Reacción #4133

Ecuación de reacción

N-[2-(5-bromo-1-indolinyl)-5-bromophenyl]-4-methyl-1-piperazinecarboxamide

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product

Rendimiento 70.3%

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

Rendimiento 70.3%

Disolventes

phosphorus oxychloride

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaunder reflux for 1 hour
2. 2
   TemperaturaThe reaction mixture was cooled
3. 3
   Concentraciónconcentrated at 50°-60° C. under vacuum
4. 4
   TemperaturaIce-chilled sodium hydroxide solution (15%, 500 ml) and dichloromethane (500 ml)
5. 5
   workup.ADDITIONwas added to the reaction mixture
6. 6
   OtroThe organic phase was separated
7. 7
   Extracciónthe aqueous phase was extracted once with dichloromethane (250 ml)
8. 8
   LavadoThe combined dichloromethane solutions were washed with 1N sodium hydroxide solution (350 ml) and brine (2×350 ml)
9. 9
   Secadodried over anhydrous sodium sulfate
10. 10
    Filtraciónfiltered
11. 11
    OtroThe filtrate was evaporated
12. 12
    OtroThe residue was purified on a silica gel column (250 gm)
13. 13
    Lavadoeluted with 2%
14. 14
    Concentraciónconcentrated

Procedimiento

A solution of N-[2-(5-bromo-1-indolinyl)-5-bromophenyl]-4-methyl-1-piperazinecarboxamide (12.3 g, 24.8 mmoles) and phosphorus oxychloride (250 ml) was heated under reflux for 1 hour. The reaction mixture was cooled and then concentrated at 50°-60° C. under vacuum. Ice-chilled sodium hydroxide solution (15%, 500 ml) and dichloromethane (500 ml) was added to the reaction mixture. The mixture was stirred for 20 minutes. The organic phase was separated and the aqueous phase was extracted once with dichloromethane (250 ml). The combined dichloromethane solutions were washed with 1N sodium hydroxide solution (350 ml) and brine (2×350 ml), dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated. The residue was purified on a silica gel column (250 gm), eluted with 2% and then 3% methanol:dichloromethane. The appropriate fractions were combined and concentrated to give 8.3 g (70%) of product. Recrystallization from isopropanol gave the analytical sample, mp 215°-216° C.

Fuente