Реакция #1006

Уравнение реакции

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

Выход 19.6%

Растворители

N,N-dimethylformamide

N,N-dimethylformamide

Условия реакции

Обработка

1. 1
   workup.STIRRINGto stir for an additional 75 minutes
2. 2
   Экстракцияextracted 2× with ethyl acetate
3. 3
   ПромывкаThe combined organic layers were washed with water
4. 4
   Сушкаdried over magnesium sulfate
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated in vacuo
7. 7
   workup.ADDITIONTo the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL)
8. 8
   Температураheated
9. 9
   Температураat reflux for 1 hour
10. 10
    ТемператураAfter cooling in an ice water bath
11. 11
    workup.ADDITIONthe reaction mixture was poured into saturated aqueous ammonium chloride
12. 12
    Экстракцияextracted 2× with ethyl acetate
13. 13
    СушкаThe combined organic layers were dried over magnesium sulfate
14. 14
    Фильтрацияfiltered
15. 15
    Концентрированиеconcentrated in vacuo
16. 16
    Другоеthe residue recrystallized from ethyl acetate

Методика

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).

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