Potassium Carbonate → 4-[2,6-dichloro-3-[N-methyl-N-[4-(methylcarbamoyl)cinnamoylglycyl]amino]benzyloxy]-1-ethoxycarbonylmethyl-2-ethyl-1H-benzimidazole

HRID 2287571Notes

Reaction equation

HRID 2287571 reaction equation
[CH2:1]([O:3][C:4]([CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[C:15]([OH:16])[C:10]=2[N:9]=[C:8]1[CH2:17][CH3:18])=[O:5])[CH3:2].[Cl:19][C:20]1[C:27]([N:28]([CH3:47])[C:29](=[O:46])[CH2:30][NH:31][C:32](=[O:45])[CH:33]=[CH:34][C:35]2[CH:40]=[CH:39][C:38]([C:41](=[O:44])[NH:42][CH3:43])=[CH:37][CH:36]=2)=[CH:26][CH:25]=[C:24]([Cl:48])[C:21]=1[CH2:22]Br.C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:19][C:20]1[C:27]([N:28]([CH3:47])[C:29](=[O:46])[CH2:30][NH:31][C:32](=[O:45])[CH:33]=[CH:34][C:35]2[CH:36]=[CH:37][C:38]([C:41](=[O:44])[NH:42][CH3:43])=[CH:39][CH:40]=2)=[CH:26][CH:25]=[C:24]([Cl:48])[C:21]=1[CH2:22][O:16][C:15]1[C:10]2[N:9]=[C:8]([CH2:17][CH3:18])[N:7]([CH2:6][C:4]([O:3][CH2:1][CH3:2])=[O:5])[C:11]=2[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 212546631-ethoxycarbonylmethyl-2-ethyl-4-hydroxy-1H-benzimidazoleHCID 538052362,6-dichloro-3-[N-[4-(methylcarbamoyl)cinnamoylglycyl]-N-methylamino]benzyl bromide

Product 1

HCID 536707184-[2,6-dichloro-3-[N-methyl-N-[4-(methylcarbamoyl)cinnamoylglycyl]amino]benzyloxy]-1-ethoxycarbonylmethyl-2-ethyl-1H-benzimidazoleYield 82.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-ethoxycarbonylmethyl-2-ethyl-4-hydroxy-1H-benzimidazole (140 mg) and 2,6-dichloro-3-[N-methyl-N-[4-(methylcarbamoyl)cinnamoylglycyl]amino]benzyl bromide (289 mg) in dimethylformamide (3 ml) was added potassium carbonate (117 mg) under ice-cooling, and the mixture was stirred for 30 minutes at the same temperature and then for 2 hours at ambient temperature. To the reaction mixture was added saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel flash chromatography (5% methanol-ethyl acetate) and pulverized with diisopropyl ether to give 4-[2,6-dichloro-3-[N-methyl-N-[4-(methylcarbamoyl)cinnamoylglycyl]amino]benzyloxy]-1-ethoxycarbonylmethyl-2-ethyl-1H-benzimidazole (317 mg) as pale yellow solid.

Workup

  1. temperaturecooling
  2. waitfor 2 hours at ambient temperature
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel flash chromatography (5% methanol-ethyl acetate)

Sources & evidence

ORD record
ord-58c83f0a948f4d0483f185b623f5d781
Source dataset
uspto-grants-2000_07
Patent number
US06083961

Reaction notes

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