JP2004323379A - Method for producing aminopyrazole derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new method for producing an aminopyrazole derivative useful as an intermediate for agrochemicals and animal medicines, and to provide a new intermediate for producing the compound. <P>SOLUTION: This method for producing the aminopyrazole derivative of formula (I) (R is an aryl or heteroaryl which may be substituted; X is N or a C-halogen) is characterized by reacting an iminopyrazole derivative of formula (II) with an alcohol compound of formula (III) (R<SP>1</SP>is a 1 to 6C alkyl) to produce the alkoxydimethylaminopyrazole derivative of formula (IV), purifying the alkoxydimethylaminopyrazole derivative of formula (IV), and then reducing the purified alkoxydimethylaminopyrazole derivative of formula (IV). <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

（式中、Ｒは置換されていてもよいアリール基又はヘテロアリール基を示す。Ｘは窒素原子又Ｃ−ハロゲン原子を示す。）で表されるイミノピラゾール誘導体と、
一般式（ＩＩＩ）：
Ｒ^１ＯＨ （ＩＩＩ）
（式中、Ｒ^１はＣ_１〜Ｃ_６アルキル基を示す。）で表されるアルコール類とを反応させ、
【０００７】
一般式（ＩＶ）：
【化８】

（式中、Ｒ、Ｒ^１及びＸは前記に同じ。）で表されるアルコキシメチルアミノピラゾール誘導体とし、次いで精製した後、還元することを特徴とする一般式（Ｉ）：
【化９】

（式中、Ｒ及びＸは前記に同じ。）で表されるアミノピラゾール誘導体の製造方法及びその中間体である一般式（ＩＶ）：
【化１０】

（式中、Ｒ、Ｒ^１及びＸは前記に同じ。）で表されるアルコキシメチルアミノピラゾール誘導体に関する。
以下、本発明を詳細に説明する。
【０００８】
【発明の実施の形態】
本発明の一般式の定義において、「アリール基又はヘテロアリール基」とは、芳香族炭化水素基又は複素環基を示し、具体的にはベンゼン、ナフタレン、フラン、チオフェン、ピロール、ピラゾール、イミダゾール、ピリジン、ピラジン、ピリミジン、ピリダジン、ピリジン、ピラジン環等が挙げられる。
「Ｃ_１〜Ｃ_６のアルキル基」とは、直鎖又は分岐していても良い炭素数１〜６のアルキル基を示し、具体的にはメチル基、エチル基、直鎖又は分岐のプロピル基、直鎖又は分岐のブチル基、直鎖又は分岐のペンチル基、直鎖又は分岐のヘキシル基等が挙げられる。
「Ｃ_１〜Ｃ_６のアルコキシ基」とは、直鎖又は分岐していても良い炭素数１〜６のアルコキシ基を示し、具体的にはメトキシ基、エトキシ基、直鎖又は分岐のプロポキシ基、直鎖又は分岐のブトキシ基、直鎖又は分岐のペンチルオキシ基、直鎖又は分岐のヘキシルオキシ基等が挙げられる。
「Ｃ_１〜Ｃ_６のアルキルチオ基」とは、直鎖又は分岐していても良い炭素数１〜６のアルキルチオ基を示し、具体的にはメチルチオ基、エチルチオ基、直鎖又は分岐のプロピルチオ基、直鎖又は分岐のブチルチオ基、直鎖又は分岐のペンチルチオ基、直鎖又は分岐のヘキシルチオ基等が挙げられる。
【０００９】
「Ｃ_１〜Ｃ_６のアルキルスルフィニル基」とは、直鎖又は分岐していても良い炭素数１〜６のアルキルスルフィニル基を示し、具体的にはメチルスルフィニル基、エチルスルフィニル基、直鎖又は分岐のプロピルスルフィニル基、直鎖又は分岐のブチルスルフィニル基、直鎖又は分岐のペンチルスルフィニル基、直鎖又は分岐のヘキシルスルフィニル基等が挙げられる。
「Ｃ_１〜Ｃ_６のアルキルスルホニル基」とは、直鎖又は分岐していても良い炭素数１〜６のアルキルスルホニル基を示し、具体的にはメチルスルホニル基、エチルスルホニル基、直鎖又は分岐のプロピルスルホニル基、直鎖又は分岐のブチルスルホニル基、直鎖又は分岐のペンチルスルホニル基、直鎖又は分岐のヘキシルスルホニル基等が挙げられる。
本発明のＲとして好ましいものは下記Ｑ１〜Ｑ４であり、特に好ましくはＱ１又はＱ２であり、
【化１１】

