反应详情

2-[(5-{{[4-(tert-Butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino}-4-iodo-1-methyl-1H-pyrazol-3-yl)oxy]ethyl acetate (Preparation 14) (1.95 g), benzeneboronic acid (0.78 g) and cesium carbonate (5.26 g) were suspended in 1,4-dioxane (50 ml) and water (5 ml). The mixture was degassed (vacuum and nitrogen atmosphere×5) and then tetrakis(triphenylphosphine)palladium(0) (50 mg) was added and the mixture degassed again. The mixture was heated at reflux for 2 hours and cooled to room temperature overnight. The reaction was quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (20 ml×3). The combined organics were washed with saturated aqueous sodium bicarbonate solution, dried with magnesium sulfate, filtered and concentrated under reduced pressure. Chromatography on silica eluting with a gradient elution of ethyl acetate:hexane (1:2 to 2:1) yielded the desired product as an off white solid (1.112 g).

1. customThe mixture was degassed (vacuum and nitrogen atmosphere×5)
2. additiontetrakis(triphenylphosphine)palladium(0) (50 mg) was added
3. customthe mixture degassed again
4. temperatureThe mixture was heated
5. temperatureat reflux for 2 hours
6. customThe reaction was quenched with saturated aqueous sodium bicarbonate solution
7. extractionextracted with ethyl acetate (20 ml×3)
8. washThe combined organics were washed with saturated aqueous sodium bicarbonate solution
9. dry with materialdried with magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. washChromatography on silica eluting with a gradient elution of ethyl acetate:hexane (1:2 to 2:1)