Patent GB-1086588-A (GB)
Title: New cycloheptadienes and process for preparing same
IPC: C07C49/675
Filed: 1965-05-24
Abstract: Novel compounds of the Formula I and acid addition-salts thereof wherein each of Ph and Ph1 represents an o-phenylene group which may be substituted by one or more halogen atoms or trifluoromethyl, C1- 7 alkyl or C1- 7 alkoxy groups; each of R1 and R2 represents a hydrogen atom or a C1- 7 alkyl group and R0 represents an aminoalkyl or aminoalkylidene group in each of which the amino group is unsubstituted or mono- or di-substituted by C1- 7 alkyl, cycloalkyl or (C1- 7 alkyl)-cycloalkyl radicals or disubstituted by a C1- 7 alkylene, oxa-alkylene, aza-alkylene or thia-alkylene group, or in which the amino group is a mono- or di-(C1- 7 alkyl) amino group in which one of the alkyl groups is bonded to the alkylene or alkylidene group linking the amino group with the methanodibenzocycloheptene nucleus, are prepared by treating a 5:10 - methanodibenzo[a:d]cyclohepta - 1:4-diene, containing in the 11-position a hydroxy group and an alkyl radical substituted by a corresponding amino group, with a strong acid to form a semi-cyclic double bond and, if desired reducing the resulting aminoalkylidene compound to the corresponding aminoalkyl compound and if desired converting any resultant amines into acid addition salts thereof. Compounds of the Formula I may also be prepared by reacting a 5:10-methanodibenzo[a,d]cyclohepta-1:4-diene containing in the 11-position, as the only substituent, an alkyl or alkylidene group substituted by a reactive esterified hydroxyl group with ammonia or with an appropriate primary or secondary amine; by reducing a compound of the Formula I wherein one of the carbon atoms adjacent to the nitrogen atom containing an oxo group with lithium aluminium hydride; by reducing a compound of the Formula I wherein the amino-alkyl or -alkylidene group is replaced by a cyano-alkyl or alkylidene group; by reducing compounds of the Formula I wherein the amino group is replaced by a hydroxylimino, imino or nitro group; by reductive alkylation of compounds of the Formula I wherein the amino nitrogen atom has attached thereto at least one hydrogen atom or reacting same with a reactive ester of an appropriate alcohol; and by hydrogenolysing compounds of the Formula I wherein the amino nitrogen atom contains as a substituent a hydrogenolytically eliminable radical, and, if desired, converting any resulting free bases into acid addition salts thereof, and, if desired, separating geometrical and/or optical isomers by known methods. <FORM:1086588/C2/1>  11 - Hydroxy - 11 - aminoalkyl - 5:10-methanodibenzo[a,d]cyclohepta-1:4-dienes may be prepared from the corresponding 11-oxo compounds by reaction with an appropriate Grignard compound, the 11-oxo compound being prepared by oxidation of the corresponding 11-hydroxy-5:10-methanodibenzo[a,d]cyclohepta-1:4-diene; the latter being suitably prepared by solvolysing an appropriate 11-sulphonyloxy - 9:10 - dihydro - 9:10 - ethanoanthracene.  Pharmaceutical and veterinary compositions with central inhibitory and histaminolytic activities, for oral and parenteral administration comprise compounds of the Formula I or physiologically tolerable acid addition salts thereof, in conjunction with suitable carriers therefor.