Ｘとして好ましくはＣ−ハロゲン原子であり、特に好ましくはＣ−Ｃｌ（炭素原子−塩素原子）であり、Ｒ^１として特に好ましくはメチル基であり、Ｒ^２として特に好ましくは水素原子である。
【００１０】
本発明は例えば以下のように図示される。
【化１２】

（式中、Ｒ、Ｒ^１及びＸは前記に同じ。）
【００１１】
一般式（ＩＩ）→一般式（ＩＶ）．
本反応で使用できる溶媒としては、反応を著しく阻害しないものであれば良く、ベンゼン、トルエン、キシレン等の芳香族炭化水素類、フルオロベンゼン、クロロベンゼン、ジクロロベンゼン等のハロゲン化芳香族炭化水素類、ジクロロメタン、クロロホルム、ジクロロエタン等のハロゲン化炭化水素類、アセトニトリル、プロピオニトリル、ベンゾニトリル等のニトリル類、ジエチルエーテル、メチルｔ−ブチルエーテル、テトラヒドロフラン、ジオキサン等のエーテル類、酢酸エチル、酢酸ブチル等のエステル類、ジメチルホルムアミド、ジメチルスルホキシド、１，３−ジメチル−２−イミダゾリジノン等を例示することができる。また、反応試薬であるアルコール類を溶媒として用いることもできる。
【００１２】
式（ＩＩＩ）のアルコール類の使用量は一般式（ＩＩ）で表されるイミノピラゾール誘導体に対して等モル以上あれば良いが、好ましくは１０〜１０００倍モルの範囲であり、更に好ましくは５０〜３００倍モルの範囲である。
反応温度は０℃〜使用する溶媒の沸点域で行うことができ、好ましくは１０℃〜使用する溶媒の沸点域である。反応時間は反応規模、反応温度等により一定しないが、数分〜４８時間の範囲で適宜選択すれば良く、好ましくは数分〜５時間である。
本反応においては、一般式（ＩＩ）で表されるイミノピラゾール誘導体は完溶していても完溶していなくてもよい。精製方法としては特に限定されるものではないが、溶媒留去による晶析、温度差による溶解度の差を利用する晶析、溶解度の低い溶媒添加による晶析、カラムクロマトグラフィー等の方法を用いることができる。
【００１３】
一般式（ＩＶ）→一般式（Ｉ）．
本反応は通常、常圧の雰囲気下で行い、所望により窒素、アルゴンなどの不活性気体雰囲気下で実施することができる。
本反応で使用できる溶媒としては、反応を著しく阻害しないものであれば良く、ジエチルエーテル、ジオキサン、テトラヒドロフラン（ＴＨＦ）等のエーテル類、メタノール、エタノール、プロパノール、２−プロパノール等のアルコール類等が挙げられる。
還元剤としては特に限定されるものではなく、一般的な還元剤を使用することができる。具体的にはボランＴＨＦ錯体、水素化ホウ素ナトリウム、水素化シアノホウ素ナトリウム、水素化ホウ素リチウム、水素化リチウムアルミニウム等が例示され、これらのうち特に水素化ホウ素ナトリウムが好ましい。使用する還元剤の量は、一般式（ＩＶ）で表されるアルコキシメチルアミノピラゾール誘導体に対して１当量以上あれば良いが、好ましくは１．５〜１００当量の範囲であり、更に好ましくは１．５〜１０当量の範囲である。
【００１４】
還元剤の添加方法については特に限定されるものはなく、還元剤を溶媒に溶解させてもさせなくてもよく、一度に加えても、少量ずつ加えてもよい。還元剤の添加は、所望により窒素、アルゴンなどの不活性気体雰囲気下で実施することができる。
反応温度は−２０℃〜１２０℃の範囲から選択すれば良く、好ましくは０℃〜室温の範囲である。反応時間は反応規模、反応温度等により一定しないが、１時間〜２４時間の範囲で適宜選択すれば良く、好ましくは１〜４時間である。
反応終了後、目的物を含む反応系から常法に従って単離すれば良く、必要に応じて晶析、蒸留、カラムクロマトグラフィー等の方法により精製することができる。
本発明の原料化合物である一般式（ＩＩ）の化合物は公知文献（例えば、特許文献１、２又は３）に記載の方法により製造することができる。
以下、実施例及び比較例により、本発明を更に具体的に説明するが、本発明はこれらに限定されるものではない。
【００１５】
実施例１
本発明の方法による１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−（２−ピリジルメチルアミノ）ピラゾール−３−カルボニトリルの製造ナスフラスコに、１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−（２−ピリジルメチルイミノ）ピラゾール−３−カルボニトリル ３０１．３ｇ（純度６３．７％、４６７．３ｍｍｏｌ）とメタノール２．５Ｌを入れた。５０℃の水浴で温めながら、生じた結晶をろ過操作ができる量のメタノールを残しロタリーエバポレーターで留去した。得られた結晶をろ取し減圧乾燥させ、１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−｛［メトキシ（２−ピリジル）メチル］アミノ｝ピラゾール−３−カルボニトリル ２０６．５ｇ（純度１００％）を得た。

