JP3159518B2 - Preparation of amino-substituted spiro compounds - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a synthetic intermediate of a compound useful as an antibacterial compound and a method for producing the same.

[0002]

2. Description of the Related Art It is becoming clear that a nitrogen-containing saturated heterocyclic substituent having a spirocyclic structure is useful as a substituent of a pyridonecarboxylic acid compound useful as a synthetic antibacterial agent. In particular, a substituent which can also be expressed as a structure having an amino group and a spiro ring in pyrrolidine is useful. For example, a 7-amino-5-azaspiro [2.4] heptane-5-yl group and an 8-amino-6-azaspiro [3.4 ] And octane-6-yl groups. To introduce the former as a substituent, a 7-amino-5-azaspiro [2.4] heptane derivative was obtained, and to introduce the latter, an 8-amino-6-azaspiro [3.4] octane derivative was obtained. Reacting is one of the simplest methods.

[0003] In order to obtain these compounds having a spirocyclic structure, for example, a 7-amino-5-azaspiro [2.4] heptane derivative has been prepared by a synthesis method starting from an acetoacetic acid derivative (Japanese Patent Laid-Open No. 2-231475). reference). this,
The method of synthesizing a 7-amino-5-azaspiro [2.4] heptane derivative from an acetoacetic acid derivative has problems in operation, yield, by-products, purification method, etc. due to the large number of steps.

Accordingly, the present inventors have intensively studied a method for obtaining a 7-amino-5-azaspiro [2.4] heptane derivative more easily. As a result, a spirocyclic structure was constructed in the γ-alkyloxy-β-ketoester derivative to obtain a compound of the formula 1, which was converted to a triol form to introduce a substituted sulfonyl group into the hydroxyl group of the compound, Converted to a compound of formula (2) which is a substituted sulfonyloxy compound. By reacting this compound with a benzylamine derivative, the desired 7-amino-5-azaspiro [2.4] heptane derivative can be obtained in a short step and easily.
The inventors have found that the present invention can be obtained with good yield, and have completed the present invention.

[0005]

According to the present invention, the formula (1)

[0006]

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(Wherein R ¹ represents a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, a halogenoalkyl group having 1 to 6 carbon atoms and a 1 to 6 carbon atoms. A benzyl group consisting of a phenyl group which may have a substituent selected from the group consisting of an alkyloxy group and methylene, a t-butyl group, methylene and an alkyloxy group having 1 to 6 carbon atoms. Alkyloxymethyl group, or a tetrahydropyran-2-yl group or a tetrahydrofuran-2-yl group, wherein R ² is a halogen atom, a nitro group, a carbamoyl group, a cyano group, 1 to 6
A phenyl group which may have a substituent selected from the group consisting of an alkyl group having 1 to 6 carbon atoms and a halogenoalkyl group having 1 to 6 carbon atoms and an alkyloxy group having 1 to 6 carbon atoms; An alkyl group or a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, a halogenoalkyl group having 1 to 6 carbon atoms, and an alkyloxy group having 1 to 6 carbon atoms A benzyl group comprising a phenyl group and a methylene group which may have a substituent selected from the group of substituents. )) And a compound represented by the formula

[0008]

Embedded image With respect to the compound represented by the formula (2)

[0009]

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Wherein X, Y and Z are the same and
An alkylsulfonyl group having 1 to 6 carbon atoms (alkyl-SO
_2- ) or a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, a halogenoalkyl group having 1 to 6 carbon atoms and an alkyloxy group having 1 to 6 carbon atoms An arylsulfonyl group (ary) composed of a phenyl group and a sulfone group (—SO ₂ —) which may have a substituent selected from the group consisting of
l-SO _2- ). ) And a compound of formula (2)

[0011]

