Dimethylformamide → 5-(2-Ethoxybenzamido)-1-n-propylimidazole-4-carboxamide

HRID 3645

Reaction equation

HRID 3645 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([O:9][C:10]1[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=1[C:12]([OH:14])=O)[CH3:8].CN(C)C=O.[NH2:24][C:25]1[N:29]([CH2:30][CH2:31][CH3:32])[CH:28]=[N:27][C:26]=1[C:33]([NH2:35])=[O:34]>ClCCl.N1C=CC=CC=1>[CH2:7]([O:9][C:10]1[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=1[C:12]([NH:24][C:25]1[N:29]([CH2:30][CH2:31][CH3:32])[CH:28]=[N:27][C:26]=1[C:33]([NH2:35])=[O:34])=[O:14])[CH3:8]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 672522-Ethoxybenzoic acidHCID 123391055-Amino-1-propyl-1H-imidazole-4-carboxamide

Product 1

HCID 537133095-(2-Ethoxybenzamido)-1-n-propylimidazole-4-carboxamideYield 77%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (1.74 g, 0.137 mol) was added dropwise to a stirred solution of 2-ethoxybenzoic acid (1.1 g, 0.00663 mol) and dimethylformamide (0.1 ml) in dichloromethane (20 ml) and the resulting mixture stirred at ambient temperature for 4 hours, then evaporated under vacuum. The residue was azeotroped with dichloromethane (2×20 ml), then added dropwise to a stirred solution of 5-amino-1-n-propylimidazole-4-carboxamide (0.9 g, 0.00536 mol) in pyridine (20 ml) The resulting solution was stirred at ambient temperature for 3 days, then evaporated under vacuum. The residue was dissolved in dichloromethane (50 ml), and the solution washed with 1N hydrochloric acid (30 ml), dried (Na2SO4) and evaporated under vacuum. Chromatography of the crude product on silica gel (15 g) using a methanol in dichloromethane elution gradient (2-6% methanol), followed by crystallisation from ethanol, gave the title compound as a colourless solid (1.3 g, 77%), m.p. 182°-184° C. Found: C,60.85; H,6.40; N,18.06. C16H20N4O3 requires C,60.74; H,6.37; N,17.71%.

Workup

  1. customevaporated under vacuum
  2. customThe residue was azeotroped with dichloromethane (2×20 ml)
  3. stirringwas stirred at ambient temperature for 3 days
  4. customevaporated under vacuum
  5. dissolutionThe residue was dissolved in dichloromethane (50 ml)
  6. washthe solution washed with 1N hydrochloric acid (30 ml)
  7. dry with materialdried (Na2SO4)
  8. customevaporated under vacuum
  9. washa methanol in dichloromethane elution gradient (2-6% methanol)
  10. customfollowed by crystallisation from ethanol

Sources & evidence

ORD record
ord-7a5e2995d24f4bac852bdb664f6ad601
Source dataset
uspto-grants-1998_03
Patent number
US05734053

Linked notes

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