JPS5920667B2 - Sulfonamide benzamide derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula [wherein R represents hydrogen, an alkyl group, a cyano group, an alkanesulfonyl group, or a dialkylamino group; R1 represents an alkyl group, an aryl group, or a dialkylamino group; R2 represents hydrogen, halogen, an alkyl group, a dialkylamino group, or an alkoxy group; R4 represents an alkoxy group; R3 and R5 each represent hydrogen, an alkyl group, or an alkoxy group; R6 represents an alkyl group or a cycloalkyl group. .

] or a salt thereof.

These target substances can be expected to be used as medicines or veterinary medicines, especially as anti-gastric ulcer agents or psychotropic agents. Specific examples of the terms used in the definition of the target substance (1) above are shown below.

Alkyl groups (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl)
, alkanesulfonyl groups (e.g. methanesulfonyl,
ethanesulfonyl, propanesulfonyl, butanesulfonyl, isobutanesulfonyl), dialkylamino group (
For example, dimethylamino, diethylamino, methylethylamino, ethylpropylamino, methylbutylamino), aryl groups (e.g. phenyl, tolyl, xylyl, naphthyl), halogens (e.g. fluorine, chlorine, bromine, iodine), alkoxy groups (eg, methoxy, ethoxy, propoxy, butoxy, pentoxy), cycloalkyl groups (eg, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl).

The target substance (1) is obtained by sulfonating the raw material aniline (0) (route A) or by reacting amines (V) with benzoic acids or their reactive derivatives (IV), as shown in the diagram below. (Route D) and, if necessary, further chemically modified by hydrolysis (Route B) or alkylation (Route C).

[In the formula, A represents a reactive group (e.g., halogen, ester residue, -0S02R1 group), A1 represents a hydroxy group or a reactive group (e.g., halogen, ester residue), R, Rl, R2, R3, R4, R5 and RO have the same meanings as above.

] Route A This reaction is a reaction in which a sulfonating agent (self) is reacted with a raw material aniline ( ) to form a sulfonamide (1).

The sulfonating agent (self) is a halide of the specified sulfonic acid (
For example, chloride, bromide), active esters (e.g., p-nitrophenyl ester, benzyl ester, trityl ester), and anhydrides (e.g., methanesulfonic anhydride, ethanesulfonic anhydride). This reaction may be carried out using a conventional sulfonation method.6 Generally, a suitable inert solvent (e.g. methylene chloride, benzene,
(tetrahydrofuran, dioxane), if necessary, with the addition of a suitable deoxidizing agent (e.g., an organic amine such as triethylamine 6-pyridine, an inorganic base such as potassium hexacarbonate, sodium bicarbonate, etc.), or
Alternatively, an organic amine (eg, pyridine, triethylamine) may be used as both a solvent and a deoxidizing agent. The reaction temperature is usually room temperature or under cooling or heating. Generally, this reaction proceeds with a good yield, but depending on the type of solvent and deoxidizing agent used, monosulfonated products, disulfonated products, or a mixture of the two may be produced. All are included in the target compound (1). Route B Among the products (1) in route A above, the disulfonated product 6 is hydrolyzed, if necessary, to form the monosulfonated product (1a
) can be converted to

This reaction is carried out in a conventional manner using an inorganic or organic base (e.g., sodium hydroxide, potassium hexahydroxide, potassium hexacarbonate, sodium bicarbonate, sodium methoxide, potassium ethoxide) in a suitable solvent (e.g., water, methanol, ethanol, It may be treated in acetone, dioxane) at room temperature or under heat. Route C Among the products (1) in Route A above, compounds having active hydrogen (R=hydrogen) can be 6-alkylated to N-
It is converted into an alkylsulfonamide (Ib: R=alkyl group).

This reaction may be carried out by a conventional method for alkylating an amino group.6 Usually dialkyl sulfuric acid (e.g., dimethyl sulfate, 6-diethyl sulfate) or alkyl halide (e.g., 6-methyl iodide, ethyl bromide, propyl chloride) is used. ) such as alkylating agents/alkali (e.g. sodium hydroxide 6
The reaction is carried out in potassium hydroxide, potassium carbonate, hexasodium bicarbonate) and a suitable solvent (for example, hexawater, acetone, dioxane, tetrahydrofuran, dimethyl sulfoxide) at room temperature or under heating. Anilines () used as raw materials in route A above are synthesized according to the method described in Japanese Patent Publication No. 44-23496.

