反应详情

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 247, 378.0 g, 0.761 moles) was dissolved in dimethylsulphoxide (1.9 L). Potassium carbonate (117.8 g, 0.8524 moles) was added and stirred to give a suspension to which was added 2-pyridazin-4-yl-4-(trifluoromethyl)phenol (Preparation 712, 182.8 g, 0.761 moles) in one portion. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate (2.7 L) and aqueous sodium hydroxide solution (2.5 L of 1 molar). The organic phase was washed with water (2×2 L) and then saturated aqueous sodium chloride solution (250 mL). The solution was concentrated in vacuo to give the crude title product. The crude product was purified by column chromatography on silica gel (2 Kg) eluting with ethyl acetate/heptane (3:1). The cleanest fractions were combined and the solvents removed in vacuo to give the title compound as a dark red foam, (440 g). This material was dried in vacuo at 45° C. for 48 hours to give the title compound as a red solid (400 g).

1. customto give a suspension to which
2. stirringThe reaction mixture was stirred at room temperature for 18 hours
3. customThe reaction mixture was partitioned between ethyl acetate (2.7 L) and aqueous sodium hydroxide solution (2.5 L of 1 molar)
4. washThe organic phase was washed with water (2×2 L)
5. concentrationThe solution was concentrated in vacuo
6. customto give the crude title product
7. customThe crude product was purified by column chromatography on silica gel (2 Kg)
8. washeluting with ethyl acetate/heptane (3:1)
9. customthe solvents removed in vacuo