Bromine → (S)-6-(4-bromo-3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-6-(3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (500 mg, 0.94 mmol), Fe powder (700 mg, 13 mmol), Br2 (300 μL, 5.9 mmol), and 1,2-dichloroethane (3 mL) was heated at 50° C. for 3 hours. The reaction mixture was then poured into aq. NaHSO3 solution. This was extracted into CH2Cl2. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under vacuum. Purification by silica gel chromatography (ethyl acetate in hexanes, 20% to 30%) yielded (S)-6-(4-bromo-3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (266 mg, 46%) as a white solid.

Provenance & Evidence