Oxalyl chloride → N-(6-Amino-5-chloropyrazin-2-yl)-5-methylisoxazole-4-carboxamide

HRID 2100350Notes

Reaction equation

HRID 2100350 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]1[O:12][N:11]=[CH:10][C:9]=1[C:13]([OH:15])=O.[Cl:16][C:17]1[C:18]([NH2:24])=[N:19][C:20]([NH2:23])=[CH:21][N:22]=1>ClCCl.CN(C)C=O.N1C=CC=CC=1>[NH2:24][C:18]1[N:19]=[C:20]([NH:23][C:13]([C:9]2[CH:10]=[N:11][O:12][C:8]=2[CH3:7])=[O:15])[CH:21]=[N:22][C:17]=1[Cl:16]

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 14252405-Methylisoxazole-4-carboxylic acidHCID 121014923-Chloropyrazine-2,6-diamine

Product 1

HCID 57799133N-(6-Amino-5-chloropyrazin-2-yl)-5-methylisoxazole-4-carboxamideYield 30.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (0.8 ml, 10.3 mmol) was added to a solution of 5-Methyl-isoxazole-4-carboxylic acid (1 g, 6.9 mmol) in dichloromethane (30 ml) followed by 1 drop of dimethylformamide. The mixture was stirred at room temperature for 5 hours before concentrating in vacuo and azeotroping with dichloromethane. The residue was taken up in pyridine (3 ml) and added to a solution of 3-chloro-pyrazine-2,6-diamine (Preparation 1) (0.65 g, 4.6 mmol) in anhydrous pyridine (30 ml) and the mixture heated at 50° C. for 3 hours before cooling to room temperature and concentrating in vacuo. The residue was purified by silica gel column chromatography, eluting with ethyl acetate:heptane 1:1, to afford the product as a white solid (360 mg).

Workup

  1. concentrationbefore concentrating in vacuo
  2. customazeotroping with dichloromethane
  3. temperaturethe mixture heated at 50° C. for 3 hours
  4. temperaturebefore cooling to room temperature
  5. concentrationconcentrating in vacuo
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with ethyl acetate:heptane 1:1

Sources & evidence

ORD record
ord-fcc19f1786764a93854115dbf73ab113
Source dataset
uspto-grants-2009_08
Patent number
US07572797B2

Reaction notes

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