反応 #325285

反応方程式

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

収率 70.2%

溶媒

DMF

反応条件

後処理

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
   抽出extracted with ethyl acetate
5. 5
   洗浄The organic layers were washed with water, brine
6. 6
   乾燥dried (MgSO4)
7. 7
   その他the volatiles were removed by evaporation
8. 8
   その他The residue was purified by column chromatography on silica
9. 9
   洗浄eluting 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
    その他evaporated
13. 13
    その他The residue was triturated with ether
14. 14
    ろ過collected by filtration
15. 15
    洗浄washed with ether
16. 16
    その他dried under vacuum at 50° C.

実験手順

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%).

出典