反应详情

温度

79 °C

Potassium hydroxide (0.483 wt, 5 eq, 242 g) is added to a suspension of 2-(6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole (1 wt, 1 eq, 501 g), and CTAB (cetyltrimethylammonium bromide) (0.031 wt, 0.05 eq, 15.5 g) in 2-methyltetrahydrofuran (10 vols, 5.01 L) then heated at reflux (79° C.) for at least 4 hrs until the reaction is complete. The mixture is cooled to 50° C. and washed at 50° C. with water (2×10 vols, 2×5 L). The solution is diluted with 2-methyl tetrahydrofuran (5 vols, 2.5 L) and filtered while at 50° C. to remove precipitated palladium residues. The organic solution is then distilled (100 mbar, 20° C.) down to 2 vols (1 L), diluted with 2-methyl tetrahydrofuran (1 vol, 0.5 L) and 3-pentanone (3 vols, 1.5 L) and distilled (100 mbar, 30° C.) down to 2 vols (1 L). The solution is again diluted with 3-pentanone (3 vols, 1.5 L) and distilled (80 mbar, 25° C.) down to 2 vol (1 L). The solution is again diluted with 3-pentanone (3 vols (1.5 L) and distilled (100 mbar, 30° C.) down to 3 vols (1.5 L). The suspension is cooled to 20° C. over 1 hr and aged at 20° C. for at least 2 hrs. The product is filtered under vacuum, washed with 3-pentanone (1 vol, 0.5 L) and dried under vacuum at 60° C. to afford 2-(6-(1H-indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole as a tan solid.

1. temperaturethen heated
2. temperatureThe mixture is cooled to 50° C.
3. washwashed at 50° C. with water (2×10 vols, 2×5 L)
4. additionThe solution is diluted with 2-methyl tetrahydrofuran (5 vols, 2.5 L)
5. filtrationfiltered while at 50° C.
6. customto remove
7. customprecipitated palladium residues
8. distillationThe organic solution is then distilled (100 mbar, 20° C.) down to 2 vols (1 L)
9. additiondiluted with 2-methyl tetrahydrofuran (1 vol, 0.5 L) and 3-pentanone (3 vols, 1.5 L)
10. distillationdistilled (100 mbar, 30° C.) down to 2 vols (1 L)
11. additionThe solution is again diluted with 3-pentanone (3 vols, 1.5 L)
12. distillationdistilled (80 mbar, 25° C.) down to 2 vol (1 L)
13. additionThe solution is again diluted with 3-pentanone (3 vols (1.5 L)
14. distillationdistilled (100 mbar, 30° C.) down to 3 vols (1.5 L)
15. temperatureThe suspension is cooled to 20° C. over 1 hr
16. waitaged at 20° C. for at least 2 hrs
17. filtrationThe product is filtered under vacuum
18. washwashed with 3-pentanone (1 vol, 0.5 L)
19. customdried under vacuum at 60° C.