DMAPO/Boc2O-Mediated One-Pot Direct N1-Acylation of Indazole with Carboxylic Acids: A Practical Synthesis of N1-Functionalized Alkyl Indazoles

This report describes the one-pot direct N-acylation of indazole with carboxylic acids using our previously developed 4-(N,N-dimethylamino)pyridine N-oxide (DMAPO)/di-tert-butyl dicarbonate (Boc(2)O) system. This simple system provides N1-acyl indazoles in high yield with high N1 selectivities and does not require the use of activated derivatives of carboxylic acids or high temperatures. This new method exhibits a wide substrate scope (>40 examples). In addition, a new synthesis of N1-functionalized alkyl indazoles utilizing N1-acyl indazoles as starting materials was achieved. This stepwise protocol is useful for the selective synthesis of structurally diverse N1-functionalized alkyl indazoles, which are difficult to synthesize by other methods such as the Mitsunobu reaction and classical S(N)2 alkylation of indazole.