Regioselective Synthesis of Pyrazolo[1,5-<i>a</i>]pyridine via TEMPO-Mediated [3 + 2] Annulation–Aromatization of<i>N</i>-Aminopyridines and α,β-Unsaturated Compounds
Amu Wang, Yazhou Liu, Zhongke Shen, Zeen Qiao, Xiaofeng Ma
Abstract
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.
Topics & Concepts
ChemistryAromatizationAnnulationRegioselectivityAminopyridinesPyridineYield (engineering)Combinatorial chemistryOrganic chemistryCatalysisMaterials scienceMetallurgySynthesis and biological activitySynthesis and Biological EvaluationMulticomponent Synthesis of Heterocycles