Reaction Steps
A mixture of the product of Example 1D (1.590 g, 4.42 mmol), 4-(trifluoromethyl)aniline (1.424 g, 8.84 mmol), and triethylamine (1.24 mL, 8.90 mmol) in dimethylformamide (30 mL) was added to palladium(II) acetate (49.3 mg, 0.220 mmol) and 2-dicyclohexylphosphino-2′-(dimethylamino)biphenyl (174.7 mg, 0.444 mmol) in a 250 mL pressure bottle under argon. The mixture was pressurized with carbon monoxide (60 psi), stirred 14 hours at ambient temperature, treated with ethyl acetate (200 mL), washed with saturated sodium bicarbonate (200 mL), brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was chromatographed on silica gel, eluting with 0-to-40% ethyl acetate in hexanes, and concentrated to a yellow oil. Repeated chromatography on silica gel, eluting with dichloromethane, then 30% ethyl acetate in dichloromethane afforded 1.424 g (81% yield) of the title compound as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.15-2.36 (m, 1H), 2.89-3.01 (m, 1H), 3.08-3.21 (m, 1H), 6.75 (s, 1H), 7.49 (ddd, J=8.13, 4.56, 0.79 Hz, 1H), 7.68 (d, J=8.33 Hz, 2H), 7.93 (d, J=8.33 Hz, 2H), 8.03 (dd, J=8.13, 1.39 Hz, 1H), 8.56 (d, J=4.76 Hz, 1H), 10.10 (s, 1H). 1H NMR (300 MHz, CDCl3) δ ppm 2.26-2.47 (m, 1H), 2.55-2.72 (m, 3H), 2.93-3.05 (m, 1H), 3.15-3.33 (m, 1H), 6.74 (s, 1H), 7.22-7.27 (m, 1H), 7.58-7.61 (m, 3H), 7.71 (d, J=8.47 Hz, 2H), 7.77 (dd, J=8.13, 1.35 Hz, 1H), 8.46 (ddd, J=4.58, 1.52, 0.85 Hz, 1H). MS (ESI) m/z 398.95 (M+H)+. Calcd for C19H15ClF4N2O: C, 57.23, H, 3.79, N, 7.02. Found: C, 57.11; H, 3.49; N, 6.92.
