Triethylamine → 1-(3-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)-3-[4-(trifluoromethyl)benzyl]urea

HRID 412346Notes

Reaction equation

HRID 412346 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[F:13][C:14]([F:24])([F:23])[C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][CH:16]=1.Cl.Cl.[NH2:27][C:28]1[CH:29]=[C:30]([CH:58]=[CH:59][CH:60]=1)[O:31][C:32]1[CH:33]=[CH:34][C:35]2[N:39]=[C:38]([CH2:40][O:41][C:42]3[CH:55]=[CH:54][C:45]([CH2:46][CH:47]4[S:51][C:50](=[O:52])[NH:49][C:48]4=[O:53])=[CH:44][CH:43]=3)[N:37]([CH3:56])[C:36]=2[CH:57]=1.C(N(CC)CC)C>CN(C)C=O>[O:52]=[C:50]1[NH:49][C:48](=[O:53])[CH:47]([CH2:46][C:45]2[CH:54]=[CH:55][C:42]([O:41][CH2:40][C:38]3[N:37]([CH3:56])[C:36]4[CH:57]=[C:32]([O:31][C:30]5[CH:29]=[C:28]([NH:27][C:1]([NH:20][CH2:19][C:18]6[CH:21]=[CH:22][C:15]([C:14]([F:23])([F:24])[F:13])=[CH:16][CH:17]=6)=[O:2])[CH:60]=[CH:59][CH:58]=5)[CH:33]=[CH:34][C:35]=4[N:39]=3)=[CH:43][CH:44]=2)[S:51]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 768044-(Trifluoromethyl)benzylamineHCID 865877725-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

Product 1

HCID 101226081-(3-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)-3-[4-(trifluoromethyl)benzyl]ureaYield 20.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1,1′-carbonyldiimidazole (130 mg) in anhydrous N,N-dimethylformamide (8 ml) was added 4-(trifluoromethyl)benzylamine (135 mg) and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added 5-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (400 mg) and triethylamine (153 mg) and the mixture was stirred at 60° C. for 1 hour and then allowed to stand at room temperature overnight. 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 as the eluant. The product insoluble in methanol was isolated by filtration and further purified by preparative reverse phase high performance liquid chromatography using acetonitrile:water=50:50→60:40 as the eluant to afford the title compound (102 mg, mp 127.9-132.4° C.).

Workup

  1. stirringthe mixture was stirred at 60° C. for 1 hour
  2. waitto stand at room temperature overnight
  3. concentrationThe reaction mixture was concentrated
  4. custompartitioned between ethyl acetate and water
  5. washThe extract was washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was chromatographed on a silica gel column
  9. customThe product insoluble in methanol was isolated by filtration
  10. customfurther purified by preparative reverse phase high performance liquid chromatography

Sources & evidence

ORD record
ord-26a6fd56b7ae42058f128adcb6b6fab7
Source dataset
uspto-grants-2003_05
Patent number
US06562849B1

Reaction notes

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