Hydrazone C-N Coupling Route to 3-Aminoindazoles

Significance

A general two-step synthesis of ­indazoles is described. The sequence involves palladium-catalyzed C-N coupling of benzo­phenone hydrazone with ortho-bromobenzo­nitriles, followed by an acidic deprotection-­cyclization to afford the indazole products in good overall yields over two steps. In a synthetically useful observation, N1-alkylation of the intermediate hydrazone was demonstrated, which allowed the regioselective synthesis of an N1-alkylated indazole, thus avoiding protection-deprotection sequences for 3-aminoindazole. The substrate scope was moderately studied and the reaction was shown to tolerate both EDGs and EWGs. Unfortunately, no other halonitriles were tested in the reaction.