Ethanol → Ethyl (5-bromo-8-morpholinoimidazo[1,2-a]pyrazin-2-yl)carbamate

HRID 1772634Notes

Reaction equation

HRID 1772634 reaction equation
[Br:1][C:2]1[N:7]2[CH:8]=[C:9](C(NN)=O)[N:10]=[C:6]2[C:5]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[N:4][CH:3]=1.N([O-])=O.[Na+].[N-:25]=[N+]=[N-].[Na+].[C:29]([O-:32])([O-])=[O:30].[Na+].[Na+].[CH3:35][CH2:36]O>Cl.O>[Br:1][C:2]1[N:7]2[CH:8]=[C:9]([NH:25][C:29](=[O:30])[O:32][CH2:35][CH3:36])[N:10]=[C:6]2[C:5]([N:15]2[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)=[N:4][CH:3]=1

Participants

8

Reactant 5

HCID 702EthanolHCID 10340Sodium CarbonateHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 1177278355-Bromo-8-morpholinoimidazo[1,2-a]pyrazine-2-carbohydrazide

Product 1

HCID 131734673Ethyl (5-bromo-8-morpholinoimidazo[1,2-a]pyrazin-2-yl)carbamate

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent3×

Procedure

A stirred solution of 5-bromo-8-morpholinoimidazo[1,2-a]pyrazine-2-carbohydrazide (1.5 g, 4.3 mmol, as prepared above) in 2N HCl (5 mL) was diluted with cold H2O (40 mL). An aqueous solution of NaNO2 (450 mg, 6.5 mmol) in water (2 mL) was then added dropwise while maintaining the temperature below 15° C. The mixture was stirred at rt for 2 h and treated with NaN3 (432 mg, 6.50 mmol) in water (10 mL). The resulting mixture was stirred at rt for 15 min, adjusted to pH 7 with aqueous Na2CO3 and extracted with DCM (3×20 mL). The combined DCM layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product obtained was suspended in EtOH (50 mL) and heated at refluxed for 4.5 h. The reaction mixture was allowed to cool to rt, the solvent was removed under reduced pressure, and the residue obtained was purified by flash column chromatography on silica gel (4:1 DCM/EtOAc) to give ethyl (5-bromo-8-morpholinoimidazo[1,2-a]pyrazin-2-yl)carbamate.

Workup

  1. temperaturewhile maintaining the temperature below 15° C
  2. stirringThe resulting mixture was stirred at rt for 15 min
  3. extractionextracted with DCM (3×20 mL)
  4. dry with materialThe combined DCM layers were dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product obtained
  7. temperatureheated
  8. temperatureat refluxed for 4.5 h
  9. temperatureto cool to rt
  10. customthe solvent was removed under reduced pressure
  11. customthe residue obtained
  12. customwas purified by flash column chromatography on silica gel (4:1 DCM/EtOAc)

Sources & evidence

ORD record
ord-726327b64e0346e9ad2922a4fa2219e2
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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