Réaction #4094

Équation de réaction

N-[5-chloro-2-(2,3-dihydro-1H-indol-1-yl)-phenyl]-4-methyl-1piperazinecarboxamide

→

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

Rendement 37.0%

Solvants

phosphorus oxychloride

Conditions de réaction

Traitement

1. 1
   AutreThe excess phosphorus oxychloride was removed at aspirator pressure with gentle warming
2. 2
   TempératureThe residue was chilled in an ice-bath (with exclusion of moisture)
3. 3
   workup.ADDITIONtreated first with 250 ml of ice-cold 2N-NaOH
4. 4
   AutreThe organic phase was separated
5. 5
   Lavagewashed four times with water
6. 6
   Séchagedried over Na2SO4
7. 7
   Concentrationconcentrated in vacuo to 5.7 g (95%) of a semi-crystalline material
8. 8
   AutreRecrystallization from acetone

Mode opératoire

A stirred solution of 6.30 g (0.017 mole) of N-[5-chloro-2-(2,3-dihydro-1H-indol-1-yl)-phenyl]-4-methyl-1piperazinecarboxamide of Example 4b in 100 ml of phosphorus oxychloride was refluxed for 6 hours under nitrogen, then cooled to room temperature. The excess phosphorus oxychloride was removed at aspirator pressure with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and then treated first with 250 ml of ice-cold 2N-NaOH, then with 250 ml of dichloromethane. The mixture was stirred vigorously until all the material passed into solution. The organic phase was separated, washed four times with water, dried over Na2SO4 and concentrated in vacuo to 5.7 g (95%) of a semi-crystalline material. Recrystallization from acetone afforded 2.20 g (37% overall yield) of 9-chloro-6-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, m.p. 154°-156° C.

Source