反应详情

温度

25 °C

A mixture of 2-bromo-1-(2,4-difluorophenyl)ethanone (107.31 g, 442.89 mmol) and 3-chloropyrazin-2-amine (98.00 g, 756.5 mmol) in ACN (800 mL) was stirred at reflux for about 20 h. The reaction mixture was cooled to about 25° C. before the resultant solid was collected. The filtrate solvent was removed in vacuo to yield a brown solid. This filtration was done to negate the bumping associated with the removal of the ACN. The combined solids were then suspended in water (750 mL) and basified, whilst stirring, with 2N NaOH (750 mL). After about 30 min, the product was partitioned between DCM (9×1000 mL) and filtered from the insoluble material to aid extraction process. The organic extracts were combined and stirred with 2.5N HCl (4×750 mL). The organic layer was finally washed with 2.0N NaOH (500 mL) and water (2×500 mL), dried over MgSO4, and filtered through a Florisil® pad (3 inch diameter×3 inch depth) to remove origin material. The Florisil® pad was washed with repeated amounts of solvent until no product was detected by TLC. The organic solvent was removed in vacuo to yield a yellow solid. The solid was suspended in IPA (200 mL) at about 80° C. for about 15 min and then cooled to about 20° C. The solid was collected and washed with ice-cold IPA (2×40 mL), followed by petroleum ether [bp 30-60° C.] (3×80 mL) to remove impurities. The solid was dried in vacuo at about 70° C. overnight to yield the title compound as a yellow powdery solid (69.75 g, 57%): LC/MS (Table 1, Method g) Rt=2.70 min; MS m/z: 266.1 (M+H)+.

1. temperatureat reflux for about 20 h
2. customwas collected
3. customThe filtrate solvent was removed in vacuo
4. customto yield a brown solid
5. filtrationThis filtration
6. custombumping associated with the removal of the ACN
7. stirringwhilst stirring, with 2N NaOH (750 mL)
8. customthe product was partitioned between DCM (9×1000 mL)
9. filtrationfiltered from the insoluble material
10. extractionextraction process
11. stirringstirred with 2.5N HCl (4×750 mL)
12. washThe organic layer was finally washed with 2.0N NaOH (500 mL) and water (2×500 mL)
13. dry with materialdried over MgSO4
14. filtrationfiltered through a Florisil® pad (3 inch diameter×3 inch depth)
15. customto remove origin material
16. washThe Florisil® pad was washed with repeated amounts of solvent until no product
17. customThe organic solvent was removed in vacuo
18. customto yield a yellow solid
19. temperaturecooled to about 20° C
20. customThe solid was collected
21. washwashed with ice-cold IPA (2×40 mL)
22. customto remove impurities
23. customThe solid was dried in vacuo at about 70° C. overnight