Application of the Pictet-Spengler reaction to aryl amine-based substrates having pyrimidine as a pi-nucleophile: Synthesis of pyrimidoquinolines with structural analogy to benzonaphthyridines present in alkaloids

Abstract

Synthesis of pyrimidine annulated quinolines, structurally analogous to biologically active benzonaphthyridines present in alkaloids, has been described. Our synthetic strategy is based on the modified Pictet-Spengler reaction involving substrates comprising deactivated pyrimidine ring as the nucleophilic partner whereas aryl amine originating from the C-4 of the pyrimidine ring served as the source for electrophilic partner. The resulting substrates 5-7 with diversity at 2 and 6-positions after condensation with a variety of aldehydes underwent 6-endo cyclization to furnish pyrimido[5,4-c]quinolines 14 in good yields. However, attempts to further extend this strategy on new structurally analogous substrate, involving the pyridine ring as nucleophilic partner failed; thus limiting the scope of the reaction.