GB1316301A - Pharmaceutical useful benzomorphanes and their production - Google Patents

Abstract

1316301 Benzomorphane derivatives BAYER AG 13 May 1970 [17 May 1969] 23213/70 Heading C2C Benzomorphane derivatives of the Formula (I) and their salts with acid and bases, wherein R is a cyclopropylmethyl or cyclobutylmethyl radical, R<SP>1</SP> and R<SP>11</SP> are the same or different and may be straight or branched chain saturated C 1-5 hydrocarbon radicals; Q is OH or X.CO-, X being OH, -OR<SP>111</SP> or in which R<SP>111</SP> is a straight or branched, saturated or unsaturated hydrocarbon radical of up to 11C, R<SP>4</SP> and R<SP>6</SP> can be H, or C 1-4 hydrocarbon radicals or can also be linked via a direct bond or via -O- to form together with the N atom a heterocyclic ring; A is a bivalent, straight or branched chain, saturated or unsaturated hydrocarbon chain of up to 10C optionally carrying one or more phenyl substituents which may themselves carry one or more alkyl, alkoxy, halo, nitro or acylamino substituents, may be obtained by reacting a compound of the Formula (XII) in which R<SP>8</SP> is an acyl or CN radical, in the presence of an acid-binding agent, optionally in the form of its metal or NH 4 salt, with a reactive ester of a compound Y-A-OH, in which Y is a free or esterified hydroxyl and the product is desacylated at the N atom and then either (a) reacylated with R<SP>6</SP>-CO-Hal (where R<SP>6</SP> is cyclopropyl or cyclobutyl) and then reduced, or (b) reacted with ROH, to form (Ia), a novel compound which is converted into a reactive ester (e.g. halide or tosylate) and reacted with a metal cyanide to form a compound of Formula (XXI) which is converted by known methods into a compound of Formula (I) in which Q is X.CO-. A compound (Ia) in which A is shorter by one CH 2 than the desired product, can be converted to a reactive ester, reacted with a salt of a malonic ester, and the product converted by hydrolysis and decarboxylation to compounds (I) where X is OH or OR<SP>111</SP>. Compounds (I) in which Q is -COX or CN and R = CH 3 , may be demethylated with simultaneous saponification of Z, followed by (a) acylation with R<SP>6</SP>COHal and reduction to form (I) where Q is -COOH, or (b) reaction with R<SP>6</SP>-CS-SR<SP>7</SP> (where R<SP>7</SP> is optionally substituted carboxymethyl or alkyl) and the product reduced to form a compound of Formula (I). Various modifications of such methods are also described. The compounds in which Q is X.CO- are claimed in Application 23212/70. Pharmaceutical compositions having analgesic activity comprise compounds of Formula (I) above together with a solid or liquid diluent or carrier, in forms suitable for oral or parenteral administration.