Reaction #3741

Reaction equation

Oxalyl chloride

2-ethoxybenzoic acid

dimethylformamide

5-amino-1-n-propylimidazole-4-carboxamide

→

title compound

Yield 77.0%

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

Yield 77.0%

Solvents

dichloromethane

pyridine

Conditions

Workup

1. 1
   Otherevaporated under vacuum
2. 2
   OtherThe residue was azeotroped with dichloromethane (2×20 ml)
3. 3
   workup.STIRRINGwas stirred at ambient temperature for 3 days
4. 4
   Otherevaporated under vacuum
5. 5
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane (50 ml)
6. 6
   Washthe solution washed with 1N hydrochloric acid (30 ml)
7. 7
   Dryingdried (Na2SO4)
8. 8
   Otherevaporated under vacuum
9. 9
   Washa methanol in dichloromethane elution gradient (2-6% methanol)
10. 10
    Otherfollowed by crystallisation from ethanol

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%.

Source