O-Toluidine → 3-Aminopyrazine-2carboxylic acid o-toluamide

HRID 430513Notes

Reaction equation

HRID 430513 reaction equation
[NH2:1][C:2]1[C:3]([C:8]([OH:10])=[O:9])=[N:4][CH:5]=[CH:6][N:7]=1.N[C:12]1[C:13](C)=[CH:14]C=[CH:16][CH:17]=1.Cl.C[N:21](C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:13]1([CH3:14])[C:3]([C:8]([NH2:21])=[O:10])=[CH:2][CH:16]=[CH:17][CH:12]=1.[NH2:1][C:2]1[C:3]([C:8]([OH:10])=[O:9])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 7242O-ToluidineHCID 726563-Amino-2-pyrazinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 697096873-Aminopyrazine-2carboxylic acid o-toluamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-aminopyrazine carboxylic acid (5.0 g, 35.94 mmol), methylene chloride (110 mL), 4-dimethylaminopyridine (10.98 g, 89.85 mmol), o-toluidine (4.22 mL, 39.53 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (8.27 g, 43.13 mmol) was stirred overnight at ambient temperature. The solvent was removed and the residue was diluted with ethyl acetate. This organic phase was extracted with 1N lithium chloride (LiCl), water, and brine, dried over calcium sulfate and concentrated. The residue was flash chromatographed on silica gel (2.75×4 inches) with elution proceeding as follows: hexane (300 mL), nil; 20% ethyl acetate/hexane (500 mL), unweighed recovered o-toluidine; 20% ethyl acetate/hexane (1000 mL) and 30% ethyl acetate/hexane (2000 mL), 4.79 g (58%) of 3-aminopyrazine-2-carboxylic acid o-toluamide as a yellow crystalline solid.

Workup

  1. customThe solvent was removed
  2. additionthe residue was diluted with ethyl acetate
  3. extractionThis organic phase was extracted with 1N lithium chloride (LiCl), water, and brine
  4. dry with materialdried over calcium sulfate
  5. concentrationconcentrated
  6. customchromatographed on silica gel (2.75×4 inches) with elution proceeding
  7. custom20% ethyl acetate/hexane (500 mL), unweighed recovered o-toluidine

Sources & evidence

ORD record
ord-30b50b024d454e2f9097c902eda62b64
Source dataset
uspto-grants-2001_11
Patent number
US06323208B1

Reaction notes

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