【００１６】
窒素雰囲気下、得られた結晶を温度計を有する３口フラスコに脱水メタノール１Ｌとともに入れた。ここに水素化ホウ素ナトリウム ９．１ｇ（２４０．５ｍｍｏｌ）を固体のまま少量ずつ添加し、２時間反応させた。反応液中に生じた結晶をろ取し、酢酸エチル６Ｌの溶液とした。この溶液を水１．５Ｌで２回、飽和食塩水５００ｍｌで１回洗浄した。溶媒をある程度留去し生じた結晶をろ取し、得られた結晶を減圧乾燥させて、１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−（２−ピリジルメチルアミノ）ピラゾール−３−カルボニトリル １７２．０ｇ（純度９８．０％）を得た。母液から溶媒をさらに留去し生じた結晶をろ取し、得られた結晶を減圧乾燥させて１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−（２−ピリジルメチルアミノ）ピラゾール−３−カルボニトリル ８．８ｇ（純度９５．０％、合計収率９１．９％）を得た。

【００１７】
比較例１
特開平１０−３３８６７６号の方法による１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−（２−ピリジルメチルアミノ）ピラゾール−３−カルボニトリルの製造
窒素雰囲気下、温度計を有する３口フラスコに脱水メタノール８００ｍｌおよび１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−（２−ピリジルメチルイミノ）ピラゾール−３−カルボニトリル ２１２．７ｇ（純度８８％、４５６．３ｍｍｏｌ）を入れた。ここに水素化ホウ素ナトリウム １７．１ｇ（４５２．０ｍｍｏｌ）を固体のまま少量ずつ添加し２時間反応させた。反応液中に生じた結晶をろ取し、これを酢酸エチル５Ｌの溶液とした。この溶液を水１Ｌで２回、飽和食塩水１Ｌで１回洗浄した。溶媒をある程度留去して生じた結晶をろ取し、得られた結晶を減圧乾燥させて１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−（２−ピリジルメチルアミノ）ピラゾール−３−カルボニトリル １４１．９ｇ（純度９８．１％）を得た。母液から溶媒をさらに留去して生じた結晶をろ取し、得られた結晶を減圧乾燥させ、１−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−５−（２−ピリジルメチルアミノ）ピラゾール−３−カルボニトリル １０．５ｇ（純度９８．３％、合計収率７９．１％）を得た。
【００１８】
【発明の効果】
本発明によれば特別な装置を用いることなくイミノピラゾール誘導体に汎用で安価なアルコールを簡便な方法で作用させるだけで、定量的に高純度なアルコキシメチルアミノピラゾール誘導体として精製できる。アルコキシメチルアミノピラゾール誘導体を経ることにより、純度の低いイミノピラゾール誘導体を用いた場合でも高収率でアミノピラゾール誘導体を製造することができ、工業的に有利なアミノピラゾール誘導体の製造方法を提供するものである。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a novel method for producing an aminopyrazole derivative useful as an intermediate for agricultural and veterinary drugs, and a novel intermediate for producing the compound.
[0002]
[Prior art]
A 1-aryl-3-cyano-5-arylmethylaminopyrazole derivative having a substituent at the 4-position is known to be useful as an insecticide, and its intermediate 1-aryl-3-cyano-5 Regarding a method for producing an arylmethylaminopyrazole derivative, a method for directly reducing an iminopyrazole derivative has been disclosed (for example, see Patent Documents 1, 2, or 3).
Also, it is known that imine can be converted into an alkoxy form which is stable, has excellent crystallinity, and is easily purified by the action of alcohol (for example, Non-Patent Documents 1, 2, 3, 4, 5, 6 or 7). Utilizing such properties, there is an example in which an acylimine is reacted with methanol to form a methoxy form, and then reduced using sodium borohydride (for example, see Non-Patent Document 8). However, there has been no example using iminopyrazole so far.
