0001] Field of the invention The manufacturing process relates E Chirenjiamin derivative having a halogen-containing force Rubamato group and Ashiru group, and than also for their production intermediates.

BACKGROUND

Echirenjiamin derivatives having In recent halogen-containing force Rubamato group and Ashiru groups are known to be useful as fungicides as disclosed in Patent Document 1. When making such compounds are very important to efficiently prepare Echirenjiamin derivative having a force Rubamato group is a production intermediate

Respect Echirenjiamin derivatives having [0003] force Rubamato group, To illustrate conventional manufacturing technology, the (I) 含力 Luba Mart § amino alcohols, phthalimide, using triphenyl phosphine, and an oxygenate chill § zone dicarboxylate after conversion to the phthalimide adduct, methods and (non-patent Document 1) deprotection with hydrazine, (II) 含力 Luba the mart aminonitrile, ethanol solvent saturated with ammonia, catalytic hydrogenation in the presence of Raney nickel way to do

(Non-Patent Document 2), and the like.

Patent Document 1: WO 2005042474

Non-Patent Document 1: first Volume 1 drone § caulking tree to tetra, 1 907-1 9 1 0 page, published in 2000 (T etrahedron:.. A s ymme try, V ol 1 1, p p 1 907- 1 9 1 0, 2000.)

Non-patent Document 2: Synth Tay poke Communications Vol. 24 No. 1 No. 2

1 767~ 1 77 2頁 1 994年発行（S y n t h e t i c C o mm u n I c a t i o n s, V o l . 24， N o. 1 2， p p. 1 / 6 ノ〜 1 7 7 2， 1 9 9 4 . )

Disclosure of the Invention

Problems that the Invention is to you'll solve

[0004] The method of the (I) described in Non-Patent Document 1, in order to use multiple and massive reaction Jefferies chill § zone dicarboxylate Ya hydrate Rajin byproducts that may and safety problems to yield in, hard to say that suitable for industrial process.

- How, the method of the (II) described in Non-Patent Document 2, the yield is also good, but also an advantage for the industrial production process. However, the method of the above (II), if example embodiment, 2, 2, 2 _ triflumizole Ruo b such as ethoxycarbonyl § amino nitrile derivative, when a response to the aminonitrile having a halogen-substituted force Rubamato group, object and the reduction reaction does not proceed to, it is that the compounds force Rubamato group is converted into a ureido group is thus obtained revealed by study of the present inventors.

That is, halogen-substituted force Rubamato groups to highly reactive as compared with the local Bamato group of conventional hydrocarbon proved possible to apply the prior art is very difficult. The outstanding reactivity Narazu only reduction of nitriles, in the preparation of compounds having a halogen-substituted force Rubamato groups became clear that a common problem. Therefore, good Manufacturing method efficient, it is necessary to develop each production intermediate.

[0005] The present invention is to solve the novel problem of the ethylenediamine derivative having a halogen-containing force Rubamato group and Ashiru group efficiently produced, an advantageous method for industrial production of E Ji Renjiamin derivatives an object of the present invention is to provide

Means for Solving the Problems

[0006] The present inventors have intensively studied went results, after the catalytic hydrogenation reaction under the presence of an acid aminonitrile having a halogen-substituted force Rubamato group, be performed § shea Le of, It was found to be effective solution of the problems. Furthermore, the amino acid amide subjected to halogen-containing force Rubamato reduction in the presence of water, followed by reaction with an oxygen scavenger, such as V i I smeier reagent, found that preparing the aminonitrile yield good raw material, the which resulted in the completion of the invention

[0007] That is, the present invention is as follows.

[1] - general formula (1)

[0008] (Formula 1)

[0009] (In the formula, R 1 represents at least one alkyl group of from 1 to 6 carbon substituted with a halogen atom, or at least one cycloalkyl group 3-6 carbon atoms which is substituted by halogen atom represents, R 2 represents hydrogen, Al kill group of from 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, optionally substituted Ariru group, or an unsubstituted or to be 亍 Roariru group, R 3 and R 4 are each independently hydrogen, substituted with an alkyl group having 1 to 6 carbon atoms, substituted 3 carbon atoms, which may be 1-6 cycloalkyl group, an optionally substituted Ariru group, substitution are also good § reel alkyl group, unsubstituted or to good heteroaryl group, or to an optionally substituted represents a heteroarylalkyl group, also, R 3 and R 4 are bonded to the number of 3 to 6 carbon atoms It may form a ring structure, or, R 3 Or either the R 2 are bonded to total atom number of 5-6 (carbon atoms 4-5 nitrogen atoms 1) of R 4 a ring structure may be formed.) And a compound represented by the by performing the catalytic hydrogenation reaction in the presence of an acid formula (2)

[0010] (spoon 2)

R1

[0011] (wherein, R 1, R2, R 3 and R 4 wherein as is.) Compounds represented by (- converted, then the general formula (3)

[0012] (spoon 3)

〇

R

(Where 5 eight

[0013], R5 is substituted by an alkyl group having 1 to 6 carbon atoms are also substituted 3 carbon atoms, which may be 1-6 cycloalkyl group, an optionally substituted Ariru group, an optionally substituted Ariru alkyl, substituted also to good heteroaryl group, also properly represents 亍 lower reel alkyl group to an optionally substituted, X is to table a leaving group. By reaction with a compound represented by), the general formula (4)

[0014] (Formula 4)

R1

[0015] (wherein, R 1, R2, R3, R 4 and R 5 are the right.) Of the method of manufacturing represented by reduction compounds with.

In [2] [1], the compound represented by the general formula (1) has the general formula (5)

[0016] (spoon 5)

[0017] (wherein, R 1, R2, R 3 and R 4 are the street.) Characterized in that it is obtained by reacting with oxygen scavenger compounds represented by, according to [1] the method of production.

[3] In the above [2], the compound represented by the general formula (5) has the general formula (6)

[0018] (spoon 6)

R3 R4

[0019] (wherein, R2, R3 and R4 are the right.) Of the compound represented by the formula

(7)

[0020] (spoon 7)

(Wherein, R 1 is as defined above, Y represents. A halogen atom), characterized in that it is obtained by reacting the compound represented by the presence of water, prepared as described in [2] Method.

[4] In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by a halogen atom is substituted, R2 is hydrogen, or represents an alkyl Le group of from 1 to 6 carbon, R3 and R4 each independently, hydrogen, represents optionally substituted alkyl group having 1 to 6 carbon atoms, optionally substituted Ariru group, or a substituted by Moyoi § reel alkyl group, also, R 3 or R 4 of either the R 2 are bonded to 5 total atom 6 (carbon atoms 4-5, nitrogen atoms 1) may form a ring structure of, or, R 5 is optionally substituted the process according to also good Ariru group, Moshiku represents a 亍 Roariru group to an optionally substituted, [1].

