反应详情

温度

100 °C

To 1-Ethyl-3-[1-methyl-2-oxo-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2-dihydro-pyridin-3-yl]-urea (50 mg, 0.16 mmol), acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-benzyl ester (65 mg, 0.16 mmol), potassium phosphate (66 mg, 0.31 mmol), 2-(dicyclohexylphoshphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (4.4 mg, 0.0092 mmol), and bis(dibenzylidineacetone)palladium(0) (2.6 mg, 0.0045 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 2 hours. This was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. This was dissolved in 2 mL tetrahydrofuran, 1 mL methanol, and 1 mL water. 1M aq. lithium hydroxide solution (0.47 mL, 0.47 mmol) was added. After stirring for 3 hours, the resulting mixture 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 preparative TLC (5% methanol/dichloromethane) to yield 1-{5-[3-(6-Dimethylamino-1-oxo-1H-isoquinolin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl}-3-ethyl-urea (33 mg, 0.068 mmol). MS (ESI) 488.1(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. dissolutionThis was dissolved in 2 mL tetrahydrofuran
8. customthe resulting mixture was partitioned between ethyl acetate and water
9. washThe ethyl acetate layer was washed with brine
10. dry with materialdried over anhydrous magnesium sulfate
11. concentrationconcentrated in vacuo
12. custompurified by preparative TLC (5% methanol/dichloromethane)