반응 #325285

반응 방정식

sodium hydride

4-bromo-2,6-difluoroaniline

4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline

→

4-(4-bromo-2,6-difluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline

수율 70.2%

용매

DMF

반응 조건

후처리

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for a further 20 hours
3. 3
   workup.ADDITIONThe mixture was poured onto water (130 ml)
4. 4
   추출extracted with ethyl acetate
5. 5
   세척The organic layers were washed with water, brine
6. 6
   건조dried (MgSO4)
7. 7
   기타the volatiles were removed by evaporation
8. 8
   기타The residue was purified by column chromatography on silica
9. 9
   세척eluting with methylene chloride/methanol (95/5)
10. 10
    workup.ADDITIONcontaining ammonia (1%) (90/10)
11. 11
    workup.ADDITIONThe fractions containing the expected product
12. 12
    기타evaporated
13. 13
    기타The residue was triturated with ether
14. 14
    여과collected by filtration
15. 15
    세척washed with ether
16. 16
    기타dried under vacuum at 50° C.

실험 절차

Under argon, sodium hydride (60%, 372 mg, 9.3 mmol) was added to a solution of 4-bromo-2,6-difluoroaniline (1.67 g, 8.08 mmol) in DMF. After stirring for 30 minutes at ambient temperature, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (1.3 g, 4.04 mmol) was added and stirring was continued for a further 20 hours. The mixture was poured onto water (130 ml) and extracted with ethyl acetate. The organic layers were washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography on silica, eluting with methylene chloride/methanol (95/5) followed by methylene chloride/methanol containing ammonia (1%) (90/10). The fractions containing the expected product were combined and evaporated. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum at 50° C. to give 4-(4-bromo-2,6-difluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (1.4 g, 70%).

출처