[5] In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by a halogen atom is substituted, R2 represents hydrogen or an alkyl Le group of from 1 to 6 carbon, R3 and R4 each independently, hydrogen, represent substituted by an alkyl group having 1 to 6 carbon atoms are also optionally substituted Ariru group, or a substituted by Moyoi § reel alkyl group, also, R 3 or R 4 of either the R 2 are bonded to total atom number of 5-6 (carbon atoms 4-5 nitrogen atoms 1) may form a ring structure of, or, R 5 is optionally substituted which may Ariru group, Moshiku represents a heteroaryl group which may be substituted, the production method according to [2].

During [6] formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms which is substituted by halogen atoms, R2 is hydrogen, or represents an alkyl Le group having 1 to 6 carbon atoms, R3 and R4 each independently, hydrogen, represents optionally substituted alkyl group having 1 to 6 carbon atoms, optionally substituted Ariru group, or a substituted by Moyoi § reel alkyl group, also, R 3 or R 4 of either the R 2 are bonded to total atom number of 5-6 (carbon atoms 4-5 nitrogen atoms 1) may form a ring structure of, or, R 5 is optionally substituted the process according to also good Ariru group, Moshiku represents a 亍 Roariru group to an optionally substituted, [3].

[7] In the formula, A process according to R 1 is at least one alkyl group of from 1 to 6 carbon fluorine atoms are substituted in [4].

During [8] type, production method according to an alkyl group having a carbon number which is substituted at least by R 1 in one fluorine atom 1-6 [5].

[9] In the formula, A process according to FM is at least one alkyl group of from 1 to 6 carbon atoms in fluorine substituted with [6].

[10] - general formula (1)

(Of 8)

[0023] (wherein, R 1, R2, R 3 and R 4 are [1]:. As described) compound represented by the carrying out the catalytic hydrogenation reaction in the presence of an acid: from the general formula ( 2)

[0024] (spoon 9)

[0025] (wherein, R 1, R2, R 3 and R 4 are as. Described in [1]) production method of converting a compound represented by.

During [1 1] where, R 1 represents at least one alkyl group having a carbon number of 1 to 6 substituted with a halogen atom, R2 represents hydrogen, or an Al kill group having 1 to 6 carbon atoms, and R3 R4 each independently represents hydrogen, substituted alkyl group which may carbon number 1 to 6, optionally substituted Ariru group, or an unsubstituted or good I § reel alkyl group, also, R 3, or either the R2 are bonded to 5 total number of atoms 6 R 4 (the number of carbon atoms 4-5, nitrogen atoms 1) may form a ring structure, the method according to [1 0] .

During [1 2] where A process according to R 1 is an alkyl group having 1 to 6 carbon atoms which is substituted with at least one fluorine atom [1 1].

[13] - general formula (5)

[0026] (Formula 10)

[0027] (wherein, R 1, R2, R 3 and R 4 are as. Described in [2]) was reacted with oxygen scavenger compound represented by the general formula (1)

[0028] (Formula 11)

R1

[0029] (wherein, R 1, R2, R 3 and R 4 are as. Described in [2]) Production method of converting a compound represented by.

During [14] Formula, R 1 represents at least one alkyl group having a carbon number of 1 to 6 substituted with a halogen atom, R2 represents hydrogen, or an Al kill group having 1 to 6 carbon atoms, and R3 R4 each independently represents hydrogen, substituted alkyl group which may carbon number 1 to 6, optionally substituted Ariru group, or an unsubstituted or good I § reel alkyl group, also, R 3, or either the R2 are bonded to 5 total number of atoms 6 R 4 (the number of carbon atoms 4-5, nitrogen atoms 1) may form a ring structure, the method according to [1 3] .

During [1 5] formula The process according to R 1 is an alkyl group having 1 to 6 carbon atoms which is substituted with at least one fluorine atom [14].

[16] - general formula (6)

[0030] (of 12)

R3 R4

[0031] (wherein, R2, R 3 and R 4 are as. Described in [) compound represented by the general formula (7)

[0032] (spoon 1 3)

〇

[0033] (Formula 1 ,

, As described in by R 1 you c A beauty Y [3]. The compound represented by) by reaction in the presence of water, the general formula (5)

[0034] (Formula 14)

[0035] (wherein, R 1, R2, R 3 and R 4 are as. Described in [3]) Production method of converting a compound represented by.

During [1 7] formula, R 1 represents at least one alkyl group having a carbon number of 1 to 6 substituted with a halogen atom, R2 represents hydrogen, or an Al kill group having 1 to 6 carbon atoms, and R3 R4 each independently represents hydrogen, substituted alkyl group which may carbon number 1 to 6, optionally substituted Ariru group, or an unsubstituted or good I § reel alkyl group, also, R 3, or either the R2 are bonded to 5 total number of atoms 6 R 4 (the number of carbon atoms 4-5, nitrogen atoms 1) may form a ring structure, production method according to [1 6] .

The process according to in [18] where, R 1 is an alkyl group having 1 to 6 carbon atoms which is substituted with at least one fluorine atom [1 7].

[19] - general formula (2)

[0036] (spoon 1 5)

[0037] (In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted or at least one cycloalkyl group having a carbon number of 3-6, which is substituted with a fluorine atom, the stands, R2 represents hydrogen, alkyl Le group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, optionally substituted Ariru group, also 亍 Roariru groups to properly which may be substituted, R3 and R4 are each independent hydrogen, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having a carbon number of 3-6, an optionally substituted Ariru group, a substituted are also good § reel alkyl group, unsubstituted or to be 亍 Roariru group, also properly represents 亍 lower reel alkyl group to an optionally substituted, also, R3 and R 4 are bonded to carbon atoms 3 may form a 6 ring structure, or had R3 or R A compound represented by either the R 2 and is bonded total atoms of 4 5-6 (number of carbon atoms 4-5, nitrogen atoms 1) may form a ring structure.).

[20] In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted, R2 represents hydrogen or an alkyl Le group having 1 to 6 carbon atoms, R3 and R4 each independently, hydrogen, represent substituted by an alkyl group having 1 to 6 carbon atoms are also optionally substituted Ariru group, or a substituted by Moyoi § reel alkyl group, also, R 3 or R 4 of either the R 2 are bonded to total atom number of 5-6 (carbon atoms 4-5 nitrogen atoms 1) may form a ring structure of a compound according to [1 9] .

