LUISI, BRIAN,路西 布莱恩,路西 布萊恩,WILLCOX, DAVID,威尔考斯 大卫,威爾考斯 大衛,ROEPER, STEFANIE,洛普 史黛芬妮,洛普 史黛芬妮,HU, KAN NIAN,胡康年,胡康年,LUONG, HOA Q.,隆 霍亚Q,隆 霍亞Q
申请号：
TW101127011
公开号：
TW201317223A
申请日:
2012.07.26
申请国别(地区):
TW
年份:
2013
代理人:
摘要：
Polymorph Forms M, H, P, X, and ZA of Compound (1) represented by the following structural formula: are described. A method of preparing polymorph Form M of Compound (1) includes stirring a mixture of Compound (1) and a solvent system that includes isopropanol, ethyl acetate, n-butyl acetate, methyl acetate, acetone, 2-butanone (methylethylketone (MEK)), or heptane, or a combination thereof at a temperature in a range of 10 ℃ to 47 ℃ to form From M of Compound (1). A method of preparing polymorph Form H of Compound (1) includes stirring a solution of Compound (1) at a temperature in a range of 48 ℃ to 70 ℃ to form Form H of Compound (1). A method of preparing polymorph Form P of Compound (1) includes stirring a mixture of Compound (1) and a solvent system that includes a solvent selected from the group consisting of dichloromethane and tetrahydrofuran (THF), and a mixture thereof at room temperature to form Form P of Compound (1). A method of preparing polymorph Form X of Compound (1) includes removing ethyl acetate from ethylacetate solvate G of Compound (1). A method of preparing polymorph Form ZA of Compound (1) includes removing n-butyl acetate from n-butyl acetate solvate A of Compound (1).本發明描述由以下結構式表示之化合物(1)之多晶形式M、多晶形式H、多晶形式P、多晶形式X及多晶形式ZA:。製備化合物(1)之多晶形式M的方法包括在10℃至47℃範圍內之溫度下攪拌化合物(1)與溶劑系統之混合物以形成化合物(1)之形式M,該溶劑系統包括異丙醇、乙酸乙酯、乙酸正丁酯、乙酸甲酯、丙酮、2-丁酮(甲基乙基酮(MEK))或庚烷或其組合。製備化合物(1)之多晶形式H的方法包括在48℃至70℃範圍內之溫度下攪拌化合物(1)之溶液以形成化合物(1)之形式H。製備化合物(1)之多晶形式P的方法包括在室溫下攪拌化合物(1)與溶劑系統之混合物以形成化合物(1)之形式P,該溶劑系統包括選自由二氯甲烷及四氫呋喃(THF)及其混合物組成之群的溶劑。製備化合物(1)之多晶形式X的方法包括自化合物(1)之乙酸乙酯溶劑合物G中移除乙酸乙酯。製備化合物(1)之多晶形式ZA的方法包括自化合物(1)之乙酸正丁酯溶劑合物A中移除乙酸正丁酯。
