( 1 H, d, J=8.1 Hz) 9.08 ( 1 H, s)
d 7.87 - 8.10 (m, 2 H) 7.59 (s, 1 H) 7.02 (dd,
4.01 1 Methyl CHF CH 0 - H J=7.5, 4.8 Hz, 1H) 6.30 (tt, J=54.8, 3.8 Hz, 1 H)
4.50 (td, J=15.0, 3.2 Hz, 2 H) 3.53 (s, 3 H);
4.012 Methyl C H OC(0)-0- -CF 3
4.013 Methyl CH CHCH 0 - -CF 3
3.90 (3 H, s) 7.75 ( 1 H, d, J=8.1 Hz) 7.79 ( 1 H, s)
4.014 Methyl Cl -CF 3 7.97 ( 1 H, d, J=7.0 Hz)
Compound R R5 R6 NMR
3.71 ( 1 H, s) 7.46 - 7.53 ( 1 H, m) 8.10 - 8.16 ( 4.015 Methyl -CN -CF3 m) 8.19 ( 1 H, s) 1 H,
0 3.54 - 3.63 (4 H, m) 3.76 - 3.83 (4 H, m) 3.89 (3
4.016 Methyl O N—S - -CF3 H, s) 7.89 ( 1 H, s) 7.94 ( 1 H, d, J=8.1 Hz) 8.10 ( 1
— 0 H, d, J=8.1 Hz)
(CH3) CHN(CH 1.23 (6 H, d, J=6.4 Hz) 2.99 (3 H, s) 3.88 (3 H, s)
4.017 Methyl 4.20 ( 1 H, dt, J=13.4,
3)-so - -CF3 6.7 Hz) 7.89 ( 1 H, s) 7.91 ( 1
H, d, J=2.7 Hz) 8.06 ( 1 H, d, J=7.5 Hz)
4.01 8 Methyl -S(0) 2Et -CN
4.019 Methyl -S(0) 2NH -CF3
TABLE C5 - Examples of herbicidal compounds of the present invention.
Compound R R5 R13a R13b NMR
9.3 (IH, m), 8.4 (lH, s), 8.3 (IH,
5.001 Ethyl -CF3 H H d), 7.7 (IH, s), 7.6 (IH, d), 4.4 (2H,
q), 1.5 (3H, t)
2.72 (s, 3 H), 2.83 (s, 3 H), 3.92 (s,
5.002 Methyl -CF3 Methyl Methyl 3 H), 7.39 (s, 1 H), 7.72 (s, 1 H),
8.41 (s, 1H)
TABLE C6 - Examples of herbicidal compounds of the present invention.
Compound R R8 R7 NMR
2.48 (3 H, s) 3.84 (3 H, s) 7.39 - 7.45
( 1 H, m) 7.47 - 7.53 (2 H, m) 7.57 -
6.001 Methyl Methyl -phenyl 7.62 (2 H, m) 7.63 ( 1 H, s) 8.25 ( 1 H,
s)
2.49 (3 H, s) 3.85 (3 H, s) 7.32 - 7.37
( 1 H, m) 7.55 ( 1 H, s) 7.63 ( 1 H, dd,
6.002 Methyl Methyl J=5.4, 1.6 Hz) 8.03 - 8.08 ( 1 H, m)
8.22 ( 1 H, s)
0.97 (3 H, t, J=7.3 Hz) 1.41 (21 H, dd,
J=15.0, 7.5 Hz) 1.77 - 1.87 (2 H, m) 6.003 Methyl Methyl n-butyl 2.42 (3 H, s) 3.83 (3 H, s) 4.19 - 4.26
(2 H, m) 7.47 ( 1 H, s) 8.08 ( 1 H, s)
TABLE C7 - Examples of herbicidal compounds of the present invention.
Compound R6 R9 NMR
d 9.51 (s, 1 H) 7.83 - 7.91 (m, 3 H) 7.79 (d, J=7.0 Hz, 1H) 7.75
7.001 4-CF 3-phenyl- (d, J=7.0 Hz, 1H) 7.68 (d, J=7.5 Hz, 2 H) 6.46 (t, J=7.0 Hz, 1
H) 3.61 (s, 3 H)
7.002 -CF3 3-NH 2-phenyl-
7.83 (IH, s), 7.73 (IH, d), 7.41-7.37 (IH, m), 7.12-7.10 (IH,
7.003 -CF3 3-MeO-phenyl- m), 7.05-7.03 (IH, m), 7.01-6.97 (IH, m), 6.70 (IH, d), 3.79
(3H, s), 3.77 (3H, s)
3-CH 3C(0)NH-
7.004 -CF3 phenyl-
7.88 (IH, s), 7.79 (IH, d), 7.55-7.51 (IH, m), 7.35-7.29 (2H,
7.005 -CF3 3-CF 30-phenyl- m), 7.23 (IH, m), 6.75 (IH, d), 3.79 (3H, s)
7.85 (IH, s), 7.72 (IH, dd), 7.24 (2H, d), 7.15 (2H, d), 6.71 (IH,
7.006 -CF3 4-CH 3-phenyl- d), 3.78 (3H, s), 2.38 (3H, s)
Compound R6 R9 NMR
2-CH 3,5F- 7.86 (IH, s), 7.81 (IH, dd), 7.27 (IH, dd), 7.05 (IH, td), 6.89
7.007 -CF 3 phenyl (IH, dd), 6.76 (IH, d), 3.79 (3H, s), 2.10 (3H, s)
