反应详情

温度

90 °C

To a 25-mL, round-bottomed flask was added N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.15 g, 0.41 mmol), bis(pinacolato)diboron (0.16 g, 0.62 mmol), potassium acetate (0.16 g, 1.6 mmol) and 1,4-dioxane (4.0 mL). The mixture was carefully evacuated and backfilled with N2. To the solution was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (0.030 g, 0.041 mmol). The mixture was carefully evacuated and backfilled with N2 again then stirred at 90° C. for 6 h. The reaction mixture was cooled to rt and treated with DMF (4.0 mL, 52 mmol), N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (0.055 g, 0.26 mmol) and 2.0 M aq. sodium carbonate (0.78 mL, 1.6 mmol). The mixture was carefully evacuated and backfilled with N2. To the solution was added trans-dichlorobis(triphenylphosphine)palladium(II) (0.018 g, 0.026 mmol) and then the solution was carefully evacuated and backfilled with N2 again. The mixture was stirred at 90° C. for 16 hours then poured into aq. NaCl (100 mL) and extracted with 25% iPrOH/CHCl3 (3×75 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to remove the DMF. The solution was then taken up in MeOH/CH2Cl2 and concentrated onto silica. Purification by silica gel chromatography (0.5 to 5.0% MeOH (2 M in NH3)/CH2Cl2) afforded the title compound as a yellow solid. MS (ESI pos. ion) m/z: 461 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.96 (s, 1H), 10.57 (s, 1H), 8.92 (d, J=2.2 Hz, 1H), 8.31-8.36 (m, 2H), 8.13 (d, J=9.4 Hz, 1H), 7.80-7.88 (m, 3H), 7.39-7.48 (m, 2H), 2.13 (s, 3H).

1. customThe mixture was carefully evacuated
2. customThe mixture was carefully evacuated
3. temperatureThe reaction mixture was cooled to rt
4. customThe mixture was carefully evacuated
5. customthe solution was carefully evacuated
6. stirringThe mixture was stirred at 90° C. for 16 hours
7. additionthen poured into aq. NaCl (100 mL)
8. extractionextracted with 25% iPrOH/CHCl3 (3×75 mL)
9. dry with materialThe combined extracts were dried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customto remove the DMF
12. concentrationconcentrated onto silica
13. customPurification by silica gel chromatography (0.5 to 5.0% MeOH (2 M in NH3)/CH2Cl2)