[21] - general formula (1)

(Spoon 1 6)

(In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted or at least one cycloalkyl group having a carbon number of 3-6, which is substituted with a fluorine atom, R2 represents hydrogen, alkyl Le group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, optionally substituted Ariru group, even heteroaryl group properly which may be substituted, R3 and R4 each independent hydrogen, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having a carbon number of 3-6, an optionally substituted Ariru group, may be substituted § reel alkyl group, substituted 亍 Roariru group to good, even properly represents 亍 lower reel alkyl group to an optionally substituted, also, R3 and R 4 are bonded to rings of 3 to 6 carbon atoms It may form a structure, or, R3 or is the R 4 Chiraka one and R 2 are combined to 5 total atom 6 (carbon atoms 4-5, nitrogen atoms 1) may form a ring structure.) The compound represented by the.

[22] In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted, R2 represents hydrogen or an alkyl Le group of from 1 to 6 carbon, R3 and R4 each independently, hydrogen, represent substituted by an alkyl group having 1 to 6 carbon atoms are also optionally substituted Ariru group, or a substituted by Moyoi § reel alkyl group, also, R 3 or R 4 of either the R 2 and is bonded total atoms 5-6 (carbon atoms 4-5 nitrogen atoms 1) may form a ring structure of the compounds described in [21].

[23] - general formula (5)

(Spoon 1 7)

(In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted or at least one cycloalkyl group having a carbon number of 3-6, which is substituted with a fluorine atom, R2 represents hydrogen, alkyl Le group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, optionally substituted Ariru group, even heteroaryl group properly which may be substituted, R 3 and R 4 each independent hydrogen, an alkyl group having 1 to 6 carbon atoms which may be substituted, substituted 3 carbon atoms, which may be 1-6 cycloalkyl group, an optionally substituted Ariru group, substituted which may § reel alkyl group, a substituted also to good heteroaryl group, also properly represents a heteroarylalkyl group to an optionally substituted, also, R 3 and R 4 are bonded to the 3 to 6 carbon atoms It may form a ring structure, or, R 3 or is R 4 A compound represented by either the R 2 are bonded to 5 total atoms 6 (number of carbon atoms 4-5, nitrogen atoms 1) may form a ring structure.).

During [2 4] formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted, R 2 represents hydrogen or an alkyl Le group of from 1 to 6 carbon, R 3 and R 4 each independently represent hydrogen, an optionally substituted alkyl group having 1 to 6 carbon atoms, optionally substituted Ariru group, or a substituted by Moyoi § reel alkyl group, and R 3 or either the R 2 6 are bonded to 5 total atoms (carbon atoms 4-5, nitrogen atoms 1) of R 4 ring structure may be formed of, [2 3] the compound according to.

Effect of the invention

[0042] According to the present invention, it is possible to provide a novel process, and novel preparation intermediates relating ethylene Jiamin derivative having a halogen-containing force Rubamato group and Ashiru group. Further, catalytic hydrogenation reaction in the present invention, it is a catalyst recyclable reaction, reducing the waste of industrial, can be produced that, or good yield avoiding the reagent to be safety problems that having a advantages such. Therefore, the present invention is environmental compatibility, economy, are those which excellent in safety, and productivity, which is useful as an industrial production method.

BEST MODE FOR CARRYING OUT THE INVENTION

[0043] Hereinafter, the present invention will be described in detail.

The present invention, by performing the catalytic hydrogenation Kahan response in the presence of an acid a compound represented by the following general formula (1) is converted into a compound represented by the following general formula (2), then the general formula ( by reacting with the compound represented by 3), it relates to a process for preparing a compound represented by the general formula (4).

(Of 1)

[0045] (In the formula, R 1 represents at least one 1 carbon atoms which is substituted by halogen atom

6 alkyl group or represents at least one cycloalkyl group from 3 6 carbon atoms which is substituted by halogen atoms, R2 is hydrogen, Al kill group of from 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, group, optionally substituted Ariru group, or represents a 亍 Roariru group to an optionally substituted, independently of R3 and R4 are each hydrogen, an optionally substituted alkyl group having 1 to 6 carbon atoms, substituted good cycloalkyl group with carbon number 3-6 also, optionally substituted Ariru group, 亍 replacement has been good § reel alkyl group, substituted with the optionally 亍 Roariru group or to an optionally substituted, It represents lower reel alkyl group, and may form a ring structure R3 and R4 and are bound 3 carbon atoms to 6, or either R3 or R 4 one and R 2 are combined to total atoms 5-6 (carbon atoms 4-5, ChissoHara Ring structure having 1) may be formed. )

[0046] (spoon 2)

R3 R4

R1 ,. People
NH 2

R 2 (2)

[0047] (as in the formula, R 1, R2, R 3 and R 4 above.)

[0048] (Formula 3)

[0049] (wherein, R5 is substituted by an alkyl group having 1 to 6 carbon atoms are also substituted 3 carbon atoms, which may be 1-6 cycloalkyl group, an optionally substituted Ariru group, optionally substituted good § reel alkyl group, unsubstituted or to be 亍 Roariru group, also properly represents a heteroarylalkyl group to an optionally substituted, X is table to a leaving group.)

[0050] (spoon 4)

[0051] (wherein, R 1, R2, R3, R 4 and R 5 are the street.)

- in the compounds represented by the general formula (1), R 1 is at least one halogen alkyl emissions atoms carbon atoms is substituted with 1-6 or at least one carbon atoms are replaced by halogen atoms 3, a cycloalkyl group of 1-6

[0052] - the halogen atom in R 1 in general formula (1) represents fluorine, chlorine, bromine, iodine.

[0053] - general formula (1) and an alkyl group having 1 to 6 carbon atoms for R 1 in the methyl group, Echiru group, propyl group, butyl group, a straight-chain, such as hexyl group pentyl group to, and, an isopropyl group, an isobutyl group, sec- butyl group, 1-Mechirubu butyl group, 2 _ methylbutyl group, 3 _-methylbutyl group, 1, 1-dimethyl propyl group, 2, 2-dimethylpropyl group, 1, 2- dimethylpropyl group, 1 _ methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 4-main Chirupenchiru group, 1, 1-dimethylbutyl group, 1, 2-dimethylbutyl group, 1, 3-dimethylbutyl group, 2, 2-dimethylbutyl group, 2, 3-dimethylbutyl group, 3 represents a fork, and 3-dimethylbutyl group. Or if there is at least one halogen atom these § alkyl group. If you substituted two or more places may be substituted with same or two or more halogens, are not particularly restricted.

[0054] - general formula (1) and the cycloalkyl group having 3 to 6 carbon atoms in R 1 of, cyclo propyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, etc. cyclohexylene.

[0055] - In the compound represented by the general formula (1), R 2 is hydrogen, § alkyl group having 1 to 6 carbon atoms, a cycloalkyl group, an optionally substituted Ariru group having 3 to 6 carbon atoms or, to optionally substituted represents a heteroaryl group.

[0056] - general formula (1) and an alkyl group having 1 to 6 carbon atoms for R 2 in the general formula (

1) the same meanings as those described in R 1 in.

