process for the production of new thiepinderivaten

摘要

1334945 Dibenzothiepinopyrrole derivatives CIBA-GEIGY AG 25 May 1971 [26 May 1970] 16904/71 Heading C2C Novel compounds of the Formula I wherein R is hydrogen, C 1-6 straight chain alkyl, isopropyl or allyl and pharmaceutically acceptable salts thereof may be prepared either by cyclizing the dibenzothiepin II with RNH 2 or when R is hydrogen hydrolysing a compound IV wherein Z is an acyl radical of an organic acid, an alkoxy carbonyl group or a cyano group. The intermediate 10,11-bis-(bromoethyl)-2- (trifluoromethyl)-dibenzo[b,f]thiepin may be prepared by N-bromosuccinimide bromination of 10,11 - dimethyl - 2 - trifluoromethyl - dibenzo- [b,f]thiepin which is prepared by dehydration of 10,11-dihydro-10,11-dimethyl-8-trifluoromethyldibenzo[b,f]thiepin-10-ol. which in turn is prepared by treating 11-methyl-8-trifluoromethyldibenzo[b,f]thiepin-10(11H)-one. The dibenzothiepinone may be prepared by cyclizing o- (,,-trifluoro-p-tolylthio)-hydratropic acid which may be prepared by methylation followed by hydrolysis of [o-(,,-trifluoro-p-tolylthio)-phenyl]-malonic acid diethyl ester which in turn is prepared by the action of ethyl carbonate on the sodio derivative, formed in situ, of ethyl[o-(,,- trifluoro-p-tolylthio)phenyl] acetate. which is formed by esterification of the free acid. The intermediate 2-ethoxycarbonyl-2,3-dihydro 5-trifluoromethyl-1H-dibenzo[2,3: 6,7] thiepino [4,5c]pyrrole may be prepared by action of ethyl chloroformate on the 2-allyl compound I. Pharmaceutical compositions of the compounds I show central depressant activity when administered orally, parenterally or rectally with the usual excipients.