Reaction #433599

Reaction equation

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

Yield 72.0%

Solvents

THF

Conditions

Workup

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

Procedure

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.

Source