Reaction Steps
A mixture of Cu(OAc)2 (16 mg, 0.09 mmol) and pyridine (7 μl, 0.09 mmol) in CH2Cl2 (1 mL) was stirred for 5 min. Added to this were methyl 2-(tert-butoxy)-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate (intermediate 5) (20 mg, 0.045 mmol), [1,1′-biphenyl]-3-ylboronic acid (17.9 mg, 0.09 mmol) and 34 mg molecular sieves. The resulting mixture was stirred, uncovered, at room temperature for 21 h. The mixture was adsorbed directly onto silica gel and purified by flash column chromatography (Biotage; 0%-50% EtOAc/hexane) to give methyl 2-(6-([1,1′-biphenyl]-3-yl)-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetate (10 mg, 37% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.58-7.52 (m, 2H), 7.41-7.35 (m, 2H), 7.35-7.30 (m, 1H), 7.27-7.16 (m, 3H), 7.08-6.99 (m, 2H), 6.79-6.70 (m, 1H), 4.88 (s, 1H), 4.01 (d, J=15.6 Hz, 1H), 3.75 (d, J=15.9 Hz, 1H), 3.73 (s, 3H), 3.56 (dt, J=13.1, 6.6 Hz, 1H), 3.49-3.41 (m, 1H), 3.38-3.30 (m, 1H), 1.59 (s, 1H), 1.51 (d, J=4.0 Hz, 6H), 1.35 (s, 3H), 1.17 (d, J=6.7 Hz, 3H), 1.02 (s, 9H). 19F NMR (500 MHz, CDCl3) δ ppm −113.64. LCMS (M+H) calcd for C38H44FN2O3: 595.33. found: 595.4.
