Hydrogen Bromide → 8-Chloroimidazo[1,2-a]pyrazine

Temperature

95 °C

Bromoacetaldehyde diethyl acetal (45 ml, 0.29 mol) was treated with water (33 ml) and 48% hydrobromic acid (33 ml) and this mixture was heated at 95° C. for 90 min. The reaction was cooled, diluted with propan-2-ol (300 ml) and treated with sodium hydrogencarbonate (33 g) added in portions. This mixture was stirred for 30 min then filtered. The filtrate was treated with 2-amino-3-chloropyrazine (25 g, 0.19 mol) and then heated at 90° C. for 16 h. The reaction was cooled to ambient temperature, concentrated to about one-third volume and then treated with 48% hydrobromic acid (25 ml). More propan-2-ol (300 ml) was added and the mixture aged for 1 h. The resulting solid was collected by filtration, washed with propan-2-ol and then dissolved in water (500 ml). This solution was made basic by adding solid sodium hydrogencarbonate and then extracted with chloroform (3×250 ml). The organics were combined, dried over anhydrous magnesium sulphate, filtered and concentrated to give a solid. Trituration with diethyl ether afforded 8-chloroimidazo[1,2-a]pyrazine as an off-white solid (18.6 g, 63%): δH (360 MHz, DMSO) 7.73 (1H, d, J 4.5), 7.87 (1H, d, J 1), 8.28 (1H, d, J 1), 8.67 (1H, d, J 4.5).

1. temperatureThe reaction was cooled
2. additionadded in portions
3. filtrationthen filtered
4. temperatureheated at 90° C. for 16 h
5. temperatureThe reaction was cooled to ambient temperature
6. concentrationconcentrated to about one-third volume
7. additiontreated with 48% hydrobromic acid (25 ml)
8. additionMore propan-2-ol (300 ml) was added
9. waitthe mixture aged for 1 h
10. filtrationThe resulting solid was collected by filtration
11. washwashed with propan-2-ol
12. dissolutiondissolved in water (500 ml)
13. additionby adding solid sodium hydrogencarbonate
14. extractionextracted with chloroform (3×250 ml)
15. dry with materialdried over anhydrous magnesium sulphate
16. filtrationfiltered
17. concentrationconcentrated
18. customto give a solid

ORD record

ord-5eb00a062307484d91ba2ce9394cb521

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07485640B2