[During the ceremony. Al, R2, R3, R4, R5 and R6 have the same meanings as above.

[Route D] This reaction is a condensation reaction of benzoic acids or their reactive derivatives (5) and amines (7), and is carried out according to a conventional method for this type of reaction.

Generally, alkyl esters of benzoic acids or acid halides and amines are mixed together in an inert solvent (e.g., The reaction may be carried out by heating in ethanol, propanol/dioxane/dimethylformamide, benzene, methylene chloride).The benzoic acids or their reactive derivatives (5) used as raw materials in route D are, for example, 6
Obtained by sulfonating the corresponding aminobenzoic acid (b).

[In the formula, 6Et represents an ethyl group. A, R, Rl, lO
R2, R3, R4 and R5 have the same meanings as above]
The target substance (1) of the present invention is an inorganic acid (e.g., hydrochloric acid, hexahydrobromic acid, sulfuric acid, phosphoric acid, thiocyanic acid) for the purpose of improving formulation, crystallization, solubility, or stability. and pharmaceutically acceptable acid addition salts of organic acids (e.g., acetic acid, succinic acid, oxalic acid, maleic acid, malic acid, phthalic acid, hexamethanesulfonic acid, citric acid, toluenesulfonic acid, hexatartaric acid). It can lead to salt.

The target substance (1) of the present invention is dextrorotatory and levorotatory light 20
It contains chemical isomers, and these can be easily separated from racemic compounds by conventional methods.

The target substance (1) and its pharmaceutically acceptable acid addition salts are useful as anti-gastric ulcer agents or psychotropic agents, particularly as antipsychotic agents (Mesier Tranquilizer 1).

For example, 6N-(1-ethyl-2-pyrrolidinylmethyl)
-2-Methoxy-4-chloro-5-methanesulfonamide benzamide was effective at 0.01 mg/Kg (oral administration) in an antiemetic test of apomorphine antagonism in adult dogs. Other target substance (1) also showed similar pharmacological effects. Sulfonamide benzamides (1) and their pharmaceutically acceptable acid addition salts can be used alone or with the addition of a pharmaceutically appropriate carrier such as wheat starch, corn starch, potato starch, gelatin, water, etc. Used orally or parenterally. The choice of carrier may be determined by the preferred method of administration, the solubility of the material used, and standard pharmaceutical practices. The dosage form to be prepared is as follows:
tablets, capsules, pills, chrysanthemum 6 suspension 6 syrup, powder,
Examples include solutions. These compositions can be formulated by conventional methods. For example, when used as an antipsychotic, 6-sulfonamide benzamides (1) and their ? A suitable dosage for adults of pharmaceutically acceptable acid addition salts is from about 1 to about 3,501,119 per day by oral administration, and examples of the present invention are shown below. Example 1 1) 2-methoxy-4-chloro-5-nitrobenzoic acid (Helv.Chim.Acta., (曵, 369(1)
959)) A mixture consisting of 9001!9 and thionyl chloride 5d is refluxed for 30 minutes to distill off thionyl hexachloride.

Benzene is added to the residue and 6 benzene is distilled off. Add triethylamine 790 and dry methylene chloride 9Tf to the residue.
1f was added, and 750 ml of 1-ethyl-2-aminomethylpyrrolidine and 4 ml of methylene chloride were added thereto under ice-cooling and stirring.
Drop a solution consisting of Stir for 15 minutes at room temperature.

An aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with methylene hexachloride. The organic layer was washed with water, dried with Glauber's salt, and the solvent was distilled off. Ether was added to the residue and extracted with 6 dilute hydrochloric acid. The aqueous layer is made alkaline with an aqueous sodium bicarbonate solution and extracted with methylene chloride. The organic layer is washed with water, dried, and the solvent is distilled off. The residue was recrystallized from ethyl acetate/isopropyl ether to give N-(1-ethyl-2-pyrrolidinylmethyl)-2 as crystals with a melting point of 107-108°C.
-methoxy-4-chloro-5-nitrobenzamide 67
97! Get 9.

