反应详情

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).

1. concentrationThe mixture was concentrated
2. dissolutionThe residue was dissolved in dichloromethane
3. washwashed with saturated sodium bicarbonate
4. concentrationconcentrated
5. washSilica gel chromatography, eluting with 0-50% ethyl acetate in hexanes