[Cl:1][C:2]1[C:3]([OH:18])=[CH:4][C:5](=[O:17])[N:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([F:16])[CH:9]=2)[CH:7]=1.O[CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH:21]1[CH3:33].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Cl:1][C:2]1[C:3]([O:18][C@@H:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][C@H:21]2[CH3:33])=[CH:4][C:5](=[O:17])[N:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([F:16])[CH:9]=2)[CH:7]=1To a mixture of 4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile (193 mg, 0.729 mmol), tert-butyl 4-hydroxy-3-methylpiperidine-1-carboxylate (173 mg, 0.802 mmol) and triphenylphosphine (230 mg, 0.875 mmol) in THF (2.0 mL) was added DEAD (0.129 mL, 0.875 mmol). The resulting mixture was stirred at room temperature overnight and then evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexane) to yield trans-tert-butyl 4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-3-methylpiperidine-1-carboxylate (183.5 mg, 50.1%) as an orange solid. 1H NMR (400 MHz, DMSO): 6 ppm 7.99-8.15 (m, 2H), 7.80 (dd, J=10.55, 1.76 Hz, 1H), 7.55 (dd, J=8.35, 1.76 Hz, 1H), 6.21 (s, 1H), 4.67-4.84 (m, 1H), 3.52 (app br s, 2H), 3.18 (app br s, 2H), 1.99 (app br s, 1H), 1.82 (app br s, 1H), 1.62-1.73 (m, 1H), 1.40 (s, 9H), 0.90 (d, J=7.03 Hz, 3H). MS (ESI) 406 (M−56+H).
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