Reaktion #4162

Reaktionsgleichung

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

1,2-dichloroethane

→

product

Ausbeute 29.5%

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

Ausbeute 29.5%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle