Réaction #1065474

Équation de réaction

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

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product

Rendement 70.3%

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

Rendement 70.3%

Solvants

phosphorus oxychloride

Conditions de réaction

Traitement

1. 1
   Températureunder reflux for 1 hour
2. 2
   TempératureThe reaction mixture was cooled
3. 3
   Concentrationconcentrated at 50°-60° C. under vacuum
4. 4
   TempératureIce-chilled sodium hydroxide solution (15%, 500 ml) and dichloromethane (500 ml)
5. 5
   workup.ADDITIONwas added to the reaction mixture
6. 6
   AutreThe organic phase was separated
7. 7
   Extractionthe aqueous phase was extracted once with dichloromethane (250 ml)
8. 8
   LavageThe combined dichloromethane solutions were washed with 1N sodium hydroxide solution (350 ml) and brine (2×350 ml)
9. 9
   Séchagedried over anhydrous sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    AutreThe filtrate was evaporated
12. 12
    AutreThe residue was purified on a silica gel column (250 gm)
13. 13
    Lavageeluted with 2%
14. 14
    Concentrationconcentrated

Mode opératoire

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.

Source