1-Propanol → HCID 58835302, compound

HRID 1187417Notes

Reaction equation

HRID 1187417 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:23][CH2:24][CH3:25])[N:14]([CH2:15][CH2:16][CH2:17][O:18][N:19]=[C:20]([CH3:22])[CH3:21])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[C:27]1(B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)CC>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)Cl.O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:23][CH2:24][CH3:25])[N:14]([CH2:15][CH2:16][CH2:17][O:18][N:19]=[C:20]([CH3:22])[CH3:21])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:5][C:4]=2[N:3]=1

Participants

10

Reactant 4

HCID 10311-PropanolHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 58835307HCID 58835307, compound

Product 1

HCID 58835302HCID 58835302, compoundYield 55.8%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
100 °C

Procedure

In a pressure vessel under a nitrogen atmosphere, acetone O-[3-(4-amino-7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]oxime (500 mg, 1.20 mmol), phenylboronic acid (219 mg, 1.80 mmol), a solution of palladium (II) acetate (2.7 mg, 0.012 mmol) in hot toluene (0.5 mL), triphenylphosphine (9.5 mg, 0.036 mmol), and 2 M aqueous sodium carbonate (0.72 mL, 1.44 mmol) were combined in 5:1 n-propanol:water (2.4 mL). The solution was placed under vacuum and back-filled with nitrogen three times. The pressure vessel was sealed and heated at 100° C. overnight, then was allowed to cool to ambient temperature. Chloroform (60 mL) was added and the mixture was washed with water (2×10 mL) and brine (10 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% CMA in chloroform) to yield a solid that was triturated twice with acetonitrile and isolated to yield 278 mg of acetone O-[3-(4-amino-7-phenyl-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]oxime as a white powder, mp 164.0-165.0° C.

Workup

  1. additionback-filled with nitrogen three times
  2. customThe pressure vessel was sealed
  3. temperatureto cool to ambient temperature
  4. washthe mixture was washed with water (2×10 mL) and brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% CMA in chloroform)
  9. customto yield a solid
  10. customthat was triturated twice with acetonitrile
  11. customisolated

Sources & evidence

ORD record
ord-13ee70f7251744e0bb474add617c9c0c
Source dataset
uspto-grants-2014_03
Patent number
US08673932B2

Reaction notes

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