| 18351744 |
Thiel OR, Bernard C, King T, Dilmeghani-Seran M, Bostick T, Larsen RD, Faul MM: Practical synthesis of a vanilloid receptor-1 antagonist. . J Org Chem. 2008 May 2;73(9):3508-15. Epub 2008 Mar 20.
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. |
2(0,0,0,2) |