The synthesis of perloline, 6-(3,4-Dimethoxyphenyl)-5-hydroxy-5,6-dihydrobenzo[c]-[2,7]naphthyridin-4(3H)-one

Abstract

Dehydroperloline is obtained in high overall yield by an intramolecular cyclization of the benzyne generated from 4-(2-bromophenyl)-N-(3,4-dimethoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (21), by use of lithium hexamethyldisilazide. A benzyne intermediate has not been established. The pyridinone (21) was prepared in three steps from 2-[1-(2-bromophenyl)ethylidene]malononitrile. Dehydroperloline was smoothly reduced by sodium bis(methoxyethoxy)aluminium hydride to perloline, isolated as its hydrochloride.