Synthesis and antiarrhythmic activity of a new benzodioxolsubstituted 4-spirocycloalkan(tetrahydropyran)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines

Abstract

By the reaction of 1-(3,4-dimethoxy)phenylcycloalkanmethan- and 4-(3,4-dimethoxyphenyl)tetrahydropyran-4-methanamines with benzo[ d ][1,3]dioxol-5-carbonyl chloride corresponding N -substituted benzo[ d ][1,3]dioxol-5-carboxamides were synthesized. Cyclization of the latter with phosphorus oxychloride gave dihydroisoquinolines reduced with sodium borohydride to the corresponding spiro-substituted tetrahydroisoquinolines, whose methylation according to Eschweiler-Clark reaction gave N -methyl derivatives. By condensation abovementioned amines with benzo[ d ][1,3]dioxol-5-carbaldehyde Schiff bases were synthesized. The reduction of the latter with sodium borohydride gave the corresponding secondary amines - non-cyclic analogues of tetrahydroisoquinolines, which undergo cyclization under the conditions of the Eschweiler-Clark reaction to form N -benzodioxolmethyl-substituted tetrahydroisoquinolines.