Regioselective Synthesis of Pyrazolo[1,5- a ]pyridine via TEMPO-Mediated [3 + 2] Annulation-Aromatization of N -Aminopyridines and α,β-Unsaturated Compounds.

A TEMPO-mediated [3 + 2] annulation-aromatization protocol for the preparation of pyrazolo[1,5- a ]pyridines from N -aminopyridines and α,β-unsaturated compounds was developed. The procedure offered multisubstituted pyrazolo[1,5- a ]pyridines in good to excellent yield with high and predictable regioselectivity. The modification of marketed drugs including Loratadine, Abiraterone, and Metochalcone, and a one-pot three-step gram scale synthesis of key intermediate for the preparation of Selpercatinib were demonstrated. Mechanism studies show that TEMPO serves both as a Lewis acid and as an oxidant.