反应详情

A solution of 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline hydrochloride (325 mg, 0.82 mmol) and 4-chloro-2-fluoro-5-hydroxyaniline (133 mg, 0.82 mmol), (as described in EP 61741 A2), in 2-pentanol (10 ml) and DMF (1 ml) was heated at reflux for 5 hours. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with acetonitrile/water containing 1% TFA (30/70). Concentrated hydrochloric acid was added to the fractions and the solvents were removed by evaporation. The residue was azeotroped with toluene, and triturated with isopropanol. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline hydrochloride (215 mg, 50%).

1. temperatureat reflux for 5 hours
2. customThe volatiles were removed by evaporation
3. customthe residue was purified by column chromatography
4. washeluting with acetonitrile/water containing 1% TFA (30/70)
5. additionConcentrated hydrochloric acid was added to the fractions
6. customthe solvents were removed by evaporation
7. customThe residue was azeotroped with toluene
8. customtriturated with isopropanol
9. filtrationThe solid was collected by filtration
10. washwashed with ether
11. customdried under vacuum