Water → 6-Carbamoyl-4-[1-(2,4-difluorophenylcarbamoyl)1H-indol-5-yloxy]-7-methoxyquinoline

HRID 853400Notes

Reaction equation

HRID 853400 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[CH:9][CH:8]=[C:7]2[O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[CH:20]2)(=[O:3])[NH2:2].[H-].[Na+].[F:28][C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=1[NH:36][C:37](=O)[O:38]C1C=CC=CC=1.O>CN(C)C=O.O1CCCC1.C(OCC)(=O)C>[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[CH:9][CH:8]=[C:7]2[O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([C:37](=[O:38])[NH:36][C:30]1[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:29]=1[F:28])[CH:21]=[CH:20]2)(=[O:3])[NH2:2]

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 13733129phenyl N-(2,4-difluorophenyl)carbamateHCID 229364686-Carbamoyl-4-(1H-indol-5-yloxy)-7-methoxyquinoline

Product 1

HCID 229370016-Carbamoyl-4-[1-(2,4-difluorophenylcarbamoyl)1H-indol-5-yloxy]-7-methoxyquinolineYield 57.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 6-carbamoyl-4-(1H-indol-5-yloxy)-7-methoxyquinoline (100 mg, 0.3 mmol) in N,N-dimethylformamide (0.5 ml), there was added sodium hydride (12 mg, 0.3 mmol) while cooling on ice and the mixture was stirred at room temperature for 15 minutes. After adding phenyl N-(2,4-difluorophenyl)carbamate (79 mg, 0.3150 mmol), the mixture was stirred at room temperature for 2 hours. Water was added to the reaction solution, extraction was performed with ethyl acetate and tetrahydrofuran, 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 ethanol and diluted with hexane, and then the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (84 mg, 0.1718 mmol, 57.28%) as colorless crystals.

Workup

  1. temperaturewhile cooling on ice
  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. additiondiluted with hexane
  7. filtrationthe crystals were filtered out
  8. washwashed with hexane
  9. customdried by aspiration

Sources & evidence

ORD record
ord-89a551e136d9468caa397c9a9862fe8f
Source dataset
uspto-grants-2007_08
Patent number
US07253286B2

Reaction notes

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