Use of Catalysis for API Manufacturing

Harnessing the Power of Catalysis for the Synthesis of CRTH2 Antagonist MK-1029

“…While significant synthetic efforts were previously undertaken for the structurally similar MK-7246, the presence of a fluorine atom on the indole and a 1,5-disubstituted 1,2,3-triazole side chain in MK-1029 necessitated the investigation of alternative chemistry to address critical bond disconnections. In considering a disconnection strategy for MK-1029, the cornucopia of catalytic methods developed over the last 20 years provided a diverse toolkit that was well-suited for developing an efficient and sustainable synthesis . Herein we present the first Good Manufacturing Practice (GMP) delivery route toward MK-1029, which incorporates five unique catalytic transformations, specifically (1) imine-Heck reaction (palladium), (2) N–H insertion (iridium), (3) asymmetric ketone reduction (ketoreductase), (4) Sonogashira reaction (palladium), and (5) azide–alkyne cycloaddition (ruthenium).…”