反应详情

(Z)-(9H-Fluoren-9-yl)methyl (3-(3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acryloyl)-3-azabicyclo[3.1.0]hexan-6-yl)carbamate (0.3 g, 1.0 eq.) in was dissolved in DMF (0.75 ml). TEA (0.75 ml) was added dropwise and the reaction mixture was stirred at room temperature for 4 h, quenched with water (10 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure (25° C., 20 mmHg) to afford 0.2 g of the crude product, which was purified by chromatography (10% Methanol in DCM) to obtain (Z)-1-(6-amino-3-azabicyclo[3.1.0]hexan-3-yl)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)prop-2-en-1-one (0.1 g; 50% yield). 1H NMR (400 MHz, DMSO) δ=9.10 (s, 1H), 8.49 (s, 2H), 8.30 (s, 1H), 7.30-7.32 (d, J=10 Hz, 1H), 6.07-6.09 (d, J=10 Hz, 1H), 3.65-3.68 (d, 1H), 3.48 (s, 1H), 3.35-3.45 (m, 1H), 3.29-3.30 (d, 1H), 2.28 (s, 1H), 1.48-1.49 (m, 2H), 1.22 (s, 1H); LCMS calcd. for C18H16F6N5O [M+H]+ 432.34. found 432.19 at 2.1 min retention time.

1. customquenched with water (10 mL)
2. extractionextracted with ethyl acetate (3×50 mL)
3. washThe combined organic layers was washed with brine (50 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure (25° C., 20 mmHg)
7. customto afford 0.2 g of the crude product, which
8. customwas purified by chromatography (10% Methanol in DCM)