反应详情

Bromoacetaldehyde diethyl acetal (200 mL, 1.3 mol) and a solution of 48% HBr (48 ml) are heated at reflux for 1.5 hours, then poured onto a suspension of NaHCO3 (100 g) in propan-2-ol (1.6 L). The resulting solid is filtered off and 2-amino-3-chloropyrazine (51.8 g, 0.4 mol) is added to the solution then heated to reflux, during which time a clear solution forms which precipitates over 2 hours. The reaction mixture is cooled and allowed to stand overnight, and the solid may be collected by filtration and washed with propan-2-ol and Et2O. The solid is added to a saturated solution of NaHCO3 (500 mL) and DCM (1 L). The aqueous layer is separated from the organic solvent and re-extracted with DCM (2×250 mL). The organic layers are combined and dried over MgSO4, filtered and evaporated to dryness, to afford a light brown solid. The propan-2-ol and Et2O liquors from washing the filter cake, are evaporated to give a pale brown solid which is washed with a saturated solution of NaHCO3 and extracted with DCM (X 3). The two solids were combined to afford compound 8-chloro-imidazo[1,2-a]pyrazine (59.1 g, 96%).

1. temperatureat reflux for 1.5 hours
2. filtrationThe resulting solid is filtered off
3. temperaturethen heated
4. temperatureto reflux, during which time a clear solution forms which
5. customprecipitates over 2 hours
6. temperatureThe reaction mixture is cooled
7. filtrationthe solid may be collected by filtration
8. washwashed with propan-2-ol and Et2O
9. additionThe solid is added to a saturated solution of NaHCO3 (500 mL) and DCM (1 L)
10. customThe aqueous layer is separated from the organic solvent
11. extractionre-extracted with DCM (2×250 mL)
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. customevaporated to dryness
15. customto afford a light brown solid
16. washThe propan-2-ol and Et2O liquors from washing the filter cake
17. customare evaporated
18. customto give a pale brown solid which
19. washis washed with a saturated solution of NaHCO3
20. extractionextracted with DCM (X 3)