JP2001058982A - Ester derivative of 5-aminopyrazole-4-carboxylic acid and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound in high yield by directly reacting an alkali metal salt of a cyano-hydroxy-ene-carboxylic ester with hydrazines. SOLUTION: (A) A compound of formula I [R1 is a (halogen-substituted) 1-4C alkyl; R3 is a 1-4C alkyl; M is an alkali metal; a bond of a polygonal line represents that the compound in the formula is not limited to either of E-isomer or Z-isomer], (e.g. sodium salt of ethyl 2-cyano-3-hydroxy-4,4,4- trifluoro-2-butenoate) is reacted with (B) a hydrazine of formula II [R2 is H, a 1-4C alkyl, a (substituted) phenyl], its sulfate or the like (e.g. methylhydrazine sulfate) preferably in the presence of an acid (e.g. trifluoroacetic acid, and pentafluoropropionic acid), preferably at 0-180 deg.C for 5 min to 72 hr to provide the objective compound of formula III (e.g. ethyl 5-amino-1-methyl-3- trifluoromethyl-pyrazol-4-carboxylate).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a 5-aminopyrazole-4-carboxylic acid ester derivative which is an important intermediate of medicines and agricultural chemicals, and a method for producing the same. For example, ethyl 5-amino-1-methyl-3-trifluoromethylpyrazole-4-carboxylate which can be produced according to the present invention is obtained by diazotizing an amino group according to a known technique and then removing the amino group to obtain a pesticide intermediate. Ethyl 1-methyl-3-trifluoromethylpyrazole-4-carboxylate (JP-A-1-106866), which is useful as a compound, can be derived.

[0002]

2. Description of the Related Art Many pharmaceuticals, agricultural chemicals, especially fungicides having various pyrazole skeletons are known. Therefore, development of a method for efficiently producing these compounds having a pyrazole skeleton has been desired. In particular, 5-aminopyrazole-4-carboxylic acid ester derivatives are useful as production intermediates in this field. Heretofore, several methods for producing 5-aminopyrazole derivatives are known. For example, Japanese Patent Application Laid-Open No. 6-503069 discloses the following formula (5).

[0003]

Embedded image

In the formula, R ⁵ represents a hydrogen atom or a C1-C4 alkyl group which may be halogen-substituted, and R ⁶ represents a cyano group, —CO—R ⁷ or CS—R ⁷ (wherein R ⁷ represents a hydroxyl group, a C1-C4 alkoxy group, an amino group, a C1-C4 alkylamino group or a di- (C1-C4) alkylamino group), L
Represents a cyanoalkene compound represented by （representing a C1-C4 alkoxy group, in the presence of a base, represented by the formula (6):

[0005]

Embedded image

Wherein R ⁸ is a C1-C8 alkyl group;
It may have a C1-C8 hydroxyalkyl group, and further has 1 to 3 halogen atoms, a nitro group,
A C1-C4 alkyl group, a partially or wholly halogenated C1-C4 alkoxy group, a C1-C4 alkylthio group or a phenyl group optionally having a group -NR ⁹ R ¹⁰ ; ⁹ R ¹⁰ represents a hydrogen atom or a C1-C4 alkyl group, and the phenyl group may further have a total of 4 or 5 halogen atoms.) A method for producing various 5-aminopyrazole derivatives by the reaction is described.

[0007] J. J. Heterocycl. Che
m. 12, Vol. 1199-1205 (1975) describes a method for synthesizing a 5-aminopyrazole derivative in which the 4-position is substituted with a cyano group, according to the following reaction formula (A) (Chem. 7).

[0008]

Embedded image (In the reaction formula, R ¹¹ represents a phenyl group, a p-substituted phenyl group, or a p-substituted benzyl group, R ¹² represents a hydrogen atom,
Methyl group, hydroxyethyl group)

As described above, in these methods, an acrylonitrile derivative in which the β-position is substituted with an alkoxy group is used as a cyanoalkene derivative condensed with hydrazines.

Examples in which the moiety L (leaving group) in the formula (5) is a substituent other than an alkoxy group include those described in Zh. Org. K
him. 17, Vol. 2, pp. 268-272 (1981) is known. This document describes a method for synthesizing 5-aminopyrazole-4-carboxylic acid ester according to the reaction formula (B) (Formula 8).