2) Add 7.339 of the above product to a solution consisting of 36.7 ml of concentrated hydrochloric acid and 73.3 ml of water and heat to 50°C,
Add 7.7 f1 tin pieces and stir at 650°C for 4 hours.

After cooling, the reaction solution is made alkaline with an aqueous sodium hydroxide solution and extracted with methylene chloride. The organic layer was washed with water, dried over Glauber's salt, and the solvent was distilled off. The residue was chromatographed on an alumina column, eluted with methylene chloride, and the solvent was distilled off. When the residue was washed with isopropyl ether/petroleum ether, N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-4-chloro-5-
5.389 aminobenzamide is obtained.

When this product is recrystallized from isopropyl ether/petroleum ether, it becomes crystals with a melting point of 85-86.5°C. (3) Add 3.18 f of methanesulfonyl chloride to a solution consisting of 4.19 of the above product, 2.939 of triethylamine, and 41 d of dry methylene chloride under ice cooling! and 7.2 d of dry methylene chloride are added dropwise.

Remove the ice bath and stir at room temperature for 45 minutes. The reaction solution is made alkaline by adding aqueous sodium bicarbonate solution, and extracted with methylene chloride. The organic layer was washed with water, dried with Glauber's salt,
The solvent is distilled off. The residue was washed with ethyl acetate-isopropyl ether to give N as crystals with a melting point of 153-155°C.
-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-4-chloro-5-N,N-bis(methanesulfonyl)aminobenzamide 5.839 is obtained. (4) The above product 5.759 and 10% sodium hydroxide 57.
The suspension consisting of 5d is heated to 50° C. and stirred for 30 minutes.

After cooling, the reaction solution was made acidic with concentrated hydrochloric acid, then made alkaline with an aqueous sodium bicarbonate solution, and saturated with common salt.
Extract with methylene chloride. The organic layer is washed with saturated brine, dried over sodium sulfate, and methylene chloride is distilled off. The residue was chromatographed on an alumina column, eluted with methylene chloride alone and 2% methanol/methylene chloride, and the solvent was distilled off from the eluate. The residue was dissolved in ethyl acetate/
After washing with isopropyl ether, N-(1-ethyl-
4.3 g of 2-pyrrolidinylmethyl)-2-methoxy-4-chloro-5-methanesulfonamide benzamide are obtained. This product is recrystallized from ethyl acetate/isopropyl ether to give colorless prismatic crystals with a melting point of 126-127.5°C. Example 2 N-(1-ethyl-2-pyrrolidinylmethino(c)-2
-87% of methanesulfonyl chloride was added to a mixture of 700119 methoxy-5-aminobenzamide, 1.029% of triethylamine, and 14d of methylene chloride with stirring at room temperature.
01!9 was added dropwise and stirred at room temperature for 1 hour.

Water is added to the reaction solution, made alkaline with an aqueous sodium bicarbonate solution, and extracted with methylene chloride. Wash the organic layer with water,
Dry with Glauber's salt. Distill off methylene chloride. The residue was subjected to column chromatography using alumina and eluted with methylene chloride. The solvent was distilled off from the eluate, and the residue 6 was crystallized from ethyl acetate/isopropyl ether.
(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-N,N-bis(methanesulfonyl)amidonobenzamide 5821!9 is obtained. This product is recrystallized from ethyl acetate to obtain crystals with a melting point of 160-161°C. The eluate was then diluted with 3% methanol/methylene chloride. N-
(1-Ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-methanesulfonamide benzamide is obtained.

After concentrating the eluate, the residue is crystallized from ethyl acetate/isopropyl ether to yield product 148. When this product is recrystallized from ethyl acetate, the melting point is 170-171℃.
It becomes a crystal. (2) N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-N,N-bis(methanesulfonyl)aminobenzamide 290W9,10
? 2.9 d of sodium hydroxide aqueous solution and 2 d of methanol
．． A suspension of 9 ml is heated on an ice bath for 5 minutes to give a clear solution.

