Reacción #433599

Ecuación de reacción

Sodium

3-(4-morpholinyl)-1-propanol

4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline

→

4-[(3,4-dichloro-6-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline

Rendimiento 72.0%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was refluxed for 18 hours
2. 2
   Otrothe solvent was thereafter partially removed under reduced pressure
3. 3
   workup.ADDITIONthe residue was diluted with water
4. 4
   Extracciónextracted with ethyl acetate
5. 5
   OtroDrying
6. 6
   Otrothe combined organic extracts, evaporation and silica gel chromatography (
7. 7
   workup.ADDITIONa mixture of 20% MeOH/30% CH2Cl2/50% EtOAc
8. 8
   Lavadoas elute)

Procedimiento

Sodium metal (5 equivalents) was added, under nitrogen atmosphere, to a solution of 3-(4-morpholinyl)-1-propanol (4 equivalents) in THF. The obtained suspension was stirred at 20° C. for two hours and was thereafter cannulated, under nitrogen atmosphere, into a solution of 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline. The reaction mixture was refluxed for 18 hours, the solvent was thereafter partially removed under reduced pressure and the residue was diluted with water and extracted with ethyl acetate. Drying the combined organic extracts, evaporation and silica gel chromatography (using a mixture of 20% MeOH/30% CH2Cl2/50% EtOAc as elute) gave 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline in 72% yield.

Fuente