反应详情

3-(4,4,4-Trifluorobutoxy)-azetidine (129 mg, 0.59 mmol), EDCI (113 mg, 0.59 mmol), HOBt (80 mg, 0.59 mmol) and diisopropylethylamine (170 μL, 0.97 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 mg, 0.039 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight then diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous layer was separated and extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (95:5 to 9:1) as eluent. The residue was finally triturated in diethylether to give the title product as a pale yellow solid (52.5 mg, 35%).

1. customThe aqueous layer was separated
2. extractionextracted with ethyl acetate (2×50 mL)
3. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL)
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated to dryness
6. customThe residue was purified by chromatography on silica gel
7. customThe residue was finally triturated in diethylether