反应详情

3-(4-methyl-thiophen-2-ylmethoxy)-azetidine hydrochloride (128.0 mg, 0.6 mmol), EDCI (113.0 mg, 0.6 mmol), HOBt (80.0 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 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 (100.0 mg, 0.4 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred at room temperature overnight and then partitioned between ethyl acetate (20 mL) and water (20 mL). The aqueous layer was separated and extracted with ethyl acetate (2×20 ml). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (99:1 to 95:5) as eluent. The residue was triturated with acetone to give a white solid (40 mg, 27%).

1. custompartitioned between ethyl acetate (20 mL) and water (20 mL)
2. customThe aqueous layer was separated
3. extractionextracted with ethyl acetate (2×20 ml)
4. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customThe residue was purified by chromatography on silica gel
9. customThe residue was triturated with acetone