After the solvent was distilled off, ice water was added to the residue, acidified with 6N hydrochloric acid, made weakly alkaline with an aqueous sodium bicarbonate solution, and extracted with methylene chloride. The organic layer was washed with water, dried over 6-milk salt, and the solvent was distilled off. Wash the residue with ethyl acetate/isopropyl ether. N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-
148 mg of methanesulfonamide benzamide are obtained.
This product is recrystallized from ethyl acetate/isopropyl ether to give crystals with a melting point of 170-171.5°C. Example 3 (1) N-(1-ethyl-2-pyrrolidinylmethyl)
-2-methoxy-5-aminobenzamide 700η, methylene chloride 14ml and triethylamine 1.039
1.359 g of benzenesulfonyl chloride was added to the mixture at room temperature, and the mixture was left at room temperature overnight.

Add water to the reaction solution, make it alkaline with an aqueous sodium bicarbonate solution, and extract with methylene chloride. Wash the organic layer with water6
Dry with Glauber's salt and evaporate the solvent. The residue was dissolved in methylene chloride and subjected to chromatography using an alumina column, eluting with methylene chloride. Methylene chloride was distilled off from the eluate, and the residue was recrystallized from ethyl acetate/isopropyl ether to give N-
(1-Ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-N,N-bis(benzenesulfonyl)aminobenzamide 839 is obtained. x (2). ．． A mixture of the above product 500, 7.5 ml of 1070 sodium hydroxide and 7.5 ml of methanol is heated on an ice bath for 5 minutes.

Methanol is distilled off from the reaction solution, water is added to the residue, acidified with hydrochloric acid, made alkaline again with an aqueous sodium bicarbonate solution, and extracted with methylene chloride. The organic layer is dried and the solvent is distilled off. Wash the residue with ethyl acetate/isokikupropyl ether. N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-benzenesulfonamide benzamide 325W19 is obtained.

This product was recrystallized from ethyl acetate, melting point 177-178℃.
It becomes a crystal. Example 4 i) N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-nitrobenzamide 1.596 A mixture of 150 mg of platinum oxide and 30 d of methanol was brought into contact by shaking in a hydrogen stream. Give back.

The reaction solution is treated in a conventional manner to distill off 6 methanol. 500 mg of sodium azide and 5 ethyl orthoformate to the residue
ml and 5 ml of acetic acid were added and heated at 680°C for 1 hour. Add ice water to the reaction solution, make alkaline with sodium carbonate, and extract with methylene chloride. Wash the organic layer with water6
Dry with Glauber's salt and evaporate the solvent. The residue was dissolved in ethyl acetate/
Crystallized from isopropyl ether, melting point 171-17
N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-(1H-tetrazole-
1-yl)benzamide 1.3f! get. 2) The above product 1.39. Ethanol 9.8ml 1. 8 d of a mixed solution consisting of 33 d of water and 6.5 d of 1070 sodium hydroxide.
Warm at 0°C for 40 minutes.

Ethanol was distilled off, and the residue was made acidic with 6N hydrochloric acid, then made basic with triethylamine, and salted out with common salt.
Extract with 5% methanol/methylene chloride. The organic layer was dried with Glauber's salt and the solvent was distilled off. The residue was washed with ethyl acetate and N-(1-ethyl-2-pyrrolidinylmethyl)-
2-Methoxy-5-cyanoaminobenzamide 641T
11f is obtained. When this product is recrystallized from ethyl acetate, it becomes crystals with a melting point of 134-139°C. (3) The above product 30
To a solution consisting of 0'11 Ifl and 1.5-pyridine was added 340 ml of methanesulfonyl chloride at room temperature, and the mixture was stirred at room temperature for 2 hours and then at 650°C for 30 minutes.

Add an aqueous sodium carbonate solution to the reaction mixture, and extract with methylene chloride. The organic layer was washed with water, dried with 6-mg sodium sulfate, and the 6-solvent was distilled off. The residue was dissolved in methylene chloride and subjected to chromatography using an alumina column and eluted with methylene hexachloride. Methylene chloride was distilled off from the eluate, the residue was washed with ether/isopropyl ether, and then recrystallized to give N-(1-ethyl-2-pyrrolidinylmethyl)-2- as crystals with a melting point of 50-54°C. Methoxy-5-N
- Obtain 99 mg of cyanomethanesulfonamide benzamide. V9V●UU Example 5 N-(1-ethyl-2-pyrrolidinylmethino(c)-2
-Methoxy-5-ethanesulfonamide benzamide 2
66111fI, dry acetone 7D, potassium carbonate 20
0111f and Dimenal Sulfate 100711f were mixed. Reflux for 30 minutes.