[0057] - general formula (1) and the cycloalkyl group having 3 to 6 carbon atoms in R 2 in have the same meanings as those described in R 1 in one general formula (1).

[0058] - general formula (1) which may Ariru group substituted in R 2 in or as a substituent in the replacement has been 亍 Roariru group to good, a methyl group, Echiru group, flop port propyl group , isopropyl group, butyl group, an isobutyl group, an alkyl group such as sec- butyl group, a cyclopropyl group, a cyclobutyl group, a cycloalkyl group such as cyclopentyl group, cyclohexyl group cyclo, triflumizole Ruo Russia methyl group, Jifuruoro methyl group, Promo difluoromethyl O b methyl, triflumizole Ruo Roe halogen-substituted alkyl group such as a methyl group, a methoxy group, an ethoxy group, a propoxy group, isopropoxy group, butoxy group, isobutoxy group, alkoxy group such as sec _ butoxy, Torifuruoro methoxy, difluoromethyl O b methoxy, triflate Ruo Russia halogen substituted alkoxy groups such as ethoxy group, methoxycarbonyl group, ethoxy Kishikarubo two group, propoxy carboxymethyl group, isopropoxycarbonyl carboxymethyl group, Butokishika Lupo group, Ariruokishi such alkoxycarbonyl groups, phenoxyethanol group such as isobutoxycarbonyl group, sec _ butoxycarbonyl sulfonyl group power Lupo group, methanesulfonyl group, ethanesulfonyl group, propanesulfonyl two group, an alkylsulfonyl group such as a butanesulfonyl group, triflate Ruo b methane sulfonyl group, difluoromethane O b methanesulfonyl group, such as triflate Ruo Roe Tan sulfonyl group halogen-substituted alkyl sulfonyl group, a methyl group, E Ji ylcarbonyl group, a propyl group, § Le kill carbonyl group such as an isopropyl group, cyclopropyl group, cyclobutyl carbonylation group, a cyclopropylcarbonyl group, a cycloalkyl Pentyl group, a cycloalkyl carboxymethyl sulfonyl group such Kishirukaruponiru groups cyclohexane, etc. § reel carbonyl group such Benzoiru group, methyl Cal Poni Ruo carboxymethyl group, E Chiruka Lupo sulfonyl O alkoxy group, propyl carbonyl O alkoxy group, Isopuropiru carboxymethyl two Ruokishi group, etc. Alkylcarbonyl O alkoxy group, cyclopropylcarbonyl O alkoxy group, consequent Russia butyl local Poni Ruo carboxymethyl group, cyclopentyl Luca Lupo sulfonyl O alkoxy group, a cycloalkyl Cal Poni Ruo dimethylvinylsiloxy groups such as hexyl Cal Poni Ruo carboxymethyl group cycloheteroalkyl, § such Ben Zoiruokishi group reel carbonyl O carboxy groups. Number of substituents on Ariru group or Heteroariru group is not limited. Further, when two or more positions Ariru group or Heteroariru group is substituted, the same if Ku may be composed of two or more types of substituents is not limited.

[0059] - general formula (1) and is Ariru group in R 2 in represents phenyl group, naphthyl group, anthranyl group, a Fuenansuriru group.

[0060] - general formula (1) The f 亍 Roariru group in R 2 in a pyridyl group, pyridinium Mijiru group, a pyrazolyl group, Birajiniru group, pyridazinyl group, imidazolyl group, indolyl group, quinolyl group, quinoxalyl group, benz nitrogen-containing heterocyclic group such as imidazolyl, 亍 tiger tetrahydrofuranyl group, furanyl group, Vila group, di Okisaniru group, 2, 3-dihydro-base emission zone [1, 4] Jiokishiniru group, benzo furanyl, etc. the heterocyclic group oxygen-containing, Okisazoriru group, isoxazolyl group, Baie Nzookisazoriru group, and a heterocyclic group containing two or more f terrorist atom such as benzo I Soki no doubt drill group.

[0061] - In the compound represented by the general formula (1), R 3 and R 4 are each independently hydrogen, substituted with an alkyl group having 1 to 6 carbon atoms, but it may also be substituted carbon C 3-6 cycloalkyl group, an optionally substituted Ariru group, it may also be substituted I § reel alkyl group, unsubstituted or to be 亍 Roariru group, if Ku is 亍 lower to an optionally substituted It represents a reel alkyl group. It is also possible to form the R 3 and R 4 are bonded to the ring structure of 3 to 6 carbon atoms, or, R 3 or atoms in total atoms bonded to the one and R 2 either R 4 5 1-6 (carbon atoms 4-5, nitrogen atoms 1) may be formed ring structure.

