反应详情

温度

75 °C

To a solution of 5-chloro-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-6-(6-trifluoromethyl-pyridin-2-ylmethoxy)-3H-pyrimidin-4-one of Step C (50 mg, 0.11 mmol) in acetonitrile (1 mL) was added 2-hydroxy-2-methylpropionamidine HCl (23 mg, 0.16 mmol) and potassium carbonate (45 mg, 0.33 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 (19 mg, 32% yield). MS (M+H): 546; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.15 (s, 3H), 2.21 (s, 3H), 5.69-5.78 (m, 2H), 7.56-7.59 (m, 2H), 7.66 (d, J=7.43 Hz, 1H), 7.82 (d, J=7.82 Hz, 1H), 7.94-8.00 (m, 2H), 8.14 (d, J=7.43 Hz, 1H), 8.78 (d, J=5.08 Hz, 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)