反应详情

温度

100 °C

To a solution of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 3 g, 8.44 mmol) and DIEA (7.35 mL, 42.2 mmol) in DMF (30 mL) was added 2,5-dichloropyrazine (2.51 g, 16.9 mmol). This mixture was degassed with nitrogen for 30 minutes then stirred at 100° C. for 4 hours under nitrogen. The mixture was poured into brine (500 mL) and extracted into ethyl acetate (3×100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an oil. Diethyl ether (200 mL) was added and a precipitate formed overnight. The ether was decanted and the solid was triturated using ethanol (100 mL) at reflux with stirring for 5 minutes. The suspension was filtered and the solid was washed using ethanol to give a solid crystal. This solid was dried over the weekend under high vacuum to provide the title compound (2.9 g, 73% yield). Mass spectrum (apci) m/z=468.1 (M+H).

1. customThis mixture was degassed with nitrogen for 30 minutes
2. additionThe mixture was poured into brine (500 mL)
3. extractionextracted into ethyl acetate (3×100 mL)
4. dry with materialThe combined organic layers were dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto give an oil
8. customa precipitate formed overnight
9. customThe ether was decanted
10. customthe solid was triturated
11. temperatureat reflux
12. stirringwith stirring for 5 minutes
13. filtrationThe suspension was filtered
14. washthe solid was washed
15. customto give a solid crystal
16. customThis solid was dried over the weekend under high vacuum