JP3274555B2 - Method for producing 1H-pyrrolo- [1,2-b] [1,2,4] triazole derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention is useful as a synthetic intermediate for physiologically active substances such as pharmaceuticals and agricultural chemicals, a photographic coupler, or a precursor for a dye or a variety of dyes for a thermal transfer dye donating material.
The present invention relates to a method for producing an H-pyrrolo- [1,2-b] [1,2,4] triazole derivative.

[0002]

2. Description of the Related Art 1H-pyrrolo- [1,2-b] [1,
2,4] triazole derivatives are available from Ukrainskii Khimiches
kii Zhurnal, Vol. 41, No. 2, pp. 181-185 (1975) and Khimiya Geterotsiklicheskikh Scedi
nenii, No. 2, pp. 261-267 (February 1974)
And US Pat. No. 4,358,4.
No. 57, No. 4,962,202 as pharmaceuticals. Also, Abstracts of the Annual Meeting of the Photographic Society of Japan 1985, JP-A-62-2778552, 6
2-279339, JP-A-1-288835, U.S. Pat. No. 4,910,127, European Patent EP0,49.
No. 1,197 A1, which is known as a magenta coupler for photography and a magenta dye. In addition, the European patent EP
No. 0,491,197A1 discloses 1H-pyrrolo- [1,
2-b] It is disclosed that a compound useful as a photographic cyan coupler can be obtained by introducing an electron-withdrawing group at the 6-position and the 7-position of a [1,2,4] triazole derivative. However, the methods for synthesizing 1H-pyrrolo- [1,2-b] [1,2,4] triazole derivatives described in these are not always efficient. In particular, it is difficult to synthesize a photographic cyan coupler which is useful as a cyan coupler substituted at the 6-position and the 7-position with an electron-withdrawing group, and further substituted at the 6-position and the 7-position with an electron-withdrawing group. 5 position where it is expected to increase the pK _a is substituted with an oxygen functional group such as an acyloxy group or a sulfonyloxy group 1H- pyrrolo - [1,2-b] [1,2,
4] The known method of synthesizing a triazole derivative was not a method of synthesizing with a realistic yield.

[0003]

An object of the present invention is to provide a 1H-pyrrolo-substituted compound in which the 6-position and the 7-position are substituted with an electron-withdrawing group.
An object of the present invention is to provide a method for producing a [1,2-b] [1,2,4] triazole derivative with a high yield.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies to achieve the above object, and as a result, by condensing a triazole derivative represented by the following general formula (I) in a molecule, The method of converting into a 1H-pyrrolo- [1,2-b] [1,2,4] triazole derivative represented by the following general formula (II) is based on 1H in which the 6-position and the 7-position are substituted with electron-withdrawing groups -Pyrrolo- [1,2-b] [1,2,4] triazole derivatives.

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Hereinafter, the present invention will be described in detail. The intramolecular condensation reaction of the present invention effectively proceeds as a ring closing reaction by using various acid halides in the presence of a base,
Heating under neutral conditions promotes ring closure as a dehydration reaction, dealcoholization reaction, and addition reaction. The reaction can be accelerated by reacting under basic or acidic conditions. R ¹ represents an alkyl group or an aryl group. The alkyl group represented by R ¹ has 1 to 36 carbon atoms.
A linear, branched or cyclic alkyl group such as methyl, ethyl, isopropyl, n-butyl, t-
Butyl, n-octyl, n-hexadecyl, 2-ethylhexyl, 2-heptylundecyl, cyclohexyl,
A 2-methylcyclohexyl group.

[0006] The alkyl group represented by R ¹ may be substituted with a substituent. Preferred substituents include a halogen atom (eg, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom), a cyano group, a nitro group, an alkenyl group (eg, vinyl, hexenyl), an alkynyl group (eg, acetylinyl, propargyl), Aryl groups (eg, phenyl, naphthyl), alkoxy groups (eg, methoxy,
Ethoxy, n-butoxy), an aryloxy group (eg, phenoxy, naphthyloxy), an alkylthio group (eg, methylthio, n-propylthio), an arylthio group (eg, phenylthio), an alkylsulfonyl group (eg, methanesulfonyl, ethanesulfonyl) ),
Arylsulfonyl group (eg, benzenesulfonyl), formyl group, acyl group (eg, acetyl, benzoyl, propionyl), acyloxy group (eg, acetyloxy, benzoyloxy), alkoxycarbonyl group (eg, methoxycarbonyl, butoxycarbonyl, n -Octyloxycarbonyl), an aryloxycarbonyl group (eg, phenoxycarbonyl), a carbonamide group (eg, acetylamino, propionylamino, benzoylamino), a sulfonamide group (eg, methanesulfonylamide, ethanesulfonylamide, benzenesulfonylamide) ), A carbamoyl group (eg, dimethylaminocarbonyl, ethylaminocarbonyl, dioctylaminocarbonyl), a sulfamoyl group (eg, methylamine Nosulfonyl, diethylaminosulfonyl, n-butylaminosulfonyl), ureido group (eg, dimethylaminocarbonylamino, anilinocarbonylamino), alkoxycarbonylamino group (eg, methoxycarbonylamino, i-butoxycarbonylamino), amino group ( For example, amino, diethylamino, dihexylamino), imide group (for example, phthalimide), heterocyclic group (for example, furyl, thienyl,
Morpholino), and these substituents may be further substituted.

