反应详情

Under a nitrogen atmosphere, a solution of 2,4-dichloro-5,6-dimethyl-3-nitropyridine (137.9 g, 0.624 mol) in anhydrous DMF (1.4 L) was cooled to 0° C., and anhydrous triethylamine (109 mL, 0.780 mol) was added. Propargyl amine hydrochloride (4.72 g, 51.6 mmol) and propargyl amine (38.4 g, 0.697 mol) were sequentially added dropwise, and the reaction was allowed to warm to room temperature and then heated at 40° C. for 22 hours. The volatiles were removed under reduced pressure, and water (1.5 L) and solid sodium carbonate (75 g) were added to the resulting oil. The mixture was then extracted with dichloromethane, and the combined extracts were washed sequentially with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting sequentially with 60:40 dichloromethane/hexane and dichloromethane) to provide 51.54 g of 2-chloro-5,6-dimethyl-3-nitro-N-prop-2-ynylpyridin-4-amine as a brown solid.

1. temperatureheated at 40° C. for 22 hours
2. customThe volatiles were removed under reduced pressure, and water (1.5 L) and solid sodium carbonate (75 g)
3. additionwere added to the resulting oil
4. extractionThe mixture was then extracted with dichloromethane
5. washthe combined extracts were washed sequentially with water and brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude product was purified by column chromatography on silica gel (
10. washeluting sequentially with 60:40 dichloromethane/hexane and dichloromethane)