Photocatalytic Direct C3-Amidation of 2H-Indazole
Chunhua Ma1, Yi Li1, Yu Ji1
1Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Research Centre of Chiral Hydroxyl Pharmaceutical, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China.
Abstract:
The direct functionalization of privileged heterocycles could efficiently and site-selectively functionalize pharmacophores to expedite the construction of a focused library for mapping druglike chemical space. A variety of biologically active 2H-indazoles have been documented, but the direct amidation of 2H-indazoles remains underdeveloped. Herein, we report the first transition metal-free 3-amidation of 2H-indazoles under photoredox conditions. Employing 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as an inexpensive photocatalyst and N-aminopyridinium salts as the amidyl radical sources, various 3-amidated 2H-indazoles were generated (22 examples, up to 90% yield). Furthermore, we also achieved photocatalytic late-stage modification of drug molecules. This protocol may represent a feasible molecular editing strategy on privileged drug scaffolds to efficiently generate a focused library.
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