Lithium Hydroxide → 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

Participants

Reaction Conditions

Reaction Steps

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)+.

Provenance & Evidence