Water → 3-Bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine

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Reaction Conditions

Reaction Steps

In step 6A-4, 2-(2,5-difluorophenyl)pyrrolidine (6-5) (1.7 g, 9.3 mmol) was added to a solution of 3-bromo-6-chloroimidazo[1,2-b]pyridazine (11-1) (1.1 g, 230.92) and potassium fluoride (2.7 g, 46 mmol) in DMSO (10 mL). The resulting solution was heated to 130° C. and stirred over-night. The resulting dark orange slurry was cooled to room temperature, poured into 50 mL of DI water and extracted with ethyl acetate (3×150 mL). The ethyl acetate was dried with sodium sulfate and then removed to yield an orange solid. This solid was reconstituted with minimal amounts of dichloromethane (DCM) and purified using a silica gel column (40 g, ISCO) and a 0-5% gradient of methanol:DCM over a 20 minute period followed by 5% methanol for an additional 10 minutes. The solvent was removed from the desired fractions to yield 3-bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (6-6) as a light yellow solid. m/z=379.2 [M+1].

Provenance & Evidence