Water → 2-[4-[N-acetyl-N-(3-dimethylaminopropyl)amino]-3-fluorophenyl]-6,8-difluoro-5-pentylamino-4H-1-benzopyran-4-one

HRID 1736197Notes

Reaction equation

HRID 1736197 reaction equation
[C:1]([N:4]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:18][C:19]3[C:27]([F:28])=[CH:26][C:25]([F:29])=[C:24]([NH2:30])[C:20]=3[C:21](=[O:23])[CH:22]=2)=[CH:13][C:12]=1[F:31])[CH2:5][CH2:6][CH2:7][N:8]([CH3:10])[CH3:9])(=[O:3])[CH3:2].[H-].[Na+].I[CH2:35][CH2:36][CH2:37][CH2:38][CH3:39].O>CN(C)C=O>[C:1]([N:4]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:18][C:19]3[C:27]([F:28])=[CH:26][C:25]([F:29])=[C:24]([NH:30][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[C:20]=3[C:21](=[O:23])[CH:22]=2)=[CH:13][C:12]=1[F:31])[CH2:5][CH2:6][CH2:7][N:8]([CH3:9])[CH3:10])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 123351-IodopentaneHCID 24758Sodium hydrideHCID 194349332-[4-[N-acetyl-N-(3-dimethylaminopropyl) amino]-3-fluorophenyl]-5-amino-6,8-difluoro-4H-1-benzopyran-4-one

Product 1

HCID 194349672-[4-[N-acetyl-N-(3-dimethylaminopropyl)amino]-3-fluorophenyl]-6,8-difluoro-5-pentylamino-4H-1-benzopyran-4-oneYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.01 g (2.33 mmol) of the above 2-[4-[N-acetyl-N-(3-dimethylaminopropyl)amino]-3-fluorophenyl]-5-amino-6,8-difluoro-4H-1-benzopyran-4-one was dissolved in 20 mL of dimethylformamide under argon atmosphere, 190 mg (4.75 mmol) of sodium hydride (60% oil dispersion) and 0.61 mL (4.7 mmol) of 1-iodopentane were added under ice-cooling and the mixture was stirred at room temperature for 50 minutes. Water was added to the reaction solution and the mixture was extracted twice with ethyl acetate. The organic layer was washed 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:methanol=20:1-9:1) to give 759 mg of 2-[4-[N-acetyl-N-(3-dimethylaminopropyl)amino]-3-fluorophenyl]-6,8-difluoro-5-pentylamino-4H-1-benzopyran-4-one (yield: 65%).

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. washThe organic layer was washed 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:methanol=20:1-9:1)

Sources & evidence

ORD record
ord-3d94e762dd1e45fdb193e6cbe509b4ed
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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