[0062] - in R 3 and R 4 in general formula (1), alkyl groups having 1 to 6 carbon atoms which may be substituted, substituted 3 carbon atoms, which may be 1-6 cycloalkyl group, optionally substituted which may Ariru group, substituted by optionally § reel alkyl group, substituted by heteroaryl group to good, or a substituent in substituted with hetero aryl aralkyl kill group to good, methyl group, Echiru group, a propyl group , isopropyl group, butyl group, an isobutyl group, an alkyl group such as sec _ butyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cycloalkyl group such as cyclohexyl group, triflate Ruo Russia methyl group, Jifuruoromechiru group, Puromojifu Ruoromechiru groups, trifluoperazine Ruo Roe halogen-substituted alkyl group such as methyl group, meth alkoxy group, an ethoxy group, a propoxy group, isopropoxy group, butoxy Group, iso-butoxy group, an alkoxy group such as sec _ butoxy, cyclopropoxy group, cyclobutoxy group, cyclopentyloxy Ruo alkoxy group, cycloalkoxy group such Kishiruokishi group cycloheteroalkyl, triflumizole Ruo b methoxy, difluoromethyl O b methoxy, DOO Riffle O b halogenated alkoxy group such as ethoxy group, methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl Cal Boniru group, butoxycarbonyl group, isobutoxycarbonyl group, an alkoxycarbonyl, such as sec- Bed Tokishikaruponiru group group, cyclopropoxy force Lupo group, a cycloalkyl butoxy carboxymethyl group, cyclopentyloxy Ruo alkoxycarbonyl group, cycloalkoxy Cal Poni Le group such Kishiruokishi force Ruponiru group cycloheteroalkyl, § reel O propoxycarbonyl etc. phenoxyethanol group Group, methanesulfonyl group, ethanesulfonyl group, propanesulfonyl group, an alkylsulfonyl group such Butansuruho group, triflate Ruo b methanesulfonyl group, Jifuruorome Tansuruhoniru group, halogen-substituted aralkyl such as triflate Ruo b ethane sulfonyl group Alkylsulfonyl group, a methyl group, E chill carbonyl group, propyl force Lupo group, an alkylcarbonyl group such as an isopropyl group, cyclopropyl group, cyclobutyl group, cyclopropylcarboxy group, cyclopentyl carbonyl group, a cycloalkyl to a cycloalkyl group such as cyclohexyl group, § reel carbonyl group such Benzoiru group, methylcarbamoyl Luca Lupo sulfonyl O alkoxy group, E Chiruka Lupo sulfonyl O alkoxy group, propyl carbonyl O alkoxy group, an alkylcarbonyl such as isopropyl carbonyl O alkoxy group Okishi group, cyclopropylcarbonyl O alkoxy group, a cycloalkyl Petit Luca Lupo sulfonyl O alkoxy group, cyclopentyl Luca Lupo sulfonyl O alkoxy group, cycloalkylcarbonyl O alkoxy group such Kishirukarupo two Ruokishi group cycloheteroalkyl, Benzoiruo Shi Ariru force Ruponiruokishi group such as, fluorine, chlorine, bromine, iodine halide, and the like. Alkyl group, a cycloalkyl group, § reel alkyl group, Heteroarirua alkyl group, with respect Ariru group or Heteroariru group, the number of the substituents is not to be limited constant. Alkyl group, a cycloalkyl group, § reel alkyl group, heteroalkyl § reel alkyl group, Ariru group or in pairs to 亍 Roariru group to, if the substituents are two or more positions, up of the same or two or more substituents well made, it is not limited. However, except to become R 3 or R 4 force "triflate Ruo port methyl, catalytic hydrogenation receive such halogen substitution aromatic compounds, for example, Kurorufueniru, Ariru halides such as bromo-phenylalanine-phenylalanine group, or even Teroari Ichiru based on the halogenated such as chlorinated pyridine except. Black alkylcarbonyl group, § reel carbonyl group such Benzoiru group, methylcarbamoyl Luca Lupo sulfonyl O alkoxy group, E Chiruka Lupo sulfonyl O alkoxy group, propyl carbonyl O alkoxy group, an alkylcarbonyl O alkoxy group such as isopropyl carbonyl O alkoxy group, cyclopropylcarbonyl Okishi group, a cycloalkyl Petit Luca Lupo sulfonyl O alkoxy group, cyclopentyl Luca Lupo sulfonyl O alkoxy group, cycloalkylcarbonyl O alkoxy group such Kishirukarupo two Ruokishi group cycloheteroalkyl, Ariru force Ruponiruokishi group such Benzoiruokishi group, fluorine, chlorine, bromine, iodine halide like it is exemplified. Alkyl group, a cycloalkyl group, § reel alkyl group, Heteroarirua alkyl group, with respect Ariru group or Heteroariru group, the number of the substituents is not to be limited constant. Alkyl group, a cycloalkyl group, § reel alkyl group, heteroalkyl § reel alkyl group, Ariru group or in pairs to 亍 Roariru group to, if the substituents are two or more positions, up of the same or two or more substituents well made, it is not limited. However, except to become R 3 or R 4 force "triflate Ruo port methyl, catalytic hydrogenation receive such halogen substitution aromatic compounds, for example, Kurorufueniru, Ariru halides such as bromo-phenylalanine-phenylalanine group, or even Teroari Ichiru based on the halogenated such as chlorinated pyridine except. Black alkylcarbonyl group, § reel carbonyl group such Benzoiru group, methylcarbamoyl Luca Lupo sulfonyl O alkoxy group, E Chiruka Lupo sulfonyl O alkoxy group, propyl carbonyl O alkoxy group, an alkylcarbonyl O alkoxy group such as isopropyl carbonyl O alkoxy group, cyclopropylcarbonyl Okishi group, a cycloalkyl Petit Luca Lupo sulfonyl O alkoxy group, cyclopentyl Luca Lupo sulfonyl O alkoxy group, cycloalkylcarbonyl O alkoxy group such Kishirukarupo two Ruokishi group cycloheteroalkyl, Ariru force Ruponiruokishi group such Benzoiruokishi group, fluorine, chlorine, bromine, iodine halide like it is exemplified. Alkyl group, a cycloalkyl group, § reel alkyl group, Heteroarirua alkyl group, with respect Ariru group or Heteroariru group, the number of the substituents is not to be limited constant. Alkyl group, a cycloalkyl group, § reel alkyl group, heteroalkyl § reel alkyl group, Ariru group or in pairs to 亍 Roariru group to, if the substituents are two or more positions, up of the same or two or more substituents well made, it is not limited. However, except to become R 3 or R 4 force "triflate Ruo port methyl, catalytic hydrogenation receive such halogen substitution aromatic compounds, for example, Kurorufueniru, Ariru halides such as bromo-phenylalanine-phenylalanine group, or even Teroari Ichiru based on the halogenated such as chlorinated pyridine except. It will not be constant. Alkyl group, a cycloalkyl group, § reel alkyl group, heteroalkyl § reel alkyl group, Ariru group or in pairs to 亍 Roariru group to, if the substituents are two or more positions, up of the same or two or more substituents well made, it is not limited. However, except to become R 3 or R 4 force "triflate Ruo port methyl, catalytic hydrogenation receive such halogen substitution aromatic compounds, for example, Kurorufueniru, Ariru halides such as bromo-phenylalanine-phenylalanine group, or even Teroari Ichiru based on the halogenated such as chlorinated pyridine except. It will not be constant. Alkyl group, a cycloalkyl group, § reel alkyl group, heteroalkyl § reel alkyl group, Ariru group or in pairs to 亍 Roariru group to, if the substituents are two or more positions, up of the same or two or more substituents well made, it is not limited. However, except to become R 3 or R 4 force "triflate Ruo port methyl, catalytic hydrogenation receive such halogen substitution aromatic compounds, for example, Kurorufueniru, Ariru halides such as bromo-phenylalanine-phenylalanine group, or even Teroari Ichiru based on the halogenated such as chlorinated pyridine except.

[0063] - general formula (1) and an alkyl group having 1 to 6 carbon atoms for R 3 or R4 in have the same meanings as those described in R 1 in the formula (1).

[0064] - general formula (1) and cycloalkyl Le group having 3 to 6 carbon atoms in R 3 or R4 in have the same meanings as those described in R 1 in the formula (1).

[0065] - general formula (1) and Ariru group in R 3 or R4 in have the same meanings as those described by the general formula (1) in R 2.

[0066] - With respect to § reel alkyl group for R 3 or R4 in general formula (1), Ariru sites Ri Ariru group synonymous, given in by R 2 in the general formula (1), the alkyl moiety carbon meanings of C1-4.

