公开(公告)号：WO2013175270A1

公开(公告)日：2013-11-28

申请号：PCT/IB2012/052645

申请日：2012-05-25

申请人： FLEMING LABORATORIES LIMITED ,  BALASUBRAMANIAM, Ravishankar ,  POLSANI, Pulla Rao ,  TOGATA, Madduleti

发明人： BALASUBRAMANIAM, Ravishankar ,  POLSANI, Pulla Rao ,  TOGATA, Madduleti

IPC分类号： C07D333/38 ,  C07D333/36 ,  A61K31/381 ,  A61P19/10

CPC分类号： C07D333/38 ,  C07D333/40

摘要： The present invention relates to an improved process for preparation of pure strontium ranelate hydrates (Ia-c) by using the intermediates, amino dimethyl ester (II) and tetramethyl ester (III), which are prepared by novel methods. The present invention also relates to a new crystalline polymorphic form of strontium ranelate monohydrate Form F, and process for the preparation thereof. Formula (Ia-c) : Ia- Strontium ranelate octahydrate: n=8 Ib- Strontium ranelate tetrahydrate: n=4 Ic- Strontium ranelate monohydrate: n=1 Formula (II) and Formula (III).

摘要翻译： 本发明涉及通过使用通过新方法制备的中间体氨基二甲酯（II）和四甲基酯（III））制备纯的雷奈酸锶水合物（Ia-c）的改进方法。 本发明还涉及雷奈酸锶一水合物形式F的新型结晶多晶型物及其制备方法。 式（Ia-c）：Ia-雷奈酸锶八水合物：n = 8lb-雷奈酸锶四水合物：n = 4 Ic-雷奈酸锶一水合物：n = 1式（II）和式（III）。

公开(公告)号：WO2009093258A2

公开(公告)日：2009-07-30

申请号：PCT/IN2008000454

申请日：2008-07-16

申请人： FLEMING LAB LTD ,  BALASUBRAMANIAM RAVISHANKAR ,  POLSANI PULLA RAO ,  TAMMIREDDY GOWRI NAIDU

发明人： BALASUBRAMANIAM RAVISHANKAR ,  POLSANI PULLA RAO ,  TAMMIREDDY GOWRI NAIDU

IPC分类号： C07F9/38

CPC分类号： C07F9/386 ,  C07F9/3873

摘要： The present invention discloses a new and an improved process for preparation of Ibandronate sodium monohydrate. According to the process pentylamine is reacted with ethylacrylate to give N-pentyl-ß-alanine ethyl ester (XXIV), which on methylation provided N-methyl-N-pentyl-ß-alanine ethylester formula (XXV). The reresulting ester on hydrolysis and subsequent treatment with hydrochloric acid furnished 3-(N-methyl-N-pentylamino)propionic acid hydrochloride formula (II). Bisphosphorylation of 3-(N-methyl-N-pentylamino)propionic acid hydrochloride formula (II) with phosphorous acid and phosphorous trichloride followed by hydrolysis and subsequent treatment with a base provided Ibandronate monosodium monohydrate of formula (I).

摘要翻译： 本发明公开了一种制备伊班膦酸钠一水合物的新方法和改进方法。 根据该方法，戊胺与丙烯酸乙酯反应得到N-戊基-β-丙氨酸乙酯（XXIV），其在甲基化时提供N-甲基-N-戊基-β-丙氨酸乙酯式（XXV）。 水解反应后的酯和随后用盐酸处理，得到3-（N-甲基-N-戊基氨基）丙酸盐酸盐配方（II）。 使用亚磷酸和三氯化磷将3-（N-甲基-N-戊基氨基）丙酸盐酸盐式（II）的二磷酸化反应水解，随后用碱处理，得到式（I）的I带膦酸单钠盐一水合物。

公开(公告)号：WO2009093258A3

公开(公告)日：2009-07-30

申请号：PCT/IN2008/000454

申请日：2008-07-16

申请人： FLEMING LABORATORIES LIMITED ,  BALASUBRAMANIAM, Ravishankar ,  POLSANI, Pulla Rao ,  TAMMIREDDY, Gowri Naidu

发明人： BALASUBRAMANIAM, Ravishankar ,  POLSANI, Pulla Rao ,  TAMMIREDDY, Gowri Naidu

IPC分类号： C07F9/38

摘要： The present invention discloses a new and an improved process for preparation of Ibandronate sodium monohydrate. According to the process pentylamine is reacted with ethylacrylate to give N-pentyl-β-alanine ethyl ester (XXIV), which on methylation provided N-methyl-N-pentyl-β-alanine ethylester formula (XXV). The reresulting ester on hydrolysis and subsequent treatment with hydrochloric acid furnished 3-(N-methyl-N-pentylamino)propionic acid hydrochloride formula (II). Bisphosphorylation of 3-(N-methyl-N-pentylamino)propionic acid hydrochloride formula (II) with phosphorous acid and phosphorous trichloride followed by hydrolysis and subsequent treatment with a base provided Ibandronate monosodium monohydrate of formula (I).