反应详情

温度

25 °C

A mixture of 3-methyl-4-(phenoxymethyl)benzoic acid (121 mg, 0.5 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (191 mg, 1 mmol), N-hydroxybenzotriazole (135 mg, 1 mmol), triethylamine (0.2 mL) and dichloromethane (5 mL) were stirred at 25° C. for half an hour. And then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (76 mg, 0.5 mmol) was added. The mixture was stirred at 25° C. for 12 hours. To the mixture, water (20 mL) was added and the mixture was extracted with dichloromethane (30 mL×3). The combined organic phase was dried by sodium sulfate and then filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-3-methyl-4-(phenoxymethyl)benzamide (Compound I-54) as a white solid (51 mg, 26%). LRMS (M+H+) m/z: calcd 376.45. found 376. HPLC purity (214 nm): 99%. 1H NMR (300 MHz, d6-DMSO): δ 11.43 (s, 1H), 8.29 (t, J=4.2 Hz, 1H), 7.69-7.63 (m, 2H), 7.43 (d, J=8.1 Hz, 1H), 7.29 (t, J=7.5 Hz, 2H), 7.03-6.91 (m, 3H), 5.85 (s, 1H), 5.11 (s, 2H), 4.29 (d, J=4.8 Hz, 2H), 2.34 (s, 3H), 2.17 (s, 3H), 2.11 (s, 3H).

1. stirringThe mixture was stirred at 25° C. for 12 hours
2. extractionthe mixture was extracted with dichloromethane (30 mL×3)
3. dry with materialThe combined organic phase was dried by sodium sulfate
4. filtrationfiltered
5. concentrationThe filtrate was concentrated in vacuo
6. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1)