7.008 -CF 3 3-MeS(0) 2-NH-
8.31 (2H, d), 7.87 (IH, s), 7.83 (IH, dd), 7.57 (2H, d), 6.78 (IH,
7.009 -CF 3 4-N0 2-phenyl d), 3.79 (3H, s)
7.010 -CF 3
3.85 (3H, s), 6.65 (IH, d), 7.4-7.8 (4H, m), 7.85 (IH, s)
3.8 (3H, s), 5.25 (lH,d), 5.75 (IH, d), 6.6 (IH, d), 6.7 (IH, dd), 7.01 1 -CF 3 3-vinyl-phenyl- 7.2-7.7 (5H, m), 7.8 (IH, s)
7.012 -CF 3 3-F-phenyl - 3.85 (3H, s), 6.6 (IH, d), 7.0-7.7 (5H, m), 7.9 (IH, s)
7.013 -CF 3 3-HC(0)-phenyl-
1.3 (6H, d), 2.9 (IH, m), 3.85 (3H, s), 6.7 (IH, d), 7.1-7.4 (5H, 7.014 -CF 3 3-z'Pr-phenyl- m), 7.9 (IH, s)
Compound R6 R9 NMR
2-MeO, 5-z'Pr- 1.2 (6H, d), 2.9 (IH, m), 3.85 (3H, s), 6.6 (IH, d), 6.9-7.45 (4H, 7.015 -CF3 phenyl- m), 7.9 (IH, s)
1.4 (3H, t), 3.85 (3H, s), 4.05 (2H, q), 6.6 (IH, d), 6.8-7.7 (5H, 7.016 -CF3 3-EtO-phenyl- m), 7.9 (IH, s)
3,4,5 3.85 (3H, s), 6.6 (IH, d), 6.9-7.7 (3H, m), 7.9 (IH, s) 7.017 -CF3 trifluorophenyl-
7.01 8 -CF3 3-CF 3-phenyl- 3.85 (3H, s), 6.6 (IH, d), 7.4-7.7 (4H, m), 7.9 (IH, s)
7.019 -CF3 3-CN-phenyl- 3.8 (3H, s), 6.7 (IH, d), 7.5-7.7 (4H, m), 7.9 (IH, s)
2.5 (3H, s), 3.85 (3H, s), 6.6 (IH, d), 7.1-7.7 (5H, m), 7.9 (IH, 7.020 -CF3 3-MeS-phenyls)
3,4,5 trimethoxy- 3.89 (3H, s), 3.85 (3H, s), 3.84 (6H, s), 6.5 (2H,s), 6.6 (IH, d), 7.021 -CF3 phenyl- 7.4 (IH, d),7.9 (IH, s)
7.022 -CF3 3,5 dichlorophenyl- 3.8(3H, s), 6.6 (IH, d), 7.2-7.5 (4H, m), 7.9 (IH, s)

Compound R6 R9 NMR
7.03 1 -CF 3 4-CN-phenyl- 3.85 (3H, s), 6.65 (IH, d), 7.45-7.75 (5H, m), 7.85 (IH, s)
2.35 (3H, s), 3.85 (3H, s), 6.6 (IH, d), 7.05 -7.5 (4H, m), 7.9 7.032 -CF 3 2-C1, 5-Me-phenyl- (IH, s)
3.84 (3H, s), 3.85 (3H, s), 6.6 (IH, d), 6.9 - 7.4 (5H, m), 7.9 7.033 -CF 3 4-MeO-phenyl- (IH, s)
3.85 (3H, s), 5.3 (IH, d), 5.8 (IH, d), 6.6 (IH, d), 6.75 (IH, dd), 7.034 -CF 3 2-vinylphenyl- 7.1 - 7.7 (5H, m), 7.9 (IH, s)
7.035 -CF 3 4-CF 3-phenyl- 3.85 (3H, s), 6.6 (IH, d), 7.4-7.7 (5H, m), 7.9 (IH, s)
2.5 (3H, s), 3.85 (3H, s), 6.6 (IH, d), 7.2-7.7 (5H, m), 7.9 (IH, 7.036 -CF 3 4-MeS-phenyls)
7.037 -CF 3 4-CH(0)-phenyl-
2.15 (3H, s), 3.85 (3H, s), 6.6 (IH, d), 7.05 -7.5 (4H, m), 7.9 7.038 -CF 3 2-Me, 4-Cl-phenyl- (IH, s)
Compound R6 R9 NMR
7.039 -CF3 2,4 dichlorophenyl- 3.85 (3H, s), 6.6 (IH, d), 7.15-7.55 (4H, m), 7.9 (IH, s)
7.040 -CF3
7.041 -CF3 2-Cl, 4-CF 3 phenyl- 3.85 (3H, s), 6.6 (IH, d), 7.15-7.5 (4H, m), 7.9 (IH, s)
2-Me, 4-CN- 2.2 (3H, s), 3.85 (3H, s), 6.65 (IH, d), 7.2 -7.6 (4H, m), 7.9 (IH, 7.042 -CF3 phenyl- s)
TABLE C8 - Examples of herbicidal compounds of the present invention.
Compound R R5 R6 NMR
2.96 - 3.10 (2 H, m) 3.22 - 3.33 (2 H,
m) 3.45 - 3.54 (2 H, m) 3.63 - 3.76
8.001 Methyl -CF 3 (10 H, m) 3.79 (3 H, s) 7.52 ( 1 H, s)
8.19 ( 1 H, s)
TABLE C9 - Examples of herbicidal compounds of the present invention.