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Wherein X, Y and Z are the same and
An alkylsulfonyl group having 1 to 6 carbon atoms, or
Halogen atom, nitro group, carbamoyl group, cyano group,
A phenyl group which may have a substituent selected from the group consisting of an alkyl group having 1 to 6 carbon atoms, a halogenoalkyl group having 1 to 6 carbon atoms and an alkyloxy group having 1 to 6 carbon atoms; And an arylsulfonyl group composed of a sulfone group. And a compound represented by the formula (3) QCH ₂ NH ₂ 3 wherein Q is a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, A phenyl group which may have a substituent selected from the group consisting of a halogenoalkyl group and an alkyloxy group having 1 to 6 carbon atoms.) (4)

[0013]

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(Wherein Q represents a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, a halogenoalkyl group having 1 to 6 carbon atoms, and an alkyl group having 1 to 6 carbon atoms. A phenyl group which may have a substituent selected from the group consisting of oxy groups).

In the compound of the formula (1) or (2),
When the substituents R ¹ , R ² , X, Y and Z are a substituent having a phenyl group, the phenyl group is a halogen atom,
A substituent selected from the group consisting of a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, a halogenoalkyl group having 1 to 6 carbon atoms, and an alkyloxy group having 1 to 6 carbon atoms. It may have a group. In this case, the phenyl group may have one or more types of substituents, or may have one or more types of substituents.

A γ-alkyloxy-β-ketoester derivative, which is a starting material for synthesizing the compound represented by the formula (1), is prepared from a 4-chloroacetoacetic ester derivative by a method described in the literature (D. Seebach et al., Synthesis, 1986, p37-
38) Can be synthesized. On the other hand, acylmerdrum acids obtained by reacting a hydroxyacetyl chloride derivative with Meldrum's acid can also be easily obtained by subjecting them to a decarboxylation alcoholysis reaction.

The compound represented by the formula (1) is obtained by preparing a compound represented by the formula (5) X _A -CH ₂ -CH ₂ -X _B 5 (wherein the γ-alkyloxy-β-keto ester derivative has a spiro ring moiety). , X _a and X _B can each be in the desorption is an atom or functional group.) the compound represented by is reacted under basic conditions in a nucleophilic substitution reaction.

With respect to the compound represented by the formula (5), specific examples of X _A and X _B include a halogen atom such as a chlorine atom, a bromine atom or an iodine atom, a p-toluenesulfonyloxy group and a methanesulfonyloxy group. And a substituted sulfonyloxy group such as a trifluoromethanesulfonyloxy group, and a dialkylsulfonium group such as a dimethylsulfonium group, a methylethylsulfonium group, and a diethylsulfonium group. In the case of this dialkylsulfonium group, an anion such as a halogen ion may be accompanied as a counter anion.

In the reaction of the γ-alkyloxy-β-ketoester derivative with the compound of the formula (5), the reaction may be carried out in the presence of a suitable solvent. Examples of the reaction solvent include the following. And these may be used as a mixed solvent.

Alcohols: methanol, ethanol,
Propanol, isopropanol, t-butanol, etc., ethers: diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran, dioxane, etc., halogenated hydrocarbons: chloroform, methylene chloride,
Amide series: N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, etc.

As the base, those exemplified below can be used.

Inorganic bases: potassium carbonate, potassium hydrogen carbonate, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, lithium hydroxide, etc. Organic bases: trialkylamines (triethylamine,
Diisopropylethylamine, tributylamine, etc.),
Dialkylanilines (N, N-dimethylaniline, N, N-diethylaniline, etc.), heterocyclic compounds (pyridine, 4-dimethylaminopyridine, morpholine, 1,8-diazabicyclo [5.4.0] undec-7-ene Alkoxides (sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.).

The compound of the formula (5) has a polymethylene chain having 2 carbon atoms, and the spiro ring to be constructed is a three-membered ring. Therefore, by reacting a compound of formula (5) in which the polymethylene chain has 3 or 4 carbon atoms, a compound having a 4- or 5-membered spiro ring will be obtained.

