Sodium hydride → 5-cyano-2-(3,5-dichloro-phenoxy)-N-(2-dimethylamino-ethyl)-N-[2-(2,5-dioxo-pyrrolidin-1-yl)-ethyl]-benzenesulfonamide

HRID 2242811Notes

Reaction equation

HRID 2242811 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:18][C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=2)=[C:7]([S:9]([NH:12][CH2:13][CH2:14][N:15]([CH3:17])[CH3:16])(=[O:11])=[O:10])[CH:8]=1)#[N:2].Br[CH2:28][CH2:29][N:30]1[C:34](=[O:35])[CH2:33][CH2:32][C:31]1=[O:36].[H-].[Na+]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:18][C:19]2[CH:20]=[C:21]([Cl:26])[CH:22]=[C:23]([Cl:25])[CH:24]=2)=[C:7]([S:9]([N:12]([CH2:13][CH2:14][N:15]([CH3:17])[CH3:16])[CH2:28][CH2:29][N:30]2[C:34](=[O:35])[CH2:33][CH2:32][C:31]2=[O:36])(=[O:10])=[O:11])[CH:8]=1)#[N:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 135613951-(2-Bromoethyl)pyrrolidine-2,5-dioneHCID 592083045-cyano-2-(3,5-dichloro-phenoxy)-N-(2-dimethylamino-ethyl)-benzenesulfonamide

Product 1

HCID 111919305-cyano-2-(3,5-dichloro-phenoxy)-N-(2-dimethylamino-ethyl)-N-[2-(2,5-dioxo-pyrrolidin-1-yl)-ethyl]-benzenesulfonamideYield 81.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-cyano-2-(3,5-dichloro-phenoxy)-N-(2-dimethylamino-ethyl)-benzene-sulfonamide (41.4 mg, 0.1 mmol) in dry DMF (2 ml) was added 1-(2-bromo-ethyl)-pyrrolidine-2,5-dione (30.9 mg, 0.15 mmol) and NaH (60%, 6.00 mg, 0.15 mmol). The mixture was stirred for 8 hours at 90° C. After cooled to room temperature, the solvent was evaporated. The mixture was diluted with EtOAc (60 ml), washed with brine, and dried over MgSO4. The solvent was evaporated and the residue was purified by preparative TLC (CH2Cl2/CH3OH=20/1) to give 5-cyano-2-(3,5-dichloro-phenoxy)-N-(2-dimethylamino-ethyl)-N-[2-(2,5-dioxo-pyrrolidin-1-yl)-ethyl]-benzenesulfonamide (44 mg, 81.6%) and the free base was converted into HCl salt by 4N HCl in dioxane.

Workup

  1. temperatureAfter cooled to room temperature
  2. customthe solvent was evaporated
  3. additionThe mixture was diluted with EtOAc (60 ml)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. customThe solvent was evaporated
  7. customthe residue was purified by preparative TLC (CH2Cl2/CH3OH=20/1)

Sources & evidence

ORD record
ord-33dfae9ddd17442dbf6ecbea0c5a5d09
Source dataset
uspto-grants-2010_03
Patent number
US07674797B2

Reaction notes

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