title: Synthesis of the HCV protease inhibitor Vaniprevir (MK-7009) using ring-closing metathesis strategy.
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.
authors.affiliation: Department of Process Research, Merck Research Laboratory, Rahway, New Jersey 07065, USA. jongrock_kong@merck.com
authors.forename: Jongrock
authors.initials: J
authors.lastname: Kong
authors.forename: Cheng-yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Jaume
authors.initials: J
authors.lastname: Balsells-Padros
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dunn
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dolman
authors.forename: Jacob
authors.initials: J
authors.lastname: Janey
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zacuto
mesh_terms: D002384:Catalysis; D003500:Cyclization; D003521:Cyclopropanes; D016174:Hepacivirus / Q000187:drug effects*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D054833:Isoindoles; D047029:Lactams, Macrocyclic; D007930:Leucine / Q000031:analogs & derivatives; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D013449:Sulfonamides
chemical_list: D003521:Cyclopropanes; D007211:Indoles; D054833:Isoindoles; D047029:Lactams, Macrocyclic; D011480:Protease Inhibitors; D013449:Sulfonamides; D012428:Ruthenium; D011392:Proline; C540393:vaniprevir; D007930:Leucine