反应详情

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.

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