Dimethylformamide → 2-(ethoxymethyl)-8-(2-morpholin-4-yl-2-oxoethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

HRID 540947Notes

Reaction equation

HRID 540947 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:10].[NH2:17][C:18]1[C:27]2[N:28]=[C:29]([CH2:34][O:35][CH2:36][CH3:37])[N:30]([CH2:31][CH2:32][CH3:33])[C:26]=2[C:25]2[CH:24]=[C:23]([OH:38])[CH:22]=[CH:21][C:20]=2[N:19]=1.CN(C=O)C>O>[CH2:36]([O:35][CH2:34][C:29]1[N:30]([CH2:31][CH2:32][CH3:33])[C:26]2[C:25]3[CH:24]=[C:23]([O:38][CH2:8][C:9]([N:11]4[CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)=[O:10])[CH:22]=[CH:21][C:20]=3[N:19]=[C:18]([NH2:17])[C:27]=2[N:28]=1)[CH3:37]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 139968762-Bromo-1-(morpholin-4-yl)ethan-1-oneHCID 689719384-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol

Product 1

HCID 588337102-(ethoxymethyl)-8-(2-morpholin-4-yl-2-oxoethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amineYield 46.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

Cesium carbonate (1.62 g, 5.00 mmol) was added to a solution of 2-bromo-1-morpholin-4-yl-ethanone (414 mg, 1.99 mmol), 4-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol (500 mg, 1.66 mmol), and anhydrous DMF (20 mL). The reaction mixture was heated at 75° C. overnight, allowed to cool, and poured into deionized water (300 mL). The resulting mixture was stirred for 30 minutes and then extracted with chloroform (3×100 mL). The combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was purified by chromatography on a HORIZON HPFC system (silica cartridge, eluting with a gradient of 0-35% methanol/dichloromethane (10:90) in dichloromethane). The resulting solid was recrystallized from acetonitrile to yield 333 mg of 2-(ethoxymethyl)-8-(2-morpholin-4-yl-2-oxoethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine as an off-white solid, mp 196-197° C. Anal. calcd for C22H29N5O4: C, 61.81; H, 6.84; N, 16.38. Found: C, 61.72; H, 6.86; N, 16.62.

Workup

  1. temperatureto cool
  2. extractionextracted with chloroform (3×100 mL)
  3. dry with materialThe combined organic fractions were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting solid was purified by chromatography on a HORIZON HPFC system (silica cartridge
  7. washeluting with a gradient of 0-35% methanol/dichloromethane (10:90) in dichloromethane)
  8. customThe resulting solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-8fe024a223414dbf88cba34b175d69ad
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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