An Eco-Friendly Industrial Fischer Indole Cyclization Process

We report an optimized Fischer indole cyclization process using toluene as both the cosolvent and extraction solvent. The process produced zero wastewater, and a high-purity product was obtained without further purification. The optimized route was applied to synthesize key intermediates of two MmpL3 inhibitors, NITD-304 and NITD-349, on a multi-kilogram scale.