[0011]

Embedded image

In this method, an alkali metal salt of 3-hydroxy-2-ene-carboxylate is chlorinated with phosphorus pentachloride, and the 2-chlorocyanoalkene derivative is reacted with hydrazine to form 5-aminopyrazole-4-.
Carboxylic acid ester derivatives are being synthesized. In this method, an isomer of the aminopyrazole derivative may be generated.

As described above, 5-aminopyrazole-4
In an existing method for producing a carboxylic acid ester derivative, an alkoxy group or a chlorine atom is used as a leaving group, so that an extra step is required for synthesizing a starting cyanoalkene derivative.

[0014]

SUMMARY OF THE INVENTION Accordingly, the present invention provides a novel and industrially easy and efficient process which produces less isomers.
An object of the present invention is to provide a method for producing an -aminopyrazole-4-carboxylic acid ester derivative and a novel 5-aminopyrazole-4-carboxylic acid ester derivative obtained by the method.

[0015]

Means for Solving the Problems The present inventors have made intensive efforts to solve the above-mentioned problems, and as a result, they can be easily synthesized from easily available carboxylic esters and cyanoacetates by known techniques. The direct reaction of an alkali metal salt of cyano-3-hydroxy-2-ene-carboxylate with hydrazines is intended for 5-aminopyrazole-
The inventors have found that a 4-carboxylic acid ester derivative is selectively and efficiently produced, and have completed the present invention.

That is, one of the present invention is represented by the following formula (1).
(Formula 9)

Embedded image

[0017] (wherein, ^{R 1} represents a C1-C4 alkyl group halogen optionally substituted straight-chain or branched, ^{R 2} represents a hydrogen atom, a linear or branched C1-C4
Represents an alkyl group or a phenyl group which may be substituted, and R ³ represents a linear or branched C1-C4 alkyl group). Modulo equation (2)
(Formula 10)

[0018]

Embedded image (Wherein, R ¹ and R ³ represent the same meaning as described above, M represents an alkali metal, and the bond in the broken line indicates that the compound in the formula is E
A single bond indicating that the compound is not limited to one of the isomer and the Z-isomer) and a compound represented by the formula (3):

[0019]

Embedded image Wherein R ² represents the same meaning as described above, the hydrazine, the hydrate, the hydrochloride, the hydrobromide, or the sulfate. Is the way.

Another aspect of the present invention is to provide a compound of the formula (4)

Embedded image

(Wherein R ^2a is a linear or branched C1
An alkyl group of -C4, R ^3a is a linear or branched C
5-aminopyrazole-4-carboxylic acid ester derivative represented by a 1-C4 alkyl group and a hydrogen atom).

The present invention is completely unique in that an alkali metal salt compound represented by the formula (2) is used for the synthesis of a heterocyclic compound.

[0023]

DETAILED DESCRIPTION OF THE INVENTION In the present invention, the reaction formula (C)
According to (Chemical Formula 13), the compound represented by the formula (2) is reacted with a hydrazine derivative represented by the formula (3), a hydrate thereof, or a salt thereof in a solvent, if necessary.
The desired compound represented by the formula (1) can be produced.

[0024]

Embedded image

The compound represented by the formula (2) is described as an enol alkali metal salt. The alkali metal salt has two isomers, E-form and Z-form. The compound of formula (D) is also a compound of formula (D)

[0026]

Embedded image As shown in the reaction formula (M represents an alkali metal atom), a tautomer can exist due to keto-enol equilibrium, and the alkali metal salt of the keto form is also acceptable. In the present invention, any of the three isomers can be used in the reaction, and a mixture of these three isomers is also acceptable.

In the formula (2), M represents an alkali metal atom, but is preferably sodium. In the formula (1), R ¹ represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a t-butyl group, a monochloromethyl group, a dichloromethyl group, a trichloromethyl group, a pentachloro group. Halogen-substituted direct substituents such as ethyl, heptachloropropyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, and pentafluoroethyl It represents a C1-C4 alkyl group of a chain or a branched chain, and it is considered that the presence of this group is considered to be in the stability of the compound represented by the formula (2). Fluorine-substituted linear or branched C1-C
And more preferably a trifluoromethyl group.

R ² represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, t
Represents a linear or branched C1-C4 alkyl group such as -butyl group, a hydrogen atom or a phenyl group which may be substituted, preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, Linear or branched C1-C such as -butyl group, isobutyl group, t-butyl group, etc.
4 alkyl group.

R ³ represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, t
A C1-C4 alkyl group having a straight or branched chain such as -butyl group.

