反应详情

N2-(4-{4-amino-1-[1-(2,2-difluoroethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide (227 mg, 0.405 mmol) was dissolved in hot ethyl acetate (25 mL). Maleic acid (94 mg, 0.810 mmol) in hot ethyl acetate (3 mL) was added. The reaction mixture was stirred at room temperature overnight. No precipitate was formed. After stirring at room temperature for 4 days, precipitate was formed at bottom of the flask. The solvent was decanted. The solid was washed with ethyl acetate and dried to give N2-(4-{4-amino-1-[1-(2,2-difluoroethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide, dimaleate salt (220 mg, 68%). 1H NMR (DMSO-d6) δ 2.05 (m, 2H), 2.40 (m, 2H), 2.84-3.32 (bm, 6H), 3.96 (s, 3H), 4.04 (s, 3H), 4.85 (m, 1H), 6.22 (s, 4H), 6.34 (t, J=56.07 Hz, 1H), 7.15 (m, 1H), 7.33 (m, 4H), 7.59 (d, J=8.45 Hz, 1H), 7.70 (d, J=7.94 Hz, 1H), 8.12 (d, J=8.19 Hz, 1H), 8.28 (s, 1H), 9.45 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 0.8 mL/min.): RT=3.32 min. MH+=561.3.

1. customNo precipitate was formed
2. stirringAfter stirring at room temperature for 4 days
3. customprecipitate was formed at bottom of the flask
4. customThe solvent was decanted
5. washThe solid was washed with ethyl acetate
6. customdried