Streamlined Scalable Synthesis of 4-Bromo-6-chloro-5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole: A Building Block for KRAS Inhibitors.

A practical, concise, and scalable synthetic route has been developed for the KRAS inhibitor building block 4-bromo-6-chloro-5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole. The route comprises six steps, four of which are telescoped, and requires no column chromatography purification. This optimized process has been successfully implemented for the large-scale production of building block 1 at up to ∼200 kg with an overall yield of 61.68%.