Diisopropylethylamine → N-((4-fluoro-1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide

Participants

Reaction Steps

To a solution of crude 2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzoic acid (0.45 g, 1 mmol) in DMF (5 mL) at rt under N2 was added HBTU (0.76 g, 2 mmol), followed by DIPEA (0.39 g, 3 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was purified by chromatography over silica gel eluted with PE-DCM (1:1) to give an activated intermediate from acid, which was used directly to mix with 6-(aminomethyl)-4-fluoro-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol (0.3 g, 1.44 mmol) in 5 mL of DMF. The reaction mixture was stirred at rt overnight. The reaction was monitored by LC-MS. The reaction solution was purified by pre-HPLC to give the final title compound (260 mg, 40.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.31 (s, 1H), 8.97 (t, 1H), 7.86 (s, 2H), 7.63-7.62 (m, 2H), 7.53-7.51 (m, 2H), 7.24 (d, 1H), 4.50 (d, J=5.6 Hz, 2H), 4.43-4.31 (m, 2H) 2.42 (s, 3H) 1.53 (s, 6H) ppm; HPLC purity: 97.9% at 220 nm and 99.6 at 254 nm; MS (ESI+): m/z=643 (M+1).

Provenance & Evidence