Triethylamine → N-[2-(4-[2-[4(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]-2,4,6-triisopropylbenzenesulfonamide hydrochloride

HRID 412352Notes

Reaction equation

HRID 412352 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)CC)C.[CH:46]([C:49]1[CH:54]=[C:53]([CH:55]([CH3:57])[CH3:56])[CH:52]=[C:51]([CH:58]([CH3:60])[CH3:59])[C:50]=1[S:61]([Cl:64])(=[O:63])=[O:62])([CH3:48])[CH3:47]>CN(C)C=O>[ClH:64].[O:31]=[C:29]1[NH:28][C:27](=[O:32])[CH:26]([CH2:25][C:24]2[CH:33]=[CH:34][C:21]([O:20][CH2:19][C:17]3[N:16]([CH3:35])[C:15]4[CH:36]=[C:11]([O:10][C:9]5[CH:8]=[CH:7][C:6]([CH2:5][CH2:4][NH:3][S:61]([C:50]6[C:51]([CH:58]([CH3:59])[CH3:60])=[CH:52][C:53]([CH:55]([CH3:57])[CH3:56])=[CH:54][C:49]=6[CH:46]([CH3:48])[CH3:47])(=[O:63])=[O:62])=[CH:38][CH:37]=5)[CH:12]=[CH:13][C:14]=4[N:18]=3)=[CH:22][CH:23]=2)[S:30]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 810422,4,6-Tris(1-methylethyl)benzenesulfonyl chlorideHCID 865877735-[4-[6-[4-(2-aminoethyl)phenoxy]-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

Product 1

HCID 18537722N-[2-(4-[2-[4(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]-2,4,6-triisopropylbenzenesulfonamide hydrochlorideYield 66.7%

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 (0.3 g), triethylamine (0.17 g) and anhydrous N,N-dimethylformamide (10 ml) was added 2,4,6-triisopropylbenzenesulfonyl chloride (0.17 g) and the mixture was stirred at room temperature for 4.5 hours. The reaction mixture was concentrated and partitioned between ethyl acetate and water. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. The residue was chromatographed on a silica gel column using ethyl acetate:n-hexane=2:1 as the eluant. To a solution of the product in ethyl acetate (15 ml) was added 4N hydrogen chloride in 1,4-dioxane (2 ml) and the mixture was stirred at room temperature for 20 minutes. The precipitate was isolated by filtration and washed with ethyl acetate to afford the title compound (0.28 g, mp 134-136° C.).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between ethyl acetate and water
  3. washThe extract was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. additionTo a solution of the product in ethyl acetate (15 ml) was added 4N hydrogen chloride in 1,4-dioxane (2 ml)
  8. stirringthe mixture was stirred at room temperature for 20 minutes
  9. customThe precipitate was isolated by filtration
  10. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-fc37fa9fdbaf4874a8b46822cc59e45e
Source dataset
uspto-grants-2003_05
Patent number
US06562849B1

Reaction notes

Loading…