Water → 2-(ethoxymethyl)-1-({1-[2-(methylsulfonyl)ethoxy]cyclohexyl}methyl)-1H-imidazo[4,5-c]quinoline

HRID 547311Notes

Reaction equation

HRID 547311 reaction equation
[H-].[Na+].[CH:3]([S:5]([CH3:8])(=[O:7])=[O:6])=[CH2:4].[CH2:9]([O:11][CH2:12][C:13]1[N:14]([CH2:26][C:27]2([OH:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:15]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:18]=[CH:17][C:16]=2[N:25]=1)[CH3:10].O>O1CCCC1>[CH2:9]([O:11][CH2:12][C:13]1[N:14]([CH2:26][C:27]2([O:33][CH2:4][CH2:3][S:5]([CH3:8])(=[O:7])=[O:6])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:15]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:18]=[CH:17][C:16]=2[N:25]=1)[CH3:10]

Participants

6

Reactant 4

HCID 962WaterHCID 19354Methyl vinyl sulfone2×HCID 24758Sodium hydride2×HCID 575153771-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclohexanol

Product 1

HCID 672040532-(ethoxymethyl)-1-({1-[2-(methylsulfonyl)ethoxy]cyclohexyl}methyl)-1H-imidazo[4,5-c]quinolineYield 16.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% dispersion in oil, 25 mg, 0.62 mmol) followed by methyl vinyl sulfone (1.30 g, 12.4 mmol) were added to a stirred solution of 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclohexanol (2.1 g, 6.2 mmol) in tetrahydrofuran (25 mL). The reaction mixture was heated at reflux for 2 hours and additional methyl vinyl sulfone (1 equivalent) and sodium hydride (60% dispersion in oil, spatula tip full) were added. The mixture was allowed to stir overnight at room temperature. Water (50 mL) was added and a precipitate formed that was removed by filtration. The filtrate was extracted with dichloromethane (2×50 mL). The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford an oil that was purified by flash chromatography (silica gel, eluted with 5% methanol in dichloromethane) to provide 0.45 g of 2-(ethoxymethyl)-1-({1-[2-(methylsulfonyl)ethoxy]cyclohexyl}methyl)-1H-imidazo[4,5-c]quinoline as a colorless oil.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 hours
  3. customa precipitate formed
  4. customthat was removed by filtration
  5. extractionThe filtrate was extracted with dichloromethane (2×50 mL)
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto afford an oil that
  11. customwas purified by flash chromatography (silica gel, eluted with 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0de65d8d51ea4c5d800cdecc4dfd9295
Source dataset
uspto-grants-2011_05
Patent number
US07939526B2

Reaction notes

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