Synthesis of Vaniprevir (MK-7009): Lactamization To Prepare a 22-Membered Macrocycle
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- 作者：Zhiguo J. Song ; 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
- 刊名：Journal of Organic Chemistry
- 出版年：2011
- 出版时间：October 7, 2011
- 年：2011
- 卷：76
- 期：19
- 页码：7804-7815
- 全文大小：1121K
- 年卷期：v.76,no.19(October 7, 2011)
- ISSN：1520-6904
文摘
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.