Triethylamine → N-(4-methoxy-3-pyridyl)-4-oxo-4,5,6,7-tetrahydro-1H-indole 3-carboxamide

HRID 910

Reaktionsgleichung

Reaktionsgleichung von HRID 910
[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(CC)CC)C.Cl[C:22]([O:24][CH2:25][CH3:26])=O.CO[C:29]1C=C[C:32]([NH2:35])=[CH:31][N:30]=1.[Cl-].[NH4+]>CN(C)C=O>[CH3:22][O:24][C:25]1[CH:26]=[CH:29][N:30]=[CH:31][C:32]=1[NH:35][C:11]([C:4]1[C:3]2[C:2](=[O:1])[CH2:10][CH2:9][CH2:8][C:7]=2[NH:6][CH:5]=1)=[O:13]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 811216-Methoxy-3-pyridinylamineHCID 153376324-Oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid

Produkt 1

HCID 18696549N-(4-methoxy-3-pyridyl)-4-oxo-4,5,6,7-tetrahydro-1H-indole 3-carboxamideAusbeute 19,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a stirring solution of 4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (179 mg, 1 mmol) and triethylamine (293 μl, 2.1 mmol) in N,N-dimethylformamide (3 mL) at 0° C. was added ethyl chloroformate (191 μl, 2 mmol). After stirring an additional 30 minutes, a solution of 2-methoxy-5-amino-pyridine (216 mg, 2 mmol) in N,N-dimethylformamide (3 mL) was added. The reaction mixture was allowed to stir for an additional 75 minutes, then poured into saturated aqueous ammonium chloride and extracted 2× with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo. To the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL), then heated at reflux for 1 hour. After cooling in an ice water bath, the reaction mixture was poured into saturated aqueous ammonium chloride and extracted 2× with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, concentrated in vacuo, and the residue recrystallized from ethyl acetate to give N-(4-methoxy-3-pyridyl)-4-oxo-4,5,6,7-tetrahydro-1H-indole 3-carboxamide (56 mg); m.p. 209°-210° C. (Compound 1).

Aufarbeitung

  1. stirringto stir for an additional 75 minutes
  2. extractionextracted 2× with ethyl acetate
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionTo the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL)
  8. temperatureheated
  9. temperatureat reflux for 1 hour
  10. temperatureAfter cooling in an ice water bath
  11. additionthe reaction mixture was poured into saturated aqueous ammonium chloride
  12. extractionextracted 2× with ethyl acetate
  13. dry with materialThe combined organic layers were dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customthe residue recrystallized from ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-d07aee7e0ad7464fbe1b6cc8f5dbc2e5
Quelldatensatz
uspto-grants-1998_03
Patentnummer
US05723462

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