反应详情

温度

50 °C

Pyrrolo[2,1-f][1,2,4]triazin-4-amine (20.5 g, 152 mmol) was dissolved in 150 mL DMF. Under ice cooling, phosphoryl chloride (31.3 mL, 336 mmol) was added dropwise at such a rate that the internal temperature did not rise above 30° C. The mixture was then heated for 2 days at 50° C. After cooling, another portion of phosphoryl chloride (14.2 mL, 152 mmol) was added, and stirring was continued for another 24 h at 50° C. After cooling, the reaction batch was slowly poured into a mixture of 2.0 L saturated aqueous sodium bicarbonate solution and 2.0 L ethyl acetate. Solid sodium bicarbonate was added until gas evolution stopped. The layers were separated, the aqueous layer was extracted with 0.5 L ethyl acetate, and the combined organic phases were dried over sodium sulfate and concentrated. The residue was suspended in 100 mL diisopropyl ether, stirred at room temperature for 10 min and then filtered. The dried residue was stirred in 6 N hydrochloric acid (500 mL) for 1 h at 50° C. and then poured into an ice/water mixture (1000 mL). The mixture was carefully neutralized with solid sodium bicarbonate, stirred for 30 min at room temperature and then filtered again. The residue was washed with water and ligroin to yield 20.6 g (83% of th.) of white crystals which were used in the next step without further purification.

1. customdid not rise above 30° C
2. temperatureAfter cooling
3. temperatureAfter cooling
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with 0.5 L ethyl acetate
6. dry with materialthe combined organic phases were dried over sodium sulfate
7. concentrationconcentrated
8. stirringstirred at room temperature for 10 min
9. filtrationfiltered
10. stirringThe dried residue was stirred in 6 N hydrochloric acid (500 mL) for 1 h at 50° C.
11. additionpoured into an ice/water mixture (1000 mL)
12. stirringstirred for 30 min at room temperature
13. filtrationfiltered again
14. washThe residue was washed with water and ligroin
15. customto yield 20.6 g (83% of th.) of white crystals which
16. customwere used in the next step without further purification