反应详情

温度

65 °C

To the product of Step 2 (100 mg, 0.13 mmol) was added chloroform (630 μL), sodium azide (24.5 mg, 0.38 mmol), and methanesulfonic acid (98 μL, 1.51 mmol). The mixture was heated to 65° C. for 1.5 h., cooled to room temperature, diluted with water, and extracted with ethyl acetate (2×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by reverse phase HPLC (35:65 to 70:30 acetonitrile:water with a 0.1% trifluoroacetic acid modifier). The fractions containing the desired product were diluted with ethyl acetate and free based with saturated aqueous sodium bicarbonate. The separated organic layer was dried over magnesium sulfate, filtered and concentrated to afford the title compound (38 mg, 0.083 mmol, 66% yield) as an orange oil. MS ESI: [M+H]+ m/z 463. 1H NMR (500 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.83 (s, 1H), 8.75 (s, 1H), 8.02 (s, 1H), 7.93 (s, 1H), 7.49 (s, 1H), 7.28 (d, J=4.7, 1H), 7.16 (s, 1H), 2.39-2.08 (m, 9H), 1.30-0.99 (m, 4H). rhSYK activity=+++

1. temperaturecooled to room temperature
2. extractionextracted with ethyl acetate (2×)
3. dry with materialThe combined organic layers were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by reverse phase HPLC (35:65 to 70:30 acetonitrile
7. additionThe fractions containing the desired product
8. additionwere diluted with ethyl acetate
9. dry with materialThe separated organic layer was dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated