Réaction #4115

Équation de réaction

N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-N',N'-dimethylurea

→

product

Rendement 48.0%

9-Bromo-6-dimethylamino-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine

Rendement 48.0%

Solvants

phosphorus oxychloride

Conditions de réaction

Traitement

1. 1
   Températureunder nitrogen, was heated
2. 2
   Températureunder reflux for 6 hours
3. 3
   AutreThe excess phosphorus oxychloride was removed under vacuum with gentle warming
4. 4
   TempératureThe residue was chilled in an ice-bath (with exclusion of moisture)
5. 5
   workup.ADDITIONtreated first with 250 ml of ice-cold 2N sodium hydroxide solution
6. 6
   workup.STIRRINGThe mixture was stirred
7. 7
   Autretriturated until all the material
8. 8
   AutreThe organic phase was separated
9. 9
   Lavagewashed with 2N sodium hydroxide solution, twice with water
10. 10
    Séchagedried over anhydrous sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated in vacuo to an oil
13. 13
    workup.DISSOLUTIONThe oil was dissolved in 50 ml of ethyl acetate
14. 14
    Concentrationthe solution was concentrated under a stream of nitrogen
15. 15
    FiltrationAt a volume of about 30 ml, the mixture was filtered
16. 16
    AutreConcentration of the filtrate was continued to a volume of about 20 ml, during which crystallization
17. 17
    Autreresulted
18. 18
    workup.DISSOLUTIONThe solid was dissolved
19. 19
    Températureby heating
20. 20
    Filtrationthe hot solution was filtered
21. 21
    Autreto crystallize

Mode opératoire

A mixture of 10.8 g (0.030 mole) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-N',N'-dimethylurea and 110 ml of phosphorus oxychloride, under nitrogen, was heated under reflux for 6 hours, with stirring, and then cooled to room temperature. The excess phosphorus oxychloride was removed under vacuum with gentle warming. The residue was chilled in an ice-bath (with exclusion of moisture) and treated first with 250 ml of ice-cold 2N sodium hydroxide solution, and then with 500 ml of dichloromethane. The mixture was stirred and triturated until all the material passed into solution. The organic phase was separated, washed with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to an oil. The oil was dissolved in 50 ml of ethyl acetate and the solution was concentrated under a stream of nitrogen. At a volume of about 30 ml, the mixture was filtered. Concentration of the filtrate was continued to a volume of about 20 ml, during which crystallization resulted. The solid was dissolved by heating, the hot solution was filtered and allowed to crystallize to afford 4.9 g (48%) of product, mp 124°-127° C.

Source