Dimethylformamide → 1-(Adamant-1-yl)-3-(4-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)urea

HRID 412334

Reaction equation

HRID 412334 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:36]=[CH:35][C:7]([O:8][C:9]2[CH:10]=[CH:11][C:12]3[N:16]=[C:15]([CH2:17][O:18][C:19]4[CH:32]=[CH:31][C:22]([CH2:23][CH:24]5[S:28][C:27](=[O:29])[NH:26][C:25]5=[O:30])=[CH:21][CH:20]=4)[N:14]([CH3:33])[C:13]=3[CH:34]=2)=[CH:6][CH:5]=1.[C:37]12([N:47]=[C:48]=S)[CH2:46][CH:41]3[CH2:42][CH:43]([CH2:45][CH:39]([CH2:40]3)[CH2:38]1)[CH2:44]2.C(N(CC)CC)C.CN(C)C=[O:60]>>[C:37]12([NH:47][C:48]([NH:3][C:4]3[CH:36]=[CH:35][C:7]([O:8][C:9]4[CH:10]=[CH:11][C:12]5[N:16]=[C:15]([CH2:17][O:18][C:19]6[CH:32]=[CH:31][C:22]([CH2:23][CH:24]7[S:28][C:27](=[O:29])[NH:26][C:25]7=[O:30])=[CH:21][CH:20]=6)[N:14]([CH3:33])[C:13]=5[CH:34]=4)=[CH:6][CH:5]=3)=[O:60])[CH2:46][CH:41]3[CH2:42][CH:43]([CH2:45][CH:39]([CH2:40]3)[CH2:38]1)[CH2:44]2

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 107279Adamantyl isothiocyanateHCID 865877685-[4-[6-(4-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

Product 1

HCID 101223331-(Adamant-1-yl)-3-(4-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)urea

Conditions

Temperature
50 °C

Procedure

A mixture of 5-[4-[6-(4-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (400 mg), 1-adamantyl isothiocyanate (284 mg), triethylamine (153 mg) and anhydrous N,N-dimethylformamide (8 ml) was stirred at room temperature for 4.5 hours, at 50° C. for 2.5 hours and then at 80° C. 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=1:1→2:1→3:1 as the eluant and the product was recrystallized from ethyl acetate to afford the title compound (192 mg, mp 164.0-166.6° C.).

Workup

  1. waitat 80° C. for 4.5 hours
  2. concentrationThe reaction mixture was concentrated
  3. custompartitioned between ethyl acetate and water
  4. washThe extract was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was chromatographed on a silica gel column
  8. customn-hexane=1:1→2:1→3:1 as the eluant and the product was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-55abd78f2e8243ba8bb97b31de87291e
Source dataset
uspto-grants-2003_05
Patent number
US06562849B1

Linked notes

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