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

HRID 1809168Notes

Reaction equation

HRID 1809168 reaction equation
C(OC(O[CH2:8][CH3:9])CBr)C.Br.C([O-])(O)=O.[Na+].[NH2:16][C:17]1[C:22]([Cl:23])=[N:21][CH:20]=[CH:19][N:18]=1>CC(O)C>[Cl:23][C:22]1[C:17]2[N:18]([CH:8]=[CH:9][N:16]=2)[CH:19]=[CH:20][N:21]=1

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 2762242-Amino-3-chloropyrazineHCID 516892Sodium Bicarbonate

Product 1

HCID 102612868-Chloroimidazo[1,2-a]pyrazineYield 96.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-1b12e9b189b94f03a9637a7c2633a453
Source dataset
uspto-grants-2013_01
Patent number
US08362018B2

Reaction notes

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