After the reaction, the resulting compound of the formula (1) can be isolated and purified by a conventional method such as silica gel chromatography, recrystallization, reprecipitation and distillation, or a combination thereof.

In the compound represented by the formula (1),
Examples of R ¹ may be a substituent of the type shown above, but the substituent R ¹ is not limited to these, and is a protecting group for a hydroxyl group as long as it can be easily removed. Good.

Next, the compound of the formula (1) is converted into the compound of the formula (2). The synthesis of a triol compound having the following structure required for obtaining the compound will be described.

[0027]

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First, the ketone or ester of the compound of the formula (1) is reduced to an alcohol. For this purpose, the reduction may be carried out using a metal hydrogen complex compound. This reaction may be usually carried out in a suitable solvent at a temperature between under cooling and the boiling point of the solvent.

Examples of the metal hydride complex include lithium aluminum hydride, lithium borohydride, sodium bis (2-methoxyethoxy) aluminum hydride, sodium borohydride and the like.

As the reaction solvent, ethers such as diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran and dioxane, and in the case of sodium borohydride, alcohols such as methanol and ethanol can be used.

The resulting compound can be isolated and purified by a conventional method such as silica gel chromatography, recrystallization, reprecipitation and distillation, or a combination thereof. Thus, a diol having the following structure can be obtained.

[0032]

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Next, the substituent R ¹ which is a protecting group for the hydroxyl group of the diol compound is removed. As a removing method, an appropriate removing method generally known according to the protecting group used may be applied. I just need. Examples thereof include a method of reacting an acid and a base, and a method of catalytic reduction in the presence of a catalyst. Thus, a triol having a spiro structure is obtained.

In order to use this triol form as a raw material for the ring closure reaction, the compound of formula (2) is converted into a tris-sulfonyloxy form. For this purpose, the triol may be dissolved in an appropriate solvent and reacted with the substituted sulfonyl chloride under basic conditions.

Examples of substituted sulfonyl chlorides include:
Methanesulfonyl chloride, trifluoromethanesulfonyl chloride, p-toluenesulfonyl chloride and the like can be mentioned.

Examples of the reaction solvent include ether solvents such as diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran and dioxane, and halogenated hydrocarbons such as chloroform, methylene chloride and ethylene chloride. .

Examples of the base include trialkylamines such as triethylamine, diisopropylethylamine and tributylamine, dialkylanilines such as N, N-dimethylaniline and N, N-diethylaniline, 4-dimethylaminopyridine, morpholine and pyridine. Can be exemplified.

When the compound represented by the formula (2) is a tris-sulfonyloxy compound, the sulfonyl group may be a substituted sulfonyl group as described above. here,
The substituted sulfonyl group forms a substituted sulfonyloxy group together with an oxygen atom and functions as a leaving group when reacting the compound of the formula (2) with an amine derivative. That is, the substituent moiety is not limited to a substituted sulfonyloxy group as long as it functions as a leaving group in a nucleophilic substitution reaction.

Next, the tris-sulfonyloxy compound is converted into the compound of the formula (4). The tris-sulfonyloxy compound is converted to a compound of the formula (3) QCH ₂ NH ₂ 3 (wherein halogen atom, carbon atom A substituent selected from the group consisting of an alkyl group having 1 to 6 carbon atoms, a halogenoalkyl group having 1 to 6 carbon atoms, an alkyloxy group having 1 to 6 carbon atoms, a nitro group, a carbamoyl group and a cyano group Represents a phenyl group which may also have the following formula :) to obtain the desired amino-substituted spiro compound.

In the reaction with the compound of the formula (3), the reaction may be carried out without a solvent or in the presence of a suitable solvent at a temperature in the range of about 20 to 150 ° C. in the presence of a base.