When a hydrazine salt is used, the salt form is preferably a monohydrochloride, dihydrochloride, hydrobromide,
Sulfates and oxalates are particularly preferred.

This reaction is carried out in an inert solvent or diluent, if necessary. Examples thereof include alcohols such as methanol, ethanol, and isopropyl alcohol; ethers such as diethyl ether, diisopropyl ether, dimethoxyethane, diethylene glycol dimethyl ether, dioxane, and tetrahydrofuran; methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate, and propionic acid. Esters such as ethyl, aromatic compounds such as benzene, toluene and xylene, carbonates such as dimethyl carbonate, diethyl carbonate and diphenyl carbonate, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene and the like. Examples thereof include halogenated hydrocarbons and polar solvents such as dimethylformamide, dimethylsulfoxide, and N-methylpyrrolidone. Further, two or more of these solvents may be used as a mixture.

In the reaction of the present invention, the compound represented by the formula (2) and the hydrazine represented by the formula (3), the hydrate, the hydrochloride, the hydrobromide or the sulfuric acid are simply used. The salt can be reacted, but the reaction is preferably performed in the presence of an acid. The acids used are preferably mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid and boric acid, organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid and pentafluoropropionic acid, sulfonic acids such as methanesulfonic acid, and pentoxide. Acid oxides such as phosphorus and sulfurous acid gas, and hydrogen sulfates such as sodium hydrogen sulfate and potassium hydrogen sulfate;
Examples include Lewis acids such as zinc chloride, solid acids such as zeolite, and ion exchange resins. Particularly preferred are fluorinated carboxylic acids such as trifluoroacetic acid and pentafluoropropionic acid.

A substance having a dehydrating ability such as anhydrous magnesium sulfate, anhydrous sodium sulfate, molecular sieves and zeolite can be added to the reaction system. Phase transfer catalysts such as quaternary ammonium salts such as tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, and benzyltriethylammonium chloride; 12-crown-4, 15-crown-5, 18-crown- You may add crown ethers, such as 6.

The starting compounds used in the reaction of the present invention are as follows:
Although used in stoichiometric amounts, either one can be used in excess. The reaction is generally carried out at 0 to 180 ° C., preferably 20 to 150 ° C., in particular in each case at the boiling point of the solvent, at normal pressure or under the vapor pressure of the solvent used. The reaction time is 5 minutes to 72 hours, preferably 3 hours to 48 hours.

The compound of the formula (2), which is a starting material in the production method of the present invention, can be easily produced from easily available carboxylic acid esters and cyanoacetates by known techniques. In addition, commercially available hydrazines of the formula (3) can be used. The 5-aminopyrazole-4-carboxylic acid ester derivative represented by the formula (1) obtained by the method of the present invention can be easily hydrolyzed in the presence of a base such as sodium hydroxide to give 5-aminopyrazole. -4-carboxylic acid derivative.

Among the compounds represented by the formula (1) which can be produced by the production method of the present invention, the compound represented by the formula (4), that is, 5-amino having a trifluoromethyl group at the 3-position of the pyrazole group Pyrazole-4-carboxylic acid derivatives are novel compounds. Tokuhyo Hei 6-503069
Japanese Patent Application Laid-Open Publication No. H11-216, discloses a huge number of compounds including the compound represented by the formula (4) of the present invention by a general formula, but specifically describes the compound represented by the formula (4) of the present invention. It has not been. It is presumed that it is difficult to produce a compound of the formula (5), which is a raw material of the formula (1), wherein R ⁵ is a trifluoromethyl group and L is an alkoxy group. In fact, there is no specific description of the raw material.

[0037]

The contents of the present invention will be specifically described with reference to the following examples and reference examples, but the present invention is not limited to these examples.

