反応 #1006

反応方程式

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

収率 19.6%

溶媒

N,N-dimethylformamide

N,N-dimethylformamide

反応条件

後処理

1. 1
   workup.STIRRINGto stir for an additional 75 minutes
2. 2
   抽出extracted 2× with ethyl acetate
3. 3
   洗浄The combined organic layers were washed with water
4. 4
   乾燥dried over magnesium sulfate
5. 5
   ろ過filtered
6. 6
   濃縮concentrated in vacuo
7. 7
   workup.ADDITIONTo the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL)
8. 8
   温度heated
9. 9
   温度at reflux for 1 hour
10. 10
    温度After cooling in an ice water bath
11. 11
    workup.ADDITIONthe reaction mixture was poured into saturated aqueous ammonium chloride
12. 12
    抽出extracted 2× with ethyl acetate
13. 13
    乾燥The combined organic layers were dried over magnesium sulfate
14. 14
    ろ過filtered
15. 15
    濃縮concentrated in vacuo
16. 16
    その他the residue recrystallized from ethyl acetate

実験手順

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).

出典