反应详情

温度

60 °C

After adding (2R)oxiran-2-ylmethyl 4-methyl-1-benzenesulfonate (103 mg, 0.499 mmol), potassium carbonate (50 mg, 0.359 mmol) and dimethylformamide (3 ml) to N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-hydroxy-6-quinolinecarboxamide (120 mg, 0.299 mmol), the mixture was stirred at 60° C. for 7 hours. Next, diethylamine (1.5 ml) was added and the mixture was further stirred overnight at 60° C. The reaction solution was distributed between ethyl acetate-tetrahydrofuran (1:1) and water, and the organic layer was washed with water and saturated brine and then dried over anhydrous sodiumsulfate. The solvent was distilled off, the residue was subjected to silica gel column chromatography (eluent—ethyl acetate:methanol=95:5), the fraction containing the target substance was concentrated, and crystals were precipitated from ethylacetate-hexane (1:1), filtered out and blow-dried to obtain the title compound (71.8 mg, 0.135 mmol, 45.2%) as white crystals.

1. waitthe mixture was further stirred overnight at 60° C
2. washthe organic layer was washed with water and saturated brine
3. dry with materialdried over anhydrous sodiumsulfate
4. distillationThe solvent was distilled off
5. additionthe fraction containing the target substance
6. concentrationwas concentrated
7. customcrystals were precipitated from ethylacetate-hexane (1:1)
8. filtrationfiltered out and
9. customblow-dried