[0003]
[Patent Document 1]
JP 2002-121191 A [Patent Document 2]
JP-A-10-338676 [Patent Document 3]
JP 2001-72676 [Non-Patent Document 1]
Journal f. prakt. Chemie. Band 323, Heft 6, 1981, S.M. 972-978
[Non-patent document 2]
J. Org. Chem. , Vol. 38, no. 6, 1973, 1065-1074
[Non-Patent Document 3]
J. Org. Chem. , Vol. 38, no. 6, 1973, 1075-1080
[Non-patent document 4]
J. Org. Chem. , Vol. 38, no. 6, 1973, 1080-1083
[Non-Patent Document 5]
J. Org. Chem. , Vol. 53, No. 10, 1988, 2251-2258
[Non-Patent Document 6]
J. Org. Chem. , Vol. 51, No. 6, 1986, 829-833
[Non-Patent Document 7]
J. Chem. Soc. Perkin Trans. 1, 1981, 2443-2450
[Non-Patent Document 8]
Tetrahedron, 1967, Vol. 23, 2869-2877
[0004]
[Problems to be solved by the invention]
In general, imine is unstable and difficult to purify. In a reduction reaction using an iminopyrazole derivative, the yield may decrease due to the purity of the iminopyrazole derivative.
In the industrial production of pharmaceuticals and agrochemicals, even if the yield reduction in each step is a few percent, it greatly affects the production cost. Therefore, a method for producing an aminopyrazole derivative in high yield even when the purity of iminopyrazole is low has been desired. .
[0005]
[Means for Solving the Problems]
The present inventors have conducted intensive studies to solve the above problems, and as a result, reacted an iminopyrazole derivative with an alcohol, converted to an alkoxymethylaminopyrazole derivative, purified the compound, and reduced it to obtain a yield. It has been found that the desired aminopyrazole derivative can be obtained and that the alkoxymethylaminopyrazole derivative is a novel compound not described in any literature, and the present invention has been completed.
[0006]
That is, the present invention provides a compound represented by the general formula (II):
Embedded image

(Wherein, R represents an aryl group or a heteroaryl group which may be substituted; X represents a nitrogen atom or a C-halogen atom);
General formula (III):
R ¹ OH (III)
(Wherein, R ¹ represents a C ₁ -C ₆ alkyl group).
[0007]
General formula (IV):
Embedded image

(Wherein R, R ¹ and X are the same as described above), and then reduced after purification, followed by purification.
Embedded image

