反应详情

3-(Thiophen-2-ylthio)-azetidine hydrochloride (170 mg, 0.82 mmol), EDCI (157 mg, 0.82 mmol), HOBt (110 mg, 0.82 mmol) and diisopropylethylamine (240 μL, 1.36 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (139 mg, 0.55 mmol) in dimethylformamide (14 mL) at room temperature. The reaction mixture was stirred overnight and then diluted by addition of ethyl acetate (40 mL) and water (40 mL). The aqueous phase was extracted with ethyl acetate (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using petroleum ether/ethyl acetate (1:0 to 95:5) as eluent. After trituration in acetone, the title product was obtained as a white solid (114 mg, 37%).

1. extractionThe aqueous phase was extracted with ethyl acetate (2×40 mL)
2. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL)
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated to dryness
6. customThe residue was purified by chromatography on silica gel