反应详情

温度

75 °C

To a solution of the 5-bromo-6-(2,4-difluoro-benzyloxy)-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-3H-pyrimidin-4-one of Step E (80 mg, 0.17 mmol) in acetonitrile (3 mL) was added 2-hydroxy-2-methylpropionamidine HCl (35 mg, 0.25 mmol) and potassium carbonate (70 mg, 0.50 mmol) and the slurry was heated at 75° 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 (58 mg, 61% yield). MS (M, M+2): 557, 559; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.17 (s, 3H), 2.20 (s, 3H), 5.50-5.60 (m, 2H), 6.87-6.94 (m, 2H), 7.54-7.58 (m, 3H), 7.92 (s, 1H), 8.13 (d, J=7.04 Hz, 1H), 8.77 (d, J=4.30, 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)