反应详情

温度

250 °C

A mixture of 5-((4-cyano-3-(3-morpholinopropoxy)anilino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione(2.96 g, 7 mmol) in DOWTHERM A, (trade mark of Fluka Chemie AG), (100 ml) was heated at 250° C. for 30 minutes. The mixture was allowed to cool, hexane was added and the solvent was decanted from the resulting gum. The residue was triturated with hexane to give crude 6-cyano-7-(3-morpholinopropoxy)-1,4-dihydroquinolin-4-one(1.0 g) as a brown solid. A portion of this product (380 mg, 1.3 mmol) was added to thionyl chloride (10 ml)and DMF (0.1 ml) and the mixture was heated at reflux for 3 hours. The volatiles were removed by evaporation and the residue was azeotroped with toluene (×3). 2-Fluoro-5-hydroxy-4-methylaniline (184 mg, 1.3 mmol), (prepared as described for the starting material in Example 1), in isopropanol (10 ml) was added to the residue, and the mixture was heated at reflux for 3 hours. The mixture was allowed to cool, the solid product was collected by filtration and recrystallised twice from methylene chloride/methanol/ethyl acetate to give 6-cyano-4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(3-morpholinopropoxy)quinoline (05 mg, 3% overall).

1. temperatureto cool
2. customthe solvent was decanted from the resulting gum
3. customThe residue was triturated with hexane
4. customto give crude 6-cyano-7-(3-morpholinopropoxy)-1,4-dihydroquinolin-4-one(1.0 g) as a brown solid
5. temperaturethe mixture was heated
6. temperatureat reflux for 3 hours
7. customThe volatiles were removed by evaporation
8. customthe residue was azeotroped with toluene (×3)
9. additionwas added to the residue
10. temperaturethe mixture was heated
11. temperatureat reflux for 3 hours
12. temperatureto cool
13. filtrationthe solid product was collected by filtration
14. customrecrystallised twice from methylene chloride/methanol/ethyl acetate