Practical Synthesis of a Vanilloid Receptor-1 Antagonist
The Journal of Organic Chemistry2008Vol. 73(9), pp. 3508–3515
Citations Over TimeTop 16% of 2008 papers
Oliver R. Thiel, Charles Bernard, Tony King, Mina Dilmeghani-Seran, Tracy Bostick, Robert D. Larsen, Margaret M. Faul
Abstract
Small molecule TRPV1 antagonists have been a recent focus in the search for pain treatment agents. We herein describe a practical and scalable synthesis of AMG 628 (1), a bis-substituted pyrimidine derivative that was identified as a highly efficacious agent, suitable for clinical development. Highlights of our approach include a practical route to a substituted benzothiazole, a scalable synthesis of an enantiopure piperazine fragment, and identification of conditions for selective coupling reactions on 2,6-dichloropyrimidine, to access the active pharmaceutical ingredient in high purity and overall yield.
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