Schering Corporation

Merck Sharp + Dohme Corp.

Tetsuo Iwama

Anantha R Sudhakar

Jeonghan Park

George S K Wong

Minzhang Chen

Ilia A Zavialov

George S Wong

Michael D Green

Hong-Chang Lee

Hoa N Nguyen

Vilas Hareshwar Dahanukar

Juergen Weber

Weidong Tong

Ingyu Jeon

Cecilia A Orr

Jennifer Ann Vance

George SK Wong

Jennifer A Vance

This disclosure relates to novel processes useful in the purification of keto-amide, ketone and aldehyde compounds, which are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease and have application in the treatment of conditions caused by HCV. The processes of this disclosure relate to purification via a bisulfite adduct. In particular, this disclosure relates to processes useful in the purification of the keto-amide compound of Formula I, (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]-amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide: 

Bisulfite purification of an alpha-keto amide

The present invention relates also to a process for the preparation of intermediate compounds useful in preparing the compounds of Formula (I) using the process of Scheme (II). 

Process for preparing (1R,2S,5S)-N-[(1S)-3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3-[(2S)-2-[[[(1,1-dimethylethyl)amino]-carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide

In one embodiment, the present application relates to a process of making a compound of formula I: and to certain intermediate compounds that are made within the process of making the compound of formula I.

Process and intermediates for the preparation of (1R,2S,5S)-3-azabicyclo[3,1,0]hexane-2-carboxamide, N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3-[(2S)-2-[[[1,1-dimethylethyl]amino]carbonylamino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl

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Scotch Plains, NJ, United States of America

Tetsuo Iwama