4-Methoxybenzenesulfonyl chloride → HCID 67160321, compound

HRID 2408818Notes

Reaction equation

HRID 2408818 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]2([NH:22][C:23]([N:25]1[CH2:30][CH2:29][N:28]([CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)[CH2:27][CH2:26]1)=[O:24])[C:13]1[C:14]([O:19][CH2:20][CH3:21])=[N:15][CH:16]=[CH:17][CH:18]=1)#[N:2].[H-].[Na+].N1C2C(=CC=CC=2)CC1=O.[CH3:50][O:51][C:52]1[CH:57]=[CH:56][C:55]([S:58](Cl)(=[O:60])=[O:59])=[CH:54][CH:53]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C.ClCCl.CO>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:58]([C:55]1[CH:54]=[CH:53][C:52]([O:51][CH3:50])=[CH:57][CH:56]=1)(=[O:60])=[O:59])[C:7](=[O:12])[C:6]2([NH:22][C:23]([N:25]1[CH2:26][CH2:27][N:28]([CH:31]2[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]2)[CH2:29][CH2:30]1)=[O:24])[C:13]1[C:14]([O:19][CH2:20][CH3:21])=[N:15][CH:16]=[CH:17][CH:18]=1)#[N:2]

Participants

9

Reactant 5

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 24758Sodium hydrideHCID 321710OxindoleHCID 516892Sodium BicarbonateHCID 67160215HCID 67160215, compound

Product 1

HCID 67160321HCID 67160321, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

80.0 mg (0.16 mmol) of N-[5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(1-methylpiperidin-4-yl)piperazine-1-carboxamide were dissolved in dimethylformamide, and 7.63 mg (0.19 mmol, 60% w/w) of sodium hydride were added at 0° C. For the deprotonation of the 1,3-dihydro-2H-indol-2-on derivative, the mixture was stirred for 10 minutes, and 39.4 mg (0.19 mmol) of 4-methoxybenzenesulphonyl chloride were then added. The mixture was then allowed to warm to room temperature and stirred for 30 minutes. The progress of the reaction was monitored by TLC (silica gel, dichloromethane/methanol 1:1). Saturated sodium bicarbonate solution and ethyl acetate were added to the reaction mixture, and the phases were then separated. The aqueous phase was reextracted with ethyl acetate (1×). The combined organic phase was washed with water (1×) and saturated sodium chloride solution (1×), dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The residue was purified by preparative MPLC (ISCO Companion, 4 g NP cartridge) using the mobile phases dichloromethane/methanol (5-20%). What was isolated were 27.3 mg (0.04 mmol, 23% yield, 90% purity) of N-[5-cyano-3-(2-ethoxypyridin-3-yl)-1-[(4-methoxyphenyl)sulphonyl]-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(1-methylpiperidin-4-yl)piperazine-1-carboxamide.

Workup

  1. customthe phases were then separated
  2. washThe combined organic phase was washed with water (1×) and saturated sodium chloride solution (1×)
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by preparative MPLC (ISCO Companion, 4 g NP cartridge)
  7. customWhat was isolated

Sources & evidence

ORD record
ord-7031cd76c75449738a7498941fd080cf
Source dataset
uspto-grants-2014_08
Patent number
US08815868B2

Reaction notes

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