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 sealable vial was charged with N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-3-(difluoromethoxy)benzenesulfonamide (765.9 mg, 1663 μmol), N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (291.8 mg, 1385 μmol, Example 1, Step 4), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (53.76 mg, 96.98 μmol, Strem Chemical, Inc., Newburyport, Mass.) and sodium carbonate (293.7 mg, 2771 μmol). The vial was sealed with a septum cap and dioxane (2 mL, 1 M) and water (1 mL, 2 M) were added via syringe. The mixture was sparged 10 min with N2, then heated at 90° C. for 18 h. The solution was cooled to rt, and concentrated for purification by MPLC (CombiFlash® Companion®, Teledyne Isco, Lincoln, Nebr.). The crude residue was taken up in minimal CH2Cl2/MeOH and absorbed 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 N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (584.0 mg, 82.83% yield) as a brown solid. LCMS (ESI) m/z: 509.1 (M+1).

Provenance & Evidence