反应详情

温度

25 °C

To a solution of the product of Example 321C (20 mg, 0.0467 mmol) in N,N-dimethylformamide (2 mL) was added 2-chlorobutyramide (8.5 mg, 0.070 mmol), tetra-n-butylammonium iodide (1.7 mg, 0.0047 mmol) and cesium carbonate (61 mg, 0.187 mmol). The mixture was stirred at 25° C. for 18 hours, then heated to 80° C. for 3 hours. After cooling to 25° C., 1N aqueous hydrochloric acid (10 mL) was added and the mixture extracted with ethyl acetate (10 mL). The resulting organic layer was separated and dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide the title compound (24 mg, 100%). The sodium salt of the title compound was prepared according to the procedure of Example 1D. MS (ESI−) m/z 512 (M−Na)−. 1H NMR (300 MHz, DMSO-d6) δ 0.99 (t, J=7.7 Hz, 3H), 1.03 (d, J=6.3 Hz, 6H), 1.83 (m, 3H), 2.50 (m, 1H), 2.75 (m, 1H), 4.46 (m, 1H), 5.94 (m, 1H), 7.08 (m, 2H), 7.17 (m, 1H), 7.23 (m, 1H), 7.32 (s, 1H), 7.58 (m, 2H), 7.64 (s, 1H), 8.07 (d, J=7.8 Hz, 1H), 16.23 (bs, 1H).

1. temperatureheated to 80° C. for 3 hours
2. temperatureAfter cooling to 25° C.
3. extractionthe mixture extracted with ethyl acetate (10 mL)
4. customThe resulting organic layer was separated
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure