Acetonitrile → 3-{2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylprop-2-enamide

HRID 244840Notes

Reaction equation

HRID 244840 reaction equation
C(#N)C.C(N(CC)CC)C.[CH3:11][N:12]([CH3:17])[C:13](=[O:16])[CH:14]=[CH2:15].Br[C:19]1[CH:28]=[CH:27][C:26]2[N:25]=[CH:24][C:23]3[N:29]=[C:30]([CH2:41][CH2:42][O:43][CH3:44])[N:31]([CH2:32][CH2:33][CH2:34][N:35]4[CH2:39][CH2:38][CH2:37][C:36]4=[O:40])[C:22]=3[C:21]=2[CH:20]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(Cl)(Cl)Cl.CO>[CH3:44][O:43][CH2:42][CH2:41][C:30]1[N:31]([CH2:32][CH2:33][CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][C:36]2=[O:40])[C:22]2[C:21]3[CH:20]=[C:19]([CH:15]=[CH:14][C:13]([N:12]([CH3:17])[CH3:11])=[O:16])[CH:28]=[CH:27][C:26]=3[N:25]=[CH:24][C:23]=2[N:29]=1

Participants

9

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 17587N,N-DimethylacrylamideHCID 219843071-{3-[8-bromo-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}pyrrolidin-2-one

Product 1

HCID 690822943-{2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylprop-2-enamideYield 86.4%

Reagents, catalysts & solvents 4

HCID 80271Tri-o-tolylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
120 °C

Procedure

A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (8 mg, 0.04 mmol), acetonitrile (50 mL), triethylamine (0.9 mL, 5.22 mmol), tri-o-tolylphosphine (30 mg, 0.10 mmol), N,N-dimethylacrylamide (189 mg, 1.91 mmol) and 1-{3-[8-bromo-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}pyrrolidin-2-one (0.75 g, 1.7 mmol). The reaction mixture was purged with nitrogen and the tube was sealed and heated at 120° C. in an oil bath. The reaction was maintained at 120° C. for 18 hours and then cooled to ambient temperature. Upon cooling a precipitate formed that was dissolved by the addition of methanol and chloroform. The remaining insoluble material was removed by filtration through a 0.2 micron PTFE membrane filter. The filtrate was concentrated under reduced pressure and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a 0-7% gradient of methanol in dichloromethane) to provide 660 mg of 3-{2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylprop-2-enamide as an off-white solid.

Workup

  1. customA thick walled glass tube, equipped with a stir bar
  2. customThe reaction mixture was purged with nitrogen
  3. customthe tube was sealed
  4. temperatureThe reaction was maintained at 120° C. for 18 hours
  5. temperaturecooled to ambient temperature
  6. temperatureUpon cooling a precipitate
  7. customformed
  8. customThe remaining insoluble material was removed by filtration through a 0.2 micron PTFE membrane
  9. filtrationfilter
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. custompurified by chromatography
  12. washeluting with a 0-7% gradient of methanol in dichloromethane)

Sources & evidence

ORD record
ord-fd2cd8463e294ccd9849cc724f8d443d
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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