Citric Acid → N,5-Dimethoxy-N-methyl-1H-indole-2-carboxamide

HRID 31548

Reaction equation

HRID 31548 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([OH:14])=O)=[CH:6]2.Cl.[CH3:16][NH:17][O:18][CH3:19].CCN=C=NCCCN(C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C(OCC)(=O)C>[CH3:19][O:18][N:17]([CH3:16])[C:12]([C:7]1[NH:8][C:9]2[C:5]([CH:6]=1)=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)=[O:14]

Participants

9

Reactant 6

HCID 311Citric AcidHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 204015-Methoxyindole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 23003326N,5-Dimethoxy-N-methyl-1H-indole-2-carboxamideYield 73.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-methoxyindole-2-carboxylic acid (5 g, 26 mmol) in N,N-dimethylformamide were added N,O-dimethylhydroxyamine hydrochloride (3.04 g, 31.2 mmol) and WSC (5.98 g, 31.2 mmol), 1-hydroxybenzotriazole (4.21 g, 31.2 mmol) and triethylamine (7.24 ml, 52 mmol), and the mixture was stirred for 6 hours. To this reaction solution were added ethyl acetate and 10% (Wt) citric acid, and the organic layer was extracted. The aqueous layer was extracted twice with ethyl acetate, and combined with the organic layer. The mixture was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated saline. The organic layer was separated, and dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give the title compound (4.5 g, 70%).

Workup

  1. extractionthe organic layer was extracted
  2. extractionThe aqueous layer was extracted twice with ethyl acetate
  3. washThe mixture was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated saline
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-7b23b6dc3dc64421a1c074c6a21315e7
Source dataset
uspto-grants-2008_09
Patent number
US07425642B2

Linked notes

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