反应详情

A mixture of 4-iodo-6-bromoquinoline (1.18 g, 3.53 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (1 g, 3.53 mmol), dichloro-[1,1′bis(diphenylphosphino) ferrocene]palladium (II) dichloromethane adduct (177 mg, 0.176 mmol), 2 M potassium carbonate (5 mL), in dioxane (15 mL) was heated at 100° C. for 1.5 h and cooled to room temperature. LCMS indicated the reaction was finished. To the finished reaction was added 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinesulfonamide (1.2 g, 4 mmol), Dichloro-[1,1′bis(diphenylphosphino) ferrocene]Palladium (II) dichloromethane adduct (177 mg, 0.176 mmol), and 2 M potassium carbonate (5 mL). The reaction was heated at 100° C. for 3 h and cooled to room temperature. The dioxane and water were separated and the dioxane evaporated to get the crude product which was purified on silica gel eluting with ethyl acetate/methanol, 0-3% methanol. The product which crystallized from ethyl acetate contained ethyl acetate. The ethyl acetate was removed by dissolving the product in a excess of acetone and evaporation. Residual acetone was then removed by triturating with distilled water at 60 deg followed by filtration and drying under vacuum. A yield of the title compound (540 mg, 31%) was obtained. MS (ES)+ m/e 484 [M+H]+.

1. customTo the finished reaction
2. temperatureThe reaction was heated at 100° C. for 3 h
3. temperaturecooled to room temperature
4. customThe dioxane and water were separated
5. customthe dioxane evaporated
6. customto get the crude product which
7. customwas purified on silica gel eluting with ethyl acetate/methanol, 0-3% methanol
8. customThe product which crystallized from ethyl acetate
9. customThe ethyl acetate was removed
10. dissolutionby dissolving the product in a
11. customexcess of acetone and evaporation
12. customResidual acetone was then removed
13. distillationby triturating with distilled water at 60 deg
14. filtrationfollowed by filtration
15. customdrying under vacuum