反应详情

trans-N2-(4-{4-Amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1H-2-indolecarboxamide (312 mg, 0.539 mmol) was dissolved in hot ethyl acetate (35 mL) and maleic acid (187 mg, 1.614 mmol) in hot ethyl acetate (5 mL) was added. The reaction mixture was stirred at room temperature for 5 hours. The solid was collected by filtration to give inhibitor 7, trans-N2-(4-{4-Amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1H-2-indolecarboxamide, tris-maleate salt (473 mg, 95%). 1H NMR (DMSO-d6) δ 1.60 (m, 2H), 2.09 (m, 6H), 2.68 (s, 3H), 2.84-3.19 (bm, 9H), 3.97 (s, 3H), 4.73 (m, 1H), 6.17 (s, 6H), 7.11 (m, 1H), 7.25 (m, 1H), 7.30 (m, 1H), 7.34 (s, 1H), 7.41 (s, 1H), 7.49 (d, J=8.21, 1H), 7.68 (d, J=8.02 Hz, 1H), 8.13 (d, J=8.15 Hz, 1H), 8.26 (s, 1H), 9.44 (s, 1H), 11.38 (s, 1H). LCMS (Finigan-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4 min. (B: acetonitrile, A: 50 mM ammonium acetate buffer, pH 4.5), 3.0 mL/min.): MH+=580.4, Rt=2.01 min.

1. filtrationThe solid was collected by filtration