(Wherein, R and X are the same as described above), and a general formula (IV) which is an intermediate of the method for producing the aminopyrazole derivative:
Embedded image

(In the formula, R, R ¹ and X are the same as described above.)
Hereinafter, the present invention will be described in detail.
[0008]
BEST MODE FOR CARRYING OUT THE INVENTION
In the definition of the general formula of the present invention, "aryl group or heteroaryl group" refers to an aromatic hydrocarbon group or a heterocyclic group, specifically, benzene, naphthalene, furan, thiophene, pyrrole, pyrazole, imidazole, Examples include pyridine, pyrazine, pyrimidine, pyridazine, pyridine, and pyrazine rings.
The “C ₁ -C ₆ alkyl group” refers to an alkyl group having 1 to 6 carbon atoms which may be linear or branched, specifically, a methyl group, an ethyl group, a linear or branched propyl group. A straight-chain or branched butyl group, a straight-chain or branched pentyl group, a straight-chain or branched hexyl group, and the like.
The “C ₁ -C ₆ alkoxy group” refers to an alkoxy group having 1 to 6 carbon atoms which may be linear or branched, and specifically, a methoxy group, an ethoxy group, a linear or branched propoxy group A straight-chain or branched butoxy group, a straight-chain or branched pentyloxy group, a straight-chain or branched hexyloxy group, and the like.
The “C ₁ -C ₆ alkylthio group” refers to an alkylthio group having 1 to 6 carbon atoms which may be linear or branched, and specifically, a methylthio group, an ethylthio group, a linear or branched propylthio group. And a linear or branched butylthio group, a linear or branched pentylthio group, a linear or branched hexylthio group, and the like.
[0009]
The “C ₁ -C ₆ alkylsulfinyl group” refers to an alkylsulfinyl group having 1 to 6 carbon atoms which may be linear or branched, specifically, a methylsulfinyl group, an ethylsulfinyl group, a linear or Examples include a branched propylsulfinyl group, a straight or branched butylsulfinyl group, a straight or branched pentylsulfinyl group, a straight or branched hexylsulfinyl group, and the like.
The “C ₁ -C ₆ alkylsulfonyl group” refers to an alkylsulfonyl group having 1 to 6 carbon atoms which may be linear or branched, specifically, a methylsulfonyl group, an ethylsulfonyl group, a linear or Examples include a branched propylsulfonyl group, a straight or branched butylsulfonyl group, a straight or branched pentylsulfonyl group, and a straight or branched hexylsulfonyl group.
Preferred as R in the present invention are the following Q1 to Q4, particularly preferably Q1 or Q2,
Embedded image

X is preferably a C-halogen atom, particularly preferably C-Cl (carbon atom-chlorine atom), R ¹ is particularly preferably a methyl group, and R ² is particularly preferably a hydrogen atom.
[0010]
The invention is illustrated, for example, as follows.
Embedded image

