New Ligandless C−H Activation Procedure for The Decoration of C-3 Position of 1H-Indazole Derivatives

Arylation of heteroaromatic rings is one of the most important strategy for the chemical space exploration (e. g. applied in medicinal chemistry). In the last two decades C−H activation reactions emerged as powerful and more sustainable synthetic methods for this kind of functionalization if compared to the classical Pd-catalysed cross-coupling reactions (e. g. Suzuki, Stille, Negishi, Hiyama). A further step in the direction of greater sustainability has been done developing ligandless C−H activation procedures with higher appeal for industrial application. Among the various N-based heterocycles exploited in medicinal chemistry, there is no reported ligandless C−H activation for 1H-indazole core, although its potential pharmaceutical applications. In this work we describe a novel synthetic procedure for the direct arylation/heteroarylation of C-3 position of 1H-indazole which was optimized using the Design of Experiment (DoE) (yield up to 72 %) and confirmed a fulfilling robustness among various aryl/heteroaryl and indazole scopes.