反应详情

温度

100 °C

Bubble nitrogen through a suspension of 2-(tert-butyl)-4-(4-fluorophenyl)-5-bromooxazole (2.0 g, 9.1 mmol), 1-isobutyl-2-amino-6-bromobenzimidazole (4.98 g, 18.6 mmol), cesium carbonate (6.06 g, 18.6 mmol), palladium(II) acetate (0.201 g) and triphenylphosphine (1.2 g, 4.5 mmol) in 15 mL dimethylformamide for 3 minutes. Stir the reaction mixture at 100° C. for 18 hours. Cool to room temperature. Partition between ethyl acetate and saturated aqueous sodium chloride. Wash the organic layer with saturated aqueous sodium chloride, dry over sodium sulfate, and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with 50:1 dichloromethane:methanol containing 2M ammonium hydroxide to provide 1-isobutyl-2-amino-6-(2-(tert-butyl)-4-(4-fluorophenyl)oxazol-5-yl)-1H-benzimidazole (1 g, 27%). This material is treated with methanesulfonic acid as previously described to provide the title compound.

1. customBubble nitrogen
2. temperatureCool to room temperature
3. customPartition between ethyl acetate and saturated aqueous sodium chloride
4. washWash the organic layer with saturated aqueous sodium chloride
5. dry with materialdry over sodium sulfate
6. concentrationconcentrate under reduced pressure
7. washeluting with 50:1 dichloromethane