反应详情

温度

50 °C

A mixture of 4.0 gm (12.6 mMol) 5-amino-3-(1-tert-butoxycarbonylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 2.7 mL (25.2 mMol) allyl chloroformate in 200 mL pyridine was heated at 50° C. for 5 hours. At this point an additional 2 mL of allyl chloroformate were added and heating was continued for another 1.5 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue partitioned between 1N sodium hydroxide and chloroform. The phases were separated and the aqueous phase was extracted well with chloroform. The organic phases were combined, washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. This residue was dissolved in 2M ammonia in methanol for two hours. The reaction mixture was concentrated under reduced pressure and the residue subjected to flash silica gel chromatography, eluting with dichloromethane containing from 2-5% methanol and 1% ammonium hydroxide. Fractions containing product were combined and concentrated under reduced pressure. The residue was crystallized from aqueous ethanol to provide 2.9 gm (60%) 5-(N-[prop-1-en-3-yloxycarbonyl]amino)-3-(1-tert-butoxycarbonylpiperidin-4-yl)pyrrolo[3,2-b]pyridine.

1. temperatureheating
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customthe resulting residue partitioned between 1N sodium hydroxide and chloroform
4. customThe phases were separated
5. extractionthe aqueous phase was extracted well with chloroform
6. washwashed with saturated aqueous sodium chloride
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated under reduced pressure
9. dissolutionThis residue was dissolved in 2M ammonia in methanol for two hours
10. concentrationThe reaction mixture was concentrated under reduced pressure
11. washeluting with dichloromethane containing from 2-5% methanol and 1% ammonium hydroxide
12. additionFractions containing product
13. concentrationconcentrated under reduced pressure
14. customThe residue was crystallized from aqueous ethanol