Dimethylformamide → N-(6-(6-chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

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Reaction Conditions

Reaction Steps

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).

Provenance & Evidence