GB841225A - Novel quinolizine derivatives and process for the manufacture of same - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:0841225/IV(b)/1> (wherein the alkyl, alkoxy and halogeno substituents are optional and R is hydrogen or an acyl group) and acid-addition salts thereof; and their preparation by reduction of the corresponding ketones by known methods and acylation of the alcohol products if desired. The reduction may be carried out by catalytic hydrogenation, by treatment with lithium aluminium hydride in an anhydrous solvent or by treatment with sodium or potassium boron hydride in methanol. The acylation may be effected with the appropriate acid anhydride in presence of a tertiary base such as pyridine or with a lower alkyl ester of the acylating acid in presence of an alkaline catalyst. Examples describe the preparation of (1) 2-hydroxy-1:2:3:4:6:7:12:12b - octahydro - indolo [2,3 - a]quinolizine and the corresponding acetoxy, butyroxy and benzoyloxy compounds therefrom; 2 - hydroxy - 3 - methyl - 1:2:3:4: 6:7:12:12b - octahydro - indolo[2,3 - a]quinolizine; (3) 2 - hydroxy - 9 - chloro - 1:2:3:4: 6:7:12:12b - octahydro - indolo[2,3 - a]quinolizine by condensing 5-chloro-tryptamine with ethoxycarbonyl-pyruvic acid and esterifying the product with ethanolic hydrochloric acid to give ethyl 6 - chloro - 2:3:4:9 - tetrahydro-1H - pyrid[3,4 - b]indole - 1 - acetate hydrochloride, converting this to the free base and heating with ethyl acrylate to give a crude product, heating this with sodium ethoxide in benzene to give a crude b -keto ester, heating this with hydrochloric acid to give 2-oxo-9-chloro - 1:2:3:4:6:7:12:12b - octahydroindolo[2,3-a]quinolizine and reducing this; and (5) 2 - hydroxy - 9:10 - dimethoxy - 1:2:3:4: 6:7:12:12b - octahydro - indolo[2,3 - a] quinolizine by heating 5:6-dimethoxy-tryptamine-2-carboxylic acid with hydrochloric acid to effect decarboxylation, condensing the product with ethoxy-carbonyl pyruvic acid and subsequently esterifying as under (4) to give ethyl - 2:3:4:9 - tetrahydro - 6:7 - dimethoxy-1H - pyrid[3,4 - b]indole - 1 - acetatehydrochloride, treating this as under (4) to give 2-oxo9:10 - dimethoxy - 1:2:3:4:6:7:12:12b-octahydro - indolo[2,3 - a]quinolizine and reducing this. Hydrochlorides of some of the products are described. Ketone starting materials are prepared by the method disclosed in Specification 840,267 or by analogous methods.