GB1317475A - Benzodiazepines the preparation thereof and compositions containing the same - Google Patents

Abstract

1317475 1 H - 2,3,4,5 - Tetrahydro - 1,5- benzodiazepin - 4 - ones BOEHRINGER INGELHEIM GmbH 10 June 1970 [11 June 1969 13 Feb 1970 23 April 1970] 28197/70 Heading C2C Novel 1H - 2,3,4,5 - tetrahydro - 1,5 - benzodiazepin-4-ones of the general formula wherein R 1 is a hydrogen atom or a straight or branched chain C 1-6 alkyl group, an unsaturated aliphatic C 2-6 hydrocarbon group, a C 2-3 alkyl group substituted by a hydroxy group in the terminal position, or a C 4-7 cycloalkylmethyl or formyl group, R 2 is an α-pyridyl group, or a phenyl group optionally substituted in the oposition thereof by a halogen atom or a nitro or trifluoromethyl group and R 3 is a hydrogen or halogen atom or a hydroxy, trifluoromethyl, nitro or cyano group, and, except when R 1 is a formyl group and R 2 is other than an α-pyridyl group, physiologically acceptable acid addition salts thereof are prepared (a) when R 1 is other than a formyl group, by reaction of a 1H-2,3,4,5- tetrahydro - 1,5 - benzodiazepin - 4 - one of the general formula wherein R 4 is as R 1 with the exception of a formyl group, with an aryl or heteroaryl halide of the general formula R 2 X, wherein X is a halogen atom; (b) when R 1 is other than a formyl group, by cyclization of an N-(2-anilinophenyl)-#-alanine of the general formula (c) when R 1 is other than a formyl group, by cyclization of an N-acyl-o-phenylenediamine of the general formula wherein Y is a vinyl or 2-haloethyl group; (d) when R 1 is other than a hydrogen atom, by reaction of a lH-2,3,4,5-tetrahydro-1,5-benzodiazepin-4-one of the general formula with a compound of the general formula R 5 Y, wherein R 5 is as R 1 with the exception of a hydrogen atom and Y is an atom or group readily removable as an anion; (e) when R 1 is a 2-hydroxyethyl group, by reaction of a 1H-2,3,4,5 - tetrahydro - 1,5 - benzodiazepin-4- one of the sixth general formula above with ethylene oxide, and (f) when R 1 is a formyl group, by reaction of a 1H-2,3,4,5-tetrahydro- 1,5 - benzodiazepin - 4 - one of the sixth general formula above with formic acid; followed optionally, where appropriate, by salification of the product. Pharmaceutical compositions having tranquillizing activity comprise, as active ingredient, at least one lH-2,3,4,5-tetrahydro-1,5-benzodiazepin-4-one of the first general formula above or physiologically acceptable acid addition salt thereof, in association with a pharmaceutical carrier or excipient, and may be administered orally, parenterally or rectally.