(In the formula, R, R ¹ and X are the same as described above.)
[0011]
General formula (II) → General formula (IV).
Solvents that can be used in this reaction may be those that do not significantly inhibit the reaction, and include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated aromatic hydrocarbons such as fluorobenzene, chlorobenzene, and dichlorobenzene; Halogenated hydrocarbons such as dichloromethane, chloroform and dichloroethane, nitriles such as acetonitrile, propionitrile and benzonitrile, ethers such as diethyl ether, methyl t-butyl ether, tetrahydrofuran and dioxane, esters such as ethyl acetate and butyl acetate , Dimethylformamide, dimethylsulfoxide, 1,3-dimethyl-2-imidazolidinone, and the like. In addition, alcohols that are reaction reagents can be used as the solvent.
[0012]
The use amount of the alcohol of the formula (III) may be at least equimolar with respect to the iminopyrazole derivative represented by the general formula (II), but is preferably in the range of 10 to 1000 times, more preferably 50 to 100 times. It is in the range of ~ 300 times mol.
The reaction can be carried out at a temperature ranging from 0 ° C to the boiling point of the solvent used, preferably from 10 ° C to the boiling point of the solvent used. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be appropriately selected within a range of several minutes to 48 hours, and is preferably several minutes to 5 hours.
In this reaction, the iminopyrazole derivative represented by the general formula (II) may or may not be completely dissolved. Although there is no particular limitation on the purification method, a method such as crystallization by distilling off a solvent, crystallization using a difference in solubility due to a temperature difference, crystallization by adding a solvent having low solubility, or column chromatography may be used. Can be.
[0013]
General formula (IV) → General formula (I).
This reaction is generally performed under an atmosphere of normal pressure, and can be performed under an atmosphere of an inert gas such as nitrogen or argon, if desired.
The solvent that can be used in this reaction may be any solvent that does not significantly inhibit the reaction, and examples thereof include ethers such as diethyl ether, dioxane, and tetrahydrofuran (THF), and alcohols such as methanol, ethanol, propanol, and 2-propanol. Can be
The reducing agent is not particularly limited, and a general reducing agent can be used. Specific examples include borane THF complex, sodium borohydride, sodium cyanoborohydride, lithium borohydride, lithium aluminum hydride, and the like. Of these, sodium borohydride is particularly preferred. The amount of the reducing agent to be used may be at least 1 equivalent to the alkoxymethylaminopyrazole derivative represented by the general formula (IV), but is preferably in the range of 1.5 to 100 equivalents, more preferably 1 to 100 equivalents. It is in the range of 0.5 to 10 equivalents.
[0014]
The method for adding the reducing agent is not particularly limited, and the reducing agent may or may not be dissolved in a solvent, and may be added at once or in small amounts. The addition of the reducing agent can be carried out under an atmosphere of an inert gas such as nitrogen or argon, if desired.
The reaction temperature may be selected from the range of -20 ° C to 120 ° C, and is preferably in the range of 0 ° C to room temperature. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be appropriately selected within the range of 1 hour to 24 hours, preferably 1 to 4 hours.
After completion of the reaction, it may be isolated from the reaction system containing the target substance according to a conventional method, and if necessary, can be purified by a method such as crystallization, distillation, or column chromatography.
The compound of the general formula (II) which is a starting compound of the present invention can be produced by a method described in a known document (for example, Patent Document 1, 2, or 3).
Hereinafter, the present invention will be described more specifically with reference to Examples and Comparative Examples, but the present invention is not limited thereto.
[0015]
Example 1
Production of 1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethylamino) pyrazole-3-carbonitrile by the method of the present invention 301.3 g (purity 63.7%, 467.3 mmol) of dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethylimino) pyrazole-3-carbonitrile and 2.5 L of methanol were charged. While warming in a 50 ° C. water bath, the resulting crystals were distilled off by a rotary evaporator, leaving an amount of methanol that could be filtered. The obtained crystals are collected by filtration and dried under reduced pressure, and 1- (2,6-dichloro-4-trifluoromethylphenyl) -5-{[methoxy (2-pyridyl) methyl] amino} pyrazole-3-carbonitrile 206 0.5 g (purity 100%) were obtained.

[0016]
Under a nitrogen atmosphere, the obtained crystals were put into a three-necked flask having a thermometer together with 1 L of dehydrated methanol. To this, 9.1 g (240.5 mmol) of sodium borohydride was added little by little as a solid, and reacted for 2 hours. The crystals generated in the reaction solution were collected by filtration to give a solution of 6 L of ethyl acetate. This solution was washed twice with 1.5 L of water and once with 500 ml of saturated saline. The solvent is distilled off to some extent, and the resulting crystals are collected by filtration, and the obtained crystals are dried under reduced pressure to give 1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethylamino). 172.0 g (purity 98.0%) of pyrazole-3-carbonitrile were obtained. The solvent was further distilled off from the mother liquor, and the resulting crystals were collected by filtration. The obtained crystals were dried under reduced pressure to give 1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethylamino). ) 8.8 g of pyrazole-3-carbonitrile (purity 95.0%, total yield 91.9%) were obtained.

