反应详情

温度

85 °C

To a solution of the 5-chloro-6-(2,4-difluoro-benzyloxy)-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-3H-pyrimidin-4-one of Step D (20 mg, 0.05 mmol) in acetonitrile (1 mL) as added 2-hydroxy-2-methylpropionamidine HCl (9 mg, 0.07 mmol) and potassium carbonate (20 mg, 0.15 mmol) and the slurry was heated at 85° C. for eighteen hours. The reaction was returned to ambient temperature and filtered to remove excess salts. The filtrate was concentrated and purified via normal phase chromatography (ethyl acetate/heptane) to provide the title compound as a white solid (12.5 mg, 50% yield). MS (M+H): 513; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.65 (s, 6H), 2.18 (s, 3H), 2.21 (s, 3H), 5.51-5.60 (m, 2H), 6.88-6.97 (m, 2H), 7.55-7.60 (m, 3H), 7.93 (s, 1H), 8.14 (d, J=8.61 Hz, 1H), 8.78 (d, J=5.09, 1H).

1. customwas returned to ambient temperature
2. filtrationfiltered
3. customto remove excess salts
4. concentrationThe filtrate was concentrated
5. custompurified via normal phase chromatography (ethyl acetate/heptane)