反应详情

A solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline hydrochloride (205 mg, 0.5 mmol), (prepared as described for the starting material in Example 7), and 2-fluoro-5-hydroxy-4-methylaniline (70 mg, 0.5 mmol), (prepared as described for the starting material in Example 1), in 2-pentanol (10 ml) and DMF (1 ml) was heated at reflux for 5 hours. The resulting solid was collected by filtration, partitioned between methylene chloride and aqueous sodium hydrogen carbonate solution. The organic layer was separated and purified by column chromatography eluting with methylene chloride/methanol (70/30). The purified solid product was dissolved in ethanol and concentrated hydrochloric acid (0.2 ml) added. The volatiles were removed by evaporation and the residue was recrystallised from isopropanol/ether to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(3-morpholinopropoxy)quinoline hydrochloride hydrate (283 mg, 73%) as a yellow solid.

1. custom(prepared
2. temperatureat reflux for 5 hours
3. filtrationThe resulting solid was collected by filtration
4. custompartitioned between methylene chloride and aqueous sodium hydrogen carbonate solution
5. customThe organic layer was separated
6. custompurified by column chromatography
7. washeluting with methylene chloride/methanol (70/30)
8. dissolutionThe purified solid product was dissolved in ethanol
9. additionconcentrated hydrochloric acid (0.2 ml) added
10. customThe volatiles were removed by evaporation
11. customthe residue was recrystallised from isopropanol/ether