A concise regiospecific synthesis of 5-chloropyrido[4,3-d]pyrimidin-4(3H)-one

ORGN 651

Yahua Liu, yliu2@gnf.org, Qiang Ding, and Xu Wu. Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr, San Diego, CA 92121
During our medicinal research program on 5-alkoxy or 5-amino pyrido[4,3-d]pyrimidin-4(3H)-ones, we developed a concise synthesis of 5-chloropyrido[4,3-d]pyrimidin-4(3H)-one (1) from a commonly used starting material 4-maino-2-chloropyridine (2). The key intermediate tert-butyl 4-(tert-butoxycarbonylamino)-2-chloronicotinate (3) was obtained as the exclusive product without its regioisomer through a unique rearrangement. Pyridopyrimidinone 1 was prepared in gram scale in overall yield 60% with only one column chromatography for this 5 steps synthesis.