Synthesis and Process Optimization of 1‐(tert‐Butoxycarbonyl)‐7‐Fluoro‐3‐Methyl‐1H‐Indazole‐5‐Carboxylic Acid

Indazole and its derivatives, prominent nitrogen‐containing heterocycles, have attracted significant attention due to their remarkable biological activities and therapeutic potential, including antitumor, analgesic, and anti‐inflammatory properties. Nevertheless, significant challenges remain in developing efficient synthetic routes to these compounds. In this study, 1‐( tert ‐butoxycarbonyl)‐7‐fluoro‐3‐methyl‐1H‐indazole‐5‐carboxylic acid, a fluorine‐containing indazole pharmaceutical intermediate, was synthesized from commercially available 2,3‐difluorobenzoic acid via a sequence of reactions, including bromination, amidation, Grignard reaction, cyclization, amine protection, Suzuki coupling, and oxidation. This synthetic strategy afforded the target compound efficiently while simultaneously improving catalytic performance, broadening the substrate scope, and enhancing the overall practicality to a notable extent. These findings provide a robust platform for the synthesis of novel indazole derivatives and the investigation of their biological activities.