Reference Example 1 Synthesis of sodium salt of ethyl 2-cyano-3-hydroxy-4,4,4-trifluoro-2-butenoate A solution obtained by dissolving 24.0 g (1.04 mol) of sodium metal in 400 ml of ethanol was added at room temperature. The mixture was stirred under the above, and 113.1 g (1.00 mol) of ethyl cyanoacetate was added dropwise. After stirring for 1 hour, 150.0 g (1.05 mol) of ethyl trifluoroacetate was added to the reaction mixture.
l) was added dropwise, and stirring was continued at the same temperature for 3 hours. After completion of the reaction, the reaction solution was concentrated as it was under reduced pressure, and the precipitated solid was purified with ethyl 2-cyano-3-hydroxy-4,4,4,4.
-Trifluoro-2-butenoate sodium salt 22
Obtained as 1.86 g (96% yield). ¹ H-NMR (acetone-d ₆ , δ ppm): 1.21
(3H, t, J = 6.9 Hz), 4.09 (2H, q,
J = 6.9 Hz)

Example 1 5-amino-1-methyl-3-
Synthesis of ethyl trifluoromethylpyrazole-4-carboxylate 2.31 g (10 mmol) of ethyl 2-cyano-3-hydroxy-4,4,4-trifluoro-2-butenoate sodium salt synthesized in Reference Example 1, methylhydrazine After suspending 2.88 g (20 mmol) of sulfate in 20 ml of dimethyl carbonate, the mixture was stirred at 80 ° C. for 20 hours. After the reaction solution was cooled to room temperature, the filtrate obtained by filtration was concentrated under reduced pressure, and the precipitated solid was recrystallized from diisopropyl ether to give the target product 5-amino-1-methyl-3- as a white solid. Trifluoromethyl-
0.95 g of ethyl pyrazole-4-carboxylate (yield 4
0%). It was confirmed by gas chromatography that this compound was not contaminated with isomers. ¹ H-NMR (CDCl ₃ , δ ppm): 1.34 (3
H, t, J = 7.3 Hz), 3.67 (3H, s),
4.30 (2H, q, J = 7.3 Hz), 5.24 (2
H, br) Melting point 120-121 ° C

Example 2 5-Amino-1-methyl-3-
Synthesis of ethyl trifluoromethylpyrazole-4-carboxylate 2.31 g (10 mmol) of ethyl 2-cyano-3-hydroxy-4,4,4-trifluoro-2-butenoate sodium salt synthesized in Reference Example 1, methylhydrazine 2.88 g (20 mmol) of sulfate and 3.0 g of molecular sieve 3A were added to dimethyl carbonate 20
The suspension was stirred at room temperature. Further, after adding 1.14 g of trifluoroacetic acid, the mixture was stirred at 80 ° C. for 20 hours. After the reaction solution was cooled to room temperature, the filtrate obtained by filtration was concentrated under reduced pressure, and the precipitated solid was recrystallized from diisopropyl ether to give the target compound 5 as a white solid.
2.02 g of ethyl -amino-1-methyl-3-trifluoromethylpyrazole-4-carboxylate (85% yield)
I got It was confirmed by gas chromatography that this compound did not contain any isomers. ¹ H-NMR (CDCl ₃ , δ ppm): 1.34 (3
H, t, J = 7.3 Hz), 3.67 (3H, s),
4.30 (2H, q, J = 7.3 Hz), 5.24 (2
H, br) Melting point 120-121 ° C

Example 3 5-Amino-1-methyl-3-
Synthesis of methyl trifluoromethylpyrazole-4-carboxylate Methyl 2-cyano- synthesized in the same manner as in Reference Example 1.
The target product, methyl 5-amino-1-methyl-3-trifluoromethylpyrazole-4-carboxylate, was obtained in the form of a white solid using 3-hydroxy-4,4,4-trifluoro-2-butenoate sodium salt according to Example 2. As obtained.
(Yield 82%) ¹ H-NMR (CDCl ₃ , δ ppm): 3.66 (3
H, s), 3.82 (3H, s), 5.92 (2H, b
r) melting point 164-165 ° C

Example 4 5-amino-1-methyl-3-
Synthesis of isopropyl trifluoromethylpyrazole-4-carboxylate Isopropyl 2-cyano-3-hydroxy-4,4,4-trifluoro-2 synthesized in the same manner as in Reference Example 1.
The desired product, isopropyl 5-amino-1-methyl-3-trifluoromethylpyrazole-4-carboxylate, was obtained as a white solid according to Example 2 using -butenoate sodium salt. (Yield 75%) ¹ H-NMR (CDCl ₃ , δ ppm): 1.31 (6
H, d, J = 7.2), 3.66 (3H, s), 5.0
9-5.21 (3H, m) Melting point 164-165 ° C