The aryl group represented by R ¹ is an aryl group having 6 to 45 carbon atoms, for example, phenyl, 1-naphthyl and 2-naphthyl groups. The aryl group represented by R ¹ may be substituted with a substituent. Preferred substituents include a halogen atom (eg, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom), a cyano group, a nitro group, an alkyl group (eg, methyl, ethyl, t-butyl, t-octyl), an alkenyl group (Eg, vinyl, hexenyl), alkynyl groups (eg, acetylinyl, propargyl), aryl groups (eg, phenyl,
Naphthyl), alkoxy groups (eg, methoxy, ethoxy, n-butoxy), aryloxy groups (eg, phenoxy, naphthyloxy), alkylthio groups (eg,
Methylthio, n-propylthio), arylthio group (eg, phenylthio), alkylsulfonyl group (eg, methanesulfonyl, ethanesulfonyl), arylsulfonyl group (eg, benzenesulfonyl), formyl group, acyl group (eg, acetyl, benzoyl, Propionyl), acyloxy group (eg, acetyloxy, benzoyloxy), alkoxycarbonyl group (eg, methoxycarbonyl, butoxycarbonyl, n-
Octyloxycarbonyl), an aryloxycarbonyl group (eg, phenoxycarbonyl), a carbonamide group (eg, acetylamino, propionylamino,
Benzoylamino), a sulfonamide group (eg, methanesulfonylamide, ethanesulfonylamide, benzenesulfonylamide), a carbamoyl group (eg, dimethylaminocarbonyl, ethylaminocarbonyl, dioctylaminocarbonyl), a sulfamoyl group (eg, methylaminosulfonyl, Diethylaminosulfonyl, n-butylaminosulfonyl), ureido group (eg, dimethylaminocarbonylamino, anilinocarbonylamino), alkoxycarbonylamino group (eg, methoxycarbonylamino, i-butoxycarbonylamino), amino group (eg, amino , Diethylamino, dihexylamino), an imide group (eg, phthalimido), a heterocyclic group (eg, furyl, thienyl, morpholino). Et substituents may be further substituted.

R ² and R ³ each represent an electron-withdrawing group having a Hammett's substituent constant σ _p value of 0.20 or more. Hammett's rule was introduced in 1935 by LP H in order to quantitatively discuss the effect of substituents on the reaction or equilibrium of benzene derivatives.
A rule of thumb proposed by ammett, which is widely accepted today. The substituent constants determined by the Hammett's rule include σ _p values and σ _m values, and these values are described in many general books.
Dean, Lange's Handbook of Chemistry, 12th edition,
1979 (McGraw-Hill), "Chemical Area Special Edition", 1
22, No. 96-103, 1979 (Nankodo). In the present invention, R ² and R ³ are defined by Hammett's substituent constant σ _p value. However, the values are not limited to only those substituents having known values in the literature described in these publications, and their values are not limited to those values. Of course, even if the document is unknown, it is included as long as it is included in the range when measured based on the Hammett's rule.

Specific examples of the electron-withdrawing groups R ² and R ³ having a σ _p value of 0.2 to 1.0 include an acyl group, an acyloxy group, a carbamoyl group, an alkoxycarbonyl group,
Aryloxycarbonyl group, cyano group, nitro group, dialkylphosphono group, diarylphosphono group, diarylphosphinyl group, alkylsulfinyl group, arylsulfinyl group, alkylsulfonyl group, arylsulfonyl group, sulfonyloxy group, acylthio group, Sulfamoyl group, thiocyanate group, thiocarbonyl group, halogenated alkyl group, halogenated alkoxy group, halogenated aryloxy group, halogenated alkylamino group,
Examples include a halogenated alkylthio group, an aryl group substituted with another electron-withdrawing group having a σ _p value of 0.20 or more, a heterocyclic group, a halogen atom, an azo group, or a selenocyanate group.

