公开(公告)号：EP1615913A2

公开(公告)日：2006-01-18

申请号：EP04755278.1

申请日：2004-06-10

申请人： Teva Pharmaceutical Industries Limited

发明人： LIBERMAN, Anita ,  SINGER, Claude ,  RAIZI, Yuriy ,  PILARSKY; Gideon ,  BRAUDE, Viviana ,  FINKELSTEIN, Nina ,  CHEN, Kobi

IPC分类号： C07D401/12

CPC分类号： C07D401/12

摘要： The present invention provides a process comprising admixing a thioether with about 1.05 to about 1.6 molar equivalents of an active chlorine-containing oxidant, preferably sodium hypochlorite, and about 2.5 to about 5.0 molar equivalents of an alkali metal base; and recovering a sulfoxide that is preferably pantoprazole, lansoprazole, omeprazole, or rabeprazole. The process may further comprise contacting the sulfoxide with a source of sodium ions, preferably sodium hydroxide, to produce the sodium salt of the sulfoxide. The invention also relates to novel chlorinated derivatives of pantoprazole including 5­(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-chloromethyl]sulfinyl]-1H- benzimidazole and 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)­chlorohydroxymethyl] sulfinyl]-1H-benzimidazole and processes for making them. The invention also relates to processes of quantifying and identifying a compound other than pantoprazole in a mixture of pantoprazole and at least one other compound.

公开(公告)号：EP1601667A2

公开(公告)日：2005-12-07

申请号：EP04720431.8

申请日：2004-03-12

申请人： Teva Pharmaceutical Industries Limited

发明人： FINKELSTEIN, Nina ,  KROCHMAL, Barnaba ,  WIZEL, Shlomit

IPC分类号： C07D401/12 ,  A61K31/4439 ,  A61B1/04

CPC分类号： C07D401/12

摘要： The present invention relates to a polymorphic form (Form I) of pantoprazole and a processes of making same. Form I has a PXRD pattern with characteristic peaks at 6.6, 13.2, 13.7, 15.7, 23.1, and 23.4 ± 0.2 °20 and a FTIR spectrum with characteristic bands at 1385, 1264, 1244, 1180, and 1027 at cm-1. The process of making Form I includes crystallizing pantaoprazole or forming slurry from amorphous pantoprazole. The present invention also relates to another polymorphic form (Form II) of pantoprazole and a process of making the same. Form II has a PXRD pattern with characteristic peaks at 5.8, 7.5, 9.3, 15.0, 22.0, and 22.6 ± 0.2 °20 and a FTIR spectrum with characteristic bands at 3195, 1196, and 1584 at cm-1. The process of making Form II includes forming a slurry from amorphous pantoprazole.

公开(公告)号：EP1178805A1

公开(公告)日：2002-02-13

申请号：EP00923457.6

申请日：2000-04-18

申请人： Teva Pharmaceutical Industries Limited ,  Teva Pharmaceuticals USA, Inc. ,  Singer, Claude ,  Liberman, Anita

发明人： SINGER, Claude ,  LIBERMAN, Anita ,  FINKELSTEIN, Nina

IPC分类号： A61K31/55 ,  A61P25/24 ,  C07D401/04 ,  C07D487/12

CPC分类号： C07D401/04 ,  C07D471/14

摘要： The present invention is directed to methods for the preparation of piperazine ring-containing compounds, particularly mirtazapine. According to the present invention, the mirtazapine intermediate 1-(3-carboxypyridyl-2)-4-methyl-2-phenyl-piperazine is made by hydrolyzing 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine with a base where the base is present in a ratio of up to about 12 moles of the base per one mole of 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine. The mirtazapine intermediate 1-(3-carboxypyridly-2)-4-methyl-2-phenyl-piperazine may be made by hydrolyzing 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine with potassium hydroxide at a temperature of at least about 130 °C. The method of the present invention also includes reacting 2-amino-3-hydroxymethyl pyridine with N-methyl-1-phenyl-2, 2'-iminodiethyl chloride to form 1-(3-hydroxymethylpyridyl-2)-4-methyl-2-phenyl piperazine, and adding sulfuric acid to the 1-(3-hydroxymethylpyridyl-2)-phenyl-4-methylpiperazine to form mirtazapine. The present invention also relates to new processes for recrystallization of mirtazapine form crude mirtazapine.

摘要翻译： 本发明涉及制备含哌嗪环化合物，特别是米氮平的方法。 根据本发明，米氮平中间体1-（3-羧基吡啶-2）-4-甲基-2-苯基 - 哌嗪是通过水解1-（3-氰基吡啶基-2）-4-甲基-2-苯基 - 哌嗪与碱相比，每1摩尔1-（3-氰基吡啶基-2）-4-甲基-2-苯基 - 哌嗪，碱的含量最多为约12摩尔碱。 米氮平中间体1-（3-羧基吡啶-2）-4-甲基-2-苯基 - 哌嗪可以通过用氢氧化钾水解1-（3-氰基吡啶基-2）-4-甲基-2-苯基 - 哌嗪来制备 温度至少约130℃。本发明的方法还包括使2-氨基-3-羟甲基吡啶与N-甲基-1-苯基-2,2'-亚氨基二乙基氯反应形成1-（3- 羟甲基吡啶-2）-4-甲基-2-苯基哌嗪，并向1-（3-羟甲基吡啶-2） - 苯基-4-甲基哌嗪中加入硫酸以形成米氮平。 本发明还涉及来自粗米氮平的米氮平重结晶的新方法。