Compound R6 R9 NMR
d 8.26 (t, J=8.1 Hz, 1 H) 8.08 (d, J=8.6 Hz, 1 H) 8.00 (d,
9.001 -CF 3
J=8.1 Hz, 1 H) 7.90 (dd, J=7.0, 2.1 Hz, 1 H) 7.77 (dd,
J=7.0, 2.1 Hz, 1 H) 6.51 (t, J=7.0 Hz, 1 H) 3.63 (s, 3 H);
d 7.93 (s, 1 H) 7.88 (dd, J=7.0, 1.6 Hz, 1 H) 7.74 (dd,
J=6.4, 1.6 Hz, 1 H) 6.56 (t, J=7.0 Hz, 1 H) 5.97 - 6.08 (m,
9.002 H CH =CH-CH - 1 H) 5.17 - 5.30 (m, 2 H) 4.71 (dt, J=5.4, 1.6 Hz, 2 H)
3.77 (s, 3 H)
d 7.91 - 7.94 (m, 1 H) 7.88 (dd, J=7.0, 2.1 Hz, 1 H) 7.80
9.003 H Methyl (dd, J=6.4, 2.1 Hz, 1 H) 6.54 (t, J=7.0 Hz, 1 H) 3.77 (s,
3H) 3.66 (s, 3 H)
d 7.91 (s, 1 H) 7.80 - 7.88 (m, 2 H) 7.28 - 7.35 (m, 2 H)
9.004 H 4-MeO-benzyl- 6.87 - 6.92 (m, 2 H) 6.54 (t, J=7.0 Hz, 1 H) 5.21 (s, 2 H)
3.76 (d, J=l.l Hz, 6 H);
d 7.91 (s, 1 H) 7.89 (dd, J=7.5, 1.6 Hz, 2 H) 7.70 - 7.75
9.005 H CF3CH - (m, 1 H) 6.54 (t, J=7.0 Hz, 1 H) 4.89 (q, J=8.6 Hz, 2 H)
3.77 (s, 3 H)
d 7.93 (s, 1 H) 7.89 (dd, J=7.5, 1.6 Hz, 1 H) 7.85 (dd,
J=6.4, 2.1 Hz, 1 H) 6.57 (t, J=7.0 Hz, 1 H) 3.95 (d, J=7.5
9.006 H cPr-CH - Hz, 2 H) 3.77 (s, 3 H) 1.29 - 1.40 (m, 1 H) 0.56 - 0.63 (m,
2 H) 0.42 - 0.49 (m, 2 H)
Compound R6 R9 NMR
d 7.96 (br. s, 1 H) 7.90 (dd, J=7.5, 1.6 Hz, 1 H) 7.71 (dd,
9.007 H CH3C(=CH )-CH - J=7.0, 1.6 Hz, 1 H) 6.58 (t, J=7.0 Hz, 1 H) 4.96 (s, 1 H)
4.67 (s, 3 H) 3.77 (s, 3 H) 1.77 (s, 3 H)
d 7.92 (s, 1 H) 7.81 - 7.90 (m, 2 H) 7.31 (m, J=4.3 Hz, 5
9.008 H Benzyl- H) 6.55 (t, J=7.0 Hz, 1 H) 5.29 (s, 2 H) 3.76 (s, 3 H)
d 7.94 (br. s, 1 H) 7.89 (dd, J=7.0, 2.1 Hz, 1 H) 7.75 (dd,
9.009 H CH3OCH CH - J=6.4, 2.1 Hz, 1 H) 6.54 (t, J=7.0 Hz, 1 H) 4.28 (t, J=4.8
Hz, 1 H) 3.78 (s, 1 H) 3.71 (t, J=5.4 Hz, 2 H) 3.34 (s, 2 H)
d 7.93 (s, 1 H) 7.88 (d, J=7.0 Hz, 1 H) 7.00 (d, J=7.5 Hz, 9.010 -CF 3 Me 1 H) 3.77 (s, 3 H) 3.69 (s, 3 H)
d 8.12 (s, 1 H) 7.85 (d, J=7.5 Hz, 1 H) 6.84 (d, J=7.5 Hz,
9.01 1 -CF 3 CH =CHCH - 1 H) 5.93 (m, J=10.9, 10.9, 5.6 Hz, 1 H) 5.18 - 5.33 (m, 2
H) 4.78 (d, J=4.8 Hz, 2H) 3.84 (s, 3H);
9.012 H 2.48 (3H, s), 3.83 (3H, s), 6.47 (IH, app.t), 6.68 (IH, m),
6.94 (IH, d), 7.68 (IH, d), 7.87 (IH, d), 8.09 (IH, s)
3.82 (3H, s), 6.51 (IH, app.t), 7.25 (IH, d), 7.44-7.51 (2H,
9.013 H m), 7.62 (IH, d), 7.91 (IH, d), 8.08 (IH, s)
3.82 (3H, s), 6.52 (IH, app.t), 7.03 (IH, m), 7.18 (IH, m),
9.014 H 7.28 (IH, m), 7.72 (IH, d), 7.86 (IH, d), 8.08 (IH, s)
Compound R6 R9 NMR
3.82 (3H, s), 6.50 (IH, app.t), 7.02 (IH, m), 7.33 (IH, m),
9.015 H 3C1, 4-F-phenyl- 7.42 (IH, d), 7.53 (IH, d), 7.89 (IH, d), 8.03 (IH, s)
9.016 H 4-MeO-phenyl-
3.81 (3H, s), 6.53 (IH, app.t), 7.31-7.59 (6H, m), 7.89
9.017 H 4-Me-phenyl (IH, d), 8.08 (IH, s)
2.53 (3H, s), 3.82 (3H, s), 6.51 (IH, app.t), 7.1 1 (2H, m),
9.01 8 H Phenyl- 7.21 (IH, m), 7.51 (IH, d), 7.89 (IH, m), 8.08 (IH, s)
2.41 (3H, s), 3.78 (3H, s), 6.52 (IH, app.t), 7.20 (IH, d),
9.019 H 3-F,4-Me-phenyl- 7.33-3.41 (2H, m), 7.50 (IH, d), 7.89 (IH, d), 8.05 (IH, s)
3.79 (3H, s), 6.53 (IH, app.t), 7.47 (IH, d), 7.62 (2H, d), 9.020 H 2-Cl,4-Me-phenyl- 7.84 (2H, d), 7.91 (IH, d), 8.06 (IH, s)
9.021 H 3-CN-phenyl-
9.022 H

TABLE CIO - Examples of herbicidal compounds of the present invention.
