923591-06-4Relevant articles and documents
Phase Separation Macrocyclization in a Complex Pharmaceutical Setting: Application toward the Synthesis of Vaniprevir
Godin, éric,Bédard, Anne-Catherine,Raymond, Micha?l,Collins, Shawn K.
, p. 7576 - 7582 (2017/07/26)
A phase separation/continuous flow strategy employing an oxidative Glaser-Hay coupling of alkynes has been applied toward the synthesis of the macrocyclic core of complex pharmaceutical vaniprevir. The phase separation/continuous flow strategy afforded similar yields at 100-500 times the concentration and at shorter reaction times than common slow addition/high dilution techniques. In addition, dendritic PEG cosolvents were employed in the phase separation strategy for the first time and shown to allow productive macrocyclization at concentrations up to 200 mM.
Synthesis of vaniprevir (MK-7009): Lactamization to prepare a 22-membered macrocycle
Song, Zhiguo J.,Tellers, David M.,Journet, Michel,Kuethe, Jeffrey T.,Lieberman, David,Humphrey, Guy,Zhang, Fei,Peng, Zhihui,Waters, Marjorie S.,Zewge, Daniel,Nolting, Andrew,Zhao, Dalian,Reamer, Robert A.,Dormer, Peter G.,Belyk, Kevin M.,Davies, Ian W.,Devine, Paul N.,Tschaen, David M.
, p. 7804 - 7815 (2011/12/14)
Development of a practical synthesis of MK-7009, a 22-membered macrocycle, is described. A variety of ring-closing strategies were evaluated, including ring-closing metathesis, intermolecular palladium-catalyzed cross-couplings, and macrolactamization. Ri
Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor
McCauley, John A.,McIntyre, Charles J.,Rudd, Michael T.,Nguyen, Kevin T.,Romano, Joseph J.,Butcher, John W.,Gilbert, Kevin F.,Bush, Kimberly J.,Holloway, M. Katharine,Swestock, John,Wan, Bang-Lin,Carroll, Steven S.,Dimuzio, Julian M.,Graham, Donald J.,Ludmerer, Steven W.,Mao, Shi-Shan,Stahlhut, Mark W.,Fandozzi, Christine M.,Trainor, Nicole,Olsen, David B.,Vacca, Joseph P.,Liverton, Nigel J.
experimental part, p. 2443 - 2463 (2010/09/03)
A new class of HCV NS3/4a protease inhibitors which contain a P2 to P4 macrocyclic constraint was designed using a molecular-modeling derived strategy. Exploration of the P2 heterocyclic region, the P2 to P4 linker, and the P1 side chain of this class of
