反应详情

温度

100 °C

To 1-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (77 mg, 0.18 mmol), 2-(3-Bromo-2-methyl-phenyl)-6-dimethylamino-3,4-dihydro-2H-isoquinolin-1-one (63 mg, 0.18 mmol), potassium phosphate (74 mg, 0.35 mmol), 2-(dicyclohexylphoshphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (5.0 mg, 0.010 mmol), and bis(dibenzylidineacetone)palladium(0) (3.0 mg, 0.0052 mmol) was added 4 mL of degassed 1:3 water/n-butanol. The headspace of the vessel was evacuated and backfilled with argon 4 times. This was heated at 100° C. for 110 minutes. This was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution 2 to 5% methanol/dichloromethane) to yield 6-Dimethylamino-2-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-3,4-dihydro-2H-isoquinolin-1-one (33 mg, 0.056 mmol). MS (ESI) 593.3 (M+H)+.

1. customof degassed 1:3 water/n-butanol
2. customThe headspace of the vessel was evacuated
3. customThis was partitioned between ethyl acetate and water
4. washThe ethyl acetate layer was washed with brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated in vacuo
7. custompurified by flash chromatography (gradient elution 2 to 5% methanol/dichloromethane)