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

  作者 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  
  选自 期刊  Journal of Organic Chemistry;  卷期  2011年76-19;  页码  7804-7815  
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[摘要]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.

 
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