反应详情

温度

75 °C

To a solution of 5-chloro-6-(6-fluoro-pyridin-2-ylmethoxy)-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-3H-pyrimidin-4-one of Step D (78 mg, 0.19 mmol) in acetonitrile (3 mL) was added 2-hydroxy-2-methylpropionamidine HCl (39 mg, 0.28 mmol) and potassium carbonate (78 mg, 0.57 mmol) and the slurry heated at 75° C. for eighteen hours. After cooling to room temperature the reaction was 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 yellow oil (29 mg, 31% yield). MS (M+H): 496; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.15 (s, 3H), 2.21 (s, 3H), 5.54-5.65 (m, 2H), 6.90 (d, J=7.83 Hz, 1H) 7.48 (d, J=6.65 Hz, 1H), 7.55-7.57 (m, 2H), 7.85-7.93 (m, 2H), 8.14 (d, J=8.22 Hz, 1H), 8.78 (d, J=5.09, 1H).

1. temperatureAfter cooling to room temperature the reaction
2. filtrationwas filtered
3. customto remove excess salts
4. concentrationThe filtrate was concentrated
5. custompurified via normal phase chromatography (ethyl acetate/heptane)