Sodium hydride → 3-Amino-1-(2,4-dimethoxyphenylsulfonyl)-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile

HRID 1035840Notes

Reaction equation

HRID 1035840 reaction equation
[H-].[Na+].[NH2:3][C:4]1([C:17]2[C:18]([O:23][CH2:24][CH3:25])=[N:19][CH:20]=[CH:21][CH:22]=2)[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10]([C:13]#[N:14])[CH:11]=2)[NH:6][C:5]1=[O:16].[CH3:26][O:27][C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=1[S:36](Cl)(=[O:38])=[O:37]>CN(C)C=O>[NH2:3][C:4]1([C:17]2[C:18]([O:23][CH2:24][CH3:25])=[N:19][CH:20]=[CH:21][CH:22]=2)[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10]([C:13]#[N:14])[CH:11]=2)[N:6]([S:36]([C:29]2[CH:30]=[CH:31][C:32]([O:34][CH3:35])=[CH:33][C:28]=2[O:27][CH3:26])(=[O:38])=[O:37])[C:5]1=[O:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27346262,4-Dimethoxybenzenesulfonyl chlorideHCID 670874773-Amino-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile

Product 1

HCID 670877293-Amino-1-(2,4-dimethoxyphenylsulfonyl)-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indole-5-carbonitrileYield 41.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

80 mg (1.68 mmol) of sodium hydride (60% dispersion in mineral oil) were added in portions to a solution of 350 mg (1.12 mmol) of 3-amino-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile in 15 ml of anhydrous dimethylformamide under a nitrogen atmosphere and while cooling in an ice bath. The mixture was stirred at 0° C. for 10 min and then 398 mg (1.68 mmol) of 2,4-dimethoxy-phenylsulfonyl chloride were added, and the mixture was stirred at room temperature for 15 min. The reaction mixture was poured into ice-water and then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulfate, and the solvent was evaporated. The residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 0 to 3% methanol in ethyl acetate). 236 mg of the title compound were obtained as a white solid.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringthe mixture was stirred at room temperature for 15 min
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customthe solvent was evaporated
  7. customThe residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 0 to 3% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-0d4d642af271458d8b8f9b5a2ed57381
Source dataset
uspto-grants-2013_10
Patent number
US08546401B2

Reaction notes

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