Patent GB-1234833-A (GB)
Title: 3-aminoacylamino-thiophens and process for preparing them
IPC: C07D333/36
Filed: 1968-07-08
Abstract: 1,234,833. 3 - Aminoacylaminothiaphenes. FARBWERKE HOECHST A.G. 8 July, 1968 [7 July, 1967], No. 32438/68. Heading C2C. [Also in Division A5] Novel 3-aminoacylaminothiophenes of the formula wherein R 1  and R 2  are H, C 1-6  alkyl, optionally substituted by one or more OH of C 1-3  alkoxy groups, C 5-6  cycloalkyl or C 2-4  alkenyl, with the proviso that one of R 1  and R 2  is other than H, or R 1  and R 2 , together with the N atom, may form a saturated 5-7-membered heterocyclic ring, optionally containing O, N or methylimino group; R 3 , R 4  and R 5 , each are H, C 1-4  alkyl or carbalkoxy and A is C 1-4  alkylene, and the physiologically tolerable acid addition salts thereof, are prepared by one of the following methods:- (a) By reacting the appropriate 3-halogeno (or alkoxy-, aralkoxy- or aryloxy-) acylaminothiophene with an amine of the formula HN(R 1 )R 2 . (b) By reacting the appropriate 3-aminothiophene or an alkali or alkaline earth metal salt or Grignard compound thereof with an aminocarboxylic acid or reactive derivative thereof of the formula HOOC-A-N(R 1 )R 2 . (c) By dehydrogenating the corresponding 3-aminoacylamino-4,5- or 2,5-dihydrothiophene. (d) By alkylating the corresponding 3- aminoacylaminothiophene of the above general formula wherein R 1  and R 2  are H. (e) By hydrolysing the corresponding 3- aminoacylaminothiophene of the above general formula wherein R 1  is an ester group. (f) By reacting the corresponding 3-aminoacylaminothiophene in which the acyl group is unsaturated with an amine of the formula HN(R 1 )R 2 . (g) By reacting the corresponding 3-isocyanothiophene with an amine of the formula HN(R 1 )R 2 , in the presence of an aliphatic aldehyde containing 1 to 4 carbon atoms. (h) By hydrolysing and decarboxylating the corresponding 3-aminoacylaminothiophene in which R 3 , R 4  and/or R 5  are carbalkoxy groups. 3 - Chloroacetylamino - 2 - carbomethoxy - 4- methylthiophene is obtained by reacting 3-amino- 2 - carbomethoxy - 4 - methylthiophene with chloroacetyl chloride. Similarly 3-chloroacetylamino - 4 - carbomethoxy - 2 - methylthiophene, 3 - chloroacetylamino - 5 - carbomethoxy - 2,4 - dimethylthiophene, 3 - α - chloropropionylamino - 2 - carbomethoxy - 4 - methylthiophene, 3 - # - chloropropionylamino - 2 - carbomethoxy - 4 - methylthiophene, 3 - chloroacetylamino - 2 - carbethoxy - 4 - methylthiophene, 3 - α - chloropropionylamino - 4 - methylthiophene, and 3 - # - chloropropionylamino - 4 - methylthiophene are prepared. 3-Chloroacetylaminothiophene is made by reacting chloroacetyl chloride with 3-aminothiophene resulting from the decarboxylation of 3 - amino - 2 - carboxythiophene. By similar processes 3-chloroacetylamino-4-methylthiophene, 3 - amino - 4 - methylthiophene, 3 - chloroacetylamino - 2,4 - dimethylthiophene and 3 - amino- 2,4-dimethylthiophene are obtained. 3 - Isocyano - 2 - carbomethoxy - 4 - methylthiophene is obtained by dehydrating 3-formylamino - 2 - carbomethoxy - 4 - methylthiophene. 3 - Crotonylamino - 4 - methylthiophene is prepared by reacting 3-amino-4-methylthiophene with crotonic acid chloride. N - Benzyloxycarbonyl - n - butylaminoacetylamino - 4 - methylthiophene and N - benzyloxycarbonyl - n - butylaminoacetyl - 5 - carbomethoxy- 2,4-dimethylthiophene are made by reacting N- benzyloxycarbonyl - n - butylaminoacetic acid with 3-amino-4-methylthiophene and 3-amino- 5-carbomethoxy-2,4-dimethylthiophene in the presence of ethyl chloroformate. 3 - n - Butylaminoacetylamino - 2 - carboxy - 4- methylthiophene is obtained by saponification of the corresponding methyl ester. 3 - Diethylaminoacetylamino - 2 - carbomethoxy - 4 - methyl - 4,5 - dihydrothiophene is prepared by reacting diethylamino with 3-chloroacetylamino - 2 - carbomethoxy - 4 - methyl - 4,5- dihydrothiophene resulting from the reaction of 2-carbomethoxy-4-methylthiophenone-(3), with ammonia or ammonium acetate and then with chloroacetyl chloride. Reference has been directed by the Comptroller to Specification 837,086.