4-Toluenesulfonyl chloride → 8-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

HRID 598382Notes

Reaction equation

HRID 598382 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[N:15]=[CH:14][C:13]3[N:19]=[C:20]([CH2:25][O:26][CH2:27][CH3:28])[N:21]([CH2:22][CH2:23][CH3:24])[C:12]=3[C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=C(C=CC=1)C(OO)=O.[OH-].[NH4+:41].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[N:15]=[C:14]([NH2:41])[C:13]3[N:19]=[C:20]([CH2:25][O:26][CH2:27][CH3:28])[N:21]([CH2:22][CH2:23][CH3:24])[C:12]=3[C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 670511278-benzyloxy-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinoline

Product 1

HCID 575453188-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

8-Benzyloxy-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinoline (2.0 g, 5.3 mmol) was dissolved in chloroform (20 mL). 3-Chloroperoxybenzoic acid (60% pure, 1.53 g, 5.3 mmol) was added in one portion and the mixture was stirred for 25 minutes. Ammonium hydroxide (20 mL) was added and the biphasic mixture was stirred for 10 minutes. p-Toluenesulfonyl chloride (1.0 g, 5.3 mmol) was added in one portion and the reaction was stirred for an additional 1 hour. The layers were separated and the aqueous fraction was extracted with dichloromethane. The organic fractions were combined and washed successively with 5% aqueous sodium carbonate, water and saturated aqueous sodium chloride. The organic fraction was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography. The purification was carried out eluting with chloroform:CMA in a gradient from 99:1 to 93:7 to provide a red-brown solid. The solid was recrystallized from acetonitrile to yield 1.1 g of 8-benzyloxy-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine as red brown crystals, mp 152.5-154.0° C.

Workup

  1. stirringthe biphasic mixture was stirred for 10 minutes
  2. stirringthe reaction was stirred for an additional 1 hour
  3. customThe layers were separated
  4. extractionthe aqueous fraction was extracted with dichloromethane
  5. washwashed successively with 5% aqueous sodium carbonate, water and saturated aqueous sodium chloride
  6. dry with materialThe organic fraction was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography
  10. customThe purification
  11. washwas carried out eluting with chloroform
  12. customCMA in a gradient from 99:1 to 93:7 to provide a red-brown solid
  13. customThe solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-85a7c8a107e341f5ba10fa9eda0412fd
Source dataset
uspto-grants-2011_03
Patent number
US07897597B2

Reaction notes

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