Phosphorus oxychloride → N-benzyl-3-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)piperidine-1-carboxamide

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A solution of N-benzyl-3-(5-cyano-4-oxo-6-(4-phenoxyphenyl)-1,4-dihydropyridin-2-yl)piperidine-1-carboxamide (167.9 mg, 0.333 mmol) and phosphorus oxychloride (0.093 mL, 0.998 mmol) in N,N-dimethylformamide (1 mL) was heated to 90° C. in a sealed tube for 50 min. The mixture was concentrated. The residue was dissolved in dichloromethane, washed with saturated sodium bicarbonate and concentrated. Silica gel chromatography, eluting with 0-50% ethyl acetate in hexanes, gave N-benzyl-3-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)piperidine-1-carboxamide as white solid (144.4 mg, 83% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.92 (2H, δ, J=8.53 Hz), 7.28-7.46 (8H, m), 7.19 (1H, t, J=7.40 Hz), 7.06-7.14 (4H, m), 5.15 (2H, s), 4.36 (1H, hr. s), 4.12-4.25 (1H, m), 3.16 (1H, br. s), 2.92 (2H, br. s), 2.07 (1H, br. s), 1.84 (2H, hr. s), 1.58-1.70 (1H, m); MS (ES+) m/z: 524 (M+H); LC retention time: 4.330 min (analytical HPLC Method A).

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