Triethylamine → 3-Chloro-N-(2,4-difluorophenyl)pyrazine-2-carboxamide

HRID 1986113Notes

Reaction equation

HRID 1986113 reaction equation
[Cl:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][N:7]=1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[F:24][C:25]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:26]=1[NH2:27]>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[C:3]([C:8]([NH:27][C:26]2[CH:28]=[CH:29][C:30]([F:32])=[CH:31][C:25]=2[F:24])=[O:10])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 97092,4-DifluoroanilineHCID 65578Oxalyl chlorideHCID 15019003-Chloro-2-pyrazine-carboxylic acid

Product 1

HCID 577213623-Chloro-N-(2,4-difluorophenyl)pyrazine-2-carboxamideYield 53.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-chloropyrazine-2-carboxylic acid (Tyger Scientific, 500 mg, 3.15 mmol) in methylene chloride (30 mL) and DMF (0.1 mL) was added oxalyl chloride (593 mg, 4.7 mmol). After stirring 30 min the reaction mixture was concentrated in vacuo. The residue was taken up in acetonitrile (12 mL) and was treated with triethylamine (920 mg, 9.1 mmol) and 2,4-difluoroaniline (430 mg, 3.3 mmol) and stirred 30 min. The reaction mixture was partitioned between ethyl acetate and brine. The organic layer was washed with brine, dried over anhydrous MgSO4, and then concentrated in vacuo. The resulting solid was recrystallized (ethyl acetate/hexanes) to give the amide (455 mg, 53%) as a solid. MS(ESI+) m/z 270 (M+H)+.

Workup

  1. concentrationwas concentrated in vacuo
  2. stirringstirred 30 min
  3. customThe reaction mixture was partitioned between ethyl acetate and brine
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting solid was recrystallized (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7933e29711dd45609b0a8e7d05c8dd98
Source dataset
uspto-grants-2009_06
Patent number
US07547782B2

Reaction notes

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