Example 5 5-Amino-1-methyl-3-
Synthesis of trifluoromethylpyrazole-4-carboxylic acid 2.37 g of ethyl 5-amino-1-methyl-3-trifluoromethylpyrazole-4-carboxylate (10 mmol
l), 0.44 g (11 mmol) of sodium hydroxide were mixed with 10 ml of water, and the mixture was stirred at 60 ° C for 10 hours. After the temperature was returned to room temperature, toluene was added and the mixture was separated, and the aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid. The precipitated solid is collected by filtration and dried,
1.78-amino-1-methyl-3-trifluoromethylpyrazole-4-carboxylic acid 1.78 as a white solid
g (85% yield). ¹ H-NMR (DMSO-d ₆ , δ ppm): 3.61
(3H, s), 6.55 (2H, br), 12.40
(1H, br) Melting point: 216-218 ° C

Comparative Example 1 Synthesis of ethyl 2-cyano-3-hydroxy-4,4,5,5,5-pentafluoro-2-pentenoate 3.39 g (30 mmol) of ethyl cyanoacetate and 6.06 g (60 mmol) of triethylamine Was dissolved in 20 ml of tetrahydrofuran and stirred at room temperature. Then, 5.47 g of pentafluoropropionic acid chloride (30 m
mol) was added dropwise, followed by stirring at room temperature for 5 hours. However, the production of the desired product could not be confirmed.

Comparative Example 2 5-amino-1-methyl-3-
Synthesis of ethyl trifluoromethylpyrazole-4-carboxylate 3.0 g (13.2 mmol) of ethyl 3-chloro-2-cyano 4,4,4-trifluoro-2-butenoate
Was added to 9 ml of ethanol, and the mixture was stirred and heated to 72 ° C.
After the temperature was raised, 0.61 g (13.2 mmol) of methylhydrazine and 1.34 g (13.2 mmol) of triethylamine dissolved in 6 ml of ethanol were added dropwise to the reaction solution over 25 minutes. After 2.5 hours, return to room temperature and HP
Analysis using LC showed that the target product, 5-amino-1-
It was confirmed that ethyl methyl-3-trifluoromethylpyrazole-4-carboxylate was produced at a reaction yield of 47%, but at the same time, an isomer of the desired product, 4-cyano-5-hydroxy-1 -Methyl-3-trifluoromethylpyrazole was produced at a reaction yield of 42%, and 4-cyano-3-hydroxy-3-methyl-5-trifluoromethylpyrazole was produced at a reaction yield of 5% (Chem. 15). It was difficult to separate and purify these isomers by a simple method.

[0046]

Embedded image

[0047]

The present invention is a novel method for producing a 5-aminopyrazole-4-carboxylic acid ester derivative represented by the formula (1). The method of the present invention generally uses raw materials which are easily available and easy to handle, and there is no isomer generation which is a problem of the industrial production method, or even if it is present, the separation operation is easy. It has features and can reduce the number of manufacturing steps. Further, the novel 5-amino-3-trifluoromethylpyrazole-4-carboxylic acid ester derivative represented by the formula (4) is useful as an important intermediate of agricultural medicine, particularly a fungicide.

────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] May 24, 2000 (2005.2.
4)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Claims

[Correction method] Change

[Correction contents]

[Claims]

Embedded image (Wherein, R ¹ represents a linear or branched C1-C4 alkyl group which may be substituted with a halogen atom;
² represents a hydrogen atom, a linear or branched C1-C4 alkyl group or a phenyl group which may be substituted,
R ³ represents a linear or branched C1-C4 alkyl group), and is a method for producing a 5-aminopyrazole-4-carboxylic acid ester derivative represented by the formula (2):

Embedded image (Wherein, R ¹ and R ³ have the same meanings as described above, M represents an alkali metal atom, and the broken line bond is a single bond indicating that the compound in the formula is not limited to one of the E-form and the Z-form) And a compound represented by the formula (3):

Embedded image Wherein R ² represents the same meaning as described above, the hydrazine, the hydrate, the hydrochloride, the hydrobromide, or the sulfate. Method.

Embedded image (Wherein, R ^2a represents a linear or branched C1-C4 alkyl group, and R ^3a represents a linear or branched C1-C4 alkyl group and a hydrogen atom). -4-carboxylic acid derivatives.

