Cyclohexanecarboxylic acid → N-[4-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl]cyclohexanecarboxamide

HRID 2303834Notes

Reaction equation

HRID 2303834 reaction equation
ClC(OCC)=O.[CH:7]1([C:13]([OH:15])=O)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.C(N(CC)CC)C.Cl.Cl.[NH2:25][C:26]1[CH:58]=[CH:57][C:29]([O:30][C:31]2[CH:32]=[CH:33][C:34]3[N:38]=[C:37]([CH2:39][O:40][C:41]4[CH:54]=[CH:53][C:44]([CH2:45][CH:46]5[S:50][C:49](=[O:51])[NH:48][C:47]5=[O:52])=[CH:43][CH:42]=4)[N:36]([CH3:55])[C:35]=3[CH:56]=2)=[CH:28][CH:27]=1>CN(C)C=O>[CH:7]1([C:13]([NH:25][C:26]2[CH:58]=[CH:57][C:29]([O:30][C:31]3[CH:32]=[CH:33][C:34]4[N:38]=[C:37]([CH2:39][O:40][C:41]5[CH:54]=[CH:53][C:44]([CH2:45][CH:46]6[S:50][C:49](=[O:51])[NH:48][C:47]6=[O:52])=[CH:43][CH:42]=5)[N:36]([CH3:55])[C:35]=4[CH:56]=3)=[CH:28][CH:27]=2)=[O:15])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 7413Cyclohexanecarboxylic acidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 865877685-[4-[6-(4-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

Product 1

HCID 18537678N-[4-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl]cyclohexanecarboxamideYield 63.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Ethyl chloroformate (87 mg) was added dropwise to a solution of cyclohexanecarboxylic acid (90 mg) and triethylamine (232 mg) in anhydrous N,N-dimethylformamide (8 ml) at ambient temperature. The mixture was stirred at the same temperature for 1.5 hours. To the reaction mixture was added 5-{4-[6-(4-aminophenoxy)-1-methyl-1H-benzimidazole-2-ylmethoxy]benzyl}thiazolidine-2,4-dione dihydrochloride (400 mg) in small portions. The mixture was stirred at 50° C. for 1.5 hours. The reaction mixture was concentrated and partitioned between ethyl acetate and water. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated. On addition of ethyl acetate to the residue insoluble product was formed and isolated by filtration and washed with ethyl acetate to give the title compound (262 mg).

Workup

  1. stirringThe mixture was stirred at 50° C. for 1.5 hours
  2. concentrationThe reaction mixture was concentrated
  3. custompartitioned between ethyl acetate and water
  4. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. additionOn addition of ethyl acetate to the residue insoluble product
  7. customwas formed
  8. customisolated by filtration
  9. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-2f33f60a43e94cca88b1b2aa9ddfb6f1
Source dataset
uspto-grants-2002_08
Patent number
US06432993B1

Reaction notes

Loading…