反应详情

To a solution of 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylic acid (23 mg, 0.052 mmol), HATU (30 mg, 0.078 mmol) and Et3N (0.02 mL, 0.104 mmol) in DMF (10 mL) was added 6-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (24 mg, 0.104 mmol). The mixture was stirred at rt overnight. EA (50 mL) was added and 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 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)indolizine-5-carboxamide (13 mg, yield 40%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.50 (t, J=6.0 Hz, 1H), 9.05 (s, 1H), 8.19 (s, 1H), 7.83 (s, 1H), 7.67 (s, 3H), 7.47 (d, J=8.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 7.11 (s, 1H), 6.94 (s, 1H), 4.57 (d, J=6.0 Hz, 2H), 4.48 (d, J=18.0 Hz, 1H), 4.38 (d, J=18.0 Hz, 1H), 1.44 (s, 6H) ppm; HPLC purity: 100.0% at 220 nm and 100.0% at 254 nm; MS: m/z=616.0 (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