Reaktion #1816476

Reaktionsgleichung

6-[4-(3-[4-aminophenoxy]propyl)piperazin-1-yl]-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione

sodium hydroxide

trimethylsilyl chloride

methanesulfonyl chloride

→

1,3-dimethyl-6-[4-(3-[4-methanesulfonylaminophenoxy]propyl)piperazin-1-yl]-2,4(1H,3H)-pyrimidinedione

Lösungsmittel

pyridine

dioxane

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITat room temperature for 30 minutes
2. 2
   TemperaturThe reaction solution was cooled to 0° C. again
3. 3
   workup.STIRRINGThe solution was stirred at the same temperature for 5 minutes and further at room temperature for 1 hour
4. 4
   Temperaturcooled on an ice water bath
5. 5
   WaschenThe resultant aqueous solution was washed with chloroform (500 ml×2)
6. 6
   Waschenwashed with chloroform (50 ml)
7. 7
   workup.ADDITIONIn succession, potassium carbonate was added to this solution
8. 8
   Extraktionthe solution was extracted with chloroform (50 ml×3)
9. 9
   Trocknendried over sodium sulfate
10. 10
    Einengenconcentrated

Vorschrift

20 ml of a dioxane solution containing 1.1 g of 6-[4-(3-[4-aminophenoxy]propyl)piperazin-1-yl]-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione obtained in Example 6 and 1.8 ml of pyridine was cooled to 0° C., and 0.95 ml of trimethylsilyl chloride was further added, followed by stirring at the same temperature for 5 minutes and then at room temperature for 30 minutes. The reaction solution was cooled to 0° C. again, and 0.6 ml of methanesulfonyl chloride was added dropwise thereto. The solution was stirred at the same temperature for 5 minutes and further at room temperature for 1 hour, and then cooled on an ice water bath. Afterward, 10 ml of ice water was added dropwise, and 50 ml of water and 70 ml of a 1N aqueous sodium hydroxide solution were further added. The resultant aqueous solution was washed with chloroform (500 ml×2), made weakly acidic with concentrated hydrochloric acid and then washed with chloroform (50 ml). In succession, potassium carbonate was added to this solution to adjust its pH to 7, and the solution was extracted with chloroform (50 ml×3), dried over sodium sulfate and then concentrated to obtain 0.9 g of crystalline 1,3-dimethyl-6-[4-(3-[4-methanesulfonylaminophenoxy]propyl)piperazin-1-yl]-2,4(1H,3H)-pyrimidinedione.

Quelle