反应详情

温度

25 °C

A solution of 2-[(phenylmethyl)oxy]-5-(4-pyridinyl)benzoic acid (may be prepared as described in Description 79; 0.12 g, 0.34 mmol), EDC (0.16 g, 0.84 mmol) and HOBT (0.13 g, 0.84 mmol) in dimethylformamide (2 ml) was stirred in air at room temperature for 1 h. 2-Fluoropyridin-3-amine (0.04 g, 0.37 mmol) was then added in one charge. The reaction mixture was stirred at 25° C. overnight. Another batch of HOBT (0.13 g, 0.84 mmol), EDC (0.161 g, 0.842 mmol) and 2-fluoropyridin-3-amine (0.04 g, 0.37 mmol) was added into the mixture and heating was continued at 40° C. for 38 hours. The reaction mixture was diluted with water (30 ml) and extracted with ethyl acetate (60 ml×3). The organic phases were combined, washed with brine (50 ml×3), dried over anhydrous MgSO4, and concentrated. The residue was purified by chromatography (silica gel, 40 g, eluent: dichloromethane/methanol=50:1, 1 L). The solid was washed by methanol (3 ml×2) and dried in vacuo to yield the title compound as a grey solid. 31 mg.

1. additioncharge
2. temperatureheating
3. waitwas continued at 40° C. for 38 hours
4. extractionextracted with ethyl acetate (60 ml×3)
5. washwashed with brine (50 ml×3)
6. dry with materialdried over anhydrous MgSO4
7. concentrationconcentrated
8. customThe residue was purified by chromatography (silica gel, 40 g, eluent: dichloromethane/methanol=50:1, 1 L)
9. washThe solid was washed by methanol (3 ml×2)
10. customdried in vacuo