Compound R6 R7 NMR
3.85 (3 H, s) 4.64 (2 H, d, J=5.9 Hz) 5.30 - 5.42 (2 H, m)
10.001 H -CH CH=CH 5.94 - 6.06 ( 1 H, m) 8.13 ( 1 H, s) 8.14 - 8.23 ( 1 H, m) 8.35 -
8.43 ( 1 H, m)
0.83 (3 H, t, J=7.5 Hz) 1.70 (2 H, dd, J=15.6, 7.5 Hz) 3.86
10.002 3-Cl-phenyl- Pr (3 H, s) 3.93 - 4.00 (2 H, m) 7.39 - 7.57 (4 H, m) 8.17 ( 1 H,
s) 8.41 ( 1 H, s)
0.95 - 1.09 (2 H, m) 1.14 - 1.29 ( 1 H, m) 1.57 ( 1 H, d,
J=14.0 Hz) 1.72 (2 H, d, J=1 1.8 Hz) 1.81 (2 H, d, J=12.9
10.003 3-F-phenyl- chexyl- Hz) 2.71 (2 H, td, J=12.8, 9.4 Hz) 3.85 (3 H, s) 3.90 - 4.00
( 1 H, m) 7.20 - 7.26 ( 1 H, m) 7.27 - 7.30 ( 1 H, m) 7.52 ( 1 H,
td, J=7.9, 5.6 Hz) 8.12 ( 1 H, s) 8.32 ( 1 H, s)
2-Me,5-Cl 2.14 (3 H, s) 3.86 (3 H, s) 7.03 - 7.14 (4 H, m) 7.16 - 7.33 (3
10.004 3-F-phenylphenyl-
H, m) 8.24 ( 1 H, s) 8.63 ( 1 H, s)
1.01 (3 H, t, J=7.3 Hz) 1.14 - 1.22 (2 H, m) 1.30 - 1.35 (2 H,
m) 1.49 (2 H, dq, J=15.0, 7.4 Hz) 1.74 - 1.85 (2 H, m) 2.01
10.005 c-propyl n-butyl ( 1 H, ddd, J=12.5, 7.9, 4.8 Hz) 3.83 (3 H, s) 4.26 - 4.33 (2
H, m) 8.07 ( 1 H, s) 8.21 ( 1 H, s)
Biological Examples
Seeds of a variety of test species are sown in standard soil in pots (Alopecurus
myosuroides (ALOMY), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG),
Solarium nigrum (SOLNI), Amaranthus retoflexus (AMARE), Ipomoea hederacea
(IPOHE)). After cultivation for one day (pre-emergence) or after 8 days cultivation
(post-emergence) under controlled conditions in a glasshouse (at 24/1 6°C, day/night;
14 hours light; 65 % humidity), the plants are sprayed with an aqueous spray solution
derived from the formulation of the technical active ingredient in acetone / water
(50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate,
CAS R 9005-64-5). Compounds are applied at 1000 g/h. The test plants are then
grown in a glasshouse under controlled conditions in a glasshouse (at 24/1 6°C,
day/night; 14 hours light; 65 % humidity) and watered twice daily. After 13 days for
pre and post-emergence, the test is evaluated for the percentage herbicidal damage
caused to the plant. The biological activities are shown in the following table on a
five point scale (5 = 80-100% damage; 4 = 60-79% damage; 3 = 40-59% damage; 2 =
20-39% damage; 1 = 0-19% damage).
