反应详情

温度

110 °C

Combine 4-(4-ethyl-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine (7.70 g, 27.86 mmol), (R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (6.06 g, 1.1 eq), N-methylpyrrolidinone (25.4 mL) and triethylamine (4.27 mL, 1.1 eq). Stir overnight at 110° C. under nitrogen, then let cool to room temperature. Dilute with ethyl acetate and water. Adjust the pH with 2 M aqueous sodium hydroxide to 10. Separate the layers. Wash the aqueous phase with ethyl acetate. Wash the organics with aqueous saturated sodium chloride. Concentrate the organics in vacuo. Dilute with ethyl acetate and water. Adjust the pH to 5. Separate the layers; discard the organic layer. Adjust the pH of the aqueous phase with 2 M aqueous sodium hydroxide to 11. Wash the aqueous phase with ethyl acetate. Wash the organics with water and aqueous saturated sodium chloride. Concentrate the organics in vacuo. Dilute with 2-methyltetrahydrofuran:hexanes (15:85, 77 mL). Stir overnight at room temperature. Filter and dry the resulting white solid under vacuum to give the title compound, (R)-4-(4-(4-ethyl-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (7.90 g, 65%). MS (ES) m/z=438 [M]+.

1. temperaturelet cool to room temperature
2. customSeparate the layers
3. washWash the aqueous phase with ethyl acetate
4. washWash the organics with aqueous saturated sodium chloride
5. concentrationConcentrate the organics in vacuo
6. additionDilute with ethyl acetate and water
7. customSeparate the layers
8. washWash the aqueous phase with ethyl acetate
9. washWash the organics with water and aqueous saturated sodium chloride
10. concentrationConcentrate the organics in vacuo
11. additionDilute with 2-methyltetrahydrofuran:hexanes (15:85, 77 mL)
12. stirringStir overnight at room temperature
13. filtrationFilter
14. customdry the resulting white solid under vacuum