反应详情

A mixture of the product of step (iv) (250 g, 0.58 mol), 3-amino-6-bromo-N-(pyridin-3-yl)pyrazine-2-carboxamide (220 g, 0.75 mol), Na2CO3 (183 g, 1.73 mol) and Pd(dppf)Cl2 (25.30 g, 35 mmol) in DMF (3 L) was stirred and degassed with N2 three times. The mixture was stirred at 70˜80° C. under N2 for 24 hours. The mixture was filtered and the filtrate concentrated to in vacuo to remove DMF. EtOAc (1.5 L) and H2O (800 mL) were charged and stirred for 1 hour at 10-25° C. The suspension was filtered, the organic phase was concentrated in vacuo and purified by column chromatography (PE: EtOAc=3:1-1:3). The crude product was re-crystallized from EtOAc-MeOH and filtered, the yellow solid was washed by EtOA and dried under reduced pressure. The subtitle compound (v) was obtained (pale yellow solid, 160 g).

1. customdegassed with N2 three times
2. stirringThe mixture was stirred at 70˜80° C. under N2 for 24 hours
3. filtrationThe mixture was filtered
4. concentrationthe filtrate concentrated to in vacuo
5. customto remove DMF
6. additionEtOAc (1.5 L) and H2O (800 mL) were charged
7. stirringstirred for 1 hour at 10-25° C
8. filtrationThe suspension was filtered
9. concentrationthe organic phase was concentrated in vacuo
10. custompurified by column chromatography (PE: EtOAc=3:1-1:3)
11. customThe crude product was re-crystallized from EtOAc-MeOH
12. filtrationfiltered
13. washthe yellow solid was washed by EtOA
14. customdried under reduced pressure