1,2-Dimethoxyethane → ethyl imidazo[1,2-a]pyrazine-2-carboxylate

Temperature

0 °C

Ethyl bromopyruvate (62.9 g) was added to the DME (258 mL) solution of 2-aminopyrazine (24.8 g) at room temperature and stirred for 2.5 h. The reaction mixture was cooled to 0° C. and stirred for 30 min to afford a pale brown precipitate. The precipitate was filtered and washed with Et2O to give pale brown crystals. The suspension of the precipitate (66.1 g) in EtOH (1.29 L) was heated at reflux temperature to turn to clear solution. After refluxing for 2 h, the reaction mixture was concentrated under reduced pressure, then mixed with CHCl3 and saturated NaHCO3aq. The mixture was filtered through a pad of Celite and the separated organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then the column was eluted with CHCl3-MeOH (99/1˜97/3), and collected fractions were concentrated under reduced pressure followed by recrystallization from CHCl3-Et2O. The titled compound was obtained as pale pink crystals. Yield: 10.9 g, 22%).

1. stirringstirred for 30 min
2. customto afford a pale brown precipitate
3. filtrationThe precipitate was filtered
4. washwashed with Et2O
5. customto give pale brown crystals
6. temperaturewas heated
7. temperatureat reflux temperature
8. temperatureAfter refluxing for 2 h
9. concentrationthe reaction mixture was concentrated under reduced pressure
10. additionmixed with CHCl3 and saturated NaHCO3aq
11. filtrationThe mixture was filtered through a pad of Celite
12. dry with materialthe separated organic layer was dried (MgSO4)
13. filtrationfiltered
14. concentrationThe filtrate was concentrated under reduced pressure
15. washthe column was eluted with CHCl3-MeOH (99/1˜97/3)
16. customcollected fractions
17. concentrationwere concentrated under reduced pressure
18. customfollowed by recrystallization from CHCl3-Et2O

ORD record

ord-84a6a17b914e44108cecd64135d18b5c

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07112582B2