Triethylamine → N-[3-(methylaminomethyl)phenyl]-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamide

HRID 322632

Reaction equation

HRID 322632 reaction equation
[O:1]=[C:2]1[CH2:10][CH2:9][CH2:8][C:7]2[NH:6][CH:5]=[C:4]([C:11]([OH:13])=O)[C:3]1=2.C([N:16]([CH2:19]C)[CH2:17][CH3:18])C.ClC(OCC)=O.FC(F)(F)C([N:31](CNC)[C:32]1[CH:37]=C[CH:35]=[CH:34][CH:33]=1)=O.[Cl-].[NH4+]>CN(C)C=O>[CH3:19][NH:16][CH2:17][C:18]1[CH:37]=[C:32]([NH:31][C:11]([C:4]2[C:3]3[C:2](=[O:1])[CH2:10][CH2:9][CH2:8][C:7]=3[NH:6][CH:5]=2)=[O:13])[CH:33]=[CH:34][CH:35]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 153376324-Oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acidHCID 57112434N-trifluoroacetyl-(methylaminomethyl)aniline

Product 1

HCID 9817695N-[3-(methylaminomethyl)phenyl]-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (100 mg, 0.6 mmol) and triethylamine (0.15 mL, 1.1 mmol) in N,N-dimethylformamide (5 mL) at 0° C. is added ethyl chloroformate (0.1 mL, 1.1 mmol). After stirring an additional 1 hour, 3-(N-trifluoroacetyl-(methylaminomethyl)aniline (0.3 g, 1.3 mmol) is added. The reaction mixture is stirrred for 4 hours, then poured into saturated aqueous ammonium chloride and extracted 2× with ethyl acetate. The combined organic layers are washed sequentially with brine, aqueous 2N hydrochloric acid, then brine, dried over sodium sulfate, filtered, and concentrated in vacuo. To the residue is added 15% aqueous potassium bicarbonate (5 mL) and methyl alcohol (3 mL), then heated at reflux for 3 hours. After cooling, the reaction mixture is extracted with ethyl acetate, the organic layer dried over sodium sulfate, filtered, and concentrated in vacuo to give N-[3-(methylaminomethyl)phenyl]-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamide; (Compound 1) m.p. 130-132° C.

Workup

  1. waitThe reaction mixture is stirrred for 4 hours
  2. extractionextracted 2× with ethyl acetate
  3. washThe combined organic layers are washed sequentially with brine, aqueous 2N hydrochloric acid
  4. dry with materialbrine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionTo the residue is added 15% aqueous potassium bicarbonate (5 mL) and methyl alcohol (3 mL)
  8. temperatureheated
  9. temperatureat reflux for 3 hours
  10. temperatureAfter cooling
  11. extractionthe reaction mixture is extracted with ethyl acetate
  12. dry with materialthe organic layer dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0ac1bd3ce1754b51b29a66257c0cdbf1
Source dataset
uspto-grants-2001_04
Patent number
US06211365B1

Linked notes

Loading…