Reacción #1006

Ecuación de reacción

2-methoxy-5-amino-pyridine

ammonium chloride

4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid

triethylamine

ethyl chloroformate

→

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

Rendimiento 19.6%

Disolventes

N,N-dimethylformamide

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGto stir for an additional 75 minutes
2. 2
   Extracciónextracted 2× with ethyl acetate
3. 3
   LavadoThe combined organic layers were washed with water
4. 4
   Secadodried over magnesium sulfate
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated in vacuo
7. 7
   workup.ADDITIONTo the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL)
8. 8
   Temperaturaheated
9. 9
   Temperaturaat reflux for 1 hour
10. 10
    TemperaturaAfter cooling in an ice water bath
11. 11
    workup.ADDITIONthe reaction mixture was poured into saturated aqueous ammonium chloride
12. 12
    Extracciónextracted 2× with ethyl acetate
13. 13
    SecadoThe combined organic layers were dried over magnesium sulfate
14. 14
    Filtraciónfiltered
15. 15
    Concentraciónconcentrated in vacuo
16. 16
    Otrothe residue recrystallized from ethyl acetate

Procedimiento

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).

Fuente