Réaction #4156

Équation de réaction

N-[2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide

→

6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine

Rendement 10.0%

Solvants

phosphorus oxychloride

Conditions de réaction

Traitement

1. 1
   Températurethis was refluxed under nitrogen overnight
2. 2
   AutreThe excess POCl3 was then removed at aspirator pressure
3. 3
   Températurewith warming
4. 4
   Autretriturated on the steam bath with 60 ml of absolute ethanol until solution
5. 5
   Autreresulted
6. 6
   TempératureThis solution was cooled
7. 7
   Autreresulting in separation of a solid
8. 8
   AutreThis solid was collected
9. 9
   Lavagewashed with ethanol, with ether, and finally hexane
10. 10
    Autredried
11. 11
    Autreto afford 19.0 g
12. 12
    AutreThis was partitioned between 200 ml of chloroform and 100 ml of water, with good stirring
13. 13
    workup.ADDITIONAddition of 2.5N-NaOH
14. 14
    AutreThis was separated
15. 15
    Lavagewashed twice with water
16. 16
    Séchagedried over Na2SO4
17. 17
    Concentrationconcentrated to 6.5 g of an oil
18. 18
    Filtrationfiltered from some insolubles
19. 19
    Concentrationthe filtrate concentrated under nitrogen to 20 ml
20. 20
    Autreto crystallize
21. 21
    workup.ADDITIONThis material was treated with 20 ml of 2N-HCl
22. 22
    workup.STIRRINGwith stirring
23. 23
    FiltrationThe resulting solution was filtered from a small amount of insolubles
24. 24
    Extractionthe product extracted into dichloromethane
25. 25
    ExtractionThe latter extract
26. 26
    Lavagewas washed twice with water
27. 27
    Séchagedried over Na2SO4
28. 28
    Concentrationconcentrated to an oil which
29. 29
    Autreto crystallize
30. 30
    workup.DISSOLUTIONThis was quickly dissolved in a small volume of boiling acetone
31. 31
    Autreto crystallize
32. 32
    AutreThe crystals were collected
33. 33
    Lavagewashed with a little acetone
34. 34
    Autredried

Mode opératoire

To 21.1 g (0.0627 mole) of N-[2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide of Example 7a was added 500 ml of phosphorus oxychloride and this was refluxed under nitrogen overnight. The excess POCl3 was then removed at aspirator pressure with warming. The residue was boiled and triturated on the steam bath with 60 ml of absolute ethanol until solution resulted. This solution was cooled and stirred resulting in separation of a solid. This solid was collected, washed with ethanol, with ether, and finally hexane, then dried to afford 19.0 g. This was partitioned between 200 ml of chloroform and 100 ml of water, with good stirring. Addition of 2.5N-NaOH rendered the medium basic, and the product base passed into the organic phase. This was separated, washed twice with water, dried over Na2SO4 and concentrated to 6.5 g of an oil. This oil was boiled with 60 ml of acetone, filtered from some insolubles, and the filtrate concentrated under nitrogen to 20 ml and allowed to crystallize. This gave 2.6 g of solid, m.p. 144°-146° C. dec. This material was treated with 20 ml of 2N-HCl with stirring. The resulting solution was filtered from a small amount of insolubles, then made basic with 2.5N-NaOH and the product extracted into dichloromethane. The latter extract was washed twice with water, dried over Na2SO4, and concentrated to an oil which began to crystallize. This was quickly dissolved in a small volume of boiling acetone and allowed to crystallize. The crystals were collected, washed with a little acetone, and dried to afford 2.00 g (10% overall yield) of 6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 149°-151° C.

Source