1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-(2,2-difluorocyclopropyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

Participants

Reaction Conditions

Reaction Steps

To a mixture of 7-(1-methyl-1H-pyrazol-4-yl)-5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (200 mg; 0.754 mmol) and DBU (56 μL; 0.37 mmol) in acetonitrile (10 mL) was added 3-(2,2-difluorocyclopropyl)acrylonitrile (0.75 mmol). The mixture was stirred in a sealed vial at 50° C. for 24 hours. Further 3-(2,2-difluorocyclopropyl)acrylonitrile (0.4 mmol) was added and the mixture was stirred for a further 24 hours at 50° C. The solvent was removed under reduced pressure and the material was purified on silica gel, eluting with methylene chloride/6% ammonium hydroxide in methanol (50:1 to 15:1) to give 3-(2,2-difluorocyclopropyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile (160 mg) as a mixture of diastereoisomers. MS (apci) m/z=395.1 (M+H).

Provenance & Evidence