反应详情

温度

95 °C

Take up 3-bromo-7-thiazol-2-yl-imidazo[1,2-a]pyridine (1.07 g, 3.82 mmol) and 4-aminophenylboronic acid hydrochloride (793 mg, 4.58 mmol, 1.2 eq) in 15 mL of dioxane and 7 mL of 2 N aqueous sodium carbonate, then deoxygenate with vacuum/nitrogen bubbling as described above. Add tetrakis (triphenylphosphine) palladium (0) (221 mg, 0.19 1 mmol, 0.05 eq), fit the reaction flask with a reflux condenser and heat the mixture to 95° C. with stirring under nitrogen for approximately 16 hours. Cool the dark brown reaction mixture, dilute with ethyl acetate (˜40 mL) and partition the layers in a separatory funnel. Dry the organic layer over solid magnesium sulfate, filter, then apply to a 10 g SCX Mega Bond-Elut™ cartridge (Varian) prewashed with 100 mL 1:1 CH2Cl2:MeOH. After loading, wash the cartridge with another 200-250 mL of the CH2Cl2:MeOH solution, then elute the product with 100 mL of CH2Cl2:2 M NH3-MeOH, concentrate to a brown-orange oil, and purify via flash chromatography with a gradient of 0 to 5% methanol in dichloromethane. Pool the clean fractions and concentrate to provide 750 mg (67%) of the title compound as a yellow-brown solid after drying. MS (ES) m/z 293 (M+1).

1. customdeoxygenate with vacuum/nitrogen bubbling
2. temperatureCool the dark brown reaction mixture
3. custompartition the layers in a separatory funnel
4. dry with materialDry the organic layer over solid magnesium sulfate
5. filtrationfilter
6. washwash the cartridge with another 200-250 mL of the CH2Cl2
7. washMeOH solution, then elute the product with 100 mL of CH2Cl2
8. concentration2 M NH3-MeOH, concentrate to a brown-orange oil
9. custompurify via flash chromatography with a gradient of 0 to 5% methanol in dichloromethane
10. concentrationconcentrate