Download PDF
Synfacts 2014; 10(8): 0783
DOI: 10.1055/s-0034-1378399
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of MK-8742

Contributor(s):
Philip Kocienski
Mangion IK, * Chen C.-y. * et al. Merck and Co., Inc., Rahway, USA
Enantioselective Synthesis of an HCV NS5a Antagonist.

Org. Lett. 2014;
16: 2310-2313
CrossrefSearch in Google Scholar
Further Information

Publication History

Publication Date:
18 July 2014 (online)

 
 PDF Download Permissions and Reprints

Key words

MK-8742 - NS5a inhibitors - asymmetric transfer hydrogenation - crystallization-induced diastereoselection

Significance

MK-8742 is an inhibitor of the hepatitis C nonstructural protein NS5a. Key steps in the synthesis depicted are (1) the asymmetric transfer hydrogenation of the imine B and (2) the crystallization-induced diastereoselection in the formation of the N,O-acetal F.


#

Comment

The dr in the N,O-acetal formation E → F (7:1) improved to >99:1 by conducting the reaction in MeCN as the solvent and with TFA as the acid catalyst. KMnO4 effects the oxidation of the indoline F without racemization of the N,O-­acetal, providing indole G in 83% yield and with >99% ee.


#
#


   Permissions and Reprints