Sodium Iodide → 2-[4-[N-Acetyl-N-(3-phthalimidopropyl)amino]-3-fluorophenyl]-5-amino-6,8-difluoro-4H-1-benzopyran-4-one

HRID 1736109Notes

Reaction equation

HRID 1736109 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[C:21]([F:22])=[CH:20][C:19]([F:23])=[C:18]([NH2:24])[C:14]=3[C:15](=[O:17])[CH:16]=2)=[CH:7][C:6]=1[F:25])(=[O:3])[CH3:2].[H-].[Na+].Br[CH2:29][CH2:30][CH2:31][N:32]1[C:36](=[O:37])[C:35]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:34]2[C:33]1=[O:42].[I-].[Na+].[Cl-].[NH4+]>CN(C)C=O>[C:1]([N:4]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[C:21]([F:22])=[CH:20][C:19]([F:23])=[C:18]([NH2:24])[C:14]=3[C:15](=[O:17])[CH:16]=2)=[CH:7][C:6]=1[F:25])[CH2:29][CH2:30][CH2:31][N:32]1[C:36](=[O:37])[C:35]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:34]2[C:33]1=[O:42])(=[O:3])[CH3:2]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 21611N-3-Bromopropylphthalimide3×HCID 24758Sodium hydride3×HCID 25517Ammonium ChlorideHCID 194349072-(4-Acetylamino-3-fluorophenyl)-5-amino-6,8-difluoro-4H-1-benzopyran-4-one

Product 1

HCID 153469942-[4-[N-Acetyl-N-(3-phthalimidopropyl)amino]-3-fluorophenyl]-5-amino-6,8-difluoro-4H-1-benzopyran-4-oneYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.81 g of Compound 27 was dissolved in 60 ml of dimethylformamide, 208 mg of sodium hydride (60% oil dispersion), 1.67 g of N-(3-bromopropyl)phthalimide and 156 mg of sodium iodide were added and the mixture was stirred at room temperature for 2.5 hours. Additional 104 mg of sodium hydride (60% oil dispersion) and 697 mg of N-(3-bromopropyl)phthalimide were added and the mixture was stirred at room temperature for 1.8 hours. Additional 62.4 mg of sodium hydride (60% oil dispersion) and 418 mg of N-(3-bromopropyl)phthalimide were added and the mixture was stirred at room temperature for 2 hours. An aqueous solution of ammonium chloride was added to the reaction solution, the solvent was distilled off under reduced pressure and the residue was extracted once with chloroform. The chloroform layer was washed 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 subjected to silica gel column chromatography (chloroform:methanol=100:1-60:1) and recrystallized from chloroform/n-hexane to give 1.72 g (62%) of Compound 28.

Workup

  1. stirringthe mixture was stirred at room temperature for 1.8 hours
  2. stirringthe mixture was stirred at room temperature for 2 hours
  3. distillationthe solvent was distilled off under reduced pressure
  4. extractionthe residue was extracted once with chloroform
  5. washThe chloroform layer was washed with an aqueous saturated solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customrecrystallized from chloroform/n-hexane

Sources & evidence

ORD record
ord-dcde743c08974f7cb1eb06c16c578e2c
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

Loading…