Sodium Iodide → 5-(3-ethoxycarbonylpropylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

HRID 1736222Notes

Reaction equation

HRID 1736222 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].Br[CH2:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[Cl-].[NH4+]>CN(C)C=O>[CH2:36]([O:35][C:33]([CH2:32][CH2:31][CH2:30][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])=[O:34])[CH3:37]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 76300Ethyl 4-bromobutyrateHCID 194349345-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

Product 1

HCID 194350065-(3-ethoxycarbonylpropylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-oneYield 54.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

1.03 g (2.64 mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 30 mL of dimethylformamide under argon atmosphere, 11.5 mL (79.2 mmol) of ethyl 4-bromobutyrate, 1.83 g (13.3 mmol) of potassium carbonate and 3.96 g (26.4 mmol) of sodium iodide were added and the mixture was stirred at 100° C. for 48 hours. The reaction solution was cooled on ice, an aqueous saturated solution of ammonium chloride was added and the mixture was extracted with ethyl acetate. The organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform:acetonitrile=25:l) and recrystallized from ethyl acetate/n-hexane to give 720 mg of 5-(3-ethoxycarbonylpropylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one (yield: 54%).

Workup

  1. temperatureThe reaction solution was cooled on ice
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed once with water and once 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 (chloroform:acetonitrile=25:l)
  7. customrecrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-b1b0f009bca342d4bdc1ebf382f52e90
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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