3-METHYL-2-QUINOXALINECARBOXAMIDE-DI-N-OXIDES

摘要

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; R1 is H, CH 3 or CH 2 CH 3 ; R11 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 R1 and R11 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, R1 is H, alkyl, phenyl or allyl; R11 is H, allyl, benzyl, optionally substituted alkyl, optionally substituted phenyl, or R1 and R11 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 R1 and R11 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.