[0017]
Comparative Example 1
Production of 1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethylamino) pyrazole-3-carbonitrile by the method of JP-A-10-338676 A thermometer was used under a nitrogen atmosphere. 800 ml of dehydrated methanol and 212.7 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethylimino) pyrazole-3-carbonitrile (88% purity, 456) .3 mmol). To this, 17.1 g (452.0 mmol) of sodium borohydride was added little by little as a solid and reacted for 2 hours. The crystals formed in the reaction solution were collected by filtration, and used as a solution of 5 L of ethyl acetate. This solution was washed twice with 1 L of water and once with 1 L of saturated saline. The solvent is distilled off to some extent, and the resulting crystals are collected by filtration, and the obtained crystals are dried under reduced pressure to give 1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethylamino). 141.9 g (purity 98.1%) of pyrazole-3-carbonitrile were obtained. The solvent was further distilled off from the mother liquor, and the resulting crystals were collected by filtration, and the obtained crystals were dried under reduced pressure to give 1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethyl). Amino) pyrazole-3-carbonitrile (10.5 g, purity 98.3%, total yield 79.1%) was obtained.
[0018]
【The invention's effect】
According to the present invention, it is possible to quantitatively purify an iminopyrazole derivative as a highly pure alkoxymethylaminopyrazole derivative simply by allowing a general-purpose and inexpensive alcohol to act on the iminopyrazole derivative without using a special apparatus. Through an alkoxymethylaminopyrazole derivative, an aminopyrazole derivative can be produced in high yield even when an iminopyrazole derivative with low purity is used, and an industrially advantageous method for producing an aminopyrazole derivative is provided. It is.

Claims (10)

General formula (II):

(Wherein, R represents an aryl group or a heteroaryl group which may be substituted; X represents a nitrogen atom or a C-halogen atom);
General formula (III):
R ¹ OH (III)
(Wherein, R ¹ represents a C ₁ -C ₆ alkyl group).
General formula (IV):

(Wherein R, R ¹ and X are the same as described above), and then reduced after purification, followed by purification.

(Wherein, R and X are the same as described above). R is Q1-Q4:

(In the formula, R ² may be the same or different, and include a hydrogen atom, a hydroxyl group, a C ₁ -C ₆ alkyl group, a C ₁ -C ₆ alkoxy group, a C ₁ -C ₆ alkylthio group, and a C ₁ -C ₆ alkylsulfinyl. And a C ₁ -C ₆ alkylsulfonyl group, a halogen atom, a nitro group or a cyano group.). The method for producing an aminopyrazole derivative according to claim 1, wherein R ¹ is a methyl group. The method for producing an aminopyrazole derivative according to claim 1, wherein X is C-Cl. The compound represented by the general formula (II) is 1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (2-pyridylmethylimino) pyrazole-3-carbonitrile. A method for producing an aminopyrazole derivative according to any one of the preceding claims. General formula (IV):

(In the formula, R represents an aryl group or a heteroaryl group which may be substituted. R ¹ represents a C ₁ -C ₆ alkyl group. X represents a nitrogen atom or a C-halogen atom.) Alkoxymethylaminopyrazole derivatives. R is Q1-Q4:

(In the formula, R ² may be the same or different, and include a hydrogen atom, a hydroxyl group, a C ₁ -C ₆ alkyl group, a C ₁ -C ₆ alkoxy group, a C ₁ -C ₆ alkylthio group, and a C ₁ -C ₆ alkylsulfinyl. group, C ₁ -C ₆ alkylsulfonyl group, a halogen atom, alkoxymethyl aminopyrazole derivative according to claim 6, wherein a.) showing one or more substituents selected from a nitro group or a cyano group. The alkoxymethylaminopyrazole derivative according to claim 6, wherein R ¹ is a methyl group. The alkoxymethylaminopyrazole derivative according to claim 6, wherein X is C-Cl. 1- (2,6-dichloro-4-trifluoromethylphenyl) -5-{[methoxy (2-pyridyl) methyl] amino} pyrazole-3-carbonitrile.