Synthesis of Vaniprevir (MK-7009): Lactamization To Prepare a 22-Membered Macrocycle

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. Ring closure via macrolactamization was found t...

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Veröffentlicht in:	Journal of organic chemistry 2011-10, Vol.76 (19), p.7804-7815
Hauptverfasser:	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
Format:	Artikel
Sprache:	eng
Schlagworte:	Chemistry Exact sciences and technology Heterocyclic compounds Heterocyclic compounds with only one n hetero atom and condensed derivatives Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings Organic chemistry Preparations and properties
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Beschreibung
Zusammenfassung:	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. 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.
ISSN:	0022-3263 1520-6904
DOI:	10.1021/jo2011494