Acetone was distilled off, water was added to the residue, and the mixture was extracted with methylene chloride. The organic layer was washed with water, dried with Glauber's salt, and the solvent was distilled off. The residue was dissolved in methylene chloride and subjected to chromatography using a 6-alumina column and eluted with methylene chloride. Methylene chloride was distilled off from the eluate, the residue was washed with isopropyl ether, and then recrystallized from ethyl acetate/isopropyl ether to give N-(1-ethyl-2-pyrrolidinyl) as crystals with a melting point of 85-87°C. methyl)-2-methoxy-5-(N-methylethanesulfonylamino)benzamide 74η is obtained. j Using the following starting compound (9), the reaction is carried out in the same manner as in Example 1 to obtain the corresponding product (1).

Example 23 (1) A solution consisting of 400 mg of methanesulfonyl chloride and 1 ml of dry methylene chloride was added dropwise to a solution consisting of 300 η of 2-methoxy-5-aminobenzoic acid methyl ester, 6 ml of dry methylene chloride, and 368 η of triethylamine under ice cooling, Stir at room temperature for 1 hour.

The reaction solution was made alkaline with an aqueous sodium bicarbonate solution,
Extract with methylene chloride. The organic layer was washed with water, dried over Glauber's salt, and methylene chloride was distilled off under reduced pressure. The residue was washed with ethyl acetate/isopropyl ether and 2-methoxy-5-
N,N-bis(methanesulfonyl)aminobenzoic acid methyl ester 520T119 is obtained. When this product is recrystallized from ethyl acetate, it becomes crystals with a melting point of 169-169.5°C. (2) Add the above product 3 to a mixture of 3 ml of tetrahydrofuran and 3 ml of 10% aqueous sodium hydroxide solution.
Add 00T9 and stir for 1 hour and 15 minutes while heating to 50'C.

The solvent was distilled off from the reaction solution under reduced pressure, the residue was acidified with 6N hydrochloric acid, salted out by adding common salt, and a small amount of methanol was extracted with methylene chloride. The organic layer was washed with saturated brine, dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue is washed with isopropyl ether to obtain 175 mg of 2-methoxy-5-methanesulfonamidobenzoic acid as crystals with a melting point of 166-167.5°C. (3) A mixture consisting of 150 ~ of the above products and 3 ml of thionyl chloride is heated under reflux for 30 minutes.

Thionyl chloride is distilled off under reduced pressure, dry benzene is added to the residue, and the solvent is distilled off again under reduced pressure. Dry the residue with methylene chloride 3
mI! dissolve in A solution consisting of 124 m9 of triethylamine, then 90 ~ 1-ethyl-2-aminomethylpyrrolidine, and 1 ml of dry methylene chloride was added dropwise to this solution under ice cooling, and the mixture was stirred at room temperature for 15 minutes. The reaction solution is made alkaline by adding an aqueous sodium bicarbonate solution, salted out with common salt, and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over sodium sulfate, and methylene chloride was distilled off under reduced pressure. The residue was chromatographed on an alumina column and eluted with 1% methanol/methylene chloride to 2% methanol/methylene chloride.

The solvent was distilled off from the eluate, and the residue was recrystallized from ethyl acetate/isopropyl ether to obtain 143 mg of N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-methanesulfonamide benzamide. When this product is recrystallized from ethyl acetate/isopropyl ether, the melting point is 1.
It becomes a crystal at 69-170.5°C. υExample 24 1) In a solution consisting of 300η of 2-methoxy-5-aminobenzoic acid methyl ester and 3ml of dry pyridine,
While cooling with ice and stirring, 210η of methanesulfonyl chloride was added dropwise, and the mixture was stirred at room temperature for 1 hour.

The reaction solution was made acidic with 6N hydrochloric acid and extracted with methylene chloride. The organic layer was washed with water, dried over sodium sulfate, and methylene chloride was distilled off under reduced pressure. The residue was chromatographed on a silica gel column, eluted with methylene chloride to 2% methanol/methylene chloride, and the solvent was distilled off from the eluate. The residue was recrystallized from ethyl acetate/isopropyl ether,
2-Methoxy-5-methanesulfonamidobenzoic acid methyl ester 3 as colorless prism crystals with a melting point of 84-86°C
81~ is obtained. 2) A solution consisting of the above product 330Tf19, 1-ethyl-2-aminomethylpyrrolidine 245W19 and 7 ml of n-propanol is refluxed under heating for 23 hours.

