半甲苯磺酸索拉非尼一水合物的制备及表征

摘要

以4-氯-N-甲基吡啶-2-甲酰胺为原料,与对氨基苯酚反应得到4-(4-氨基苯氧基)-N-甲基-2-吡啶甲酰胺,再与4-氯-3-三氟甲基苯基异氰基酸酯缩合得到索拉非尼碱,将其悬浮于乙醇中,加入甲苯磺酸一水合物搅拌升温至80℃,滴加水,降温析晶,得到半甲苯磺酸索拉非尼一水合物.通过研究发现了索拉非尼的新晶型,其稳定性好,结晶度高,适合产业化.%Sorafenib base was synthesized by condensing 4-(4-aminophenoxy)-2-(methylcarbamoyl)pyri-dine, which was obtained from 4-chlor-N-2-(methylcarbamoy1)pyridin via nucleophilic substitution with 4-aminophenol, and 4-chloro-3-(trifluoromethyl)phenylisocyanate. The sorafenib base was suspended in ethanol, after adding tosylate monohydrate and stirring up to 80℃, dropping water and cooling, sorafenib Hemi-tosylate monohydrate was formed through devitrification. A new crystal of sorafenib has been found in this study, which is more stable, purer and suitable for industrialization.