Reaktion #4142

Reaktionsgleichung

4-methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide

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product

Ausbeute 56.0%

10-Bromo-7-(4-methyl-1-piperazinyl)- 2,3-dihydro-1H-quino[1,8-ab][1,5]benzodiazepine

Ausbeute 56.0%

Lösungsmittel

phosphorus oxychloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturunder reflux under nitrogen for 6 hours
2. 2
   Sonstigeexcess phosphorus oxychloride was removed at aspirator pressure
3. 3
   Temperaturwith heating
4. 4
   TemperaturThe residue was chilled in an ice-bath (with exclusion of moisture)
5. 5
   workup.ADDITIONtreated with ice-cold 2N sodium hydroxide solution (250 ml) and dichloromethane (250 ml)
6. 6
   Sonstigetriturated until the residue
7. 7
   workup.DISSOLUTIONdissolved
8. 8
   SonstigeThe organic phase was separated
9. 9
   Waschenwashed again with 2N sodium hydroxide solution, twice with water
10. 10
    Trocknendried over sodium sulfate
11. 11
    Einengenconcentrated in vacuo
12. 12
    Filtrationfiltered
13. 13
    workup.STIRRINGthe filrate was stirred 15 minutes with charcoal
14. 14
    FiltrationAfter filtration
15. 15
    workup.STIRRINGthe solution was stirred with dichloromethane (100 ml)
16. 16
    workup.ADDITIONby the addition of cold 2N sodium hydroxide solution
17. 17
    SonstigeThe organic phase was separated
18. 18
    Waschenwashed twice with water
19. 19
    Trocknendried over sodium sulfate
20. 20
    FiltrationAfter filtration
21. 21
    Einengenthe solution was concentrated

Vorschrift

A stirred solution of 4-methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide (8.6 g, 0.020 mole) in phosphorus oxychloride (200 ml) was heated under reflux under nitrogen for 6 hours. The reaction mixture was cooled to room temperature and excess phosphorus oxychloride was removed at aspirator pressure with heating. The residue was chilled in an ice-bath (with exclusion of moisture), and treated with ice-cold 2N sodium hydroxide solution (250 ml) and dichloromethane (250 ml). The mixture was stirred and triturated until the residue dissolved. The organic phase was separated, washed again with 2N sodium hydroxide solution, twice with water, dried over sodium sulfate, and concentrated in vacuo. The residue was taken up in 4N hydrochloric acid (100 ml), filtered, and the filrate was stirred 15 minutes with charcoal. After filtration, the solution was stirred with dichloromethane (100 ml), and the mixture was made alkaline by the addition of cold 2N sodium hydroxide solution. The organic phase was separated, washed twice with water, dried over sodium sulfate, and boiled 15 minutes with charcoal. After filtration, the solution was concentrated to give 4.6 g (56%) of product, as an oil, which crystallized on standing. The product was taken up in boiling methanol (20 ml) and allowed to crystallize first at room temperature, then in the refrigerator. Recrystallization from methanol afforded the analytical sample, mp 153°-156° C.

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