TABLE Bl
Compound POST Application PRE Application
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
1.026 5 5 5 5 5 5 5 5 5 5 5 5
1.027 5 5 5 1 5 5 4 5 3 1 5 1
1.028 5 5 5 5 5 5 5 5 5 5 5 5
1.029 5 5 5 5 5 5 5 5 5 5 5 5
1.030 5 5 2 1 4 3 4 5 1 1 2 1
1.03 1 5 5 5 2 5 5 2 5 4 1 5 1
1.032 5 5 5 5 5 5 5 5 5 5 5 4
1.033 5 5 1 2 2 5 5 5 1 1 2 1
1.034 5 5 5 4 5 5 5 5 5 2 5 3
1.035 5 5 1 2 5 5 3 5 1 1 5 4
1.036 5 5 5 5 5 5 1 3 2 3 2 1
1.037 5 5 4 4 4 4 5 5 4 4 5 1
1.038 5 5 5 4 4 4 5 5 3 3 5 1
1.039 5 5 5 4 5 5 4 5 3 2 5 5
1.040 5 5 5 4 5 5 5 5 5 5 5 4
1.041 5 5 5 4 5 5 2 4 2 3 4 1
1.042 5 5 5 5 5 4 5 5 5 5 5 1
1.043 5 5 4 2 4 4 1 1 1 1 1 1
1.044 5 5 5 5 5 5 5 5 5 5 5 1
1.045 4 2 1 1 1 1 1 1 1 1 1 1
1.046 5 5 5 5 5 5 5 5 3 5 5 1
1.047 4 3 1 1 1 3 1 1 1 1 1 1
1.049 5 5 5 5 5 5 5 5 3 2 5 1
1.050 5 5 4 2 5 5 3 5 2 1 5 1
1.05 1 5 5 2 1 2 4 1 5 1 2 4 1
1.052 5 5 5 4 5 5 5 5 4 4 5 1
1.053 5 5 4 5 5 5 5 5 4 5 5 2
1.054 5 5 5 5 5 4 5 5 5 5 5 3
1.055 5 5 1 1 4 4 4 5 1 1 2 2
1.056 5 5 5 5 5 5 4 5 1 5 5 1
1.057 5 5 5 5 5 5 5 5 5 5 5 2
1.058 5 5 5 5 5 5 5 5 5 5 5 5
1.059 5 5 5 5 5 5 5 5 5 5 5 5
1.061 5 5 5 5 5 5 5 5 5 5 5 4
1.062 4 5 4 2 5 5 1 1 1 1 1
1.063 2 3 1 1 1 3 1 1 1 1 1 1
1.064 5 5 1 1 1 4 1 1 1 1 1 1
1.065 4 5 5 1 5 4 1 5 2 1 3
1.066 3 1 1 2 1 2 4 4 1 3 2 5
1.067 5 5 4 2 5 5 3 4 1 1 5 2
1.068 5 5 3 3 5 5 4 4 2 2 5 3
1.069 4 5 1 2 5 4 2 2 2 1 5 4
1.070 4 3 4 1 4 1 1 1 1 1 1 1
1.071 5 5 4 3 5 5 5 5 4 4 5 2
1.072 5 5 5 4 5 5 5 5 5 4 5 5
1.073 5 5 5 4 5 5 5 5 5 5 5 2
1.074 5 5 5 2 5 5 1 5 1 2 4 1
1.075 5 5 2 3 5 5 5 5 1 1 5 2
1.076 4 5 1 2 2 4 2 5 1 1 1 1
1.077 2 4 1 1 1 2 3 3 1 1 1 1
1.078 5 5 5 1 5 4 5 5 5 2 5 2
1.081 5 5 5 5 5 5 5 5 5 5 5 2
1.082 4 2 1 1 1 2 1 1 1 1 1 1
1.084 4 4 2 1 3 4 1 1 1 1 1 1
1.086 1 1 1 1 1 1 1 1 1 1 1 1
Compound POST Application PRE Application
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
1.088 5 5 1 1 5 1 1 5 1 1 1 1
1.089 1 1 1 1 1 1 1 1 1 1 1 1
1.090 2 1 1 1 1 1 1 1 1 1 1 1
1.091 2 1 1 1 1 1 1 1 1 1 1 1
1.092 2 1 1 1 1 2 1 1 1 1 1 1
1.093 2 1 1 1 1 1 1 1 1 1 1 1
1.094 2 1 1 1 1 1 1 1 1 1 1 1
1.095 1 1 1 1 1 1 1 1 1 1 1 1
1.096 1 1 1 1 1 2 1 1 1 1 1 1
1.098 3 2 1 1 1 2 1 1 1 1 1 1
1.099 2 3 1 1 1 2 1 1 1 1 1 1
1.100 2 2 1 1 1 2 1 1 1 1 1 1
1.101 1 1 1 1 1 1 1 1 1 1 1 1
1.103 2 1 1 1 1 1 1 1 1 1 1 1
1. 105 5 5 1 5 5 4 5 1
1.106 4 5 4 2 1 4 1 1 1 1
1.108 3 3 1 1 1 1 1 1 1 1 1 1
1.109 4 5 1 1 2 4 2 5 1 1 1 1
1. 1 10 5 5 1 1 3 5 1 5 1 1 1 1
1. 1 11 3 2 1 1 1 1 1 1 1
1. 1 12 4 5 1 1 1 4 1 1 1 1 1 1
1. 1 13 5 5 2 5 4 5 1 1 1
1. 1 14 1 1 1 1 1 1 1 1 1 1 1 1
1. 1 15 5 2 1 1 1 4 4 4 1 1
1. 1 16 5 4 2 1 2 4 3 5 2 2 1 1
1. 1 18 3 4 1 1 2 2 1 1 1 1 1 1
1. 1 19 5 5 5 5 5 5 5 5 5 5 5
1.120 5 5 5 5 5 5 4 5 4 3 5
1.125 5 5 5 5 5 5 4 5 5 4 5 1
1.126 4 5 2 1 2 3 1 1 1 1 1
1.128 4 1 2 1 1 3 1 1 1 1 1 1
1.129 3 3 2 1 2 2 1 1 1 1 1 1
1.13 1 5 5 4 5 5 4 3 1 1 1 1
1.133 2 1 1 1 3 2 1 1 1 1 1 1
1.134 5 5 2 1 2 5 5 5 1 1 1
1.135 5 5 5 5 5 5 5
1.137 5 5 5 1 5 5 3 2 1 1 1 1
1.138 5 5 5 1 4 1 1 1 1 1 1 1
1.139 5 5 5 5 5 5 5 1 5 5 4
1.140 5 5 3 5 5 5 5 5 1 5 5 2
1.141 5 5 5 5 5 5 5 5 5 5 5 5
1.143 4 1 1 2 2 1 1 3 1 2 1 1
1.144 5 5 5 5 5 5 5 5 4 5 5 4
1.145 5 5 5 3 5 5 2 5 2 1 4 1
1.146 5 5 5 5 5 5 5 5 2 4 5 4
1.147 3 1 1 1 1 1 1 2 2 1 1 1
1.148 3 2 4 1 2 3 1 1 1 1 1 2
1.149 4 4 1 2 1 1 1 1 1 1 1 1
1.150 4 1 1 1 1 1 1 2 1 1 1 2
1.15 1 5 5 5 5 5 5 4 5 2 2 5 5
1.152 1 1 1 1 1 2 2 2 5 4 2 1
1.153 4 2 1 1 1 2 2 2 1 1 2 3
1.154 5 5 5 4 5 5 2 5 2 2 5 5
1.157 5 5 5 3 5 5 3 5 3 2 5 3
1.158 5 5 5 5 5 5 4 5 3 3 5 3
