反应详情

To a stirring solution of tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-45 (118 mg, 0.152 mmol) in THF (1 mL) and acetonitrile (1 mL) were added sodium carbonate (0.30 mL, 0.30 mmol, 1 M aqueous solution) and p-tolylboronic acid (25.0 mg, 0.18 mmol). The reaction mixture was de-gassed and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (5.50 mg, 7.60 μmol) was added. The reaction mixture was heated in a microwave at 130° C. for 30 min. The reaction mixture was diluted with DCM (4 mL) and NaHCO3 (10 mL), stirred for 15 min and split through a hydrophobic frit. The organics were evaporated and purified by column chromatography (EA/isohexanes) to yield tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate. To tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate in DCM (2 mL) was added TFA (2 mL) and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was evaporated and re-slurried from acetonitrile (4 mL) to afford 59 mg (53%) of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(2-(4′-methyl-[1,1′-biphenyl]-4-yl)oxazol-4-yl)benzyl)benzamido)acetic acid 364 as a white solid. LCMS-ESI (m/z) calculated for C42H34F3N3O6: 733; found 734 [M+H]+, tR=9.36 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.76 (s, 1H), 10.34 (s, 1H), 8.75 (s, 1H), 8.13 (d, J=6.7 Hz, 2H), 7.90-7.85 (m, 4H), 7.70-7.59 (m, 4H), 7.50-7.42 (m, 2H), 7.41-7.31 (m, 5H), 7.25-7.16 (m, 2H), 4.70 (s, 1H), 4.62 (s, 1H), 4.02 (s, 1H), 3.92 (s, 1H), 3.86 (s, 2H), 3.83 (s, 3H), 2.37 (s, 3H).

1. customThe reaction mixture was evaporated