反应详情

4-(4-Aminophenoxy)-6-cyano-7-((2R)-oxiran-2-yl)methoxyquinoline (322 mg, 0.966 mmol) and thiazol-2-ylcarbamic acid phenyl ester (255 mg, 1.26 mmol) were heated and stirred in dimethylsulfoxide (2 ml) at 85° C. for 4 hours. The reaction solution was distributed between an ethyl acetate-tetrahydrofuran mixed solvent and water, the organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate, and the drying agent was filtered off and the filtrate distilled off under reduced pressure. The obtained product and pyrrolidine (343 mg, 4.83 mmol) were stirred in dimethylformamide (3 ml) at room temperature for 15 hours. The reaction solution was distributed between ethyl acetate and water, the organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate, the drying agent was filtered off, and the filtrate was distilled off under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (eluent—ethyl acetate:methanol=15:1), the fraction containing the target substance was concentrated and suspended in ethyl acetate, the suspension was diluted with hexane, and the crystals were filtered out, washed with hexane and blow-dried to obtain the title compound (45 mg, 0.085 mmol, 9%) as light yellow crystals.

1. washthe organic layer was washed with water and saturated brine
2. dry with materialdried over anhydrous magnesium sulfate
3. filtrationthe drying agent was filtered off
4. distillationthe filtrate distilled off under reduced pressure
5. washthe organic layer was washed with water and saturated brine
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationthe drying agent was filtered off
8. distillationthe filtrate was distilled off under reduced pressure
9. customThe obtained crude product
10. additionthe fraction containing the target substance
11. concentrationwas concentrated
12. additionthe suspension was diluted with hexane
13. filtrationthe crystals were filtered out
14. washwashed with hexane
15. customblow-dried