Reaction Steps
To a solution of (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (32 mg, 0.06 mmol, prepared as described in Procedure 14) in DMF (0.5 mL) was added Cs2CO3 (39 mg, 0.12) and ICF2CO2Et (28 mg, 0.12 mmol). The mixture was heated at 60° C. for 3 days. NaHCO3 was added. It was extracted with CH2Cl2. The organic layer was washed with 10% citric acid, brine, dried over MgSO4, concentrated and the crude mixture was purified by preparative HPLC (phenominex C18 column, 21×100 mm, 5 μ) using MeOH/H2O (0.1% TFA) to give two products, (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-ethoxy-5-fluorophenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (2.5 mg, 7% yield) as a pale yellow solid, LCMS: 4.38 min [M+1] 561.44 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 1.33-1.40 (m, J=6.88, Hz, 3 H), 3.61 (d, J=12.88 Hz, 1 H), 3.93-4.00 (m, 2 H), 4.54 (d, J=12.88 Hz, 1 H), 6.49-6.56 (m, 3 H), 6.76 (dt, J=9.85, 1.89 Hz, 1 H), 6.84 (s, 1 H), 7.02 (t, J=7.45 Hz, 2 H), 7.11 (t, J=7.33 Hz, 1 H), 7.22-7.31 (m, 3 H), 7.70 (dd, J=8.59, 2.27 Hz, 1 H), 7.85-7.90 (m, 1 H), 8.03 (dd, J=6.82, 2.02 Hz, 1 H), 8.32 (d, J=2.53 Hz, 1 H), 9.11 (s, 1 H), and (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-(difluoromethoxy)-5-fluorophenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (3 mg, 7% yield) as a pale yellow foam, LCMS: 4.28 min [M+1] 583.32 (4 min gradient, MeOH/H2O 0.1% TFA); 1 H NMR (400 MHz, CDCl3) δ ppm 3.61 (d, J=12.88 Hz, 1 H), 4.54 (d, J=12.88 Hz, 1 H), 6.51 (m, 3 H), 6.76-6.83 (m, 1 H), 7.00-7.08 (m, 4 H), 7.13 (t, J=7.45 Hz, 1 H), 7.20-7.29 (m, 2 H), 7.74 (dd, J=8.59, 2.27 Hz, 1 H), 7.87 (ddd, J=8.46, 4.67, 2.27 Hz, 1 H), 8.02 (dd, J=6.69, 1.89 Hz, 1 H), 8.35 (d, J=2.27 Hz, 1 H), 9.11 (s, 1 H).
