反应详情

A solution of cis-1-[4-(4-methylpiperazino)cyclohexyl]-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate AJ) (0.53 g, 0.0011 mol) in a mixture of ethyl acetate (25 mL) and ethanol (4 mL) was heated at reflux and a preheated solution of maleic acid (0.51 g, 0.0044 mol) in ethyl acetate (15 mL) was added. The mixture was refluxed for another 10 min, cooled to ambient temperature and the precipitate collected by filtration, washed with ethyl acetate and dried to yield cis-1-[4-(4-methylpiperazino)cyclohexyl]-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo [3,4-d]pyrimidin-4-amine dimaleate as a white solid (0.61 g, 0.00084 mol): 1H NMR (DMSO-d6, 400 MHz) 8.38 (s, 1H), 8.25 (s, 1H), 8.06 (d, 1H), 7.46 (t, 2H), 7.22 (m, 4H), 6.15 (s, 4H), 4.85 (m, 1H), 3.1 (br, 9H), 2.70 (s, 3H), 2.25 (m, 2H), 2.04 (m, 2H), 1.74 (m, 4H); RP-HPLC (Delta Pak C18, 5 μm, 300A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 11.93 min. MS: MH+485.

1. temperaturewas heated
2. temperatureat reflux
3. temperatureThe mixture was refluxed for another 10 min
4. filtrationthe precipitate collected by filtration
5. washwashed with ethyl acetate
6. customdried