反应详情

温度

100 °C

A microwave vial was charged with a solution of 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.496 mmol) in DME (3 ml). Sodium carbonate (2M in water, 0.530 ml, 1.061 mmol), tetrakis(triphenylphosphine)palladium(0) (0.025 g, 0.021 mmol), and 1-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamine (0.100 g, 0.354 mmol) were added and the resulting solution was sparged with nitrogen for 5 minutes and then heated to 100° C. for 90 minutes via microwave. The vessel was then cooled to room temperature and the reaction mixture was filtered through Celite™. The filter cake was washed with ethyl acetate and the filtrate was washed with saturated sodium chloride and concentrated under reduced pressure to provide a brown oil. The crude product was added to a HPLC column and was eluted with 5-100% acetonitrile in water (0.05% TFA buffer) to provide the mono-TFA salt of 1-(4-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-((dimethylamino)methyl)pyrimidin-2-yl)phenyl)-3-cyclopropylurea (0.073 g, 49%) as a light yellow solid. MS; 423.2, M+H.

1. customthe resulting solution was sparged with nitrogen for 5 minutes
2. temperatureThe vessel was then cooled to room temperature
3. filtrationthe reaction mixture was filtered through Celite™
4. washThe filter cake was washed with ethyl acetate
5. washthe filtrate was washed with saturated sodium chloride
6. concentrationconcentrated under reduced pressure
7. customto provide a brown oil
8. washwas eluted with 5-100% acetonitrile in water (0.05% TFA buffer)