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

Participants

Reaction Conditions

Reaction Steps

In step 6A-5, palladium tetrakis (25 mg, 0.02 mmol) was added to a solution of 3-bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (6-6) (77 mg, 0.23 mmol), sodium carbonate (85 mg, 0.81 mmol), and 4-cyanophenylboronic acid (60 mg, 0.41 mmol) in 2 mL of dioxane and 0.5 mL of water contained in a microwave reaction tube. The resulting solution was heated in a microwave for 25 minutes at 150° C. and the yellow slurry was cooled to room temperature and filtered through a 0.2 μm nylon frit. The solvent was removed from the mother liquor and the remaining residue was reconstituted in methanol and further purified by preparative LC/MS. The desired fractions were dried to yield the desired product as a racemic mixture, which was then purified by chiral LC to yield (R)-4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile (6-7) as a chiral pure white solid along with (S)-4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile as a chiral pure white solid.

Provenance & Evidence