Water → 4-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-yl morpholine-4-carboxylate

HRID 2203628Notes

Reaction equation

HRID 2203628 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[C:17]2[N:18]=[C:19]([CH2:24][O:25][CH2:26][CH3:27])[N:20]([CH2:21][CH2:22][CH3:23])[C:16]=2[C:15]2[CH:14]=[C:13]([OH:28])[CH:12]=[CH:11][C:10]=2[N:9]=1.[N:29]1([C:35](Cl)=[O:36])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.O>CN(C=O)C>[N:29]1([C:35]([O:28][C:13]2[CH:12]=[CH:11][C:10]3[N:9]=[C:8]([NH2:7])[C:17]4[N:18]=[C:19]([CH2:24][O:25][CH2:26][CH3:27])[N:20]([CH2:21][CH2:22][CH3:23])[C:16]=4[C:15]=3[CH:14]=2)=[O:36])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 848104-Morpholinecarbonyl chlorideHCID 689719384-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol

Product 1

HCID 588336324-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-yl morpholine-4-carboxylateYield 88.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cesium carbonate (1.62 g, 5.00 mmol) was added to a solution of 4-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol (500 mg, 1.66 mmol, prepared in Parts A and B of Example 566) in anhydrous DMF (30 mL). The reaction was stirred for ten minutes, and 4-morpholinecarbonyl chloride (275 mg, 1.83 g) was then added. The reaction was stirred overnight at ambient temperature and poured into deionized water (300 mL). The resulting mixture was stirred for one hour and then extracted with chloroform (3×100 mL). The combined organic fractions were concentrated under reduced pressure, and the resulting solid was purified by chromatography on a HORIZON HPFC system (silica cartridge, eluting with a gradient of 0-20% CMA in chloroform). The resulting solid was recrystallized from acetonitrile and dried under vacuum to yield 606 mg of 4-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-yl morpholine-4-carboxylate as a white, crystalline solid, mp 193-196° C. Anal. calcd for C21H27N5O4: C, 61.00; H, 6.58; N, 16.94. Found: C, 61.01; H, 6.51; N, 17.21.

Workup

  1. stirringThe reaction was stirred overnight at ambient temperature
  2. stirringThe resulting mixture was stirred for one hour
  3. extractionextracted with chloroform (3×100 mL)
  4. concentrationThe combined organic fractions were concentrated under reduced pressure
  5. customthe resulting solid was purified by chromatography on a HORIZON HPFC system (silica cartridge
  6. washeluting with a gradient of 0-20% CMA in chloroform)
  7. customThe resulting solid was recrystallized from acetonitrile
  8. customdried under vacuum

Sources & evidence

ORD record
ord-233941ccac834070a9b9fe3cdad28061
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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