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

HRID 1737258Notes

Reaction equation

HRID 1737258 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 1 N 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 1 N 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-6b848e229996479db5a0acba98ffc334
Source dataset
uspto-grants-1999_10
Patent number
US05962457

Reaction notes

Loading…