Pyridine → 3,5-Dichloro-6-(propan-2-yl)pyrazine-2-carboxamide

HRID 869242Notes

Reaction equation

HRID 869242 reaction equation
[Cl:1][C:2]1[C:3]([C:13]([NH2:15])=[O:14])=[N:4][C:5]([C:9](O)([CH3:11])[CH3:10])=[C:6]([Cl:8])[N:7]=1.N1C=CC=CC=1.S(Cl)(C)(=O)=O.[H][H]>[Pd].C1COCC1.C(O)C>[Cl:1][C:2]1[C:3]([C:13]([NH2:15])=[O:14])=[N:4][C:5]([CH:9]([CH3:11])[CH3:10])=[C:6]([Cl:8])[N:7]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 86662050HCID 86662050, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 707007903,5-Dichloro-6-(propan-2-yl)pyrazine-2-carboxamideYield 25.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3,5-dichloro-6-(1-hydroxy-1-methylethyl)pyrazine-2-carboxamide (2.64 g) and pyridine (30 mL), mesyl chloride (2.45 mL) was added under ice cooling. After stirring at room temperature for 5 hours, pyridine was distilled off under reduced pressure, and the resulting residue was partitioned using ethyl acetate and water. The resulting organic layer was washed with 10% aqueous citric acid, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was distilled off to give a light brown syrup. To the light brown syrup, ethanol (60 mL) and THF (30 mL) were added, and then 10% palladium on carbon (0.7 g) was added and stirred at room temperature for 14 hours under 3 atmospheric pressure of hydrogen. After filtration through celite, the filtrate was distilled off under reduced pressure, and the residue was diluted with ethyl acetate and then washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. After the solvent was distilled off, the residue was purified by silica gel column chromatography (eluent; chloroform:methanol=100:0 to 40:1). The resulting crude product was washed with diisopropyl ether to give 3,5-di-chloro-6-isopropylpyrazine-2-carboxamide (632 mg) as a white solid.

Workup

  1. additionwas added under ice cooling
  2. distillationpyridine was distilled off under reduced pressure
  3. customthe resulting residue was partitioned
  4. washThe resulting organic layer was washed with 10% aqueous citric acid, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off
  7. customto give a light brown syrup
  8. filtrationAfter filtration through celite
  9. distillationthe filtrate was distilled off under reduced pressure
  10. additionthe residue was diluted with ethyl acetate
  11. washwashed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride
  12. distillationAfter the solvent was distilled off
  13. customthe residue was purified by silica gel column chromatography (eluent; chloroform:methanol=100:0 to 40:1)
  14. washThe resulting crude product was washed with diisopropyl ether

Sources & evidence

ORD record
ord-0c633ed7c516408fa829d2ae2c236588
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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