If R ² and R ³ are described in more detail, σ _p
Examples of the electron-withdrawing group having a value of 0.2 to 1.0 include an acyl group (eg, acetyl, 3-phenylpropanoyl, benzoyl, 4-dodecyloxybenzoyl), an acyloxy group (eg, acetoxy), a carbamoyl group ( For example, carbamoyl, N-ethylcarbamoyl, N-phenylcarbamoyl, N, N-dibutylcarbamoyl, N
-(2-dodecyloxyethyl) carbamoyl, N-
(4-n-pentadecanamido) phenylcarbamoyl, N-methyl-N-dodecylcarbamoyl, N- {3
-(2,4-di-t-amylphenoxy) propyl @ carbamoyl), an alkoxycarbonyl group (for example, methoxycarbonyl, ethoxycarbonyl, t-butyloxycarbonyl, i-butyloxycarbonyl, n-butyloxycarbonyl, t- Octyloxycarbonyl,
Diisopropylmethylmethoxycarbonyl, dodecyloxycarbonyl, octadecyloxycarbonyl, 2,
6-di-t-butyl-4-methyl-cyclohexyloxycarbonyl, 2,4,6-trimethylcyclohexyloxycarbonyl), an aryloxycarbonyl group (for example, phenoxycarbonyl), a cyano group, a nitro group,
A dialkylphosphono group (eg, dimethylphosphono),
A diarylphosphono group (eg, diphenylphosphono), a diarylphosphinyl group (eg, diphenylphosphinyl), an alkylsulfinyl group (eg, 3
-Phenoxypropylsulfinyl), an arylsulfinyl group (eg, 3-pentadecylphenylsulfinyl), an alkylsulfonyl group (eg, methanesulfonyl, octanesulfonyl), an arylsulfonyl group (eg, benzenesulfonyl, toluenesulfonyl), a sulfonyloxy group ( Methanesulfonyloxy,
Toluenesulfonyloxy), acylthio group (for example,
Acetylthio, benzoylthio), sulfamoyl group (for example, N-ethylsulfamoyl, N, N-dipropylsulfamoyl, N- (2-dodecyloxyethyl) sulfamoyl, N-ethyl-N-dodecylsulfamoyl, N , N-diethylsulfamoyl), thiocyanate group, thiocarbonyl group (eg, methylthiocarbonyl, phenylthiocarbonyl), alkyl halide group (eg, trifluoromethyl, heptafluoropropyl), halogenated alkoxy group (eg, trifluorofluorocarbon) Methyloxy), a halogenated aryloxy group (for example, pentafluorophenyloxy), a halogenated alkylamino group (for example, N, N-di- (trifluoromethyl) amino), a halogenated alkylthio group (for example, difluoromethylthio, 1,1,2 2-tetrafluoroethane ethyl thio), an aryl group which sigma _p value is substituted with 0.20 or more other electron-withdrawing groups (e.g., 2,4-dinitrophenyl, 2,4,6-trichlorophenyl, pentachlorophenyl ), A heterocyclic group (eg, 2-benzoxazolyl, 2-benzothiazolyl, 1-phenyl-2-benzimidazolyl, 5-chloro-1-tetrazolyl, 1-pyrrolyl), a halogen atom (eg, chlorine atom, bromine Atom), an azo group (for example, phenylazo) or a selenocyanate group.

Preferably, R ² and R ³ are a cyano group or —CO ₂ R ²³ . Here, R ²³ represents an alkyl group or an aryl group. The alkyl group and the aryl group represented by R ²³ have the same meanings as the alkyl group and the aryl group represented by R ¹ , and —CO ₂ R ²³ is the aforementioned alkoxycarbonyl group and aryloxycarbonyl group. R ²
And R ³ may be the same or different.

More preferably, R ³ is a cyano group and R ² is —CO ₂ R ²³ . Here, preferred R ²³ is an alkyl group, and more preferred R ²³ is a tertiary alkyl group (eg, t-butyl, t-octyl, diisopropylmethylmethyl) or an alkyl group in which at least the 2- and 6-positions are substituted. Cyclohexyl group (for example, 2,6
-Di-t-butyl-4-methylcyclohexyl, 2,
4,6-trimethylcyclohexyl).

