American Chemical Society
op5b00388_si_001.pdf (2.16 MB)

Development of a Multikilogram Scale Synthesis of a TRPV1 Antagonist

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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.