Methanol → 1-ethoxy-1H-imidazo[4,5-c]quinolin-4-amine

HRID 2105482Notes

Reaction equation

HRID 2105482 reaction equation
[CH2:1]([O:3][N:4]1[C:16]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N+:9]([O-])=[CH:8][C:7]=2[N:6]=[CH:5]1)[CH3:2].ClC(Cl)(Cl)C([N:22]=C=O)=O.CO>ClCCl>[CH2:1]([O:3][N:4]1[C:16]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[C:8]([NH2:22])[C:7]=2[N:6]=[CH:5]1)[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 76400Trichloroacetyl isocyanateHCID 675068741-ethoxy-5-oxido-1H-imidazo[4,5-c]quinoline

Product 1

HCID 575388221-ethoxy-1H-imidazo[4,5-c]quinolin-4-amineYield 22.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-ethoxy-5-oxido-1H-imidazo[4,5-c]quinoline (2.4 g, 10.5 mmol) in dichloromethane (75 mL) was cooled to 0° C., and trichloroacetyl isocyanate (1.9 mL, 16 mmol) was added. The reaction was stirred for ten minutes at 0° C. and then stirred overnight at room temperature. Methanol (15 mL) was added, and the mixture was stirred for 15 minutes and concentrated under reduced pressure. The residue was dissolved in methanol (15 mL), and sodium methoxide (0.5 mL of a 25% w/w solution in methanol) was added. The mixture was stirred at room temperature for three hours and concentrated under reduced pressure. The residue was stirred with methanol (15 mL) and water (15 mL), and a solid formed. The solid was collected by filtration, recrystallized from methanol/water, and purified by column chromatography on silica gel (eluting with 5% methanol in dichloromethane containing 2 mL of aqueous ammonium hydroxide per liter of eluent). The resulting solid was recrystallized from methanol/water and dried overnight under vacuum to provide 0.54 g of 1-ethoxy-1H-imidazo[4,5-c]quinolin-4-amine as brown crystals, mp 179-181° C.

Workup

  1. stirringstirred overnight at room temperature
  2. stirringthe mixture was stirred for 15 minutes
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in methanol (15 mL)
  5. additionsodium methoxide (0.5 mL of a 25% w/w solution in methanol) was added
  6. stirringThe mixture was stirred at room temperature for three hours
  7. concentrationconcentrated under reduced pressure
  8. stirringThe residue was stirred with methanol (15 mL) and water (15 mL)
  9. customa solid formed
  10. filtrationThe solid was collected by filtration
  11. customrecrystallized from methanol/water
  12. custompurified by column chromatography on silica gel (eluting with 5% methanol in dichloromethane containing 2 mL of aqueous ammonium hydroxide per liter of eluent)
  13. customThe resulting solid was recrystallized from methanol/water
  14. customdried overnight under vacuum

Sources & evidence

ORD record
ord-f8a6807dfe2242a99514b5de4b0533a2
Source dataset
uspto-grants-2009_08
Patent number
US07579359B2

Reaction notes

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