Y is condensed with a triazole ring in the molecule to form 1
H-pyrrolo- [1,2-b] [1,2,4] represents a group capable of forming a triazole derivative. Z is 1H-pyrrolo- [1,2-b] by condensing Y with a triazole ring in the molecule.
[1,2,4] represents a group resulting from the formation of a triazole derivative or a derivative thereof. Y is, shea Anomoto and -COR
(R is a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an alkyl group,
Represents an aryl group. ) . Specifically, a cyano group,
Formyl group, -COCl, -COOH, methoxycarbonyl, ethoxycarbonyl, acetyl, benzoyl and the like. In this case, Z represents the following group.
When Y represents a cyano group, Z represents an amino group or a derivative thereof. When Y represents -COR (R = hydrogen atom), Z
Represents a hydrogen atom . Y is -COR (R = halogen atom,
Z represents a hydroxyl group or a derivative thereof when representing a hydroxyl group, an alkoxy group, or an aryloxy group). Y is -COR
When (R = alkyl group), Z represents an alkyl group . When Y represents -COR (R = aryl group), Z is
Represents an aryl group .

In the intramolecular condensation reaction of the present invention, it is most preferred that Y in the general formula (I) is -COOH,
Using a compound represented by the general formula R ⁴ —X , a triazole derivative in which Y in the general formula (I) is —COOH is used to form 1H-pyrrolo- [in which Z in the general formula (II) is —OR ^4. 1,
2-b] [1,2,4] triazole derivatives are particularly effective. Z in the general formula (II) is by the said derivative is a -OR ^4, it can be isolated in high yield. The scheme is as follows.

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[0015] Te present invention smell, a compound represented by a general formula R ⁴ -X, R ⁴ is, -COR ^41, -CO
_{^{2 R 42, -CONR 43 R 44}} , -SO 2 R 45 or -P
(O) R ⁴⁶ represents R ⁴⁷ , R ^{41 to} R ⁴⁵ each represent a hydrogen atom, an alkyl group or an aryl group, and R ⁴⁶ and R ⁴⁷ each represent a hydrogen atom, an alkyl group, an aryl group, an alkoxy group or an aryloxy group And a compound in which X represents a halogen atom is hereinafter referred to as an acid halide. Hereinafter, the scheme will be described in detail.

In the above scheme I, R ¹ , R ² , R ³
Has the same meaning as R ¹ , R ² and R ³ in formulas (I) and (II). R ^{4 _{is, -COR 41, -CO 2 R 42}} , -C
ONR ⁴³ R ⁴⁴ , —SO ₂ R ⁴⁵ or —P (O) R ⁴⁶ R ⁴⁷ . Here, R ^{41 to} R ⁴⁵ each represent a hydrogen atom, an alkyl group or an aryl group, and R ⁴⁶ and R ⁴⁷ each represent a hydrogen atom, an alkyl group, an aryl group, an alkoxy group or an aryloxy group. X represents a halogen atom. R ^{41 to} R
^The alkyl group and aryl group represented by ⁴⁷ have the same meanings as the alkyl group and aryl group represented by R ¹ . R ⁴⁶ ,
The alkoxy group represented by R ⁴⁷ is a linear, branched or cyclic alkoxy group having 1 to 36 carbon atoms, and may be substituted with a substituent which the alkyl group of R ¹ may have. Good. For example, methoxy, ethoxy, i-butoxy, t-
Butoxy, 2-ethylhexyloxy, cyclohexyloxy and the like. The aryloxy group represented by R ⁴⁶ or R ⁴⁷ is an aryloxy group having 6 to 45 carbon atoms, and may be substituted with a substituent which the aryl group of R ¹ may have. For example, it is a group such as phenoxy, o-methylphenoxy, p-ethylphenoxy and the like. R ⁴³ , R ⁴⁴
May be the same or different, and may form a ring with each other. R ⁴⁶ and R ⁴⁷ may be the same or different, and may form a ring with each other. Examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and a chlorine atom is particularly preferable. R ⁴ is preferably —COR ⁴¹ [preferred R ⁴¹ is a tertiary alkyl group (eg, t-butyl, t-amyl, t-amyl)
-Octyl) or a phenyl group in which at least the 2- and 6-positions are substituted with an alkyl group (for example, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl,
2,4,6-triisopropylphenyl)], -CO ₂
R ⁴² and —CONR ⁴³ R ⁴⁴ are preferred. Specific examples of the acid halide used in the present invention include, as R ⁴¹ COX, for example, acetyl chloride, propionyl chloride, pivaloyl chloride, benzoyl chloride, 2,4,6-trimethylbenzoyl chloride, 2,6-diisopropylbenzoyl Examples of chloride, acetyl bromide, pivaloyl bromide, acetyl iodide, and R ⁴² OCOX include methyl chloroformate, ethyl chloroformate, isobutyl chloroformate, phenyl chloroformate, p-nitrophenyl chloroformate, octyl chloroformate, As isobutyl bromoformate and R ⁴³ R ⁴⁴ NCOX, for example, dimethyl carbamic acid chloride, diethyl carbamic acid chloride,
Examples of di-n-butylcarbamic acid chloride and R ⁴⁵ SO ₂ X include, for example, methanesulfonyl chloride, ethanesulfonyl chloride, n-butanesulfonyl chloride, benzenesulfonyl chloride, p-toluenesulfonyl chloride, 2,4,6-trimethyl Benzenesulfonyl chloride, 2,4,6-triisopropylbenzenesulfonyl chloride, methanesulfonyl bromide, methanesulfonyl fluoride, R ⁴⁶ R ⁴⁷ P (O) X include, for example, diethyl chlorophosphate, dibutyl chlorophosphate, diphenyl Chlorophosphate, chlorodiphenylphosphene oxide and the like can be mentioned.

