4-Toluenesulfonyl chloride → 2-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylsulfonyl)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine

HRID 244813Notes

Reaction equation

HRID 244813 reaction equation
[C:1]1([S:7]([CH:10]=[CH:11][C:12]2[CH:13]=[CH:14][C:15]3[C:16]4[N:24]([CH2:25][CH2:26][CH2:27][O:28][CH:29]([CH3:31])[CH3:30])[C:23]([CH2:32][O:33][CH2:34][CH3:35])=[N:22][C:17]=4[CH:18]=[N:19][C:20]=3[CH:21]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC1C=C(C=CC=1)C(OO)=O.[OH-].[NH4+:48].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[CH2:34]([O:33][CH2:32][C:23]1[N:24]([CH2:25][CH2:26][CH2:27][O:28][CH:29]([CH3:31])[CH3:30])[C:16]2[C:15]3[CH:14]=[CH:13][C:12](/[CH:11]=[CH:10]/[S:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)(=[O:8])=[O:9])=[CH:21][C:20]=3[N:19]=[C:18]([NH2:48])[C:17]=2[N:22]=1)[CH3:35]

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 690814007-(2-benzenesulfonylvinyl)-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinoline

Product 1

HCID 119970312-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylsulfonyl)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

7-(2-Benzenesulfonylvinyl)-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinoline (0.600 g, 1.22 mmol) was dissolved in chloroform (12 mL). 3-Chloroperoxybenzoic acid (60% purity, 0.351 g, 1.22 mmol) was added. The reaction was stirred for 30 minutes. Ammonium hydroxide (8 mL) was added and the mixture was stirred for 10 minutes. p-Toluenesulfonyl chloride (0.232 g, 1.22 mmol) was added in one portion and the reaction was stirred for an additional 16 hours. The layers were separated and the aqueous fraction was extracted with chloroform. The combined organic fractions were sequentially washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using a Horizon HPFC system (an automated, modular high-performance flash purification product available from Biotage, Inc.; Charlottesville, Va., USA). The polar component of the eluent was chloroform:methanol:ammonium hydroxide 80:18:2 (CMA). The purification was carried out with a silica cartridge eluting with a linear gradient of 1-22% CMA in chloroform. The resulting material was subsequently recrystallized from acetonitrile to yield 0.320 g 2-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylsulfonyl)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine as green needles, mp 188.5-190.0° C.

Workup

  1. stirringthe mixture was stirred for 10 minutes
  2. stirringthe reaction was stirred for an additional 16 hours
  3. customThe layers were separated
  4. extractionthe aqueous fraction was extracted with chloroform
  5. washThe combined organic fractions were sequentially washed with water and saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography
  10. custommodular high-performance flash purification product available from Biotage, Inc
  11. customThe purification
  12. washeluting with a linear gradient of 1-22% CMA in chloroform
  13. customThe resulting material was subsequently recrystallized from acetonitrile

Sources & evidence

ORD record
ord-427d1de9bc294451be028631b9702102
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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