Ring-Closing Metathesis on Commercial Scale: Synthesis of HCV Protease Inhibitor Simeprevir

被引：15

作者：

Horvath, Andras ^{[1
]}

Depre, Dominique ^{[1
]}

Vermeulen, Wim A. A. ^{[1
]}

Wuyts, Stijn L. ^{[1
]}

Harutyunyan, Syuzanna R. ^{[1
,2
]}

Binot, Gregori ^{[1
,3
]}

Cuypers, Jef ^{[1
]}

Couck, Wouter ^{[1
]}

Van den Heuvel, Dirk ^{[1
]}

机构：

[1] Janssen Pharmaceut NV, 30 Turnhoutseweg, B-2340 Beerse, Belgium

[2] Univ Groningen, Stratingh Inst, Dept Organ Chem & Mol Inorgan Chem, Nijenborgh 4, NL-9747 AG Groningen, Netherlands

[3] Syngenta Crop Protect Monthey SA, Case Postale 400, CH-1870 Monthey 1, Switzerland

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2019年 / 84卷 / 08期

关键词：

EFFICIENT SYNTHESIS; HEPATITIS-C; MACROCYCLIZATION; TMC435;

D O I：

10.1021/acs.joc.8b03124

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The key macrocyclization step in the synthesis of simeprevir, a hepatitis C virus (HCV) antiviral drug, was studied. N-Boc substitution on the diene precursor changes the site of insertion of the metathesis catalyst and, consequently, the kinetic model of the ring closing metathesis (RCM), enabling a further increase in the macrocyclization efficiency under simulated high dilution (SHD) conditions. NMR of the inserted species of both first and second generation RCM catalysts are reported and discussed.

引用

页码：4932 / 4939

页数：8

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