Compound POST Application PRE Application
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
1.159 5 5 5 4 5 5 5 5 5 5 5 1
1.160 5 5 4 3 5 5 4 5 1 1 5 2
1.161 4 5 4 3 4 2 1 3 1 1 1 1
1.163 5 5 5 5 5 5 5 5 5 5 5 4
1.164 5 5 5 1 5 5 2 3 2 1 4 4
1.165 1 1 1 1 1 1 1 1 1 1 1 1
* Applied at 250 g/ha
TABLE B2
Compound POST Application PRE Application
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
2.053 5 5 2 3 3 5 5 5 2 3 5 1
2.054 5 5 5 5 5 5 5 5 5 5 5 4
2.055 5 5 5 3 5 3 2 4 1 2 2 1
2.056 5 5 5 5 5 5 5 5 5 4 5 3
TABLE B3
TABLE B4
TABLE B5
TABLE B6
TABLE B7
Compound POST Application PRE Application
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
7.001 4 3 3 2 4 2 1 1 1 1 1 1
7.003 5 5 3 4 5 3 5 5 4 4 4 3
7.005 5 5 4 4 5 4 5 5 4 4 5 1
Compound POST Application PRE Application
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
7.006 5 4 3 3 5 3 5 5 4 3 5 2
7.007 5 5 5 5 5 5 5 5 5 5 5 4
7.009 5 5 5 5 5 5 5 5 5 5 5 4
7.010 5 5 5 5 5 5 5 5 5 5 5 5
7.01 1 5 5 3 1 5 3 5 5 2 2 1 2
7.012 5 5 5 5 5 5 5 5 5 5 5 1
7.014 5 5 4 1 5 3 5 5 4 3 3 1
7.015 5 5 3 2 4 3 5 5 4 3 3 4
7.016 5 5 2 2 2 1 5 5 2 2 2 1
7.017 5 5 5 5 5 5 5 5 5 5 5 4
7.01 8 5 5 5 5 5 3 5 5 5 5 5 2
7.019 5 5 5 5 5 2 5 5 5 5 5 2
7.021 5 5 5 5 5 4 5 5 5 5 5 4
7.022 5 5 5 4 5 2 5 5 5 5 5 2
7.023 5 5 4 1 4 1 5 5 4 2 2 2
7.027 5 5 5 3 5 2 5 5 3 3 5 1
7.029 5 5 2 3 5 4 5 5 1 2 2 1
7.030 5 5 5 5 5 5 5 5 4 5 5 4
7.03 1 5 5 5 5 5 5 5 5 5 5 5 5
7.032 5 5 5 3 5 5 5 5 5 4 5 5
7.033 5 5 5 5 5 3 5 5 5 5 5 4
7.034 5 5 3 1 3 2 5 5 1 2 1 1
7.035 5 5 5 5 5 4 5 5 5 5 5 3
7.036 5 5 3 2 4 4 5 5 2 2 1 4
7.038 5 5 3 5 5 5 5 5 3 5 5 4
TABLE B8
Compound POST Application PRE A ^plication
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
8.001 5 5 2 1 5 5 5 5 2 1 5 3
TABLE B9
Compound POST Application PRE Application
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
9.001 4 3 4 4 4 1 1 2 1 3 2 1
9.002 5 4 2 1 2 2 1 1 1 1 1 1
9.003 4 4 2 1 1 2 1 2 1 1 1 1
9.004 4 4 1 1 1 3 1 1 1 1 1 1
9.005 4 2 1 1 1 2 1 1 1 1 1 1
9.006 3 3 2 2 1 2 1 1 1 1 1 1
9.007 4 3 2 1 1 2 1 1 1 1 1 1
9.008 3 3 1 1 1 1 2 1 1 4 1
9.009 5 4 3 2 3 3 1 1 1 1 1 1
9.010 5 5 2 2 4 4 1 5 1 1 5 1
9.01 1 5 5 5 4 5 4 1 4 2 5 1
9.016 5 5 3 3 4 2 1 1 1 2 1 1
9.017 4 3 2 2 5 2 1 1 1 2 1 2
TABLE B10
Compound POST Application PRE Application
SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE
10.002 5 5 1 1 2 4 1 4 1 1 1 1
10.003 5 5 4 1 5 4 1 5 1 1 1 1
10.004 5 5 3 1 4 4 1 2 1 1 1 1
10.005 5 5 5 2 5 4 5 5 1 1 2 1
Claims
1. A compound Formula (I):
or an agronomically acceptable salt thereof,
wherein: -
R1 is selected from the group consisting of hydrogen, C -C lkyl, C3-
Cecycloalkyl, C2-C6alkenyl, C2-C6alkynyl, Ci-Cehaloalkyl, Ci-Cealkoxy-Ci-
C3-alkyl, Cs-CecycloalkylCi-Cs-alkyl-, tetrahydropyranyl- and benzyl-,
wherein the benzyl is optionally substituted by one or more R1 1
R is selected from the group consisting of Al, A2 and A3
(Al) (A2) (A3)
wherein
X1 is N or CR7;
X2 is N or CR8;
X3 is N or CR9;
X4 is N or CR6;
R is selected from the group consisting of hydrogen, hydroxyl, halo, nitro,
amino, cyano, C -C lk l, CrQalkoxy-, C3-C6cycloalkyl, C2-C6alkenyl, C -
C6alkynyl, Ci-Cehaloalkyl, Ci-Cealkoxy-CrQ-alkyl, Cs-Cecycloalkyl-Ci-Qalkyl,
C1-C6alkyl-S(0) p-, C1-C6alkyl-S(0) p- Ci-C3-alkyl, Ci-Cehaloalkyl-
S(0)p-, Ci-Csalkylamino, Ci-Csdialkylamino and C1-C6haloalkyl-S(0) p-C1-
C3-alkyl;
R4 is selected from the group consisting of hydrogen, Ci-Cealkylcarbonyl-,
arylcarbonyl-, Ci-Cealkoxycarbonyl-, Ci-C6alkyl-S(0) p-, Ci-Cealkyl-
