Triethylamine → 1-(2,4-Difluorophenyl)-3-[2-(4-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]urea

HRID 412347Notes

Reaction equation

HRID 412347 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.[F:46][C:47]1[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:48]=1[N:54]=[C:55]=[O:56]>CN(C)C=O>[F:46][C:47]1[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:48]=1[NH:54][C:55]([NH:3][CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][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:37][CH:38]=1)=[O:56]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 5932582,4-Difluorophenyl isocyanateHCID 865877735-[4-[6-[4-(2-aminoethyl)phenoxy]-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

Product 1

HCID 101224091-(2,4-Difluorophenyl)-3-[2-(4-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)ethyl]ureaYield 58.3%

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 (0.3 g), triethylamine (65 mg) and anhydrous N,N-dimethylformamide (5 ml) was added 2,4-difluorophenyl isocyanate (81 mg) and the mixture was stirred at room temperature for 4.5 hours and then allowed to stand for 2 days. 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 the residue was added ethyl acetate and the precipitate was isolated by filtration and washed with ethyl acetate to afford the title compound (0.2 g, mp 161-164° C.).

Workup

  1. waitto stand for 2 days
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with water and tetrahydrofuran
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. additionTo the residue was added ethyl acetate
  9. customthe precipitate was isolated by filtration
  10. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-a7d4f6b6ba614b3391516cfbc807e19c
Source dataset
uspto-grants-2003_05
Patent number
US06562849B1

Reaction notes

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