Reaction #4110

Reaction equation

4-methyl-1,2-dihydrobenzo[c]pyrrolo[1,2,3-ef][1,5]benzodiazepin-7-one

N-methylpiperazine

→

product

4-Methyl-7-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[c]pyrrolo[1,2,3-ef][1,5]benzodiazepine

Solvents

Toluene

toluene

Conditions

Workup

1. 1
   TemperatureThe mixture was heated
2. 2
   Temperatureunder reflux for two hours
3. 3
   Otherthe insoluble material was removed by filtration
4. 4
   OtherThe organic phase was separated
5. 5
   ExtractionThe aqueous phase was extracted with toluene (200 ml)
6. 6
   WashThe combined toluene solutions were washed with water (300 ml), brine (2 times, 300 ml)
7. 7
   Dryingdried over anhydrous sodium sulfate
8. 8
   OtherThe solvent was evaporated
9. 9
   OtherThe residue was triturated with ethanol
10. 10
    OtherRecrystallization of the solid from chloroform

Procedure

A solution of 4-methyl-1,2-dihydrobenzo[c]pyrrolo[1,2,3-ef][1,5]benzodiazepin-7-one (3.6 g, 14.3 mmoles), N-methylpiperazine (16 ml) and toluene (350 ml) was heated to 110° C. Titanium tetrachloride (4.3 ml) was added in three portions in two minute intervals. The mixture was heated under reflux for two hours and cooled to room temperature. Toluene (500 ml) and ice-water (500 m) were added. The mixture was stirred for 30 minutes and the insoluble material was removed by filtration. The organic phase was separated. The aqueous phase was extracted with toluene (200 ml). The combined toluene solutions were washed with water (300 ml), brine (2 times, 300 ml) and dried over anhydrous sodium sulfate. The solvent was evaporated. The residue was triturated with ethanol:hexane to a solid. Recrystallization of the solid from chloroform:hexane yielded 2.4 g of product. The mother liquor was concentrated and the residue was purified on a silica gel column (60 g, 230-400 mesh) to give a second crop of 1.3 g of product (77% overall yield). Recrystallization from 2-propanol gave the analytical sample, mp 173°-174° C.

Source