As the solvent, methanol, ethanol,
Alcohol solvents such as propanol, isopropanol and t-butanol, ether solvents such as diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran and dioxane, halogenated hydrocarbon solvents such as chloroform, methylene chloride and ethylene chloride, N, Amide solvents such as N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, and aromatic hydrocarbon solvents such as benzene and xylene may be used. In addition, water may be used as the solvent, or a combination of the above solvents may be used.

As bases, inorganic bases such as potassium carbonate, potassium hydrogen carbonate, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, lithium hydroxide, etc .; and as organic bases, triethylamine, diisopropylethylamine, tributylamine and the like. Trialkylamines, N, N-dimethylaniline, dialkylanilines such as N, N-diethylaniline, pyridine, 4-dimethylaminopyridine, morpholine, 1,8-diazabicyclo [5.
4.0] Heterocyclic compounds such as undec-7-ene and alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide can be exemplified.

After the reaction, the resulting compound of the formula (4) can be isolated and purified by a conventional method, for example, a method such as silica gel chromatography, recrystallization, reprecipitation and distillation, or a combination thereof.

The compound of the formula (4) obtained as described above is a racemic compound based on the asymmetric carbon at the 7-position, and each enantiomer can be resolved by a generally known method. Further, when the compound of the formula (1) is reduced, asymmetric hydrogenation using a catalyst having an optically active ligand or reduction using a metal hydrogen complex compound having an optically active ligand may be used. By carrying out the reduction, the compound of the formula (2) can be synthesized by controlling the stereo, and one of the stereoisomers of the formula (4) can be selectively obtained by subjecting the compound to the above-mentioned conversion. It is.

In the reduction, there is also a method in which both the ketone and the ester are simultaneously reduced to a diol form.
After first reducing only the ketone and protecting the resulting hydroxyl group,
It is also conceivable to reduce the ester, then remove R ¹ to form a diol form and react it with the substituted sulfonyl chloride, then perform ring closure, and then convert the hydroxyl group to an amine.

[0046]

Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.

Reference Example 1. 170 mg of methyl imidazole 4-benzyloxyacetoacetate was dissolved in 5 ml of dichloromethane, and benzyloxyacetyl chloride 4
A solution of 10 mg dissolved in 5 ml of dichloromethane was added dropwise. 10 minutes later, 4-dimethylaminopyridine 3 was added under ice-cooling and stirring.
05 mg was added and the mixture was stirred for 30 minutes. Here Meldrum acid 288 m
g was added and stirred at room temperature for 12 hours. The solvent was distilled off under reduced pressure, and the residue was partitioned between ethyl acetate and 1N hydrochloric acid. After separating the organic layer, it was washed with saturated saline, dried over anhydrous magnesium sulfate, and filtered, and the solvent was distilled off from the filtrate under reduced pressure.

10 ml of methanol was added to the obtained residue.
The mixture was heated under reflux for 12 hours. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography. From a mixed solvent of ethyl acetate and n-hexane (1: 5, v / v), 352 mg of the title compound was obtained as an oil.

¹ H-NMR (CDCl ₃ , 90 MHz) δ: 3.52 (2H, s), 3.
69 (3H, s), 4.12 (2H, s), 4.57 (2H, s), 7.33 (5H, s).

Example 1 1-benzyloxyacetyl-1-
Methoxycarbonylcyclopropane 12.8 g of methyl 4-benzyloxyacetoacetate and 13.6 g of 1,2-dibromoethane in anhydrous N, N-dimethylformamide
The solution was dissolved in 60 ml, potassium carbonate (15.9 g) was added, and the mixture was stirred at room temperature for 2 days. The reaction solution was added to 40 ml of ice water, and extracted three times with 150 ml each of ethyl acetate. The organic layer was washed with a 15% saline solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography. The title compound was obtained as an oil from a mixed solvent of ethyl acetate and n-hexane (1: 5, v / v).
7.93 g was obtained.

¹ H-NMR (CDCl ₃ , 90 MHz) δ: 1.52 (4H, s), 3.
67 (3H, s), 4.57 (2H, s), 7.34 (5H, s).

