Sodium hydride → HCID 67087741, compound

HRID 57200

Reaction equation

HRID 57200 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]3([C:32]4[C:33]([O:38][CH2:39][CH3:40])=[N:34][CH:35]=[CH:36][CH:37]=4)[C:27]4[C:22](=[CH:23][C:24]([F:30])=[C:25]([C:28]#[N:29])[CH:26]=4)[NH:21][C:20]3=[O:31])=[O:17])[CH2:12][CH2:11]2)[CH2:6][CH2:5]1.[CH3:41][O:42][C:43]1[CH:48]=[C:47]([O:49][CH3:50])[CH:46]=[CH:45][C:44]=1[S:51](Cl)(=[O:53])=[O:52]>CN(C)C=O>[CH3:3][N:4]1[CH2:5][CH2:6][CH:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]3([C:32]4[C:33]([O:38][CH2:39][CH3:40])=[N:34][CH:35]=[CH:36][CH:37]=4)[C:27]4[C:22](=[CH:23][C:24]([F:30])=[C:25]([C:28]#[N:29])[CH:26]=4)[N:21]([S:51]([C:44]4[CH:45]=[CH:46][C:47]([O:49][CH3:50])=[CH:48][C:43]=4[O:42][CH3:41])(=[O:53])=[O:52])[C:20]3=[O:31])=[O:17])[CH2:12][CH2:11]2)[CH2:8][CH2:9]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27346262,4-Dimethoxybenzenesulfonyl chlorideHCID 670876865-Cyano-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(1-methylpiperidin-4-yl)piperazine-1-carboxylate

Product 1

HCID 67087741HCID 67087741, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

9.2 mg (0.19 mmol) of sodium hydride (50% dispersion in mineral oil) were added to a solution of 50 mg (0.10 mmol) of 5-cyano-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(1-methylpiperidin-4-yl)piperazine-1-carboxylate in 2 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 29 mg (0.12 mmol) of 2,4-dimethoxyphenylsulfonyl chloride were added, and stirring was continued at room temperature for 30 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 20% methanol in dichloromethane). 34 mg of the title compound were obtained as a white solid.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringstirring
  3. waitwas continued at room temperature for 30 min
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed with saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent was evaporated
  8. customThe residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 0 to 20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-78edea1a860d41b79ae8177c3c12aa49
Source dataset
uspto-grants-2016_09
Patent number
US09434713B2

Linked notes

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