Water → 4-[1-(2,4-Difluorophenylcarbamoyl)-1H-indol-5-yloxy]-6,7-dimethoxyquinoline

HRID 1010274Notes

Reaction equation

HRID 1010274 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][CH:12]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[N:35]=[C:36]=[O:37].O>CN(C)C=O.C(OCC)(=O)C>[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[NH:35][C:36]([N:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][CH:12]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)=[O:37]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 5932582,4-Difluorophenyl isocyanateHCID 221326454-[(1H-Indol-5-yl)oxy]-6,7-dimethoxyquinoline

Product 1

HCID 589309404-[1-(2,4-Difluorophenylcarbamoyl)-1H-indol-5-yloxy]-6,7-dimethoxyquinolineYield 58.94%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 4-(1H-indol-5-yloxy)-6,7-dimethoxyquinoline (40 mg, 0.1249 mmol, described in WO9717329) in N,N-dimethylformamide (0.7 ml), sodium hydride (10 mg,) was added and the mixture was stirred at room temperature for 15 minutes. 2,4-Difluorophenyl isocyanate (0.018 ml, 0.1561 mmol) was further added, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the filtrate was distilled off under reduced pressure. The obtained crystals were suspended in diethyl ether:ethanol=10:1 and diluted with hexane, and then the crystals were filtered out, washed with diethyl ether:ethanol=10:1 and dried by aspiration to obtain the title compound (35 mg, 0.0736 mmol, 58.94%) as colorless crystals.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature for 2 hours
  3. washthe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe filtrate was distilled off under reduced pressure
  6. additionethanol=10:1 and diluted with hexane
  7. filtrationthe crystals were filtered out
  8. washwashed with diethyl ether
  9. dry with materialethanol=10:1 and dried by aspiration

Sources & evidence

ORD record
ord-c531846535d642eda8af67ba9769da6e
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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