Sodium Carbonate → N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

A sealable vial was charged with N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-iodoimidazo[1,2-b]pyridazin-2-yl)acetamide (129.0 mg, 203 μmol), 4-pyridylboronic acid (30.0 mg, 244 μmol, Alfa Aesar, Ward Hill, Mass.), sodium carbonate (86.2 mg, 813 μmol), and dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (11.3 mg, 20.3 μmol, Strem Chemical, Inc., Newburyport, Mass.). The vial was sealed with a septum cap, and 1,4-dioxane (2 mL) was added under positive N2 flow followed by water (0.2 mL). The mixture was sparged with N2 for 10 min and then heated at 80° C. for 18 h. The solution was cooled to rt and absorbed directly onto a 25 g silica loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (80 g) (Teledyne Isco, Lincoln, Nebr.) using a gradient of 1% MeOH in CH2Cl2 to 10% MeOH in CH2Cl2 to afford the title compound, N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (67.0 mg, 56.3% yield) as a yellow solid. LCMS (ESI positive ion) m/z: 586 (M+1); 1H NMR (400 MHz, MeOH) δ ppm 2.21 (s, 3H); 6.61-6.97 (m, 1H); 7.33-7.40 (m, 1H); 7.48 (t, J=8.07 Hz, 1H); 7.56 (s, 1H); 7.95 (d, J=9.49 Hz, 1H); 8.06 (d, J=4.99 Hz, 2H); 8.17 (d, J=9.49 Hz, 1H); 8.67-8.74 (m, 2H); 8.80 (d, J=1.96 Hz, 2H).

Provenance & Evidence