반응 #4090

반응 방정식

N-[2-(2,3-dihydro-1H-indol-1-yl)-5-fluorophenyl]-4-methyl-1-piperazine carboxamide

→

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

수율 20.8%

용매

phosphorus oxychloride

반응 조건

후처리

1. 1
   온도was refluxed for 6 hours under nitrogen
2. 2
   기타The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming
3. 3
   온도The residue was chilled in an ice-bath (with exclusion of moisture)
4. 4
   workup.ADDITIONtreated first with 250 ml of ice-cold 2N-NaOH
5. 5
   기타The organic phase was separated
6. 6
   세척washed thrice with water
7. 7
   건조dried over Na2SO4
8. 8
   농축concentrated in vacuo to 9.1 g of an oil
9. 9
   workup.ADDITIONcontaining 400 g of alumina
10. 10
    세척Elution with CH2Cl2
11. 11
    농축concentrated
12. 12
    기타to afford
13. 13
    기타3.5 g (35% overall yield) of product which
14. 14
    기타crystallized
15. 15
    기타This was recrystallized from a small volume of acetone

실험 절차

A stirred mixture of 10.6 g (0.030 mole) of N-[2-(2,3-dihydro-1H-indol-1-yl)-5-fluorophenyl]-4-methyl-1-piperazine carboxamide of Example 2c in 250 ml of phosphorus oxychloride was refluxed for 6 hours under nitrogen, then cooled to room temperature. The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and then treated first with 250 ml of ice-cold 2N-NaOH, then with 500 ml of dichloromethane. The mixture was stirred vigorously until all the material passed into solution. The organic phase was separated, washed thrice with water, dried over Na2SO4 and concentrated in vacuo to 9.1 g of an oil. This material was adsorbed on a tall chromatography column containing 400 g of alumina made up in CH2Cl2. Elution with CH2Cl2 brought forth fractions of pure tetracycle which were combined and concentrated to afford 3.5 g (35% overall yield) of product which crystallized. This was recrystallized from a small volume of acetone to furnish 2.1 g of 9-fluoro-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 151°-153° C.

출처