反应详情

温度

-5 °C

Homopiperazine (3.413 g) was dissolved in tetrahydrofuran (57 ml) with stirring. After cooling the solution to −5° C., 5-isoquinolinesulfonyl chloride hydrochloride (3.00 g) was added while maintaining the internal temperature at 10° C. or less. The mixture was stirred at 5° C. or less for four hours. The reaction mixture was allowed to stand to reach room temperature and filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure, followed by the addition of ethyl acetate (57 ml), water (17 ml), and 3 N hydrochloric acid aqueous solution (6.4 ml). The mixture was separated into layers to obtain a water layer. After washing the water layer with ethyl acetate (7 ml), water (6 ml), ethyl acetate (57 ml), and 6 N sodium hydroxide aqueous solution (3 ml) were added to separate the mixture into layers and obtain an organic layer. The organic layer was concentrated under reduced pressure and the residue was dried under reduced pressure to obtain fasudil (1.36 g). The yield was 41%. The fasudil is processed by the method described in JP-A-9-71582 to obtain fasudil hydrochloride.

1. temperaturewhile maintaining the internal temperature at 10° C. or less
2. stirringThe mixture was stirred at 5° C. or less for four hours
3. customto reach room temperature
4. filtrationfiltered
5. customto remove insoluble matter
6. concentrationThe filtrate was concentrated under reduced pressure
7. additionfollowed by the addition of ethyl acetate (57 ml), water (17 ml), and 3 N hydrochloric acid aqueous solution (6.4 ml)
8. customThe mixture was separated into layers
9. customto obtain a water layer
10. washAfter washing the water layer with ethyl acetate (7 ml), water (6 ml), ethyl acetate (57 ml), and 6 N sodium hydroxide aqueous solution (3 ml)
11. additionwere added
12. customto separate the mixture into layers
13. customobtain an organic layer
14. concentrationThe organic layer was concentrated under reduced pressure
15. customthe residue was dried under reduced pressure