4-Chlorobenzenesulfonyl chloride → 4-Chloro-N-[2-(4-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]benzenesulfonamide hydrochloride

HRID 412351

Reaction equation

HRID 412351 reaction equation
Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[CH:38]=[CH:37][C:9]([O:10][C:11]2[CH:12]=[CH:13][C:14]3[N:18]=[C:17]([CH2:19][O:20][C:21]4[CH:34]=[CH:33][C:24]([CH2:25][CH:26]5[S:30][C:29](=[O:31])[NH:28][C:27]5=[O:32])=[CH:23][CH:22]=4)[N:16]([CH3:35])[C:15]=3[CH:36]=2)=[CH:8][CH:7]=1.C(N(CC)C(C)C)(C)C.[Cl:48][C:49]1[CH:54]=[CH:53][C:52]([S:55](Cl)(=[O:57])=[O:56])=[CH:51][CH:50]=1>CN(C)C=O>[ClH:48].[Cl:48][C:49]1[CH:54]=[CH:53][C:52]([S:55]([NH:3][CH2:4][CH2:5][C:6]2[CH:7]=[CH:8][C:9]([O:10][C:11]3[CH:12]=[CH:13][C:14]4[N:18]=[C:17]([CH2:19][O:20][C:21]5[CH:34]=[CH:33][C:24]([CH2:25][CH:26]6[S:30][C:29](=[O:31])[NH:28][C:27]6=[O:32])=[CH:23][CH:22]=5)[N:16]([CH3:35])[C:15]=4[CH:36]=3)=[CH:37][CH:38]=2)(=[O:57])=[O:56])=[CH:51][CH:50]=1

Participants

5

Reactant 3

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 865877735-[4-[6-[4-(2-aminoethyl)phenoxy]-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

Product 1

HCID 185376064-Chloro-N-[2-(4-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]benzenesulfonamide hydrochlorideYield 118.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-[4-[6-[4-(2-aminoethyl)phenoxy]-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (0.4 g), N,N-diisopropylethylamine (0.27 g) and anhydrous N,N-dimethylformamide (15 ml) was added 4-chlorobenzenesulfonyl chloride (0.15 g) and the mixture was stirred at room temperature for 3.5 hours. The reaction mixture was concentrated and diluted with water and tetrahydrofuran and then extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. To a solution of the residue in tetrahydrofuran (10 ml) was added 4N hydrogen chloride in ethyl acetate (5 ml) and the mixture was stirred at room temperature for 1.5 hours. To the reaction mixture was added diethyl ether (10 ml) and this mixture was stirred at room temperature for 30 minutes and then was irradiated with ultrasound for 30 minutes. The precipitate was isolated by filtration and washed with acetone, ethyl acetate and n-hexane to afford the title compound (0.3 g, mp 155-160° C.).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water and tetrahydrofuran
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. additionTo a solution of the residue in tetrahydrofuran (10 ml) was added 4N hydrogen chloride in ethyl acetate (5 ml)
  8. stirringthe mixture was stirred at room temperature for 1.5 hours
  9. additionTo the reaction mixture was added diethyl ether (10 ml)
  10. stirringthis mixture was stirred at room temperature for 30 minutes
  11. customwas irradiated with ultrasound for 30 minutes
  12. customThe precipitate was isolated by filtration
  13. washwashed with acetone, ethyl acetate and n-hexane

Sources & evidence

ORD record
ord-7b6de217c5484cfaac502bfb85a7fa7f
Source dataset
uspto-grants-2003_05
Patent number
US06562849B1

Linked notes

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