Development of a One‐Pot Borylation/Suzuki Cross‐Coupling Using Tetrahydroxydiboron en Route to Remibrutinib

A one‐pot borylation/Suzuki cross‐coupling using tetrahydroxydiboron has been developed for the synthesis of the active pharmaceutical ingredient 6 . This process is characterized by the utilization of remarkably low loadings of Pd‐catalyst, the avoidance of pinacol hydrate precipitates in the final product, and the use of methanol as a green alcoholic solvent over both steps. This process is applied to Remibrutinib (LOU064) and addresses some of the previous problems associated with the use of bis(pinacolato)diboron as a borylating reagent, thus becoming a more atom‐efficient and cost‐effective approach.