反应详情

3-(Thiophen-2-ylmethoxy)-azetidine hydrochloride (243 mg, 1.18 mmol), EDCI (227 mg, 1.18 mmol), HOBt (160 mg, 0.6 mmol) and diisopropylethylamine (340 μL, 1.97 mmol) were successively added to a solution of (E)-3-(3-(2-ethoxy-2-oxoethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylic acid hydrochloride (270 mg, 0.79 mmol) in dimethylformamide (15 mL) at room temperature. The reaction mixture was stirred for 2 days then partitioned between ethyl acetate (30 mL) and water (40 mL). The aqueous layer was separated and successively extracted with ethyl acetate (2×30 mL) and dichloromethane (2×30 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 dichloromethane/methanol (10:0 to 98:2) as eluent. The title product was obtained as an off-white solid (215 mg, 60%).

1. customthen partitioned between ethyl acetate (30 mL) and water (40 mL)
2. customThe aqueous layer was separated
3. extractionsuccessively extracted with ethyl acetate (2×30 mL) and dichloromethane (2×30 mL)
4. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customThe residue was purified by chromatography on silica gel