In the present invention, the base used is triethylamine, diisopropylethylamine,
Pyridine, picoline, lutidine, collidine, 1,8-diazabicyclo [5,4,0] -7-undecene, 1,5
-Diazabicyclo [4,3,0] -5-nonene, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like. Preferred are triethylamine, diisopropylethylamine, pyridine, lutidine, picoline and collidine. The molar ratio of the base and the acid halide used in the present invention to the compound represented by the general formula (I) is 0.01 to 100, preferably 0.1 to 10, and more preferably 2 to 5, respectively. As the solvent used in the present invention, methylene chloride,
Chloroform, 1,2-dichloroethane, acetonitrile, ethyl acetate, N, N-dimethylformamide, N,
N-dimethylacetamide, dimethylsulfoxide, N
-Methylpyrrolidone, dioxane, tetrahydrofuran, carbon tetrachloride, benzene, pyridine and the like.
The reaction temperature in the present invention is -78 ° C to 150 ° C, preferably -40 ° C to 50 ° C, more preferably -10 ° C to
30 ° C. The reaction time in the present invention is 1 minute to 72 minutes.
Time, preferably 15 minutes to 48 hours, more preferably 30 minutes to 36 hours. The ring closure reaction in Scheme I is considered to proceed as in Scheme II below.

[0018]

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That is, a mixed acid anhydride A is produced by reacting various acid halides with a compound represented by the general formula (Ia) in the presence of a base. The mixed acid anhydride A quickly reacts with the triazole ring in the molecule to form a compound B. Compound B
Is converted to a compound C by tautomerism, and the generated hydroxyl group further reacts with an acid halide to form a compound represented by the general formula (II)
The compound represented by a) is obtained. Next, a method for synthesizing the compound represented by the general formula (I) will be described. General formula (I)
Is a group in which Y is a cyano group or -COR ⁶ (where R ⁶ is a hydrogen atom, an alkoxy group, an aryloxy group, an alkyl group,
In this case, for example, Scheme III {Step 1: Halogenation of the compound represented by the general formula (Ib), Step 2: Compound represented by the general formula (Ic) and an active methylene compound Substitution reaction with. It can be synthesized by the route shown in｝.

[0020]

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Further, when Y in the general formula (I) is —COOH, Step 3 in which the ester moiety is converted into a carboxyl group is added to the above-mentioned Scheme III. Halogenation of compound of formula (Ib), step 2: general formula (I
Nucleophilic substitution reaction between the compound represented by c) and the active methylene compound, Step 3: conversion reaction of the ester portion (—CO ₂ R ⁵ ) of the compound represented by the general formula (Id) into a carboxyl group. It can be synthesized by the route shown in｝.

[0022]

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When Y is —COR ⁷ (where R ⁷ represents a halogen atom), it can be easily derived from the compound of the general formula (Ia) in the scheme IV by a conventional method. it can. Hereinafter, each step of the schemes III and IV will be described in detail. First, step 1 will be described in detail. In Step 1, the triazole compound represented by the general formula (Ib) is synthesized by a known method, for example, JCS, 1961, No. 518.
JCS, 1962, p. 5149, Angew, Chem.
72, p. 956 (1960), Berichte.
97, p. 3436 (1964), and the literature cited therein or a similar method. Examples of the halogenating agent in the halogenation in Step 1 include chlorine, sulfuryl chloride, copper (II) chloride, N-chlorosuccinimide, N
-Bromocaprolactam, N-bromophthalimide,
Examples thereof include 1,3-dibromo-5,5-dimethylhydantoin, bromine, N-bromosuccinimide, phenyltrimethylammonium tribromide, pyridinium bromide perbromide, and pyrrolidone hydrotribromide. Preferably, sulfuryl chloride, N-chlorosuccinimide, bromine, N-bromosuccinimide, pyridinium bromide perbromide. The molar ratio of the halogenating agent to the triazole compound represented by the general formula (Ib) in Step 1 is from 0.01 to 100, preferably from 0.5 to 10, more preferably from 1.0 to 3.0. is there.

