反应详情

温度

40 °C

Sodium hydride (60% in mineral oil; 21.00 g; 525 mmol) was added to a 4-neck (2 L) flask under nitrogen with mechanical stirrer, condenser, thermocouple and addition funnel attached. Dry diglyme (450 mL) was added. A solution of 2-(4-isopropylpiperazin-1-yl)ethanol (90.45 g; 525 mmol) in diglyme (150 mL) was added slowly with stirring. The temperature was slowly increased to 40° C. until effervescence had ceased. The mixture was allowed to cool and 4-chloropyridin-2-amine (45.00 g; 350 mmol) was added. The mixture was heated at 157° C. for 16 hours and allowed to cool. Water (300 mL) was added followed by THF (750 mL). Sodium chloride was added (sufficient to saturate the aqueous phase). The phases were separated and the aqueous phase was further extracted with THF (3×600 mL). The combined organic phases were dried with sodium sulfate (600 g) for 16 hours and then filtered. The solvent was removed under vacuum (8 mm Hg, bath temperature at 60° C., to remove the diglyme). The residue was dissolved in THF (1000 mL) and filtered (Celite) to remove some fine particulates. The solvent was removed under vacuum to give a pale brown oil. The material was placed under high vacuum. A solid slowly formed (about 130 g). Ether (200 mL) was added and the material was physically broken up. Hexane (about 200 mL) was added, and the resulting solids were mechanically stirred to break them up. The solids were collected by filtration and washed (hexane/ether 1:1). The material was dried under vacuum to give the desired product (38.4 g) as a cream colored solid.

1. additionthermocouple and addition funnel
2. temperatureto cool
3. temperatureThe mixture was heated at 157° C. for 16 hours
4. temperatureto cool
5. concentrationto saturate the aqueous phase)
6. customThe phases were separated
7. extractionthe aqueous phase was further extracted with THF (3×600 mL)
8. dry with materialThe combined organic phases were dried with sodium sulfate (600 g) for 16 hours
9. filtrationfiltered
10. customThe solvent was removed under vacuum (8 mm Hg, bath temperature at 60° C.
11. customto remove the diglyme)
12. dissolutionThe residue was dissolved in THF (1000 mL)
13. filtrationfiltered (Celite)
14. customto remove some fine particulates
15. customThe solvent was removed under vacuum
16. customto give a pale brown oil
17. customA solid slowly formed (about 130 g)
18. stirringthe resulting solids were mechanically stirred
19. filtrationThe solids were collected by filtration
20. washwashed (hexane/ether 1:1)
21. customThe material was dried under vacuum