Sodium hydride → 1H-Indole-2-carboxamide

HRID 1383328Notes

Reaction equation

HRID 1383328 reaction equation
CN1CCN([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH:10]=[C:11]([C:17]([OH:19])=[O:18])[NH:12]3)CC1.C(N1C=CN=C1)([N:22]1C=CN=C1)=O.[H-].[Na+]>CN(C)C=O>[NH:12]1[C:13]2[C:9](=[CH:8][CH:16]=[CH:15][CH:14]=2)[CH:10]=[C:11]1[C:17]([NH2:22])=[O:19].[NH:12]1[C:13]2[C:9](=[CH:8][CH:16]=[CH:15][CH:14]=2)[CH:10]=[C:11]1[C:17]([O-:19])=[O:18]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 21187590HCID 21187590, compound

Product 2

HCID 5948321H-Indole-2-carboxamideHCID 4288522Indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-(4-methylpiperazin-1 yl)indole-2-carboxylic acid (0.259 g, 1.00 mmol) in anhydrous N,N-dimethylformamide (6 mL) at room temperature was added carbonyldiimidazole (0.574 g, 2.00 mmol, 2.0 equivalents). The resulting reaction solution was stirred at room temperature under nitrogen for 2 hours. Then, the appropriate amine (4.00 mmol, 4.0 equivalents) or alcohol (4.00 mmol, 4.0 equivalents) was added directly, and the resulting reaction solution was stirred at room temperature under nitrogen overnight. In the case of alcohols, sodium hydride (60% in oil, 0.160 g, 4.00 mmol, 4.0 equivalents) was added, and the resulting reaction was heated an additional 2 hours at 50° C. The reaction solution was then evaporated under reduced pressure, and redissolved in chloroform (5 mL). Undissolved solid was removed via filtration through Celite®, and the filtrate was evaporated under reduced pressure. The residue was column chromatographed using silica gel (approximately 50 g) and elution with an appropriate solvent system to afford the corresponding indole-2-carboxamide or indole-2-carboxylate.

Workup

  1. customThe resulting reaction solution
  2. customthe resulting reaction solution
  3. stirringwas stirred at room temperature under nitrogen overnight
  4. customthe resulting reaction
  5. temperaturewas heated an additional 2 hours at 50° C
  6. customThe reaction solution was then evaporated under reduced pressure
  7. dissolutionredissolved in chloroform (5 mL)
  8. customwas removed via filtration through Celite®
  9. customthe filtrate was evaporated under reduced pressure
  10. customchromatographed
  11. washsilica gel (approximately 50 g) and elution with an appropriate solvent system

Sources & evidence

ORD record
ord-d56ea81f7def48caa237f78534e91ef4
Source dataset
uspto-grants-2001_07
Patent number
US06255306B1

Reaction notes

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