Processes and intermediates for preparing a macrocyclic protease inhibitor of HCV

US9227965B2 · kind B2 · utility

Assignee

• Janssen Pharmaceuticals, Inc. · BE

Inventors

• Andras Horvath · Turnhout, BE
• Dominique Paul Michel Depré · Hamme-Mille, BE
• Dominic John Ormerod · Hoogstraten, BE

Key dates

• Filing date: Sep 21, 2012
• Grant date: Jan 5, 2016
• Expiry date: Sep 21, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D453/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Disclosed is a process for the preparation of a cinchonidine salt of formula (IV) via an aqueous solution of a racemic 4-hydroxy-1,2-cyclopentanedicarboxylic acid, which is subjected to cyclization without removing water, by the addition of a water-miscible organic solvent to the aqueous solution and, again without removing water, adding cinchonidine to the aqueous-organic solvent solution so as to obtain the cinchonidine salt of the lactone acid. The cinchonidine salt is allowd to crystallize so as to obtain the enantiomerically purified crystalline lactone acid cinchonidine salt (IV). The enantiomerically pure salt is an intermediate in the synthesis of HCV inhibitor compound of formula (I).