Piperazine → 7-chloro-2-(methylsulfanyl)-11-(piperazin-1-yl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine

HRID 1877804Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1877804
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[NH:16][C:15](=O)[C:14]3=[CH:18][C:19]([S:21][CH3:22])=[CH:20][N:13]3[CH2:12][C:11]=2[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.[Cl-].[NH4+]>C(Cl)(Cl)Cl.C(#N)C>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[N:16]=[C:15]([N:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[C:14]3=[CH:18][C:19]([S:21][CH3:22])=[CH:20][N:13]3[CH2:12][C:11]=2[CH:23]=1

Komponenten

8

Edukt 5

HCID 4837PiperazineHCID 10796Cesium carbonateHCID 24813Phosphorus oxychlorideHCID 25517Ammonium ChlorideHCID 681559627-chloro-2-(methylsulfanyl)-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one

Produkt 1

HCID 681561457-chloro-2-(methylsulfanyl)-11-(piperazin-1-yl)-5H-pyrrolo[2,1-c][1,4]benzodiazepineAusbeute 60,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6212ChloroformLösungsmittelHCID 6342AcetonitrileLösungsmittel2×

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-cc8ae3c0760c40e8a3932b85b95834f5
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08314092B2

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