Sodium Carbonate → 2-ethyl-7-(2-morpholin-4-ylethoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine

HRID 540949Notes

Reaction equation

HRID 540949 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.[NH2:17][C:18]1[C:27]2[N:28]=[C:29]([CH2:38][CH3:39])[N:30]([CH2:31][CH:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[C:26]=2[C:25]2[CH:24]=[CH:23][C:22]([OH:40])=[CH:21][C:20]=2[N:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[CH2:38]([C:29]1[N:30]([CH2:31][CH:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[C:26]2[C:25]3[CH:24]=[CH:23][C:22]([O:40][CH2:9][CH2:10][N:11]4[CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)=[CH:21][C:20]=3[N:19]=[C:18]([NH2:17])[C:27]=2[N:28]=1)[CH3:39]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 10796Cesium carbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 1363478564-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-ol

Product 1

HCID 588336722-ethyl-7-(2-morpholin-4-ylethoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amineYield 62.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

Cesium carbonate (1.41 g, 4.32 mmol) was added to a solution of 4-(2-chloroethyl)morpholine hydrochloride (348 mg, 1.87 mmol) and 4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-ol (471 mg, 1.44 mmol, prepared in Parts A and B of Example 553) in anhydrous DMF (25 mL). The reaction mixture was heated at 75° C. overnight, allowed to cool, and poured into 1% aqueous sodium carbonate (300 mL). The resulting mixture was stirred for two hours and then extracted with chloroform (4×100 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 0-40% methanol/dichloromethane (20:80) in dichloromethane). The resulting solid was recrystallized from acetonitrile and dried under vacuum to yield 393 mg of 2-ethyl-7-(2-morpholin-4-ylethoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine as an off-white solid, mp 230-232° C. Anal. calcd for C24H33N5O3: C, 65.58; H, 7.57; N, 15.93. Found: C, 65.48; H, 7.39; N, 15.91.

Workup

  1. temperatureto cool
  2. extractionextracted with chloroform (4×100 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 0-40% methanol/dichloromethane (20:80) in dichloromethane)
  8. customThe resulting solid was recrystallized from acetonitrile
  9. customdried under vacuum

Sources & evidence

ORD record
ord-dc8fe43aa05b4f54bd8d21fb14310fe2
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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