Reaction #4162

Reaction equation

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

1,2-dichloroethane

→

product

Yield 29.5%

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

Yield 29.5%

Solvents

dichloromethane

Conditions

Workup

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

Procedure

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.

Source