Example 2.1 1- (1′-Benzyloxy-2′-hydroxyethyl) -1-hydroxymethylcyclopropane To 150 ml of anhydrous tetrahydrofuran was added 2.43 g of lithium aluminum hydride, and the mixture was stirred under ice-cooling and stirring. 1-benzyloxyacetyl-1-methoxycarbonylcyclopropane
A solution of 7.93 g in 40 ml of anhydrous tetrahydrofuran was added dropwise. Stirred at room temperature for 40 minutes, then heated to reflux. 26 ml of water and 15% aqueous sodium hydroxide under ice-cooling
26 ml and water 76 ml were sequentially added. The precipitate was removed by filtration, the filtrate was dried, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography. From a mixed solvent of ethyl acetate and n-hexane (1: 1, v / v), 4.58 g of the title compound was obtained as an oil.

¹ H-NMR (CDCl ₃ , 90 MHz) δ: 0.54 (4H, m), 2.
92 (2H, brs), 3.37 (2H, m), 3.64 (2H, s), 3.71 (2H, q),
4.59 (2H, s), 7.34 (5H, s).

Example 3.1 1- (1 ', 2'-Dihydroxyethyl) -1-hydroxymethylcyclopropane 1- (1'-benzyloxy-2'-hydroxyethyl) -1-hydroxymethylcyclopropane 4.58 g was dissolved in a mixed solvent of 1 ml of acetic acid and 25 ml of methanol, 1.5 g of 5% palladium on carbon was added, and the mixture was catalytically reduced under a hydrogen gas atmosphere under a pressure of 2 atm. After 6 hours, the reaction was stopped, the catalyst was removed by filtration, and the solvent in the filtrate was distilled off under reduced pressure. 2.2 g of the title compound were obtained as an oil.

¹ H-NMR (CDCl ₃ + D ₂ O, 90 MHz) δ: 0.48 (4H,
m), 3.16 (2H, m), 3.64 (3H, m).

Example 4.1 1- [1 ', 2'-bis (methanesulfonyloxy) ethyl] -1-methanesulfonyloxymethylcyclopropane 5.29 g, 1- (1', 2'-dihydroxy) (Ethyl) -1-hydroxymethylcyclopropane
Dissolve 1.05 g in 30 ml of anhydrous tetrahydrofuran,
To this solution, 4.67 g of triethylamine was added dropwise with stirring under ice-cooling, and the mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure,
Ethyl acetate was added to the residue, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by silica gel chromatography. 2.19 g of the title compound was obtained as white crystals from a mixed solvent of ethyl acetate and n-hexane (2: 1, v / v).

Melting point: 60-60.5 ° ¹ H-NMR (CDCl ₃ , 90 MHz) δ: 0.94 (4H, m), 3.04 (3H, s),
3.07 (3H, s), 3.12 (3H, s), 3.81-4.62 (5H, m).

Example 5.7 7-benzylamino-5-benzyl
-5-Azaspiro [2.4] heptane 1- [1 ', 2'-bis (methanesulfonyloxy) ethyl] -1-
Methanesulfonyloxymethylcyclopropane 366 mg
Was dissolved in 2 ml of benzylamine and heated at 100 ° C. for 2 hours. After distilling off benzylamine under reduced pressure, the residue was purified by silica gel chromatography. From a mixed solvent of ethyl acetate and n-hexane (1: 1, v / v), 164 mg of the title compound was obtained as an oil.

¹ H-NMR (CDCl ₃ , 90 MHz) δ: 0.20-1.12 (4H,
m), 1.48 (2H, brs), 2.44-3.12 (5H, s), 3.56-3.92
(4H, m), 7.31 (5H, s), 7.35 (5H, s).

