Asymmetric Synthesis of MK-7845, an Investigational Treatment for COVID-19

An enantioselective seven-step synthesis of MK-7845, an investigational protease inhibitor for the treatment of COVID-19 is described. Key features of the synthesis include the preparation of a chiral isonitrile intermediate utilizing an asymmetric ruthenium-catalyzed reductive amination reaction to set the key amine stereocenter; a highly enantioselective, biocatalytic oxidation reaction with a monoamine oxidase enzyme to furnish a bicyclic imine; and, finally, the union of these fragments via a diastereoselective three-component Joullié-Ugi coupling reaction en route to MK-7845.