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 applica- tion. 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 pharma- ceutical 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.