反应详情

To a solution of compound 1-benzhydryl-3-hydrazinylazetidine hydrochloride (15.5 g, 49.6 mmol) in ethanol (150 mL), a mixture of (E)-1-(2-bromo-5-(trifluoromethyl)phenyl)-3-(dimethylamino)prop-2-en-1-one (16 g, 49.6 mmol) in acetic acid (15 mL) was added slowly at 0° C. The reaction was stirred at the same temperature for 8 h. After warming to rt, the solvent was completely evaporated off. The residue was diluted with ethyl acetate (500 mL), washed with water (500 mL), and saturated aqueous sodium bicarbonate (30 mL). Organic part was dried over sodium sulfate, filtered and concentrated under a vacuum to give the crude which was further purified by column chromatography using silica gel (100 to 200 mesh) eluting with 0% to 10% ethyl acetate in hexanes to obtain 1-(1-benzhydrylazetidin-3-yl)-5-(2-bromo-5-(trifluoromethyl)phenyl)-1H-pyrazole (10 g, 39.3%) as a sticky yellow solid. MS (ESI, positive ion) m/z (M+1): 512.01. 1H NMR (400 MHz, DMSO) δ 8.03 (d, J=8.3 Hz, 1H), 7.80 (d, J=8.5 Hz, 1H), 7.77 (s, 1H), 7.68 (d, J=1.5 Hz, 1H), 7.43 (d, J=7.4 Hz, 4H), 7.26 (t, J=7.5 Hz, 4H), 7.17 (t, J=7.3 Hz, 2H), 6.41 (d, J=1.5 Hz, 1H), 4.66-4.59 (m, 1H), 4.57 (s, 1H), 3.46 (dt, J=26.3, 7.3 Hz, 4H).

1. additionwas added slowly at 0° C
2. customthe solvent was completely evaporated off
3. additionThe residue was diluted with ethyl acetate (500 mL)
4. washwashed with water (500 mL), and saturated aqueous sodium bicarbonate (30 mL)
5. dry with materialOrganic part was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under a vacuum
8. customto give the crude which
9. customwas further purified by column chromatography
10. washeluting with 0% to 10% ethyl acetate in hexanes