反应详情

温度

45 °C

Add phosphoryl chloride (5 equiv; 2.21 mL, 3.64 g, 23.76 mmoles) to 7-chloro-2-(methylsulfanyl)-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one (1.38 g, 4.75 mmoles) in chloroform (20 mL) and heat and stir at 45° C. for 2 h. Raise the temperature of the reaction to 60° C. and stir for a further 2 h. Remove the chloroform in vacuo and dissolve the residue in DCM (100 mL) and wash with saturated sodium bicarbonate solution (100 mL). Filter the DCM layer through a phase separation frit and evaporate the solvent in vacuo to give a viscous oil. Dissolve the oil in acetonitrile (10 mL) and add cesium carbonate (3 equiv; 4.65 g, 14.26 mmoles). Add to this mixture piperazine (10 equiv; 4.09 g, 47.52 mmoles) in dry acetonitrile (10 mL) and heat and stir the mixture under reflux overnight. Cool the reaction mixture and add saturated ammonium chloride solution (100 mL) and extract into EtOAc (2×50 mL). Combine the organic layers and wash with water (3×100 mL), dry over MgSO4, filter and evaporate the solvent in vacuo to give 7-chloro-2-(methylsulfanyl)-11-(piperazin-1-yl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.0 g, 60%). MS (m/z): 347.13 (M+1).

1. temperatureheat
2. temperatureRaise
3. customthe temperature of the reaction to 60° C.
4. stirringstir for a further 2 h
5. customRemove the chloroform in vacuo
6. dissolutiondissolve the residue in DCM (100 mL)
7. washwash with saturated sodium bicarbonate solution (100 mL)
8. filtrationFilter the DCM layer
9. customthrough a phase separation frit
10. customevaporate the solvent in vacuo
11. customto give a viscous oil
12. temperatureheat
13. stirringstir the mixture
14. temperatureunder reflux overnight
15. temperatureCool the reaction mixture
16. extractionextract into EtOAc (2×50 mL)
17. washCombine the organic layers and wash with water (3×100 mL)
18. dry with materialdry over MgSO4
19. filtrationfilter
20. customevaporate the solvent in vacuo