Sodium Cyanide → 5-Aminopyrazine-2-carbonitrile

HRID 1639927Notes

Reaction equation

HRID 1639927 reaction equation
[Cu]([C:4]#[N:5])C#N.[C-]#N.[Na+].Br[C:10]1[N:11]=[CH:12][C:13]([NH2:16])=[N:14][CH:15]=1>CN(C=O)C.CCOC(C)=O.O>[NH2:16][C:13]1[N:14]=[CH:15][C:10]([C:4]#[N:5])=[N:11][CH:12]=1

Participants

6

Reactant 3

HCID 8929Sodium Cyanide3×HCID 5995392-Amino-5-bromopyrazineHCID 178418260HCID 178418260, compound2×

Product 1

HCID 139252945-Aminopyrazine-2-carbonitrileYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
135 °C

Procedure

Heat a suspension of 1.85 g (20.7 mmol) of copper cyanide and 1 g (20.7 mmol) of sodium cyanide in 20 ml of DMF to 135° C., while stirring. Add 3.6 g (20.7 mmol) of 5-bromopyrazin-2-amine to the solution obtained, and maintain the temperature of 135° C. for 18 h. Then add 2 equivalents of sodium cyanide and of copper cyanide and continue heating for a further 24 h. After cooling, add 100 mL of 0.3N aqueous solution of sodium cyanide, stir the mixture for 1 h at 40° C., then distribute it in 300 mL of EtOAc/water 1:1 mixture. After washing with 2×100 mL of water, dry the organic phase over Na2SO4 and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a cyclohexane/EtOAc gradient from 0 to 100% of EtOAc. After concentration under reduced pressure, we obtain 1.24 g of 5-aminopyrazine-2-carbonitrile in the form of oil.

Workup

  1. temperatureHeat
  2. customobtained
  3. temperatureAfter cooling
  4. stirringstir the mixture for 1 h at 40° C.
  5. washAfter washing with 2×100 mL of water
  6. dry with materialdry the organic phase over Na2SO4
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue
  9. customobtained by silica gel column chromatography
  10. washeluting with a cyclohexane/EtOAc gradient from 0 to 100% of EtOAc
  11. concentrationAfter concentration under reduced pressure, we

Sources & evidence

ORD record
ord-45b7054903164f53a5a4c12b36a11840
Source dataset
uspto-grants-2012_02
Patent number
US08110579B2

Reaction notes

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