| 摘要 |
1335129 Dibenzocyclohepta[1,2-c]pyrrole CIBA-GEIGY AG 25 May 1971 [25 May 1970] 16661/71 Heading C2C [Also in Division C5] Novel compounds of the Formula (I) wherein R denotes H, C 1-4 alkyl or allyl, and X denotes H, Cl, CH 3 or CH 3 O, and the addition salts with inorganic or organic acids, may be obtained (1) by reacting a reactive ester of a compound of the Formula II with ammonia or an amine of formula RNH 2 , or (2) by hydrolysing a compound of the Formula IV wherein Z denotes the acyl radical of an organic acid or the cyano group, and when required converting the product into a pharmaceutically acceptable acid addition salt thereof. The preparation of intermediates is described as follows: (9,10-dihydroanthracen-9-yl)methyl ketone is methylated with CH 3 I to give (9- methyl-9,10-dihydroanthracen-9-yl)methyl ketone which is reduced by NaBH 4 to α, 9-dimethyl-9,10- dihydro-9-anthracenemethanol which is rearranged, according to Wagner-Meerwein, in dilute H 2 SO 4 and rearranged to 10,11-dimethyl-5H- dibenzo[a,d]cycloheptene. This latter product can also be obtained by condensing α-phenyl-o-tolylacetonitrile with diethylcarbonate to α-phenyl-otolylcyano-acetic acid ethyl ester, methylating with CH 3 I and boiling with KOH solution to form o-benzyl-hydratropic acid, converting in polyphosphoric acid to 11-methyl-5,11-dihydro- 10H-dibenzo[a,d]cycloheptene-10-one, reacting with CH 3 MgI to form 10,11-dimethyl-10,11- dihydro-5H-dibenzo[a,d]cyclohepten-10-ol and dehydrating in H 2 SO 4 to form 10,11-dimethyl-5H- dibenzo[a,d]cycloheptene. Similar intermediates substituted in the 2-position by chlorine, methyl or methoxy can likewise be obtained. The 10,11- dimethyl-5H-dibenzo[a,d]cycloheptene can be oxidized with SeO 2 to 5H-dibenzo[a,d]cycloheptene-10,11-dicarboxaldehyde which is reduced with NaBH 4 to 5H-dibenzo[a,d]cycloheptene- 10,11-dimethanol which reacts with PBr 3 to form 10,11 - bis - bromomethyl - 5H - dibenzo[a,d]cycloheptene, a compound of Formula II. Corresponding Cl-, CH 3 - and CH 3 O- intermediate compounds are similarly obtained.1,2,3,8-Tetrahydrodibenzo[3,4 : 6,7]cyclohepta[1,2-c]pyrrole - 2-carboxylic acid ethyl ester is obtained by reacting 2 - allyl - 1,2,3,8 - tetrahydrodibenzo[3,4 : 6,7]- cyclohepta[1,2-c] pyrrole with ethyl chloroformate. Pharmaceutical compositions possessing CNS depressant action, adrenolytic and histamineantagonistic action, comprise compounds of Formula (1) above or pharmaceutically acceptable acid addition salts thereof together with a pharmaceutically acceptable carrier or diluent, in forms suitable for administration orally, rectally or parenterally. |
