反应详情

温度

140 °C

Dissolve methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate dihydrochloride (1.61 g, 5.89 mmoles) in water and load on to two SCX-2 (10 g) cartridges. Wash the cartridges with methanol and elute with 2M ammonia in methanol. Concentrate in vacuo, then dissolve the resultant oil in acetonitrile (40 mL). Add 7,11-dichloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.167 g, 4.4 mmoles) to the acetonitrile solution. Divide the acetonitrile solution and place in to 2 microwave tubes, add potassium carbonate (0.89 g, 6.79 mmoles) to each microwave tube and heat and stir at 140° C. in the microwave for 3.5 hr. Allow the reaction mixture to cool, filter, wash the solid collected on the sinter with acetonitrile then concentrate the filtrate in vacuo, add methanol and then evaporate to dryness. Treat with more methanol and collect the resultant precipitate, wash the precipitate with methanol to give methyl 3-[4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoate as a crystalline solid (1.1 g). MS (m/z): 429.18 (M+1).

1. washWash the cartridges with methanol
2. washelute with 2M ammonia in methanol
3. concentrationConcentrate in vacuo
4. dissolutiondissolve the resultant oil in acetonitrile (40 mL)
5. temperatureheat
6. temperatureto cool
7. filtrationfilter
8. washwash the solid
9. customcollected on the sinter with acetonitrile
10. concentrationthen concentrate the filtrate in vacuo
11. additionadd methanol
12. customevaporate to dryness
13. additionTreat with more methanol
14. customcollect the resultant precipitate
15. washwash the precipitate with methanol