2. Academic Validation
  3. Synthesis of the HCV protease inhibitor Vaniprevir (MK-7009) using ring-closing metathesis strategy

Synthesis of the HCV protease inhibitor Vaniprevir (MK-7009) using ring-closing metathesis strategy

  • J Org Chem. 2012 Apr 20;77(8):3820-8. doi: 10.1021/jo3001595.
Jongrock Kong 1,  Cheng-yi Chen,  Jaume Balsells-Padros,  Yang Cao,  Robert F Dunn,  Sarah J Dolman,  Jacob Janey,  Hongmei Li,  Michael J Zacuto
Affiliations

Affiliation

  • 1 Department of Process Research, Merck Research Laboratory, Rahway, New Jersey 07065, USA. [email protected]
PMID: 22458448 DOI: 10.1021/jo3001595
Abstract

A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M.

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