Water → 1-[4-amino-2-(ethoxymethyl)-7-(2-morpholin-4-yl-2-oxoethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

HRID 540952Notes

Reaction equation

HRID 540952 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([OH:24])=[CH:5][C:4]=2[N:3]=1.Br[CH2:26][C:27]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C.C(#N)C>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:18])([OH:19])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:24][CH2:26][C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[O:28])=[CH:5][C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 139968762-Bromo-1-(morpholin-4-yl)ethan-1-oneHCID 1363405384-amino-2-ethoxymethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol

Product 1

HCID 588337331-[4-amino-2-(ethoxymethyl)-7-(2-morpholin-4-yl-2-oxoethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-olYield 76.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 4-amino-2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol (prepared as described above, 750 mg, 2.27 mmol), 4-(bromoacetyl)morpholine (565 mg, 2.72 mmol), and cesium carbonate (2.22 g, 6.81 mmol) in DMF (30 mL) was heated at 75° C. overnight. The reaction mixture was allowed to cool and was poured into water (300 mL). After 30 minutes, the solution was extracted with chloroform (6×75 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated to dryness. The resulting solid was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% methanol/dichloromethane (1:10) in dichloromethane) The appropriate fractions were combined and concentrated to yield an off white solid that was slurried in boiling acetonitrile for 15 minutes. The slurry was allowed to cool with stirring. The solid was isolated by filtration and dried to yield 797 mg of 1-[4-amino-2-(ethoxymethyl)-7-(2-morpholin-4-yl-2-oxoethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as an off-white solid, mp 209-211° C.

Workup

  1. temperatureto cool
  2. extractionthe solution was extracted with chloroform (6×75 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe resulting solid was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% methanol/dichloromethane (1:10) in dichloromethane) The appropriate fractions
  7. concentrationconcentrated
  8. customto yield an off white solid
  9. customfor 15 minutes
  10. temperatureto cool
  11. customThe solid was isolated by filtration
  12. customdried

Sources & evidence

ORD record
ord-115946ae0b0e4431a13db3fa29bef1e1
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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