S(0) pcarbonyl- and aryl-S(0) p-, wherein said aryl groups may be optionally
substituted by one or more R1 1
R5 is selected from the group consisting of hydroxyl, halogen, Ci-Cealkyl, Ci-
C6cycloalkyl, Ci-Cehaloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl,
-C alkoxy-, C2-C6 alkenyloxy-, Q-CecycloalkylCi-Q-alkyl-, C -C
alkoxyCi-Csalkyl-, Ci-C alkoxy-C2-C6alkoxy-, C -C alkoxy-C2-C6alkoxy-
Ci-Csalkyl-^i-Ce haloalkoxy-, C -C haloalkoxy-Ci-Csalkyl-, Ci-Cealkyl-
S(0)p-, C1-C6haloalkyl-S(0)p-, aryl, aryl-S(0) p-, heterocyclyl, heterocyclyl-
S(0)p-, aryloxy-, aryl-C2-C6alkyl-, aryl-Ci-Cealkoxy-, heterocyclyloxy-,
heterocyclyl-C i-C3alkoxy-Ci-C3alkyl-, hydroxycarbonyl, hydroxycarbonyl-
Ci-C3 alkoxy-, Ci-C3 alkoxycarbonyl-, Ci-C3 alkoxycarbonyl-Ci-C 3 alkoxy-,
Ci-Qalkylamino-, Ci-Csdialkylamino-, Ci-C3 alkylamino-S(0) p-, Ci-C3
alkylamino-S(0)p-C 1-C3alkyl-, Ci-C3 dialkylamino-S(0) p-, Ci-C3
dialkylamino-S(0)p-C 1-C3alkyl-, Ci-Csalkylaminocarbonyl-, C -
Csalkylaminocarbonyl-Ci-Csalkyl-, Ci-Csdialkylaminocarbonyl-, Ci-C3
dialkylaminocarbonyl-Ci-Csalkyl-, Ci-Csalkylcarbonylamino-, Ci-C3 alkyl-
S(0)p-amino-, C1-C3alkyl-S(0) p-C1-C3alkylamino-, Ci-C3alkyl-S(0)paminoCi-
Qalkyl-, cyano and nitro, wherein said heterocyclyls are five or six
membered heterocyclyls containing from one to three heteroatoms each
independently selected from the group consisting of oxygen, nitrogen and
sulphur, and wherein the aryl or heterocyclyl components may be optionally
substituted by one or more substituents selected from the group consisting of
halo, Ci-C3alkyl, Ci-Cshaloalkyl, Ci-C3 alkoxy, Ci-C3 haloalkoxy, Ci-Cealkyl-
S(0) p-, phenyl, cyano and nitro;
R6 and R9 are independently selected from the group consisting of hydrogen,
hydroxyl, halogen, Ci-Cealkyl, Ci-Cecycloalkyl, Ci-Cehaloalkyl, C2-C6alkenyl,
C2-C6haloalkenyl, C2-C6alkynyl, Ci-Ce alkoxy-, C2-C6 alkenyloxy-, C3-
CecycloalkylCi-Cs-alkyl-, C -C alkoxyCi-Csalkyl-, C -C alkoxy-C2-
C6alkoxy-, -C alkoxy-C2-C6alkoxy-C1-C3alkyl-,C1-C6 haloalkoxy-, -C
haloalkoxy-Ci-Csalkyl-, C1-C6alkyl-S(0) p-, C1-C6haloalkyl-S(0) p-, aryl, aryl-
S(0) p-, heterocyclyl, heterocyclyl-S(0) p-, aryloxy-, aryl-C2-C6alkyl-, aryl-Ci-
C6alkoxy-, heterocyclyloxy-, heterocyclyl-Ci-Qalkoxy-Ci-Qalkyl-,
hydroxycarbonyl, hydroxycarbonyl-Ci-Csalkoxy-, Ci-C3 alkoxycarbonyl-, Ci-
C3alkoxycarbonyl-Ci-C 3 alkoxy-, Ci-Csalkylamino-, Ci-Csdialkylamino-, Ci-
C3alkylamino-S(0) p-, Ci-C3 alkylamino-S(0) p-C1-C3alkyl-, Ci-C3
dialkylamino-S(0) p-, Ci-C3 dialkylamino-S(0) p-C1-C3alkyl-, C -
C3alkylaminocarbonyl-, Ci-Qalkylaminocarbonyl-Ci-Qalkyl-, Ci-
C3dialkylaminocarbonyl-, Ci-C3 dialkylaminocarbonyl-Ci-Csalkyl-, Ci-
C3alkylcarbonylamino-, Ci-C3 alkyl-S(0) p-amino-, C1-C3alkyl-S(0) p-C1-
C3alkylamino-, C1-C3alkyl-S(0)p- aminoCi-Csalkyl-, cyano and nitro, wherein
said heterocyclyls are five or six membered heterocyclyls containing from one
to three heteroatoms each independently selected from the group consisting of
oxygen, nitrogen and sulphur, and wherein the aryl or heterocyclyl
components may be optionally substituted by one or more substituents
selected from the group consisting of halo, Ci-C3alkyl, CrCshaloalkyl, Ci-C3
alkoxy, Ci-C3 haloalkoxy, C1-C6alkyl-S(0) p-, phenyl, cyano and nitro;
R7' and R8 are independently selected from the group consisting of hydrogen,
halogen, Ci-C3 alkyl-, Ci-C3 alkoxy-, C2-C3alkenyl-, C2-C3alkynyl-, Ci-C3
haloalkyl- and CrQhaloalkoxy-;
and wherein R5 and R9 can together form a saturated or unsaturated 5- or 6-
