반응 #4133

반응 방정식

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

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product

수율 70.3%

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

수율 70.3%

용매

phosphorus oxychloride

반응 조건

후처리

1. 1
   온도under reflux for 1 hour
2. 2
   온도The reaction mixture was cooled
3. 3
   농축concentrated at 50°-60° C. under vacuum
4. 4
   온도Ice-chilled sodium hydroxide solution (15%, 500 ml) and dichloromethane (500 ml)
5. 5
   workup.ADDITIONwas added to the reaction mixture
6. 6
   기타The organic phase was separated
7. 7
   추출the aqueous phase was extracted once with dichloromethane (250 ml)
8. 8
   세척The combined dichloromethane solutions were washed with 1N sodium hydroxide solution (350 ml) and brine (2×350 ml)
9. 9
   건조dried over anhydrous sodium sulfate
10. 10
    여과filtered
11. 11
    기타The filtrate was evaporated
12. 12
    기타The residue was purified on a silica gel column (250 gm)
13. 13
    세척eluted with 2%
14. 14
    농축concentrated

실험 절차

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.

출처