反应详情

Sodium hydride (80 mg, 2.07 mmol) was added to a solution of 6-cyanooxindole (280 mg, 1.78 mmol), (prepared as described for the starting material in Example 57), in dry, degassed DMF (10 ml) and the suspension stirred for 15 minutes at ambient temperature. A solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (200 mg, 0.59 mmol), (prepared as described for the starting material in Example 5), in a dry, degassed mixture of DMF (2 ml) and THF (2 ml) was added dropwise and the reaction mixture was heated at 60° C. for 3 hours. The mixture was allowed to cool, the solvents were removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated and the aqueous phase extracted with ethyl acetate (50 ml×3). The ethyl acetate fractions were combined, dried (MgSO4), the solvent removed by evaporation and the residue was purified by flash column chromatography eluting with methylene chloride/methanol (100/13). The purified product was triturated in boiling ether and the solid product collected by filtration to give 4-(6-cyanooxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (36 mg, 13%) as an orange solid.

1. custom(prepared
2. customin dry
3. customdegassed DMF (10 ml)
4. customdegassed
5. additionmixture of DMF (2 ml) and THF (2 ml)
6. additionwas added dropwise
7. temperaturethe reaction mixture was heated at 60° C. for 3 hours
8. temperatureto cool
9. customthe solvents were removed by evaporation
10. customthe residue was partitioned between ethyl acetate and water
11. customThe organic phase was separated
12. extractionthe aqueous phase extracted with ethyl acetate (50 ml×3)
13. dry with materialdried (MgSO4)
14. customthe solvent removed by evaporation
15. customthe residue was purified by flash column chromatography
16. washeluting with methylene chloride/methanol (100/13)
17. customThe purified product was triturated
18. filtrationthe solid product collected by filtration