membered carbocyclic or heterocyclic ring, said heterocyclic ring comprising
one or more nitrogen and/or oxygen heteroatoms, the 5- or 6-membered ring
12 being optionally substituted by one or more R ; or
R6 and R9 can together form a saturated or unsaturated 5- or 6-membered
carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more
hetereoatoms selected from the group consisting of nitrogen, oxygen and
S(0) 2, the 5- or 6-membered ring being optionally substituted by one or more
R12; or
R6 and R8 can together form a saturated or unsaturated 5- or 6-membered
carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more
nitrogen heteroatoms, the 5- or 6-membered ring being optionally substituted
13 by one or more R ; and
selected from the group consisting of halo-, Ci-C3alkyl, Ci-C3 haloalkyl
and Ci-Cealkoxy;
R is selected from the group of hydrogen, cyano, halo-, oxy-, -
C3alkylS(0)p-, Ci-C3 alkyl, C2-C3alkenyl, C2-C3alkynyl, Ci-C3 alkoxy and Ci
C3 haloalkyl;
13 R is selected from the group of hydrogen, cyano, halo-, Ci-C3alkylS(0)p-,
Ci-C3 alkyl, C2-C3alkenyl, C2-C3alkynyl, morpholinyl- and Ci-C3 haloalkyl;
and
p = 0, 1 or 2.
A compound according to claim 1, wherein R and/or R4 is hydrogen.
3. A compound according to claim 1 or claim 2, wherein R is selected from the
group consisting of Ala, Alb, Ale, Aid, Ale, Alf, Alg, Alh, A2a, A2b, A3a
A3b and A3c:
A compound according to claim 3, wherein R is Ala.
A compound according to any one of the previous claims, wherein R5 is
selected from the group consisting of hydroxyl, halo, C -C lkyl, C -
C6cycloalkyl, Ci-Cehaloalkyl, C -C alkoxy, -C alkoxyCi-Csalkyl, C -C
alkoxy-C2-C6alkoxy-C1-C3alkyl, C -C haloalkoxyCi-Csalkyl, Ci-Cealkyl-
S(0) p-, aryl, aryloxy, heterocyclyl-Ci-Csalkoxy-Ci-Csalkyl, Ci-
Csdialkylamino-, C1-C3alkyl-S(0) p-amino-C1-C3dialkyl, cyano and nitro.
6. A compound according to claim 5, wherein R5 is selected from the
consisting of chloro, fluoro, methyl, trifluoromethyl, 2-fluoroethylmethoxyethoxymethyl-,
trifluoromethoxymethyl-, methylS(0) p-, aryl,
isoxazolinyl, morpholinyl, methyl-S(0) p-dimethylamino-, cyano and nitro,
wherein the aryl or heterocyclyl components may be optionally substituted by
one or more substituents selected from the group consisting of chloro, methyl
or trifluoromethyl.
7. A compound according to any one of the previous claims, wherein R6 is
selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-
Cehaloalkyl, Ci-C6alkyl-S(0) p-, C2-C6alkenyl and C2-C6alkynyl.
8. A compound according to any one of the previous claims, wherein R7 and R8
are independently selected from the group consisting of hydrogen, halogen and
Ci-C3 alkyl-.
9. A compound according to any one of the previous claims, wherein R9 is
selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-
Cehaloalkyl, Ci-C6alkyl-S(0) p-, C2-C6alkenyl and C2-C6alkynyl.
10. A herbicidal composition comprising a herbicidal compound according to any
one of the previous claims and an agriculturally acceptable formulation
adjuvant.
11. A herbicidal composition according to claim 10, further comprising at least
one additional pesticide.
12. A herbicidal composition according to claim 11, wherein the additional
pesticide is a herbicide or herbicide safener.
13. A method of controlling weeds at a locus comprising application to the locus
of a weed controlling amount of a composition according to any one of claims
10 to 12.
14. Use of a compound of Formula (I) as defined in claim 1 as a herbicide.