The solvent used in Step 1 includes methylene chloride, chloroform, 1,2-dichloroethane,
Acetonitrile, N, N-dimethylformamide, N,
N-dimethylacetamide, dimethylsulfoxide, N
-Methylpyrrolidone, dioxane, tetrahydrofuran, water, carbon tetrachloride, acetic acid, methanol, ethanol,
Benzene, pyridine and the like can be mentioned. The reaction temperature of Step 1 is -78 ° C to 150 ° C, preferably -20 ° C to 8 ° C.
0 ° C, more preferably -10 ° C to 30 ° C. The reaction time of step 1 is 1 minute to 72 hours, preferably 15 minutes.
Minutes to 48 hours, more preferably 30 minutes to 36 hours.

Step 2 will be described in detail. A halogenated compound (general formula (Ic)) of the triazole derivative represented by the general formula (Ib) obtained in Step 1 and an active methylene compound R ³ CH ₂ Y ₁ (preferably R
³ CH ₂ CO ₂ R ⁵ : R ⁵ is an alkyl group or an aryl group, preferably a methyl, ethyl or benzyl group. ), N-butyllithium, t-butyllithium, lithium diisopropylamide, sodium hydride, potassium hydride, lithium hydride, potassium t-butoxy, sodium methoxy , Potassium methoxide,
Lithium methoxide, sodium ethoxide, sodium amide and the like. Preferred are lithium diisopropylamide, n-butyllithium, sodium hydride, potassium t-butoxide, sodium methoxide, and sodium ethoxide. The molar ratio of the base used in Step 2 to the active methylene compound represented by the general formula (Ic) is from 0.1 to 10, preferably from 0.5 to 10.
-2.0, more preferably 0.9-1.1. The general formula (I) of the active methylene compound used in Step 2
The molar ratio to the compound represented by c) is from 0.01 to 1
00, preferably 0.1 to 10, more preferably 0.5 to 2.0.

The solvent used in step 2 includes methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, tetrahydrofuran, dioxane, benzene, toluene, xylene, petroleum ether, diethyl ether, n-hexane and the like. . Preferred are methylene chloride, tetrahydrofuran, dioxane, toluene and diethyl ether. The reaction temperature of Step 2 is -78 ° C to 150 ° C, preferably -40 ° C to 50 ° C.
° C, more preferably -20 ° C to 30 ° C. The reaction time of Step 2 is 1 minute to 72 hours, preferably 15 minutes to 48 hours, more preferably 30 minutes to 36 hours.

Step 3 will be described in detail. The ester moiety (—CO ₂ ) of the compound represented by the general formula (Id)
R ⁵ : R ⁵ is an alkyl group or an aryl group, preferably a methyl, ethyl or benzyl group) to a carboxyl group (Step 3), by a conventional method (for example, W, Green,
Protective Groups in Organic Synthesis, Jhon Wile
y and Sons, inc. New York 1981, p. 152-p. 178).

Specific examples of the triazole derivative represented by the general formula (I) obtained by the schemes III and IV and used in the production method of the present invention are shown below, but are not limited thereto.

[0029]

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[0030]

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[0031]

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[0032]

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Next, 1H-pyrrolo- [1,2-b] [1,2,2] which can be synthesized by the production method of the present invention.
4] Specific examples of the triazole derivative are shown below, but the invention is not limited thereto. Further, for representative compounds, M ⁺ represents the value of the parent peak (M ⁺ ) in the mass spectrum. Table 1 shows the melting points (mp) of some of them.

[0034]

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[0035]

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[0036]

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[0037]

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[0038]

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[0039]

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[0040]

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[0041]

[Table 1]

[0042]

EXAMPLES Next, specific synthetic examples of the present invention will be described. Synthesis of Compound II-1 II-1 was synthesized according to Scheme V.

