تفاعل #4133

معادلة التفاعل

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

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product

المردود 70.3%

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

المردود 70.3%

المذيبات

phosphorus oxychloride

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةunder reflux for 1 hour
2. 2
   درجة الحرارةThe reaction mixture was cooled
3. 3
   تركيزconcentrated at 50°-60° C. under vacuum
4. 4
   درجة الحرارةIce-chilled sodium hydroxide solution (15%, 500 ml) and dichloromethane (500 ml)
5. 5
   workup.ADDITIONwas added to the reaction mixture
6. 6
   أخرىThe organic phase was separated
7. 7
   استخلاصthe aqueous phase was extracted once with dichloromethane (250 ml)
8. 8
   غسيلThe combined dichloromethane solutions were washed with 1N sodium hydroxide solution (350 ml) and brine (2×350 ml)
9. 9
   تجفيفdried over anhydrous sodium sulfate
10. 10
    ترشيحfiltered
11. 11
    أخرىThe filtrate was evaporated
12. 12
    أخرىThe residue was purified on a silica gel column (250 gm)
13. 13
    غسيلeluted with 2%
14. 14
    تركيزconcentrated

الإجراء التجريبي

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.

المصدر