Reacción #418028

Ecuación de reacción

4-pyrrolidin-1-yl-2,6,7-trichloro-pteridine

piperazine

lithium diisopropylamine

2,2-difluorethanol

→

6-chloro-7-(2,2-difluorethyloxy)-2-piperazin-1-yl-4-pyrrolidin-1-yl-pteridine

Disolventes

water

tetrahydrofuran

water

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe mixture is stirred for one hour at −10° C.
2. 2
   Otroto come up to ambient temperature
3. 3
   workup.STIRRINGstirred for another four hours
4. 4
   Extracciónextracted with dichloromethane
5. 5
   OtroThe organic phase is dried on sodium sulphate
6. 6
   TemperaturaThe mixture is refluxed for approx. 16 hours
7. 7
   Temperaturacooled to ambient temperature
8. 8
   Extracciónextracted with dichloromethane
9. 9
   OtroThe organic phase is dried on sodium sulphate
10. 10
    workup.ADDITIONDiisopropylether is added
11. 11
    Otroa yellowish solid is obtained

Procedimiento

a)+b) 50 μl (0.82 mmol) 2,2-difluorethanol are dissolved in 12 ml of tetrahydrofuran and under protective gas combined with 410 μl (0.82 mmol) of a 2 molar solution of lithium diisopropylamine in tetrahydrofuran. The mixture is stirred for 30 minutes and then the mixture is added to a solution of 250 mg (0.82 mmol) 4-pyrrolidin-1-yl-2,6,7-trichloro-pteridine in 12 ml of tetrahydrofuran cooled to −10° C. The mixture is stirred for one hour at −10° C., slowly allowed to come up to ambient temperature and stirred for another four hours. The solvent is eliminated in vacuo, the residue is combined with 50 ml of water and extracted with dichloromethane. The organic phase is dried on sodium sulphate and the solvent is eliminated in vacuo. The residue is taken up in 15 ml of tetrahydrofuran and combined with a solution of 313 mg (3.6 mmol) piperazine in 10 ml of tetrahydrofuran. The mixture is refluxed for approx. 16 hours, cooled to ambient temperature and the solvent is eliminated in vacuo. The residue is mixed with water and extracted with dichloromethane. The organic phase is dried on sodium sulphate and the solvent is eliminated in vacuo. Diisopropylether is added and a yellowish solid is obtained. Yield 225 mg (70% of theoretical)

Fuente