Reference Example 2.7 7-benzylamino-5-benzyl
-5-Azaspiro [2.4] heptane 7-amino-5-benzyl-5-azaspiro [2.4] heptane
6.69 g, 3.86 g of benzaldehyde 400 ml of toluene
Then, 760 mg of p-toluenesulfonic acid monohydrate was added, and the mixture was heated under reflux for 2 days while removing water. After the solvent was distilled off under reduced pressure, 200 ml of methanol was added to the residue, 1.26 g of sodium borohydride was added under ice-cooling and stirring, and the mixture was heated and stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure, ethyl acetate and a small amount of water were added to the residue, and the mixture was shaken, and then the organic layer was separated. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography. From a mixed solvent of ethyl acetate and n-hexane (1: 1, v / v), 5.03 g of the title compound was obtained as an oil. ^{The 1} H-NMR spectrum is shown in Example 5.
Was consistent with that obtained in.

The reactions according to Examples 1 to 5 are summarized in the following formula. In the formula, Bn represents a benzyl group, Me represents a methyl group, and Ms represents a methanesulfonyl group.

[0062]

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──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI C07C 255/54 C07C 255/54 255/55 255/55 255/58 255/58 C07D 209/96 C07D 209/96 (56) Reference Reference JP-A-2-231475 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 31/27 A61K 31/40 ADZ C07C 69/757 C07C 205/37 C07C 253/30 C07C 255/54 C07C 255/55 C07C 255/58 C07D 209/96

Claims (4)

(57) [Claims] (1) Formula 1 (Wherein, R ¹ is a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, and 1 to 6 carbon atoms.
A benzyl group consisting of a phenyl group and a methylene group which may have a substituent selected from the group consisting of a halogenoalkyl group and an alkyloxy group having 1 to 6 carbon atoms, a t-butyl group, a methylene group; An alkyloxymethyl group composed of an alkyloxy group having 1 to 6 carbon atoms, or a tetrahydropyran-2-yl group or a tetrahydrofuran-2-yl group, wherein R ² is a halogen atom, nitro Group, carbamoyl group, cyano group, alkyl group having 1 to 6 carbon atoms, 1 to 6 carbon atoms
A phenyl group which may have a substituent selected from the group consisting of a halogenoalkyl group and an alkyloxy group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms, or a halogen atom, a nitro group Carbamoyl group, cyano group, alkyl group having 1 to 6 carbon atoms, 1 to 6 carbon atoms
And a benzyl group comprising a methylene and a phenyl group which may have a substituent selected from the group consisting of a halogenoalkyl group and an alkyloxy group having 1 to 6 carbon atoms. Compound represented by) 2. The formula: Compound represented by 3. Formula 2 (Wherein, X, Y and Z are the same and are an alkylsulfonyl group having 1 to 6 carbon atoms, or a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, Number 1 to 6
And an arylsulfonyl group comprising a phenyl group and a sulfone group which may have a substituent selected from the group consisting of a halogenoalkyl group and an alkyloxy group having 1 to 6 carbon atoms. Compound represented by) 4. Formula 2 (Wherein, X, Y and Z are the same and are an alkylsulfonyl group having 1 to 6 carbon atoms, or a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, Number 1 to 6
And an arylsulfonyl group comprising a phenyl group and a sulfone group which may have a substituent selected from the group consisting of a halogenoalkyl group and an alkyloxy group having 1 to 6 carbon atoms. ) And a compound of formula 3 QCH ₂ NH ₂ 3 wherein Q is a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, and a halogenoalkyl having 1 to 6 carbon atoms. A phenyl group which may have a substituent selected from the group consisting of a group and an alkyloxy group having 1 to 6 carbon atoms, which may have a substituent.) Formula 5 (Wherein Q represents a halogen atom, a nitro group, a carbamoyl group, a cyano group, an alkyl group having 1 to 6 carbon atoms, a halogenoalkyl group having 1 to 6 carbon atoms, and an alkyloxy group having 1 to 6 carbon atoms. A phenyl group which may have a substituent selected from the group consisting of substituents.)