Development of a Multikilogram Scale Synthesis of
a TRPV1 Antagonist

Kuethe, Jeffrey T.; Journet, Michel; Peng, Zhihui; Zhao, Dalian; McKeown, Arlene; Humphrey, Guy R.

doi:10.1021/acs.oprd.5b00388.s001

Development of a Multikilogram Scale Synthesis of a TRPV1 Antagonist

journal contribution

posted on 2016-01-13, 00:00 authored by Jeffrey T. Kuethe, Michel Journet, Zhihui Peng, Dalian Zhao, Arlene McKeown, Guy R. Humphrey

A highly efficient, regioselective five-step synthesis of the TRPV1 antagonist 1 is described. The coupling of piperazine 7 with dichloropyrimidine 8 proceeded via a regioselective Pd-mediated amination affording product 11 in excellent yield. Conversion of the penultimate product 14 afforded 1 through formation of a magnesium ate complex and trapping with CO₂.