After cooling, n-propanol is distilled off under reduced pressure, the residue is dissolved in dilute hydrochloric acid, and extracted with unreacted ester methylene chloride.
The hydrochloric acid acidic aqueous layer is made alkaline with sodium bicarbonate, salted out with common salt, and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over sodium sulfate, and methylene chloride was distilled off under reduced pressure. The residue was chromatographed on an alumina column and eluted with 2% methanol/methylene chloride.
The solvent is distilled off from the eluate. The residue was recrystallized from ethyl acetate/isopropyl ether to obtain 143 m9 of N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-5-methanesulfonamide benzamide as colorless scale crystals with a melting point of 171-172°C. .

Example 25 N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy-4-chloro-5-methanesulfonamide A reaction was carried out as in Example 5 using benzamide and dimethyl sulfuric acid, N-(1-ethyl-2-pyrrolidinylmethyl) as a crystal with a melting point of 140.5-142°C
- Obtain 2-methoxy-4-cucaro-5-(N-methylmethanesulfonamido)benzamide.

Example 26 Using 2-methoxy-5-(N-methylmethanesulfonamido)benzoic acid methyl ester, Example 2
The reaction was carried out in the same manner as in 5(2), and N-(1-ethyl-2-pyrrolidinylmethyl) was obtained as crystals with a melting point of 97-98°C.
-2-Methoxy-5-(N-methylmethanesulfonamido)benzamide is obtained.

Example 27 Using 2-methoxy-4-methyl-5-[(methyl)(dimethylaminosulfonyl)amino]benzoic acid methyl ester, the reaction was carried out in the same manner as in Example 24(2),
N-(1-ethyl-2) as a crystal with a melting point of 83-84°C
-pyrrolidinylmethyl)-2-1methoxy-4-methyl-5-[(methyl)(dimethylaminosulfonyl)
[Amino]benzamide is obtained.

Claims (1)

[Claims] 1 General formula▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R represents hydrogen, an alkyl group, a cyano group, an alkanesulfonyl group, or a dialkylamino group; R^1 is an alkyl group, represents an aryl group or a dialkylamino group; R^2 represents hydrogen, halogen, an alkyl group, a dialkylamino group, or an alkoxy group; R^4 represents an alkoxy group; R^3 and R^5 each represent hydrogen or alkyl or an alkoxy group; R^6 represents an alkyl group or a cycloalkyl group. ] or its salt. 2 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R represents hydrogen, an alkyl group, a cyano group, an alkanesulfonyl group, or a dialkylamino group; R^2 represents hydrogen, a halogen, an alkyl group, or a dialkylamino group. R^4 represents an alkoxy group; R^3 and R^5 each represent hydrogen, an alkyl group or an alkoxy group; R^6 represents an alkyl group or a cycloalkyl group. ] The compound represented by the general formula A-SO_2R' [wherein A represents a reactive group; R' represents an alkyl group, an aryl group or a dialkylamino group. ] There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by reacting a sulfonating agent shown in ^1, R^2
, R^3, R^4, R^5 and R^6 have the same meanings as above. ] A method for producing a sulfonamide-based benzamide derivative. 3 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R represents hydrogen, an alkyl group, a cyano group, an alkanesulfonyl group, or a dialkylamino group; R^1 represents an alkyl group, an aryl group, or a dialkylamino group represents; R^2 represents hydrogen, halogen, alkyl group, dialkylamino group, or alkoxy group; R^4 represents an alkoxy group; R^3 and R^5 each represent hydrogen, an alkyl group, or an alkoxy group; ;A^1 represents a hydroxy group or a reactive group. ] Compounds represented by the general formula ▲ have mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^6 represents an alkyl group or a cycloalkyl group. ] There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by the reaction of amines shown in [In the formula, R, R^1, R^2, R^3, R^4, R^ 5
and R^6 have the same meanings as above. ] A method for producing a sulfonamide-based benzamide derivative.