GB1336634A - 5,10-methano-dibenzo-a,d-cycloheptene derivatives and a process for their manufacture - Google Patents

Abstract

1336634 5,10 - Methanodibenzocycloheptane derivatives CIBA-GEIGY AG 19 April 1971 [13 Feb 1970 12 Jan 1971] 21368/71 Heading C2C Novel amines of the Formula (I) R 1 -alk-A, wherein R 1 is a 10,11-dihydro-5,10-methano- 5H - dibenzo - [a,d] - cycloheptenyl - (10) radical, alk is C 1-7 alkylene or alkylidene and A is a free, mono-substituted or disubstituted amino group in which amino group a substituent may be bonded to the alk radical or in which disubstituted amino group the substituents may be bonded together, may be obtained (a) by reducing X in a compound of formula R 1 -X in which X is a radical which can be converted to -alk-A by reduction and which has an oxo group on a carbon atom adjacent to the amino group, or (b) in a compound R 1a -alk-A in which R 1a is a 9,10-dihydro-9,10-ethano anthryl- (11) radical corresponding to the 10,11-dihydro- 5,10 - methano - 5H - dibenzo - [a,d] - cycloheptenyl-(10) radical R 1 , which in the 11-position has a radical which can be split off to leave a carbonium ion (e.g. a free or reactive esterified hydroxyl group), this radical is split off with rearrangement to R 1 (e.g. by solvolysis) and, if desired, in the resulting compounds, in the 11- position, a hydroxyl, C 1-7 alkoxy or acyloxy radical is replaced by H, or a hydroxyl or acyloxy group is oxidized to the oxo group. Novel starting materials of the Formula IXa: wherein -alk b -CH 2 - is the same as -alk-, may be obtained by amidizing a compound of the formula R 1 -alk b -COOH or a derivative thereof which is functionally modified at the carboxyl group, or by solvolysing a compound of the formula R 1a -alk b -CO-A, where R 1a is as defined above. The preparation of intermediates is described as follows: 11-oxo-9,10-dihydro-9,10-ethanoanthracene is reacted with γ-dimethylaminopropyl magnesium chloride to give 11-(γ-dimethylaminopropyl) - 11 - hydroxy - 9,10 - dihydro - 9,10 - ethano - anthracene; 10 - carboxy- 11 - hydroxy - 10,11 - dihydro - 5,10 - methano- 5H - dibenzo - [a,d] - cycloheptene is hydrogenated in the presence of palladium/charcoal to yield 5,11 - dihydro - 5,10 - methano - 5H - dibenzo - [a,d] - cyclohextene - 10 - carboxylic acid which is converted to the acid chloride by warming with oxalyl chloride. Pharmaceutical compositions, useful as psychotropic and sedative agents, comprise compounds of Formula I above together with a pharmaceutical carrier in forms suitable for oral administration. The compounds may also be added to animal fodder since they result in better foodstuff utilization and weight increase of the animals. Compounds with a N-(α-alkylaralkyl)-substituted aminoalkyl group in the 10- position are also useful for the treatment of angina pectoris. The amides of Formula IXa are also useful as psychotropic agents and may be similarly formulated into pharmaceutical compositions.