Triethylamine → HCID 69084207, compound

HRID 244836Notes

Reaction equation

HRID 244836 reaction equation
C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:30][N:31]([CH3:36])[C:32](=[O:35])[CH:33]=[CH2:34].Br[C:38]1[CH:39]=[CH:40][C:41]2[C:42]3[N:50]([CH2:51][C:52]([CH3:55])([OH:54])[CH3:53])[C:49]([CH2:56][CH3:57])=[N:48][C:43]=3[CH:44]=[N:45][C:46]=2[CH:47]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)(Cl)Cl.CO.C(#N)C>[CH2:56]([C:49]1[N:50]([CH2:51][C:52]([OH:54])([CH3:55])[CH3:53])[C:42]2[C:41]3[CH:40]=[CH:39][C:38]([CH:34]=[CH:33][C:32]([N:31]([CH3:36])[CH3:30])=[O:35])=[CH:47][C:46]=3[N:45]=[CH:44][C:43]=2[N:48]=1)[CH3:57]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 17587N,N-DimethylacrylamideHCID 80271Tri-o-tolylphosphineHCID 219842201-(7-bromo-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol

Product 1

HCID 69084207HCID 69084207, compoundYield 86.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (50 mg, 0.22 mmol), acetonitrile (50 mL), triethylamine (1.80 mL, 13.0 mmol), tri-o-tolylphosphine (200 mg, 0.65 mmol), N,N-dimethylacrylamide (511 mg, 5.16 mmol) and 1-(7-bromo-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol (1.50 g, 4.30 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, eluting with a 0-25% gradient of CMA in chloroform). The resulting product was washed with 1% aqueous sodium carbonate and filtered to provide 1.37 g of 3-[2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylprop-2-enamide as an off-white solid, mp 196-198° C.

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 0-25% gradient of CMA in chloroform)
  13. washThe resulting product was washed with 1% aqueous sodium carbonate
  14. filtrationfiltered

Sources & evidence

ORD record
ord-169d0131231f450585d2a0ac379d145f
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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