反応 #62662

反応方程式

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

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product

収率 70.3%

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

収率 70.3%

溶媒

phosphorus oxychloride

反応条件

後処理

1. 1
   温度under reflux for 1 hour
2. 2
   温度The reaction mixture was cooled
3. 3
   濃縮concentrated at 50°-60° C. under vacuum
4. 4
   温度Ice-chilled sodium hydroxide solution (15%, 500 ml) and dichloromethane (500 ml)
5. 5
   workup.ADDITIONwas added to the reaction mixture
6. 6
   その他The organic phase was separated
7. 7
   抽出the aqueous phase was extracted once with dichloromethane (250 ml)
8. 8
   洗浄The combined dichloromethane solutions were washed with 1N sodium hydroxide solution (350 ml) and brine (2×350 ml)
9. 9
   乾燥dried over anhydrous sodium sulfate
10. 10
    ろ過filtered
11. 11
    その他The filtrate was evaporated
12. 12
    その他The residue was purified on a silica gel column (250 gm)
13. 13
    洗浄eluted with 2%
14. 14
    濃縮concentrated

実験手順

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.

出典