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

HRID 606048Notes

Reaction equation

HRID 606048 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:22]=[N:23][CH:24]=[CH:25][CH:26]=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]>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:22]=[N:23][CH:24]=[CH:25][CH:26]=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

4

Reactant 2

HCID 222AmmoniaHCID 866168744-chloro-2-(ethoxymethyl)-1-[(3-pyridin-3-ylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline

Product 1

HCID 590267032-(ethoxymethyl)-1-[(3-pyridin-3-ylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinolin-4-amineYield 45%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A slurry of 4-chloro-2-(ethoxymethyl)-1-[(3-pyridin-3-ylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline (1.52 g, 3.62 mmol) in a solution of 7 M ammonia in methanol (15 mL) was heated at 150° C. for 20 hours in a Parr pressure vessel. The volatiles were removed under reduced pressure and the resulting residue was partitioned between dichloromethane and 1 M aqueous sodium hydroxide. The aqueous layer was extracted with several portions of dichloromethane. The organic phases were combined, washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, gradient elution 10% to 30% CMA/chloroform) to yield 2-(ethoxymethyl)-1-[(3-pyridin-3-ylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinolin-4-amine (653 mg, 45%) as white powder that was dried under vacuum at 70° C., mp 240.0-242.0° C. 1H NMR (300 MHz, DMSO-d6) δ 8.99 (d, J=1.7 Hz, 1H), 8.64 (dd, J=3.2, 1.6 Hz, 1H), 8.16-8.20 (m, 1H), 7.97 (d, J=7.5 Hz, 1H), 7.61 (d, J=7.4 Hz, 1H), 7.41-7.50 (m, 2H), 7.17 (t, J=7.0 Hz, 1H), 6.97 (s, 1H), 6.17 (s, 2H), 5.75 (s, 2H), 4.88 (s, 2H), 3.50 (q, J=7.0 Hz, 2H), 0.98 (t, J=7.0, 3H).

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe resulting residue was partitioned between dichloromethane and 1 M aqueous sodium hydroxide
  3. extractionThe aqueous layer was extracted with several portions of dichloromethane
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by flash chromatography (silica gel, gradient elution 10% to 30% CMA/chloroform)

Sources & evidence

ORD record
ord-2902f22e3a1c48839f39c1c1f37e3a05
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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