[0067] - general formula (1) and f 亍 Roariru group in R 3 or R4 in the pyridyl group, a pyrimidyl group, a pyrazolyl group, Birajiniru group, pyridazinyl group, I imidazolyl group, indolyl group, quinolyl group, quinoxalyl group, Benzuimida Zoriru nitrogen-containing heterocyclic group such as a group, tetrahydrofuranyl group, furanyl group, Pi Ranil group, Jiokisaniru group, 2, 3-dihydro-base emission zone [1, 4] Jiokishini group, including such as benzofuranyl group oxygen heterocyclic group, Okisazoriru group, Isokisa Zoriru group, benzo O hexa benzotriazolyl group, and a heterocyclic group containing two or more hetero atoms, such as benzisoxazolyl group.

[0068] - general formula (1) between the hetero § reel alkyl group for R 3 or R4 in is synonymous with Heteroariru groups described in Heteroariru sites R 2 in the general formula (1), the alkyl moiety carbon representing those having 1 to 4.

[0069] When the compound represented by the general formula (1) has a asymmetric points may use the optically active form, or racemic.

[0070] Formula perform catalytic hydrogenation a compound represented by (1) in the presence of an acid, it can be converted to the compound represented by the general formula (2).

Thus, generation of by-products is suppressed, the compound represented by the general formula (2) can be obtained in high yield.

[0071] - in the compound represented by general formula (2), R 1, R2, R 3 and R 4 are - the same meaning as described in general formula (1).

[0072] The acid used has the general formula (1) or the general formula is not particularly limited as long as a compound as it does not disassemble represented by (2), for example, you to use the organic or inorganic acid it can.

The [0073] organic acid, formic acid, acetic acid, methanesulfonic acid, etc. Examples of the inorganic acid can be exemplified hydrochloric acid, sulfuric acid, phosphoric acid and the like.

[0074] The amount of the acid is not a this is limited by setting as the intended reaction proceeds, is usually 1 20 equivalents or less equivalents or more.

For the [0075] catalytic hydrogenation method, palladium, platinum, rhodium, a method of performing a metal such as ruthenium and the like. These metals, metal oxides, can also be used in the form of such metal chlorides.

[0076] The amount of metals to be used in performing the catalytic hydrogenation method, although not in particular be limited constant if the reaction proceeds, equivalent or more relative to the weight of the general formula (1) from the economic point of view below it is preferred.

[0077] the form of a metal to be used, activated carbon, S i 0 2 , AI 2 0 3 , Ba S0 4 , T i 0 2 , Z r 0 2 , MgO, T h0 2 those supported by, Keisou soil etc. it can be used. Its form is not limited, from an economic point of view, it is preferable to use a reusable carrier.

[0078] The solvent to be used in performing the catalytic hydrogenation method is not limited to the Japanese so long as the reaction proceeds. Specific examples include methanol, ethanol, alcohol solvents such isoprene propanol, hexane, benzene, toluene, aromatic solvents such as xylene, to, hydrocarbon solvents such as heptane, dimethylformamide, dimethyl § Seth amide, 1-methyl amide solvents 2-pyrrolidone, etc., Jefferies Chirueteru, diisopropyl ether, 1, 2-dimethoxy E Tan, 亍 tiger hydrofuran, ether solvents such as Jiokisan, acetic Echiru, acetic heptyl, ester solvents such as isopropyl acetate, water and the like. It alone can also use the child, it is also possible to mix two or more at an arbitrary ratio.

[0079] is not particularly limited with respect to the amount of the solvent, but usually 3-40 times the weight relative to the weight of the general formula (1) are preferred.

[0080] The reaction forms is not particularly limited, the general formula (1) or the general formula diluted with the solvent (1), it is preferred to dropwise to a solvent containing a metal and an acid in the presence of a hydrogen source .

[0081] with respect to the reaction temperature is not Rukoto limited by setting such compounds does not decompose, usually less one 1 0 ° C over 1 5 0 ° C or less or the boiling point of the solvent.

[0082] With respect to the reaction pressure is not particularly limited, and may be either at atmospheric pressure under pressure

[0083] The hydrogen source to be used for catalytic hydrogenation, the reaction is not be particularly limited as long as progress, in addition to hydrogen gas, the internal hydrogen evolution method using hexene, formate and formic acid salts such as cyclohexane it can be used.

[0084] Internal hydrogen production method in cyclohexene to use when carrying out the reaction, formic acid and ants salt equivalent is the amount of hydrogen to be generated is 2 is as it is not particularly limited if set to be equivalent or more, 2 equivalents or more from an economical viewpoint 1 0 or less is preferably equivalent.

[0085] With respect to the above compound represented by the resulting formula in reaction (2), using forms definitive to the next step are not specifically limited. The reaction solution containing the compound represented by the general formula (2), be used in the next step without isolation and purification evaporated, the ordinary post-treatment of the separated or the like after one row or, hydrochloric, sulfuric, or organic acids such as phosphoric acid, oxalic acid, fumaric acid, maleic acid, formic acid, acetic acid, can be used after the form of a salt with an organic acid such as methanesulfonic phosphate in the next step be

[0086] The compound represented by the general formula (2) also includes salts formed with inorganic acids and organic acids. Examples of the inorganic acids include hydrochloric acid, sulfuric acid, phosphoric acid and the like, oxalic acid as an organic acid, full circle acid, maleic acid, formic acid, acetic acid, and methanesulfonic acid.

claims

[1] - general formula (1)

(Of 1)

(In the formula, R 1 represents at least one alkyl group of from 1 to 6 carbon substituted with a halogen atom or at least one cycloalkyl group 3-6 carbon atoms which is substituted by halogen atom,, R2 is hydrogen, Al kill group of from 1 to 6 carbon, a cycloalkyl group, an optionally substituted Ariru group or substituted also to good heteroaryl group, having 3 to 6 carbon atoms, R3 and R4 are each independently Te, hydrogen, substituted alkyl groups having 1 to 6 which may carbons, a cycloalkyl group having 3 to 6 carbon atoms which may be substituted, an optionally substituted Ariru group, substitution which may be § reel alkyl groups, substituted also to good heteroaryl group, or to an optionally substituted represents a heteroarylalkyl group and may form a ring structure R3 and R4 are bonded to carbon atoms having 3 to 6, Alternatively, the R3 or R 4 Chiraka one and R 2 are combined to total atom number of 5-6 (carbon atoms 4-5 nitrogen atoms 1) may form a ring structure.) Represented by the compounds in the presence of an acid with by performing the catalytic hydrogenation reaction, the general formula (2)

(Of 2)

(Wherein, R 1, R2, R 3 and R 4 are the street.) And a compound represented by (- converted, then the general formula (3)

(Of 3)

Eight

(Wherein, R5 is substituted by an alkyl group having 1 to 6 carbon atoms are also substituted 3 carbon atoms, which may be 1-6 cycloalkyl group, an optionally substituted Ariru group, an optionally substituted Ariru alkyl group, the optionally substituted heteroaryl group, also properly represents 亍 lower reel alkyl group to an optionally substituted, X is by reacting a compound represented the leaving group in Table to.) the general formula (4)

(Of 4)

(Wherein, R 1, R2, R3, R 4 and R 5 are the right.) Of the method of manufacturing represented by reduction compounds with.

