Synthesis of 6-(3,4-Dimethoxyphenyl)-4-oxo-3,4-dihydrobenzo[C][2,7]naphthyridin-6-ium Chloride (Perloline Chloride)

Abstract

Perloline was synthesized as its chloride, 6-(3,4-dimethoxypheny1)-4-oxo-3,4-dihydrobenzo-[c][2,7]naphthyridin-6-ium chloride (lb), by utilizing the photochemical rearrangement of the N-oxide (6) of 5-(3,4-dimethoxyphenyl) benzo [c][2,7]naphthyridin-4(3 H)-one (2) to 6-(3,4-dimethoxyphenyl ) benzo [c][2,7]naphthyridine-4,5(3 H,6 H)- dione (7) ( dehydroperloline), which was then selectively reduced with sodium bis( methoxyethoxy ) aluminium hydride. The naphthyridinone (2) was prepared conveniently by reaction of 2-(3,4-dimethoxypheny1)-4-methylquinoline-3-carbonitrile (4) with dimethylformamide dimethyl acetal, and cyclization of the enamine product (5) with polyphosphoric acid.