Patent GB-1274261-A (GB)
Title: Dibenzocycloheptene derivatives and the manufacture thereof
IPC: C07C13/547
Filed: 1969-05-01
Abstract: 1,274,261. 1,5 - Disubstituted - dibenzocycloheptenes. F. HOFFMANN-LA ROCHE & CO. A.G. 1 May, 1969 [3 May, 1968], No. 22175/69. Heading C2C. Novel compounds of Formula I in which R 1  represents a hydrogen atom or a methyl group, R represents a methyl or acetyl group and the dotted bonds can be hydrogenated, N-oxides of compounds of Formula I in which R 1  represents a methyl group, geometric and optical isomers of said compounds, and N-oxides and acid addition salts of said compounds, N-oxides and isomers; with the exception of 1-methyl-5-(3-methylaminopropylidene) - 5H - dibenzo - [a,d] - cycloheptene and 1 - acetyl - 5 - (3 - methylaminopropyl)-5H- dibenzo 10,11-dihydrocycloheptene, are prepared by one of the following methods: (a) reduction of a compound of formula (b) dehydration of one of the compounds of formulµ where R<SP>1</SP> is methyl or a ketalized acetyl group, (c) reacting a compound of formula wherein W represents a halogen atom, with a 3-dimethylaminopropyl magnesium halide, (d) treating a compound of one of the general formulµ wherein Z represents a halogen atom or a substituted sulfonyloxy group and A represents the anion of an acid, with methylamine, dimethylamine or dimethylhydroxylamine, (e) methylating a primary amine of the general formula wherein E represents an amino group or an N-hydroxy-N-methyl group, (f) debenzylating a compound of the general formula (g) heating a compound of either of formulµ wherein P 1  represents a hydrogen atom or a hydroxyl group and P 2  represents a hydrogen atom or P 1  and P 2  together represent an additional bond, Q represents the residue of an aldehyde and B represents the anion of an acid, (h) reacting a compound of the general formula wherein T is an alkali metal atom with a compound of formula L.CH 2 .CH 2 .CH 2 N(CH 3 ) 2 , wherein L is a halogen atom or a substituted sulphonyloxy group, and (i) hydrolytically cleaving a compound of formula wherein D represents an acyl or esterified carboxyl group, whereupon, in any desired sequence and if desired, a resulting compound in which R 1  represents a hydrogen atom is methylated, if desired, a compound in which R 1  represents a methyl group is oxidized or converted into a compound in which R 1  represents a hydrogen atom by demethylation, if desired, an unsaturated product obtained is hydrogenated, if desired, a 10,11-dihydro compound obtained is dehydrogenated, if necessary, a ketal obtained is deketalized, if desired, the geometric and/or optical isomers are isolated from an isomer mixture obtained and, if desired, a base obtained is converted into an acid addition salt. 1 - Methyl - 5 - chloro - 5H - dibenzo[a,d]cycloheptene and the 10,11-dihydro-compound are prepared by the action of thionyl chloride on the corresponding 5-hydroxy-compounds which are obtained by reduction of the 5-keto compounds. Pharmaceutical compositions in conventional forms for oral or parenteral administration and having antidepressant, adrenolytic, anihistamine and local anaesthetic activity comprise an above novel compound and a carrier therefor.