反应详情

温度

100 °C

To a solution of (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-phenyl-3-piperidinecarboxamide (10 g, 23.2 mmol) in EtOH (400 mL) was added hydrazine (22.8 mL, 465 mmol). The resulting mixture was heated in seal tube at 100° C. overnight, cooled down, and concentrated in vacuo. The crude solution was purified by the silica gel chromatography (200 g column) eluting from 100% CHCl3 to CHCl3/CH3OH/NH4OH (9:1:0.1). The pure fractions that contained the desired product were combined and concentrated in vacuo to afford the title compound (3 g). LC-MS (ES) m/z=443 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.18 (d, J=6.8 Hz, 3H), 1.75 (s, 2H), 1.83 (m, 1H), 1.92 (m, 1H), 5.37 (s, 2H), 6.10 (s, 2H), 6.64 (s, 1H), 7.03 (s, 1H), 7.32 (s, 2H), 7.29-7.34 (m, 2H), 7.64 (d, J=7.3 Hz, 4H), 7.96 (s, 1H), 8.32 (s, 1H), 10.06 (s, 1H), 11.49 (s, 1H). The rest of fractions that contained the desired product and a small amount of impurities were combined, concentrated in vacuo and crystallized from CH3OH (˜10 mL). The crystalline material was obtained (3.6 g).

1. temperaturecooled down
2. concentrationconcentrated in vacuo
3. customThe crude solution was purified by the silica gel chromatography (200 g column)
4. washeluting from 100% CHCl3 to CHCl3/CH3OH/NH4OH (9:1:0.1)
5. concentrationconcentrated in vacuo