[2] In Claim 1, the compound represented by the general formula (1) has the general formula (5)

(Of 5)

(Wherein, R 1, R2, R 3 and R 4 are the street.) Characterized in that it is obtained by reacting the oxygen scavenger compound represented by the preparation of placing serial to claim 1 Method.

[3] In Claim 2, the compound represented by the general formula (5) has the general formula (6)

(Of 6)

R3 R4

(Wherein, R2, R 3 and R 4 are as. Above) the compounds represented by the general formula

(7)

(Of 7)

〇

Rl , Y O people

(Wherein, R 1 is as defined above, Y represents. A halogen atom), characterized in that it is obtained by reacting the compound represented by the presence of water, prepared as described in claim 2 Method.

[4] In the formula, R 1 represents at least one carbon atoms which is substituted 1 to a halogen atom

Represents an alkyl group, R 2 represents hydrogen or an alkyl group of carbon number 1-6, R 3 and R 4 are each independently hydrogen, substituted alkyl groups which may the number of carbon atoms from 1 to 6 , optionally substituted Ariru group, or represents a optionally substituted § reel alkyl group, also, R 3, or either of R 4 and R 2 are bonded total atoms 5-6 (number of carbon atoms 4-5, ring nitrogen atoms 1) may form the shape of, or, R 5 represents a 亍 Roariru group which may be substituted Ariru group or to optionally substituted, in claim 1 the method according.

[5] In the formula, R 1 represents at least one carbon atoms which is substituted 1 to a halogen atom

Represents an alkyl group, R 2 represents hydrogen or an alkyl group having 1 to 6 carbon atoms, R 3 and R 4 are each independently hydrogen, substituted 1 carbon atoms which may be 1-6 alkyl group represents unsubstituted or optionally Ariru group or an optionally substituted § reel alkyl group, and, R 3, or either the R 2 and is bonded total atoms 5-6 (number of carbon atoms of R 4 4-5, ring nitrogen atoms 1) may form the shape of, or, R 5 represents a Teroari Ichiru group which may be substituted Ariru group or to optionally substituted, according to claim 2 the method according to.

During [6] formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms with a halogen atom is substituted, R 2 represents hydrogen or an alkyl group having 1 to 6 carbon atoms, and R 3 R 4 are each independently hydrogen, substituted alkyl group of good carbon number 1-6 and each represents optionally substituted Ariru group optionally or optionally substituted § reel alkyl group, and, R 3, or either the R 2 are bonded to 5 total number of atoms 6 R 4 (the number of carbon atoms 4-5, nitrogen atoms 1) may form a form a ring structure, or, R 5 is substituted represent a 亍 Roari Ichiru group which may Ariru group or to optionally substituted, the process according to claim 3.

[7] In the formula, A process according to claim 4 R 1 is an alkyl group having 1 to 6 carbon atoms which is substituted with at least one fluorine atom.

During [8] type, production method of claim 5 R 1 is at least one alkyl group having 1 to 6 carbon atoms which fluorine atoms are substituted with.

[9] In the formula, The process according to claim 6 R 1 is an alkyl group having 1 to 6 carbon atoms which is substituted with at least one fluorine atom.

[10] - general formula (1)

(Of 8)

(In the formula, R 1 represents at least one alkyl group of from 1 to 6 carbon substituted with a halogen atom or at least one cycloalkyl group 3-6 carbon atoms which is substituted by halogen atom,, R2 is hydrogen, Al kill group of from 1 to 6 carbon, a cycloalkyl group, an optionally substituted Ariru group or unsubstituted or to be 亍 Roariru group of 3-6 carbon atoms, R3 and R4 are each independently and hydrogen, an alkyl group having 1 to 6 carbon atoms which may be substituted, substituted 3 carbon atoms, which may be 1-6 cycloalkyl group, an optionally substituted Ariru group, which may be substitution Ariru alkyl, substituted also to good heteroaryl group, or represents a heteroarylalkyl group to an optionally substituted, also may form a ring structure R3 and R4 and are bound 3 carbon atoms 1-6 or, of R3 or R 4 Either the R 2 are bonded to total atom number of 5-6 (1-4 carbon atoms 5, the nitrogen atoms 1) represented by the compound in the presence of acid ring structure may be formed.) by performing the catalytic hydrogenation reaction, the general formula (2)

(Of 9)

(Wherein, R 1, R2, R 3 and R 4 are the street.) Manufacturing method of converting a compound represented by.

[11] In the formula, R 1 represents at least one carbon atoms which is substituted 1 to a halogen atom

Represents an alkyl group, R2 is hydrogen, or an alkyl group having a carbon number of 1-6, R3 and R4 are each independently hydrogen, an optionally substituted alkyl group having a carbon number of 1-6, it is replaced which may be Ariru group, or represents a optionally substituted § reel alkyl group, also, R 3, or either of R 4 and R2 are bonded to 5 total atom 6 (carbon atoms 4-5, ring nitrogen atoms 1) may form the shape of the method according to claim 1 0.

[12] In the formula, The process according to claim 1 1 R 1 is at least one alkyl group having 1 to 6 carbon atoms which fluorine atoms are substituted with.

[13] - general formula (5)

(Of 10)

(In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms which is substituted by halogen atom or at least one cycloalkyl group having 3 to 6 carbon atoms with a halogen atom is substituted,, R2 is hydrogen, Al kill group having 1 to 6 carbon atoms, a cycloalkyl group, an optionally substituted Ariru group or substituted also to good heteroaryl group, having 3 to 6 carbon atoms, R3 and R4 are each independently Te, hydrogen, substituted alkyl groups having 1 to 6 which may carbon atoms, a cycloalkyl group optionally carbon atoms 3-6 be substituted, an optionally substituted Ariru group, substitution which may be § reel alkyl group, substituted with the optionally 亍 Roariru group, or represents a 亍 lower reel alkyl group to an optionally substituted, also to form a ring structure having 3 to 6 carbon atoms bonded with R3 and R4 well, or the R3 or R 4 Chiraka one and R 2 are combined to total atom number of 5-6 (carbon atoms 4-5, nitrogen atoms 1) and oxygen scavenger compound represented by ring structure may be formed.) by reacting the general formula (1)

(Of 11)

(Wherein, R 1, R2, R 3 and R 4 are the street.) Manufacturing method of converting a compound represented by.

