Enantioselective synthesis of an HCV NS5a antagonist

Ian K Mangion; Cheng-yi Chen; Hongmei Li; Peter Maligres; Yonggang Chen; Melodie Christensen; Ryan Cohen; Ingyu Jeon; Artis Klapars; Shane Krska; Hoa Nguyen; Robert A Reamer; Benjamin D Sherry; Ilia Zavialov

doi:10.1021/ol500971c

Enantioselective synthesis of an HCV NS5a antagonist

Org Lett. 2014 May 2;16(9):2310-3. doi: 10.1021/ol500971c. Epub 2014 Apr 11.

Authors

Ian K Mangion¹, Cheng-yi Chen, Hongmei Li, Peter Maligres, Yonggang Chen, Melodie Christensen, Ryan Cohen, Ingyu Jeon, Artis Klapars, Shane Krska, Hoa Nguyen, Robert A Reamer, Benjamin D Sherry, Ilia Zavialov

Affiliation

¹ Department of Process Chemistry, Merck and Co., Inc. , P.O. Box 2000, Rahway, New Jersey 07065, United States.

PMID: 24724971
DOI: 10.1021/ol500971c

Abstract

A concise, enantioselective synthesis of the HCV NS5a inhibitor MK-8742 (1) is reported. The features of the synthesis include a highly enantioselective transfer hydrogenation of an NH imine and a dynamic diastereoselective transformation. The synthesis of this complex target requires simple starting materials and nine linear steps for completion.

MeSH terms

Benzofurans / chemical synthesis*
Benzofurans / chemistry
Hydrogenation
Imidazoles / chemical synthesis*
Imidazoles / chemistry
Imines / chemistry
Molecular Structure
Stereoisomerism
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Benzofurans
Imidazoles
Imines
Viral Nonstructural Proteins
elbasvir
NS-5 protein, hepatitis C virus