Water → HCID 19434997, compound

HRID 1736142Notes

Reaction equation

HRID 1736142 reaction equation
[NH2:1][C:2]1[C:7]2[C:8](=[O:26])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14]([F:25])[CH:13]=3)[O:11][C:6]=2[C:5]([F:27])=[CH:4][C:3]=1[F:28].[H-].[Na+].Br[CH2:32][CH2:33][CH2:34][Cl:35].O>CN(C)C=O>[Cl:35][CH2:34][CH2:33][CH2:32][NH:1][C:2]1[C:7]2[C:8](=[O:26])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14]([F:25])[CH:13]=3)[O:11][C:6]=2[C:5]([F:27])=[CH:4][C:3]=1[F:28]

Participants

6

Reactant 4

HCID 962WaterHCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 19434934HCID 19434934, compound

Product 1

HCID 19434997HCID 19434997, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

814 mg (2.09 mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 15 ml of dimethylformamide under argon atmosphere, 256 mg of sodium hydride (60% oil dispersion) and 0.42 ml of 1-bromo-3-chloropropane were added under ice-cooling and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction solution and the mixture was extracted twice with ethyl acetate. The organic layer was washed twice with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1) to give 193 mg (20%) of 5-(3-chloropropylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. washThe organic layer was washed twice with an aqueous saturated solution of sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1)

Sources & evidence

ORD record
ord-5548901e8bc442e0822d775726d7fb65
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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