반응 #4098

반응 방정식

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

수율 10.0%

용매

phosphorus oxychloride

반응 조건

후처리

1. 1
   온도this was refluxed under nitrogen overnight
2. 2
   기타The excess POCl3 was then removed at aspirator pressure
3. 3
   온도with warming
4. 4
   기타triturated on the steam bath with 60 ml of absolute ethanol until solution
5. 5
   기타resulted
6. 6
   온도This solution was cooled
7. 7
   기타resulting in separation of a solid
8. 8
   기타This solid was collected
9. 9
   세척washed with ethanol, with ether, and finally hexane
10. 10
    기타dried
11. 11
    기타to afford 19.0 g
12. 12
    기타This 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
    기타This was separated
15. 15
    세척washed twice with water
16. 16
    건조dried over Na2SO4
17. 17
    농축concentrated to 6.5 g of an oil
18. 18
    여과filtered from some insolubles
19. 19
    농축the filtrate concentrated under nitrogen to 20 ml
20. 20
    기타to crystallize
21. 21
    workup.ADDITIONThis material was treated with 20 ml of 2N-HCl
22. 22
    workup.STIRRINGwith stirring
23. 23
    여과The resulting solution was filtered from a small amount of insolubles
24. 24
    추출the product extracted into dichloromethane
25. 25
    추출The latter extract
26. 26
    세척was washed twice with water
27. 27
    건조dried over Na2SO4
28. 28
    농축concentrated to an oil which
29. 29
    기타to crystallize
30. 30
    workup.DISSOLUTIONThis was quickly dissolved in a small volume of boiling acetone
31. 31
    기타to crystallize
32. 32
    기타The crystals were collected
33. 33
    세척washed with a little acetone
34. 34
    기타dried

실험 절차

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.

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