Rh-Catalyzed C–H Functionalization of the (Pyrazol-5-yl)pyridine Core of GBT-440

Abstract

The Rh-catalyzed cross dehydrogenative coupling (CDC)/alkylation of the pyrazolylpyridine unit of the GBT-440 proceeded smoothly at ambient conditions and selectively on the pyrazole unit while being directed by the pyridine. The scope of these reactions has been established by employing simple as well as conjugated olefins for CDC and various diazoesters and the TIPS-EBX reagent for alkylation. At the outset, a focused small molecule library around the bis-heterocyclic core of GBT-440 has been developed via C-H functionalization.