Sulfuric Acid → HCID 178500118, compound

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere methyl 2-[4-(6-amino-5-nitro-2-pyridyl)-5-(2,4-difluorophenyl)-1H-imidazol-2-yl]-2-methyl-propanoate methanesulfonate (68.9 g, 134.2 mmol), dimethyl sulfoxide (275.5 mL), THF (116.2 mL), and water (303.2 mL) are added and the mixture is stirred at 20-25° C. Sulfuric acid 95-97% (93.6 mL) is added dropwise to the reaction mixture and the temperature is maintained below 30° C. The reaction mixture is cooled to 0-5° C., and a solution of sodium nitrite (18.6 g, 0.27 mmol) in water (82.7 mL) is added at 0-10° C. The reaction mixture is stirred for 1-2 h at this temperature. 10% Aqueous sodium dihydrogen phosphate (930.0 mL) is added dropwise to maintain the temperature below 25° C. The resulting mixture is stirred for 2-3 h at 15-25° C., and the solids are collected by filtration. The filtercake is washed with water (138 mL) and the solids are transferred into a reaction vessel. Methanol (566 mL) is added and the mixture is heated to 60-65° C. for 1-2 h. Water (87 mL) is added and the mixture is stirred at 60-65° C. for 1-2 h. The reaction mixture is cooled to 15-25° C. and the mixture is stirred at 15-25° C. for 2-4 h. The mixture is filtered, the cake is washed with methanol (87 mL), and is dried under a vacuum below 70° C. to provide the title compound as a yellow solid (53.28 g, 93%).

Provenance & Evidence