- McCauley JA, McIntyre CJ, Rudd MT, Nguyen KT, Romano JJ, Butcher JW, Gilbert KF, Bush KJ, Holloway MK, Swestock J, Wan BL, Carroll SS, DiMuzio JM, Graham DJ, Ludmerer SW, Mao SS, Stahlhut MW, Fandozzi CM, Trainor N, Olsen DB, Vacca JP, Liverton NJ (March 2010). "Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor". J. Med. Chem. 53 (6): 2443–63.doi:10.1021/jm9015526. PMID 20163176.
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
Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Strategy.J. Org. Chem. 2012; 77: 3820-3828
2,6-Dichloro-1,4-benzoquinone was added to suppress isomerization of the allyl alkene in the isoindoline unit in C and consequent competing formation of a 19-membered ring by-product. An important contributor to the success of the RCM reaction was the high purity of crystalline B.........................................J. Org. Chem., 2012, 77 (8), pp 3820–3828
J Org Chem 2012, 77(8): 3820
Song, Z.G.J.; Tellers, D.M.; Journet, M.; et al.
Synthesis of vaniprevir (MK-7009): Lactamization to prepare a 22-membered macrocycle
J Org Chem 2011, 76(19): 9553