[0043]

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Synthesis of Compound d In 100 ml of ethanol, hydrazide a of o-2-ethylhexyloxybenzoic acid (40 g, 151 mmol) and imidate b of ethyl cyanoacetate (25 g, 15 g) were used.
(5 mmol) was stirred and refluxed for 5 hours. Ethanol was distilled off under reduced pressure. Sodium hydroxide (12.2 g,
(306 mmol) aqueous solution (350 ml) was added and the mixture was stirred and refluxed for 2 hours. 31 ml of concentrated hydrochloric acid was added to the reaction solution, and the mixture was extracted with 200 ml of ethyl acetate. After the organic phase was washed with water and dried over sodium sulfate, the solvent was distilled off under reduced pressure. The residue was recrystallized from ethyl acetate / hexane (1: 1) to give compound d (20 g, 60.4 mmol, 40%).

Synthesis of Compound e 2,6-Di-tert-butyl-4-methylcyclohexanol (17 g, 75 mmol) in acetonitrile 200 m
trifluoroacetic anhydride (10.6 m
1, 75 mmol) were added dropwise, followed by compound d (20
g, 60.4 mmol) was added slowly. After the reaction solution was stirred at room temperature for 2 hours, 300 ml of water was added, and the mixture was extracted with 300 ml of ethyl acetate. The organic phase was washed with aqueous sodium bicarbonate, water and brine. After drying over sodium sulfate, the solvent was distilled off under reduced pressure to obtain a crude compound e (19 g). The crude compound e (19 g) was used in the next step without purification.

Synthesis of Compound f 200 ml of crude compound e (19 g) in tetrahydrofuran
To the solution was added pyridinium bromide perbromide (12.7 g, 40 mmol) at room temperature and stirred for 8 hours.
After adding 200 ml of a 2 g aqueous solution of sodium sulfite to the reaction solution, the mixture was extracted with 300 ml of ethyl acetate. The organic phase was washed with water and brine, and dried over sodium sulfate. The solvent was distilled off under reduced pressure to obtain a crude compound f (20 g). The crude compound f (20 g) was used in the next step without purification.

Synthesis of Compound g Sodium hydride (3.2 g, 80 mmol) was slowly added to a solution of methyl cyanoacetate (9.5 g, 96 mmol) in 50 ml of tetrahydrofuran at 0 ° C., followed by stirring at room temperature for 30 minutes (solution). s). The solution s was added dropwise to a solution of the crude compound f (20 g) in tetrahydrofuran 100 ml at 0 ° C., and the mixture was stirred at room temperature for 1 hour. 1N hydrochloric acid 2
00 ml and 200 ml of ethyl acetate were added for extraction. The organic phase was washed with water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography to give compound g (1
0.5 g, 16.5 mmol, 27.5% in 3 steps).

Synthesis of Compound h To a solution of Compound g (10.5 g, 16.5 mmol) in 100 ml of methanol was added 5 g of sodium hydroxide and 50 m of an aqueous solution.
and stirred at 50 ° C. for 2 hours. The reaction mixture was extracted by adding 200 ml of 1N hydrochloric acid and 200 ml of ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. When 100 ml of hexane was added to the obtained oil, it crystallized. The compound h (9.5 g, 92%) was obtained by filtering and drying the crystals.
I got

Synthesis of Compound II-1 A solution of Compound h (0.8 g, 1.28 mmol) in 10 ml of ethyl acetate was added at 0 ° C. with isobutyl chloroformate (0.5 g).
ml, 3.85 mmol) was added dropwise, followed by triethylamine (0.55 ml, 3.85 mmol). After stirring at 0 ° C. for 15 minutes, 10 ml of 1N hydrochloric acid was added. The organic phase was washed with water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from acetonitrile to give compound II-1 (0.6
g, 67%).

Synthesis of Compound II-2 Compound h (2.0 g, 3.2 mmol) in pyridine 20
At 0 ° C., diethylcarbamic acid chloride (1.0 ml, 1.8 mmol) was added dropwise to the ml solution. After stirring at room temperature for 20 hours, 100 ml of ethyl acetate and 100 ml of 1N hydrochloric acid were added. The organic phase was washed with 1N hydrochloric acid, water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from acetonitrile to give compound II-2 (1.2 g, 1.7 mmol, 53
%).

Synthesis of Compound II-3 Compound h (0.31 g, 0.5 mmol) in pyridine 3
pivaloyl chloride (0.185 m
l, l. 5 mmol) was added dropwise. After stirring at room temperature for 2 hours, 10 ml of ethyl acetate and 10 ml of 1N hydrochloric acid were added. The organic phase was washed with 1N hydrochloric acid, water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from acetonitrile to give compound II-3.
(0.15 g, 0.22 mmol, 44%).

