Ammonia → 2-(ethoxymethyl)-1-[(3-phenylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinolin-4-amine

HRID 606043Notes

Reaction equation

HRID 606043 reaction equation
Cl[C:2]1[C:11]2[N:12]=[C:13]([CH2:27][O:28][CH2:29][CH3:30])[N:14]([CH2:15][C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH:17]=3)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[NH3:31].[OH-].[Na+]>CO>[CH2:29]([O:28][CH2:27][C:13]1[N:14]([CH2:15][C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:17]=2)[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:31])[C:11]=2[N:12]=1)[CH3:30]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 14798Sodium HydroxideHCID 866168724-chloro-2-(ethoxymethyl)-1-[(3-phenylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline

Product 1

HCID 590266852-(ethoxymethyl)-1-[(3-phenylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinolin-4-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-Chloro-2-(ethoxymethyl)-1-[(3-phenylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline (1.48 g, 3.53 mmol) was treated with a solution of 7 M ammonia in methanol (25 mL) at 150° C. for 17 hours. The volatiles were removed under reduced pressure and the resulting oil was diluted with dichloromethane and 1 M hydrochloric acid. A white solid formed and 50% aqueous sodium hydroxide was added to dissolve the solid. The aqueous layer was separated and extracted with dichloromethane. The organic layers were combined, washed with brine, dried over magnesium sulfate, filtered, and concentrated to an oil. Upon treatment of the oil with diethyl ether, a solid formed. The solid was purified by flash chromatography (silica gel, eluting with a mixture of 95% dichloromethane and 5% of a solution of 80% chloroform, 18% methanol, and 2% NH4OH (CMA)) followed by several recrystallizations from acetonitrile to provide 2-(ethoxymethyl)-1-[(3-phenylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinolin-4-amine (0.505 g) as a white powder, mp 215.0-216.0° C.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. additionthe resulting oil was diluted with dichloromethane and 1 M hydrochloric acid
  3. customA white solid formed
  4. dissolutionto dissolve the solid
  5. customThe aqueous layer was separated
  6. extractionextracted with dichloromethane
  7. washwashed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to an oil
  11. customUpon treatment of the oil with diethyl ether, a solid formed
  12. customThe solid was purified by flash chromatography (silica gel
  13. washeluting with a mixture of 95% dichloromethane and 5% of a solution of 80% chloroform, 18% methanol, and 2% NH4OH (CMA))
  14. customfollowed by several recrystallizations from acetonitrile

Sources & evidence

ORD record
ord-686899c25a66426abb9b755f0e5c9e05
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

Loading…