反应详情

To the solution of 2-(4-(4-methyl-5-(pyridin-3-ylmethylcarbamoyl)thiazol-2-yl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)ethyl methanesulfonate (0.40 g, 0.91 mmol) in anhydrous tetrahydrofuran (10 mL) was added potassium carbonate (0.32 g, 2.28 mmol). The reaction mixture was stirred at ambient temperature for 1 minute, followed by the addition of (4-fluorophenyl)methanamine (0.10 mL, 0.91 mmol). The reaction mixture was stirred at ambient temperature for 17 hours, and then partitioned between ethyl acetate and brine. The organic layer was separated, washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate to afford the title compound as a white solid in 77% yield (0.36 g): mp 149-150° C. (ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.58 (br s, 1H), 8.49 (br s, 1H), 8.22 (s, 1H), 7.72-7.64 (m, 1H), 7.31-7.14 (m, 3H), 7.00-6.89 (m, 2H), 6.54 (t, J=5.8 Hz, 1H), 5.33 (t, J=5.9 Hz, 1H), 4.59 (d, J=5.8 Hz, 2H), 4.38 (t, J=5.1 Hz, 2H), 4.25 (d, J=5.9 Hz, 2H), 4.06 (t, J=5.1 Hz, 2H), 2.62 (s, 3H); MS (ES+) m/z 512.4 (M+1).

1. stirringThe reaction mixture was stirred at ambient temperature for 17 hours
2. custompartitioned between ethyl acetate and brine
3. customThe organic layer was separated
4. washwashed with brine
5. dry with materialdried over anhydrous sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography
9. washeluted with ethyl acetate