Synthesis of Compound II-4 Compound h (3.0 g, 4.8 mmol) in pyridine 30
methanesulfonyl chloride (1.0
ml, 12.9 mmol) was added dropwise. After stirring at room temperature for 1 hour, 100 ml of ethyl acetate and 100 ml of 1N hydrochloric acid were added.
ml was added. The organic phase was washed with 1N hydrochloric acid, water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from acetonitrile to obtain compound II-4 (2.2 g, 3.22 mmol, 67%).

Synthesis of Compound II-5 Diethylphosphonic chloride (1.1 ml, 1.8 mmol) was added dropwise at 0 ° C. to a solution of Compound h (2.0 g, 3.18 mmol) in 30 ml of ethyl acetate. , Triethylamine (1.15 ml, 1.8 mmol) was added dropwise. After stirring at room temperature for 4 hours, 1N hydrochloric acid 30 ml
added. The organic phase was washed with water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from acetonitrile to give compound II-5 (1.
(3 g, 55%).

Synthesis of Compound II-6 Compound h (2.0 g, 3.18 mmol) of pyridine 2
1,0,2,5-Trimethylbenzoic acid chloride (1.5 ml, 1.8 mmol) was added dropwise to the 0 ml solution at 0 ° C.
After stirring at room temperature for 5 hours, 100 ml of ethyl acetate and 100 ml of 1N hydrochloric acid were added. The organic phase was washed with 1N hydrochloric acid, water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from acetonitrile to give compound II-6 (1.6 g, 2.13 mmol, 67%).

Synthesis of Compound II-7 Compound II-7 was synthesized according to Scheme VI. In addition,
Compound i was synthesized in the same manner as compound h.

[0056]

Embedded image

To a solution of compound i (2.25 g, 3.18 mmol) in 30 ml of ethyl acetate was added dropwise isopropyl chloroformate (1.1 ml.8 mmol) at 0 ° C., followed by triethylamine (1.15 ml, 8 mmol). ) Was added dropwise. After stirring at 0 ° C for 30 minutes, 1N hydrochloric acid 30m
l was added. The organic phase was washed with water and brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography to give compound II-
7 (1.3 g, 53%).

[0058]

Industrial Applicability According to the present invention, it is useful as a synthetic intermediate for physiologically active substances such as medicines and agricultural chemicals, a photographic coupler, or a precursor for a dye or a variety of dyes for a thermal transfer dye-donating material, and particularly useful as a photographic cyan coupler. 1H-pyrrolo- [1,
2-b] [1,2,4] triazole derivatives can be easily and inexpensively produced.

──────────────────────────────────────────────────の Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) C07D 487/00-487/22 CA (STN) REGISTRY (STN) WPI (DIALOG)

Claims (3)

(57) [Claims] 1. A condensation and ring-closing reaction of a triazole derivative represented by the following general formula (I) in a molecule:
1H-pyrrolo- [1,2- represented by the following general formula (II)
b] 1H-pyrrolo- [1,2-b] [1,2,4], characterized in that a [1,2,4] triazole derivative is synthesized.
4] A method for producing a triazole derivative. Embedded image Wherein said intramolecular condensation-cyclization reaction in the presence of a base, a general formula R compounds represented by ⁴ -X, R ^{4
_{But, -COR 41, -CO 2 R 42}} , -CONR 43 R 44, -
Represents SO ₂ R ⁴⁵ or ^{-P (O) R 46 R 47} , R 41 ~R 45
Represents a hydrogen atom, an alkyl group or an aryl group, respectively.
And R ⁴⁶ and R ⁴⁷ each represent a hydrogen atom, an alkyl group,
X, an alkoxy group or an aryloxy group;
Is a compound representing a halogen atom, wherein 1H-pyrrolo- [1,2-b] is used.
[1,2,4] A method for producing a triazole derivative. 3. In the general formula (I), Y is -CO.
The triazole derivative which is an OH group is represented by the general formula R ⁴
With a compound represented by -X, Z in the general formula (II) is a -OR ⁴ 1H-pyrrolo - [1,2-b]
3. The 1H-pyrrolo- [1,2-b] according to claim 2, wherein a [1,2,4] triazole derivative is synthesized.
[1,2,4] A method for producing a triazole derivative. Here, R ⁴ is -COR ⁴¹ , -CO ₂ R ⁴² , -CONR ⁴³
R ^{44 represents} —SO ₂ R ⁴⁵ or —P (O) R ⁴⁶ R ⁴⁷ . Here, R ^{41 to} R ⁴⁵ each represent a hydrogen atom, an alkyl group or an aryl group, and R ⁴⁶ and R ⁴⁷ each represent a hydrogen atom, an alkyl group, an aryl group, an alkoxy group or an aryloxy group. X represents a halogen atom.