Ethyl orthoformate → HCID 67041325, compound

HRID 606129Notes

Reaction equation

HRID 606129 reaction equation
[CH:1](OCC)(OCC)OCC.Cl.N1C=CC=CC=1.[CH2:18]([C:22]1[O:26][N:25]=[C:24]([CH2:27][NH:28][C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]=[CH:31][C:30]=2[NH2:39])[CH:23]=1)[CH2:19][CH2:20][CH3:21]>C(#N)C>[CH2:18]([C:22]1[O:26][N:25]=[C:24]([CH2:27][N:28]2[C:29]3[C:38]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[N:32]=[CH:31][C:30]=3[N:39]=[CH:1]2)[CH:23]=1)[CH2:19][CH2:20][CH3:21]

Participants

5

Reactant 3

HCID 31214Ethyl orthoformate2×HCID 10176127Pyridinium chloride2×HCID 86247648HCID 86247648, compound

Product 1

HCID 67041325HCID 67041325, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Triethyl orthoformate (0.80 mL, 4.80 mmol) and pyridine hydrochloride (0.092 g, 0.80 mmol) were sequentially added to a solution of N4-[(5-butylisoxazol-3-yl)methyl]quinoline-3,4-diamine (1.19 g, 4.00 mmol) in acetonitrile (100 mL), and the solution was heated gently at reflux overnight. An analysis by HPLC indicated the presence of starting material, and additional triethyl orthoformate and pyridine hydrochloride were added. The solution was heated at reflux for an additional 24 hours. The solvents were removed under reduced pressure, and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The aqueous layer was separated and extracted with dichloromethane, and the combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (eluting with 3% to 8% methanol in dichloromethane) to provide 1.06 g of 1-[(5-butylisoxazol-3-yl)methyl]-1H-imidazo[4,5-c]quinoline as an orange solid.

Workup

  1. temperaturethe solution was heated gently
  2. temperatureat reflux overnight
  3. additionwere added
  4. temperatureThe solution was heated
  5. temperatureat reflux for an additional 24 hours
  6. customThe solvents were removed under reduced pressure
  7. customthe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  8. customThe aqueous layer was separated
  9. extractionextracted with dichloromethane
  10. washthe combined organic fractions were washed with brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe crude product was purified by flash column chromatography on silica gel (eluting with 3% to 8% methanol in dichloromethane)

Sources & evidence

ORD record
ord-8f8196b7da0b479284c42ebc595748c4
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

Loading…