(R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-urea → (R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Participants

Reaction Steps

A solution of (R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-urea (380 mg, 0.76 mmol) (from Example 38d supra) in tetrahydrofuran (10 mL) was treated at room temperature with potassium tert-butoxide (160 mg, 1.14 mmol) (Aldrich). The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue (395 mg, yellow oil) was purified by flash chromatography to give (R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a colorless oil. (Yield 102 mg, 30%).

Provenance & Evidence