Реакция #4104

Уравнение реакции

N-[2-(5-chloro-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide

1,2-dichloroethane

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product

Выход 29.5%

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

Выход 29.5%

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   ТемператураThe solution was cooled
2. 2
   ДругоеThe layers were separated
3. 3
   ПромывкаThe organic layer was washed with 2 l of 2N sodium hydroxide
4. 4
   Сушкаwith brine (500 ml), and dried over anhydrous magnesium sulfate
5. 5
   ДругоеRemoval of the solvent at reduced pressure
6. 6
   Другоеgave an oil
7. 7
   ДругоеThe oil was purified by flash chromatography on a silica gel column (1 kg, 230-400 mesh)
8. 8
   Промывкаeluted initially with dichloromethane

Методика

To N-[2-(5-chloro-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide (13.5 g, 36.5 mmoles) was added a solution of polyphosphoric acid ethyl ester and 1,2-dichloroethane (250 ml). The solution was heated at 75° C. for 4 hours with exclusion of moisture. The solution was cooled and poured into a mixture of ice-sodium hydroxide solution (2 l) and dichloromethane (1.2 l). The mixture was stirred for 15 minutes. The layers were separated. The organic layer was washed with 2 l of 2N sodium hydroxide, then with brine (500 ml), and dried over anhydrous magnesium sulfate. Removal of the solvent at reduced pressure gave an oil. The oil was purified by flash chromatography on a silica gel column (1 kg, 230-400 mesh), packed and eluted initially with dichloromethane, then with dichloromethane containing an increasing methanol content in 1% increments to a final content of 5% (total 8 l). Concentration of the 5% methanol/dichloromethane eluent gave 3.8 g (28%) of product. Recrystallization from 2-propanol (50 ml) gave the analytical sample, mp 182°-183° C.

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