反应详情

To a solution of 2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)benzoic acid (150 mg, 0.33 mmol), HATU (188 mg, 0.495 mmol) and Et3N (0.15 mL, 0.99 mmol) in DMF (10 mL) was added 6-(1-aminoethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (0.93 mmol). The mixture was stirred at rt overnight and EA (50 mL) was added. The mixture was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC to give the title compound N-(1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)ethyl)-2-methyl-4-(5-(3,4,5-tri-chlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide (103 mg; yield 18% over 5 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.00 (s, 1H), 8.82 (d, J=7.6 Hz, 1H), 7.84 (s, 2H), 7.37-7.67 (m, 6H), 5.16 (m, 1H), 4.40 (d, J=18.0 Hz, 1H), 4.33 (d, J=18.0 Hz, 1H), 2.33 (s, 3H), 1.47-1.44 (m, 9H) ppm; HPLC purity: 99.88% at 220 nm and 99.77% at 254 nm; MS: m/z=639.8 (M+1, ESI+).

1. washThe mixture was washed with brine
2. dry with materialdried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by prep-HPLC