Synthesis and Functionalization of C6/C7 Substituted Pyrido[3,2-d]pyrimidines

An efficient synthesis of functionalized pyrido[3,2-d]pyrimidines is reported. Starting from 4-aminopyrimidine-3-carbaldehydes, a Horner-Wadsworth-Emmons olefination followed by a photoisomerization/cyclization installed the fused pyridine ring. Using substituted HWE-reagents various substituents could be introduced in the 7-position of the pyrido[3,2-d]pyrimidines. Functionalization of the pyridone substructure allowed late variation in the 6-position. In order to obtain amine-linked bis-pyridopyrimidines, 7-bromo-pyridopyrimidines were converted with their 7-amino-counterpart by Hartwig-Buchwald amination.