반응 #481918

반응 방정식

Sodium

3-morpholinopropan-1-ol

4-[(3-bromophenyl)amino]-7-fluoro-6-nitro-quinazoline

→

4-[(3-bromophenyl)amino]-7-[(3-morpholino)propyloxy]-6-nitroquinazoline

수율 65.0%

용매

THF

THF

water

반응 조건

후처리

1. 1
   온도The solution was then heated
2. 2
   온도at reflux for 24 hours
3. 3
   추출extracted with EtOAc
4. 4
   건조The combined organic extracts were dried over anhydrous Na2SO4
5. 5
   농축concentrated under reduced pressure
6. 6
   기타chromatographed on alumina eluting with EtOAc/hexane (1:1) to MeOH/CH2Cl2/EtOAc (2:3:5)

실험 절차

Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitro-quinazoline, J Med Chem, 1996 (39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc/hexane (1:1) to MeOH/CH2Cl2/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]-7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.

출처