反应详情

To a solution of 2-(1-(2,2-difluoro-2-phenylethyl)-1H-1,2,3-triazol-4-yl)-4-methylthiazole-5-carboxylic acid (0.10 g, 0.28 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.07 g, 0.34 mmol) and N,N-diisopropylethylamine (0.09 mL, 0.51 mmol) in N,N-dimethylformamide (2 mL) was added 1-hydroxy-benzotriazole (0.10 g, 0.74 mmol). The resulting mixture was stirred at ambient temperature for 15 minutes and 3-(aminomethyl)pyridine (0.04 mL, 0.04 mmol) was added. The reaction mixture was stirred at ambient temperature for 17 hours, then diluted with ethyl acetate (30 mL), washed with water and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography to the title compound as a white solid (0.03 g, 7%): mp 150-151° C.; 1H NMR (300 MHz, CDCl3) δ 8.57 (br s, 1H), 8.53-8.47 (m, 1H), 8.23 (s, 1H), 7.74-7.64 (m, 1H), 7.55-7.39 (m, 5H), 7.32-7.22 (m, 1H), 6.56 (t, J=5.6 Hz, 1H), 5.02-4.93 (m, 2H), 4.60 (d, J=5.6 Hz, 2H), 2.70 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 161.8, 157.6, 157.3, 149.2, 149.1, 143.1, 135.7, 133.7, 132.8, 131.2, 129.0, 125.0, 124.6, 123.7, 122.9, 118.6, 56.1, 41.6, 17.3; MS (ES+) m/z 441.4 (M+1).

1. stirringThe reaction mixture was stirred at ambient temperature for 17 hours
2. washwashed with water and brine
3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by column chromatography to the title compound as a white solid (0.03 g, 7%)