تفاعل #1006

معادلة التفاعل

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

المردود 19.6%

المذيبات

N,N-dimethylformamide

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGto stir for an additional 75 minutes
2. 2
   استخلاصextracted 2× with ethyl acetate
3. 3
   غسيلThe combined organic layers were washed with water
4. 4
   تجفيفdried over magnesium sulfate
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated in vacuo
7. 7
   workup.ADDITIONTo the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL)
8. 8
   درجة الحرارةheated
9. 9
   درجة الحرارةat reflux for 1 hour
10. 10
    درجة الحرارةAfter cooling in an ice water bath
11. 11
    workup.ADDITIONthe reaction mixture was poured into saturated aqueous ammonium chloride
12. 12
    استخلاصextracted 2× with ethyl acetate
13. 13
    تجفيفThe combined organic layers were dried over magnesium sulfate
14. 14
    ترشيحfiltered
15. 15
    تركيزconcentrated in vacuo
16. 16
    أخرىthe residue recrystallized from ethyl acetate

الإجراء التجريبي

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).

المصدر