反应详情

A stirred mixture of 9.14 g (0.022 mole) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide of Example 3c in 250 ml of phosphorus oxychloride was refluxed for 7 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 8.5 g (98%) of an oil. This material was adsorbed on a tall chromatography column containing 350 g of alumina made up in CH2Cl2. Elution with CH2Cl2 brought forth fractions of virtually pure tetracycle which were combined and concentrated to afford 4.6 g (53% overall yield) of product as a foam. This was crystallized from a small volume of methanol to furnish 2.6 g of 9-bromo-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 153°-155° C.

1. temperaturewas refluxed for 7 hours under nitrogen
2. customThe excess phosphorus oxychloride was removed at aspirator pressure with gentle warming
3. temperatureThe residue was chilled in an ice-bath (with exclusion of moisture)
4. additiontreated first with 250 ml of ice-cold 2N-NaOH
5. customThe organic phase was separated
6. washwashed thrice with water
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo to 8.5 g (98%) of an oil
9. additioncontaining 350 g of alumina
10. washElution with CH2Cl2
11. concentrationconcentrated
12. customto afford
13. custom4.6 g (53% overall yield) of product as a foam
14. customThis was crystallized from a small volume of methanol