反应详情

温度

110 °C

Combine (R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (15.69 g, 1.2 eq), triethylamine (10.14 mL, 1.1 eq), 4-[1-(2-pyrrolidin-1-yl-ethyl)-4-(tetrahydro-pyran-4-yl)-1H-imidazol-2-yl]-piperidine (22 g, 66.17 mmol) and N-methylpyrrolidinone (66 mL). Stir at 110° C. for 16 hours, then allow to cool to room temperature. Dilute with ethyl acetate (110 mL) and water (220 mL). Add 5 M aqueous sodium hydroxide to adjust the pH to 12. Extract with ethyl acetate (2×200 mL). Wash the organics with saturated aqueous sodium chloride. Add water (220 mL) to the organics and aqueous 85% phosphoric acid to adjust the pH to 3. Wash the resulting acidic aqueous layer with ethyl acetate (2×100 mL). Add 5 M aqueous sodium hydroxide to adjust the pH to 12. Extract with ethyl acetate (3×70 mL). Wash the organics with saturated aqueous sodium chloride (50 mL). Dry the organics over anhydrous magnesium sulfate and concentrate in vacuo to give the final compound as a light brown solid (21.5 g, 64%). MS (ES) m/z=494 [M]+.

1. temperatureto cool to room temperature
2. extractionExtract with ethyl acetate (2×200 mL)
3. washWash the organics with saturated aqueous sodium chloride
4. washWash the resulting acidic aqueous layer with ethyl acetate (2×100 mL)
5. additionAdd 5 M aqueous sodium hydroxide
6. extractionExtract with ethyl acetate (3×70 mL)
7. washWash the organics with saturated aqueous sodium chloride (50 mL)
8. dry with materialDry the organics over anhydrous magnesium sulfate
9. concentrationconcentrate in vacuo