Sodium Carbonate → 4-(6-(2-(2,5-Difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile

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Reaction Conditions

Reaction Steps

In step 12-1, [Pd(Dppf)2]Cl2 (90 mg, 0.11 mmol), sodium carbonate (0.41 g, 3.9 mmol), and 4-cyano-3-fluorophenylboronic acid (0.36 g, 2.2 mmol) were added to a solution of 3-bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (6-6) (0.42 g, 1.1 mmol) in 3 mL of dioxane and 1 mL of DI water. The reaction mixture was heated in a microwave for twenty minutes at 150° C., and the slurry was then cooled to room temperature and filtered through a 0.2 μM nylon fit. The solvent was removed from the mother liquor and the remaining residue was reconstituted in dichloromethane (DCM). This solution was loaded onto a 12 g silica gel column and eluted using a 0-10% methanol in DCM gradient over 30 minutes. The solvent was removed from the desired fractions to yield 4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile. m/z=420.2 [M+1].

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