A synthesis of aaptamine from 6,7-dimethoxy-1-methylisoquinoline

Abstract

6,7-Methoxy-1-methylisoquinoline 3a was nitrated at C-8, oxidised to the nitro aldehyde 3r and then condensed with nitromethane using alumina as base to give the alcohol 3s, dehydration of which produced the nitroethene 3t. Iron-acetic acid treatment of compound 3t produced aaptamine 1a. Isoquinoline-1 -carbaldehydes 3q and r reacted with ammonium acetate to produce imidazo[5,1-a]isoquinolines 6a and 6b. 1 -Lithiomethyl-6,7-dimethoxyisoquinoline reacted with ethyl chloroformate to give the ester 3I which was, in turn, easily oxidised to the α-keto ester 3n. The latter was nitrated to give 3o, and this was reductively cyclised to afford the 1H-benzo[d,e][1,6]naphthyridine-2,3-dione 4.