Patent GB-1325581-A (GB)
Title: 3-methyl-2-quinoxalinecarboxamide-di-n-oxides
IPC: C07D241/52
Filed: 1970-07-09
Abstract: 1325581 Quinoxaline - 1,4 - di - N - oxides PFIZER Inc 9 July 1970 [22 July 1969 (2) 28 Jan 1970] 33489/70 Heading C2C [Also in Division A5] The invention comprises novel quinoxaline derivatives of the Formula III wherein X is a 6- or 7-position substituent selected from H, CH 3 , OCH 3 , Cl, F, CF 3 , sulphamoyl, N-methyl or N,N-dimethylsulphamoyl; Y is 6- or 7-position substituent selected from H, CH 3 , OCH 3  or Cl; R<SP>1</SP> is H, CH 3  or CH 2 CH 3 ; R<SP>11</SP> is C 1-4  alkyl N(R 3 )R 4 , C 1-4  alkyl OR 5  or C 1-4  alkyl COR 6 , wherein R 3  is H, R 4  is H or C 1-4  alkanoyl; or R 3  and R 4  when taken together with the N atom to which they are attached are 1 - [4 - (C 1-4  alkyl)piperazinyl]; R 5  is C 1-4  alkanoyl, R 6  is OH or NR 7 R 8  wherein R 7  and R 8  are H, CH 3  or CH 5 CH 3 ; or R<SP>1</SP> and R<SP>11</SP> when taken together with the N atom to which they are attached form a piperazine ring of the formula wherein W is C 1-4  alkyl, C 1-4  alkanoyl, CONH 2 , C 1-4  alkoxycarbonyl, carboxy (C 1-4  alkyl), C 1-4  alkoxy - carbonyl - C 1-4  alkyl, or carbamoyl-C 1-4  alkyl; and the pharmaceutically acceptable salts of those compounds having an acidic or a basic group; their preparation and the preparation of compounds of the above Formula III wherein X and Y are as defined above, R<SP>1</SP> is H, alkyl, phenyl or allyl; R<SP>11</SP> is H, allyl, benzyl, optionally substituted alkyl, optionally substituted phenyl, or R<SP>1</SP> and R<SP>11</SP> when taken together with the nitrogen atom to which they are attached are 1-pyrrolyl, 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl 1-[4- (C 1-4  alkyl)]piperazinyl, 1 - [4 - hydroxy- (C 1-4  alkyl)]piperazinyl, 1 - [4 - (C 1-4  alkanoyl)]- piperazinyl, 1 - [4 - (C 1-4  alkoxy)carbonyl]- piperazinyl, 1 - [4 - carbamoyl]piperazinyl, 1 - [4 - carboxy(C 1-4  alkyl)]piperazinyl, 1- [4 - (C 1-4  alkoxy)carbonyl - (C 1-4  alkyl)]- piperazinyl, or 1 - [4 - carbamoyl - (C 1-4  alkyl)]- piperazinyl. The compounds are prepared by one of the following processes: (a) reacting benzofuroxans of the Formula II with enamines of the appropriate ketones; (b) reacting benzofuroxans of Formula II above with #-ketoamides of the formula (c) reacting the alkyl esters of the corresponding 3 - methyl - 2 - quinoxaline - carboxylic acid- 1,4-dioxides with amines of the formula (d) reacting the products resulting from the reaction of the corresponding 3-methyl-2- quinoxolinecarboxylic acid - 1,4 - dioxides with carbodiimides with amines of the formula (e) reacting benzofuroxans of the above Formula II with diketone and amines of the formula Compounds in which R<SP>1</SP> and R<SP>11</SP> together with the N atom form 1-piperazinyl may also be obtained by hydrolysing the corresponding compounds in which W is C 1-4  alkoxycarbonyl with concentrated sulphuric acid. S - Trifluoromethylbenzofuroxan is obtained by heating 4 - azido - 3 - nitrobenzotrifluoride obtained by reacting the diazonium salt of 4- amino - 3 - nitrobenzotrifluoride with sodium azide. S - Sulphamoyl, S - N - methyl and S - N,N- dimethylsulphamoyl - benzofuroxan are obtained by cyclizing the 2-nitro-4-sulphamoyl (or -N methyl or N,N-dimethyl-sulphamoyl)-anilines. 1 - [C 1-4  alkoxy carbonyl - C 1-4  alkyl]piperazines are obtained by reacting alkyl chloroalkanoates with piperazine. 2 - (1 - Piperazinyl)acetamido, 3 - (1 - piperazinyl)propionamide and 4 - (1 - piperazinyl)- butyramide are obtained by reacting piperazine with the appropriate chloroalkanoic acid amides. Ethyl ester of 3-methyl-2-quinoxalinecarboxylic acid 1,4-dioxides are made by reacting the appropriate benzofuroxans with ethyl acetoacetate. Reference has been directed by the Comptroller to Specification 1,215,815.