Synthesis of vaniprevir (MK-7009): lactamization to prepare a 20-membered [corrected] macrocycle

  • J Org Chem. 2011 Oct 7;76(19):7804-15. doi: 10.1021/jo2011494.
Zhiguo J Song  1 ,  David M Tellers ,  Michel Journet ,  Jeffrey T Kuethe ,  David Lieberman ,  Guy Humphrey ,  Fei Zhang ,  Zhihui Peng ,  Marjorie S Waters ,  Daniel Zewge ,  Andrew Nolting ,  Dalian Zhao ,  Robert A Reamer ,  Peter G Dormer ,  Kevin M Belyk ,  Ian W Davies ,  Paul N Devine ,  David M Tschaen
Affiliations
  • 1. Department of Process Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, United States. [email protected]
PMID: 21838271 DOI: 10.1021/jo2011494
Abstract

Development of a practical synthesis of MK-7009, a 20-membered [corrected] macrocycle, is described. A variety of ring-closing strategies were evaluated, including ring-closing metathesis, intermolecular palladium-catalyzed cross-couplings, and macrolactamization. Ring closure via macrolactamization was found to give the highest yields under relatively high reaction concentrations. Optimization of the ring formation step and the synthesis of key intermediates en route to MK-7009 are reported.

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