Reaktion #4133

Reaktionsgleichung

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

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product

Ausbeute 70.3%

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

Ausbeute 70.3%

Lösungsmittel

phosphorus oxychloride

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle