Development of a Bulk Enabling Route to Maraviroc (UK-427,857), a CCR-5 Receptor Antagonist

Abstract

A bulk enabling synthesis of the CCR-5 receptor antagonist, Maraviroc (UK-427,857) ( 1 ), is presented. Synthesis of the three key fragments, β-amino ester 3, 4,4-difluorohexanecarboxylic acid ( 2 ), and 1,3,4-triazole-substituted tropane fragment 4 are described. Coupling strategies for these fragments are discussed and described, including synthetic challenges, protection strategies, impurity generation, and final scale-up of the developed route to 1 .