反应详情

To a suspension of 3-[4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoic acid (24.25 g, 58.44 mmoles) in isopropyl alcohol (250 mL) at 60° C., add a 4M dioxane solution of hydrogen chloride (2.4 equiv; 35.07 mL, 140.26 mmoles) over 10 minutes to give a clear solution. Allow to cool slightly then evaporate to an off-white solid. Triturate with a small amount of diethyl ether and collect the powdery cream solid by filtration. Dry in a vacuum oven at 40° C. overnight. Grind to a fine powder and dry in a vacuum oven at 60° C. for 6 h. Monitor levels of residual isopropyl alcohol by 1H NMR. Dissolve in warm ethanol (350 mL) and evaporate to dryness. Triturate with ethanol (50 mL) and evaporate to dryness again. Triturate with dry diethyl ether (200 mL) and collect the resulting solid by filtration. Dry for 6 h in a vacuum oven at 50° C. to give 3-[4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoic acid dihydrochloride (26.9 g, 94% yield) MS (m/z): 415.2 (M+1).

1. customto give a clear solution
2. temperatureto cool slightly
3. customthen evaporate to an off-white solid
4. customTriturate with a small amount of diethyl ether
5. customcollect the powdery cream solid
6. filtrationby filtration
7. customDry in a vacuum oven at 40° C. overnight
8. customGrind to a fine powder
9. customdry in a vacuum oven at 60° C. for 6 h
10. dissolutionDissolve in warm ethanol (350 mL)
11. customevaporate to dryness
12. customTriturate with ethanol (50 mL)
13. customevaporate to dryness again
14. customTriturate with dry diethyl ether (200 mL)
15. customcollect the resulting solid
16. filtrationby filtration
17. customDry for 6 h in a vacuum oven at 50° C.