Development of a Synthesis Process for a Novel HCV NS5A Inhibitor, Emitasvir

A new approach to the synthesis of Emitasvir (DAG181), a small molecule hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, is described. Enantioselective enzymatic desymmetrization with hydrolases in the synthetical approach can significantly avoid the loss of chiral raw materials in the resolution process. The synthesis route is further optimized and scaled-up to establish a new process that is applied to the preparation of kilogram scales of target active pharmaceutical ingredients (APIs). Compared with our initial process, the overall yield of target API was dramatically improved from 17 to 40%.