[14] In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms with a halogen atom is substituted, R2 represents hydrogen or an alkyl group having 1 to 6 carbon atoms, R3 and R4 each independently hydrogen, an alkyl group having 1 to 6 carbon atoms which may be substituted, represents a unsubstituted or may Ariru group or optionally substituted § reel alkyl group, and, of R 3 or R 4 either the R2 are bonded to total atom number of 5-6 (carbon atoms 4-5 nitrogen atoms 1) ring structures may form the shape of method according to claim 1 3.

[15] In the formula, The process according to claim 1 4 R 1 is at least one alkyl group having 1 to 6 carbon atoms which fluorine atoms are substituted with.

- general formula (6)

(Of 12)

R3 R4

(Wherein, R2 is hydrogen, an alkyl group having 1 to 6 carbon atoms, Shikuroa alkyl group having 3 to 6 carbon atoms, optionally substituted Ariru group or the optionally substituted represents a hetero Ariru group, and R3 R4 are each independently hydrogen, substituted have good an alkyl group containing 1 to 6 carbon atoms, unsubstituted or good 3 to 6 carbon atoms and a cycloalkyl group, an optionally substituted Ariru group, substituted which may § reel alkyl group, unsubstituted or to be 亍 Roariru group, or represents a hetero § reel alkyl group to an optionally substituted, also, R3 and R4 are bonded to the ring structure of 3 to 6 carbon atoms It may form, or to form a ring structure of R 3 or either of R 4 and R 2 are bonded total atoms 5-6 (number of carbon atoms 4-5, nitrogen atoms 1) which may be.) with the compound represented by the general formula (7)

(Of 13)

(In the formula, R 1 represents at least one alkyl group having a carbon number of 1 to 6 substituted by a halogen atom or at least one cycloalkyl group having 3 to 6 carbon atoms with a halogen atom is substituted,, Y by reacting a compound table and represented.) the halogen atom in the presence of water, the general formula (5)

(Of 14)

(Wherein, R 1, R2, R 3 and R 4 are the street.) Manufacturing method of converting a compound represented by.

[17] In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms with a halogen atom is substituted, R2 represents hydrogen or an alkyl group having 1 to 6 carbon atoms, R3 and R4 each independently hydrogen, an alkyl group having 1 to 6 carbon atoms which may be substituted, represents a unsubstituted or may Ariru group or optionally substituted § reel alkyl group, and, of R 3 or R 4 either the R2 are bonded to 5 total atom 6 (carbon atoms 4-5, nitrogen atoms 1) ring structures may form the shape of method according to claim 1 6.

[18] In the formula, The process according to claim 1 7 R 1 is an alkyl group having 1 to 6 carbon atoms which is substituted with at least one fluorine atom.

[19] - general formula (2)

(Formula 15)

(In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted or at least one cycloalkyl group having a carbon number of 3-6, which is substituted with a fluorine atom, R 2 represents hydrogen, alkyl Le group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, optionally substituted Ariru group, also 亍 Roariru groups to properly which may be substituted, R 3 and R 4 are each independent hydrogen, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having a carbon number of 3-6, an optionally substituted Ariru group, a substituted which may be § reel alkyl group, the optionally substituted 亍 Roariru group, also properly represents 亍 lower reel alkyl group to an optionally substituted, also, R 3 and R 4 are bonded to carbon atoms It may form a 3-6 ring structure, or, R 3 or is R 4 A compound represented by either the R 2 are bonded to 5 total number of atoms 6 (the number of carbon atoms 4-5, nitrogen atoms 1) ring structures may be formed.).

[20] In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted, R 2 is table hydrogen or an alkyl group having 1 to 6 carbon atoms, R 3 and R 4 each independently represent hydrogen, substituted with an alkyl group having 1 to 6 carbon atoms is also optionally substituted Ariru group, or an optionally substituted § reel alkyl group, also, R 3 or either the R 2 and is bonded total atoms 5-6 (carbon atoms 4-5 nitrogen atoms 1) of R 4 may form a ring structure, according to claim 1 9 Compound.

[21] - general formula (1)

(Formula 16)

(In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted or at least one cycloalkyl group having a carbon number of 3-6, which is substituted with a fluorine atom, R2 represents hydrogen, alkyl Le group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, optionally substituted Ariru group, even heteroaryl group properly which may be substituted, R3 and R4 each independent hydrogen, an optionally substituted alkyl group having 1 to 6 carbon atoms, an optionally substituted cycloalkyl group having a carbon number of 3-6, an optionally substituted Ariru group, may be substituted § reel alkyl group, substituted 亍 Roariru group to good, even properly represents 亍 lower reel alkyl group to an optionally substituted, also, R3 and R 4 are bonded to rings of 3 to 6 carbon atoms It may form a structure, or, R3 or is the R 4 Chiraka one and R 2 are combined to 5 total atom 6 (carbon atoms 4-5, nitrogen atoms 1) may form a ring structure.) The compound represented by the.

[22] In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms substituted with fluorine atoms, R2 is hydrogen, or to display the number of 1-6 alkyl carbon, R3 and R4 each independently, represent hydrogen, substituted with an alkyl group having 1 to 6 carbon atoms are also optionally substituted Ariru group or an optionally substituted § reel alkyl group, and, R 3 or R 4 either the R 2 are bonded to total atom number of 5-6 (carbon atoms 4-5 nitrogen atoms 1) may form a ring structure, the compounds according to claim 21.

[23] - general formula (5)

(Of 17)

(In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted or at least one cycloalkyl group having a carbon number of 3-6, which is substituted with a fluorine atom, R2 represents hydrogen, alkyl Le group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, optionally substituted Ariru group, even heteroaryl group properly which may be substituted, R 3 and R 4 each independent hydrogen, substituted alkyl groups having 1 to 6 which may carbons, optionally substituted cycloalkyl group having a carbon number of 3-6, an optionally substituted Ariru group, substituted which may § reel alkyl group, the optionally substituted 亍 Roariru group, also properly represents 亍 lower reel alkyl group to an optionally substituted, also, R 3 and R 4 are bonded to 3 carbon atoms It may form a 6 ring structure, or, R 3 or is R 4 A compound represented by either the R 2 are bonded to 5 total atoms 6 (number of carbon atoms 4-5, nitrogen atoms 1) may form a ring structure.). In the formula, R 1 represents at least one alkyl group having 1 to 6 carbon atoms by fluorine atoms is substituted, R 2 is table hydrogen or an alkyl group of one to 6 carbon, R 3 and R 4 each independently, hydrogen, represent substituted by an alkyl group having 1 to 6 carbon atoms, optionally substituted Ariru group, or an optionally substituted § reel alkyl group, also, R 3 or R 4 either the R 2 are bonded to total atom number of 5-6 (carbon atoms 4-5 nitrogen atoms 1) may form a ring structure, the compounds according to claim 2 3.