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0039

[Correction method] Change

[Correction contents]

Example 1 5-amino-1-methyl-3-
Synthesis of ethyl trifluoromethylpyrazole-4-carboxylate 2.31 g (10 mmol) of ethyl 2-cyano-3-hydroxy-4,4,4-trifluoro-2-butenoate sodium salt synthesized in Reference Example 1, methylhydrazine After suspending 2.88 g (20 mmol) of sulfate in 20 ml of dimethyl carbonate, the mixture was stirred at 80 ° C. for 20 hours. After the reaction solution was cooled to room temperature, the filtrate obtained by filtration was concentrated under reduced pressure, and the precipitated solid was recrystallized from diisopropyl ether to give the target product 5-amino-1-methyl-3- as a white solid. trifluoromethyl Lupi <br/> Razoru 4-carboxylic acid ethyl 0.95 g (yield: 40
%). It was confirmed by gas chromatography that this compound was not contaminated with isomers. ¹ H-NMR (CDCl ₃ , δ ppm): 1.34 (3
H, t, J = 7.3 Hz), 3.67 (3H, s),
4.30 (2H, q, J = 7.3 Hz), 5.24 (2
H, br) Melting point 120-121 ° C

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] 0045

[Correction method] Change

[Correction contents]

Comparative Example 2 5-amino-1-methyl-3-
Synthesis of ethyl 3-chloro-2-shear Bruno -4-trifluoromethylpyrazole-4-carboxylate, 4,4-trifluoro-2-butenoate 3.0g (13.2mmo
l) was added to 9 ml of ethanol, stirred, and heated to 72 ° C. After the temperature was raised, 0.61 g (13.2 mmol) of methylhydrazine and 1.34 g (13.2 mmol) of triethylamine dissolved in 6 ml of ethanol were added dropwise to the reaction solution over 25 minutes. After 2.5 hours, the temperature was returned to room temperature, and the reaction solution was
As a result of analysis using PLC, it was found that the target product, 5-amino-1
It was confirmed that ethyl -methyl-3-trifluoromethylpyrazole-4-carboxylate was produced at a reaction yield of 47%, but at the same time, the target isomer 4-cyano-5-hydroxy- 1-methyl-3-trifluoromethylpyrazole was produced at a reaction yield of 42%, and 4-cyano-3-hydroxy-3-methyl-5-trifluoromethylpyrazole was produced at a reaction yield of 5%. . It was difficult to separate and purify these isomers by a simple method.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Toshio Kitajima 1144 Togo, Mogo-shi, Chiba Mitsui Chemicals Co., Ltd. Kenji Odaka 1144 Togo, Mobara-shi, Chiba Mitsui Chemicals, Inc. F-term (reference) 4H039 CA40 CG10

Claims (9)

[Claims] (1) Formula (1) (Wherein, R ¹ represents a linear or branched C1-C4 alkyl group which may be substituted with a halogen atom;
² represents a hydrogen atom, a linear or branched C1-C4 alkyl group or a phenyl group which may be substituted,
R ³ represents a linear or branched C1-C4 alkyl group), and is a method for producing a 5-aminopyrazole-4-carboxylic acid ester derivative represented by the formula (2): 2] (Wherein, R ¹ and R ³ have the same meanings as described above, M represents an alkali metal atom, and the broken line bond is a single bond indicating that the compound in the formula is not limited to one of the E-form and the Z-form) And a compound represented by the formula (3): Wherein R ² represents the same meaning as described above, the hydrazine, the hydrate, the hydrochloride, the hydrobromide, or the sulfate. Method. 2. The method according to claim 1, wherein the reaction is carried out in the presence of an acid. 3. The method according to claim 1, wherein the reaction is carried out in the presence of a dehydrating agent. 4. The 5-aminopyrazole-4 according to claim 1, wherein R ¹ is a linear or branched C1-C4 alkyl group substituted by a fluorine atom.
-A method for producing a carboxylic acid ester derivative. 5. The method for producing a 5-aminopyrazole-4-carboxylic acid ester derivative according to claim 4, wherein R ¹ is a trifluoromethyl group. 6. C1-C4 wherein R ² is linear or branched
The method for producing a 5-aminopyrazole-4-carboxylic acid ester derivative according to any one of claims 1 to 5, which is an alkyl group represented by the formula: 7. The method according to claim 6, wherein R ² is a methyl group.
A method for producing an aminopyrazole-4-carboxylic acid ester derivative. 8. The method for producing a 5-aminopyrazole-4-carboxylic acid ester derivative according to claim 1, wherein M is a sodium atom. 9. Formula (4) (Wherein, R ^2a represents a linear or branched C1-C4 alkyl group, and R ^3a represents a linear or branched C1-C4 alkyl group and a hydrogen atom). -4-carboxylic acid derivatives.