反应详情

温度

90 °C

A mixture of the trifluoroacetic acid salt of 4-(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (3.2 g, 7.4 mmol), potassium carbonate (6.1 g, 44.2 mmol) and 3-(4-methyl-1-piperazinyl)propyl-4-toluene sulphonate (3.0 g, 9.6 mmol) in DMF (60 ml) was stirred at 90° C. for 5 hours and allowed to cool to ambient temperature. The reaction mixture was poured into water (700 ml) and extracted 5 times with ethyl acetate. The combined extracts were washed with water, saturated aqueous sodium hydrogen carbonate, water and saturated brine. The ethyl acetate solution was dried over magnesium sulphate, filtered and the solvent removed under vacuum to give a residue which was purified by silica column chromatography, eluting with dichloromethane/methanol/0.880 aqueous ammonia (100/8/1). The relevant fractions were combined and evaporated under vacuum to give a residue which was triturated with ether, filtered and dried to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (1.64 g, 48%).

1. temperatureto cool to ambient temperature
2. extractionextracted 5 times with ethyl acetate
3. washThe combined extracts were washed with water, saturated aqueous sodium hydrogen carbonate, water and saturated brine
4. dry with materialThe ethyl acetate solution was dried over magnesium sulphate
5. filtrationfiltered
6. customthe solvent removed under vacuum
7. customto give a residue which
8. customwas purified by silica column chromatography
9. washeluting with dichloromethane/methanol/0.880 aqueous ammonia (100/8/1)
10. customevaporated under vacuum
11. customto give a residue which
12. customwas triturated with ether
13. filtrationfiltered
14. customdried