反应详情

To a solution of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (3.6 g, 8.3 mmol) and HATU (5.24 g, 13.8 mmol) in DMF (25 mL) was added DIPEA (3.3 mL, 18.4 mmol). The reaction mixture was stirred at rt for 10 min and 6-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (2.1 g, 9.2 mmol) was added. The reaction mixture was stirred overnight. Water was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel eluted with PE:EA (3:1 to 1:1) to give the final title compound 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-2-methylbenzamide (3.1 g; yield 61%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.94 (t, J=6.0 Hz, 1H), 7.84 (d, J=6.5 Hz, 2H), 7.66-7.62 (m, 3H), 7.53-7.43 (m, 3H), 4.49 (d, J=6.0 Hz, 2H), 4.39 (d, J=18.5 Hz, 1H), 4.36 (d, J=18.5 Hz, 1 H), 2.42 (s, 3 H), 1.47 (s, 6H) ppm; HPLC purity: 100% at 220 nm and 99.75% at 254 nm; MS: m/z=608.8 (M+1, ESI+).

1. stirringThe reaction mixture was stirred overnight
2. extractionthe mixture was extracted three times with ethyl acetate
3. washThe combined organic layers were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by column chromatography over silica gel
8. washeluted with PE