Dimethylcarbamoyl Chloride → 4-[1-(dimethylcarbamoyl)-5-(cyclopentyloxycarbonyl)amino-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid

HRID 1739584Notes

Reaction equation

HRID 1739584 reaction equation
[H-].[Na+].[CH:3]1([O:8][C:9]([NH:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][CH:16]=[C:15]3[CH2:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([OH:28])=[O:27])=[CH:24][C:23]=2[O:31][CH3:32])=[O:10])[CH2:7][CH2:6][CH2:5][CH2:4]1.[CH3:33][N:34]([CH3:38])[C:35](Cl)=[O:36]>CN(C)C=O>[CH3:33][N:34]([CH3:38])[C:35]([N:17]1[C:18]2[C:14](=[CH:13][C:12]([NH:11][C:9]([O:8][CH:3]3[CH2:4][CH2:5][CH2:6][CH2:7]3)=[O:10])=[CH:20][CH:19]=2)[C:15]([CH2:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([OH:28])=[O:27])=[CH:24][C:23]=2[O:31][CH3:32])=[CH:16]1)=[O:36]

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 24758Sodium hydrideHCID 146268444-(5-Cyclopentyloxycarbonylamino-1H-indol-3-ylmethyl)-3-methoxy-benzoic acid

Product 1

HCID 545237914-[1-(dimethylcarbamoyl)-5-(cyclopentyloxycarbonyl)amino-1H-indol-3-ylmethyl]-3-methoxy-benzoic acidYield 90.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a slurry of sodium hydride (60% by wt in mineral oil, 0.037 grams, 0.77 mmol) in dimethylformamide (5 mL), at 0° C., was added a solution of 4-[5-(cyclopentyloxycarbonyl)amino-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid (0.15 grams, 0.37 mmol) in dimethylformamide (5 mL). The resulting solution was stirred at 0° C. for 20 minutes, then dimethylcarbamoyl chloride (0.071 mL, 0.77 mmol) was added. The solution was warmed to room temperature and stirred for 1 hour. The reaction was quenched by addition of 1 M sodium hydroxide (aq), and the mixture was extracted with ethyl acetate. The combined organics were washed with 1 M hydrochloric acid (aq) and set aside. The aqueous phase was made acidic with 1 M hydrochloric acid (aq) and extracted with ethyl acetate. All the organics were combined and dried over magnesium sulfate and concentrated. Chromatography on silica gel (2% methanol/methylene chloride) gave 4-[1-(dimethylcarbamoyl)-5-(cyclopentyloxycarbonyl)amino-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid (0.16 grams, 89% yield).

Workup

  1. temperatureThe solution was warmed to room temperature
  2. stirringstirred for 1 hour
  3. customThe reaction was quenched by addition of 1 M sodium hydroxide (aq)
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe combined organics were washed with 1 M hydrochloric acid (aq)
  6. extractionextracted with ethyl acetate
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3b6acd72c9874b288cdf93b946f2c5f1
Source dataset
uspto-grants-1999_10
Patent number
US05965745

Reaction notes

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