Sodium Carbonate → N-(6-(6-Chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-3-(difluoromethoxy)benzenesulfonamide (1.1 g, 2.4 mmol), N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (0.25 g, 1.2 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (87 mg, 0.012 mmol, Strem Chemical, Inc., Newburyport, Mass.), sodium carbonate (0.25 g, 2.4 mmol), and dioxane-H2O (5 mL, 4:1). Ar was bubbled in the solution for 1 minute. The reaction mixture was sealed and heated at 100° C. for 2 h and then was concentrated in vacuo. Purification by silica gel chromatography (5-20% MeOH/CH2Cl2), followed by further purification by preparative HPLC (Phenomenex Synergi 4μ MAX-RP 150×21.2 mm, 30 to 80% CH3CN/H2O, 0.1% TFA, over 12 min) (Phenomenex, Torrance, Calif.) provided the title compound (0.18 g, 30% yield) as a tan solid. MS (ESI positive ion) m/z: 524 (M+1). 1H NMR (400 MHz, MeOH-d): δ ppm 2.22 (s, 3H), 6.88 (t, J=73.07 Hz, 1H), 7.43 (dd, J=8.12, 1.86 Hz, 1H), 7.54-7.62 (m, 2H), 7.63-7.68 (m, 1H), 7.74 (d, J=9.59 Hz, 1H), 7.98 (d, J=9.59 Hz, 1H), 8.44 (s, 1H), 8.57 (d, J=2.15 Hz, 1H), 8.82 (d, J=2.35 Hz, 1H).

Provenance & Evidence