Regioselective synthesis of 5-azaindazoles based on the intramolecular amination reaction of 5-acyl-4-pyridones with hydrazines†‡

The labile tautomerism of N-unsubstituted 5-acyl-4-pyridones, which exist in the form of 4-pyridone or 4-hydroxypyridine depending on the solvent, has been demonstrated. This equilibrium determines the reactivity of pyridones and their ability to undergo substitution reactions of the OH group. A regioselective and convenient method for the construction of functionalized pyrazolo[4,3-c]pyridines (30–93%) based on the intramolecular amination reaction of 4-pyridones with hydrazines has been developed. The heterocyclization of N-alkyl-4-pyridones is accompanied by a dealkylation reaction. The reaction with hydroxylamine as a nucleophile can be used for the construction of the isoxazolo[4,5-c]pyridine core. Methods have been developed for further modification of the 5-azaindazole fragment via alkylation and decarboxylation. The antiproliferative properties of the prepared 5-azaindazoles were studied in relation to cancer (Hep-2, MCF) and normal cell lines (FH and Vero), and the compounds demonstrated relevant biological activity for further design of new molecules for antitumor therapy.