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1. 发明授权

US08188285B2 Purification process of Montelukast and its amine salts 失效
标题翻译：孟鲁司特及其胺盐的净化过程
公开(公告)号：US08188285B2
公开(公告)日：2012-05-29
申请号：US12376779
申请日：2007-08-07
申请人： Yolanda Gasanz Guillén , Pedro Talavera Escasany , Montserrat Monsalvatje Llagostera
发明人： Yolanda Gasanz Guillén , Pedro Talavera Escasany , Montserrat Monsalvatje Llagostera
IPC分类号： C07D215/18
CPC分类号： C07D215/18
摘要： It comprises a process for the purification of Montelukast, or its salts or its solvates, including any stereoisomer or mixture thereof, which comprises converting Montelukast acid or a solvate thereof, including any stereoisomer or mixtures thereof, into an amine salt selected from the group consisting of tris-(hydroxymethyl)aminomethane, L-(+)-treo-2-amino-1-phenyl-1,3-propanediol, and L-(+)-α-phenylglycinol salt, in the presence of an appropriate solvent. It also comprises novel salts of Montelukast, in particular, tris-(hydroxymethyl)aminomethane, L-(+)-treo-2-amino-1-phenyl-1,3-propanediol, and L-(+)-α-phenylglycinol salts.
摘要翻译：它包括净化Montelukast或其盐或其溶剂化物，包括任何立体异构体或其混合物的方法，其包括将蒙特鲁卡斯特酸或其溶剂合物（包括其任何立体异构体或其混合物）转化成选自以下的胺盐：的三 - （羟甲基）氨基甲烷，L - （+） - 高-2-氨基-1-苯基-1,3-丙二醇和L - （+） - α-苯基甘氨醇盐。它还包括Montelukast的新型盐，特别是三 - （羟甲基）氨基甲烷，L - （+） - 高-2-氨基-1-苯基-1,3-丙二醇和L - （+） - - - - - - - - - - - 盐。

2. 发明申请

US20080306270A1 Process for the Preparation of a Leukotriene Antagonist and Intermediates Thereof 审中-公开
标题翻译：制备白三烯拮抗剂及其中间体的方法
公开(公告)号：US20080306270A1
公开(公告)日：2008-12-11
申请号：US12092554
申请日：2006-11-03
申请人： Laura Coppi , Marti Bartra Sanmarti , Yolanda Gasanz Guillen , Montserrat Monsalvatje Llagostera , Pedro Talavera Escasany
发明人： Laura Coppi , Marti Bartra Sanmarti , Yolanda Gasanz Guillen , Montserrat Monsalvatje Llagostera , Pedro Talavera Escasany
IPC分类号： C07D215/18
CPC分类号： C07D215/18
摘要： It comprises a preparation process of Montelukast from a new intermediate compound of formula (VI), which is previously prepared by reaction of the corresponding sulfonate with 1-(mercaptomethyl)cyclopropyl)methanol. Compound (VI) is reacted with a Grignard reactant to convert the ester group into a tertiary alcohol, followed by conversion of the primary alcohol into a sulfonate, substitution of the sulfonate group by a cyano group, and finally transforming the cyano compound to the carboxilic acid compound by a hydrolysis reaction to afford Montelukast. Montelukast can also be prepared by a hydrolysis reaction of the corresponding amide. It also comprises new intermediate compounds useful in such preparation process.
摘要翻译：它包括由新的式（VI）中间体化合物制备Montelukast的制备方法，其通过相应的磺酸酯与1-（巯基甲基）环丙基）甲醇反应而制备。使化合物（VI）与格氏反应物反应，将酯基转化为叔醇，然后将伯醇转化成磺酸盐，用磺酰基取代氰基，最后将氰基化合物转化为羧酸酸化合物通过水解反应得到蒙特鲁卡斯特。孟鲁司特也可以通过相应酰胺的水解反应制备。它还包括在这种制备过程中有用的新的中间体化合物。

3. 发明申请

US20100029945A1 Process for the purification of Montelukast 审中-公开
标题翻译：蒙特鲁卡斯净化工艺
公开(公告)号：US20100029945A1
公开(公告)日：2010-02-04
申请号：US12376773
申请日：2007-08-07
申请人： Yolanda Gasanz Guillén , Pedro Talavera Escasany , Montserrat Monsalvatje Llagostera
发明人： Yolanda Gasanz Guillén , Pedro Talavera Escasany , Montserrat Monsalvatje Llagostera
IPC分类号： C07D215/04
CPC分类号： C07D215/18
摘要： It relates to a process for the purification of Montelukast, or pharmaceutically salts thereof, or solvates thereof, including stereoisomers or mixture thereof which comprises carrying out a specific set of selective solvent extractions of Montelukast or its impurities in a mixture of an organic solvent and water at specific ranges of pH and temperature which depend on the type of impurities to remove. In particular, it comprises at least one wash of an aqueous phase containing crude Montelukast in salt form with an organic solvent, at a pH comprised between 12.0 and 13.5; and optionally one or more washes of the resulting aqueous phase with an organic solvent at a pH comprised between 8.5 and 10.0. Montelukast is recovered by acidification at a pH comprised between 4.5 and 8.0 and solvent extraction, and is isolated either as acid or in salt form.
摘要翻译：本发明涉及纯化Montelukast或其药学上可接受的盐或其溶剂化物，包括立体异构体或其混合物的方法，其包括在有机溶剂和水的混合物中进行特定的选择性溶剂萃取孟鲁司特或其杂质在特定的pH和温度范围内，这取决于要除去的杂质的类型。特别地，其包含至少一次含有盐形式的粗壮孟鲁司特与有机溶剂的水相洗涤，pH在12.0和13.5之间; 并且任选地用pH为8.5至10.0的有机溶剂一次或多次洗涤所得水相。通过在4.5至8.0之间的pH下酸化回收孟鲁司特并进行溶剂萃取，并以酸或盐形式分离。

4. 发明申请

US20090247759A1 Purification process of Montelukast and its Amine Salts 失效
标题翻译：蒙特鲁卡斯特及其胺盐的净化过程
公开(公告)号：US20090247759A1
公开(公告)日：2009-10-01
申请号：US12376779
申请日：2007-08-07
申请人： Yolanda Gasanz Guillen , Montserrat Monsalvatje Llagostera , Pedro Talavera Escasany
发明人： Yolanda Gasanz Guillen , Montserrat Monsalvatje Llagostera , Pedro Talavera Escasany
IPC分类号： C07D215/18
CPC分类号： C07D215/18
摘要： It comprises a process for the purification of Montelukast, or its salts or its solvates, including any stereoisomer or mixture thereof, which comprises converting Montelukast acid or a solvate thereof, including any stereoisomer or mixtures thereof, into an amine salt selected from the group consisting of tris-(hydroxymethyl)aminomethane, L-(+)-treo-2-amino-1-phenyl-1,3-propanediol, and L-(+)-α-phenylglycinol salt, in the presence of an appropriate solvent. It also comprises novel salts of Montelukast, in particular, tris-(hydroxymethyl)aminomethane, L-(+)-treo-2-amino-1-phenyl-1,3-propanediol, and L-(+)-α-phenylglycinol salts.
摘要翻译：它包括净化Montelukast或其盐或其溶剂化物，包括任何立体异构体或其混合物的方法，其包括将蒙特鲁卡斯特酸或其溶剂合物（包括其任何立体异构体或其混合物）转化成选自以下的胺盐：的三 - （羟甲基）氨基甲烷，L - （+） - 高-2-氨基-1-苯基-1,3-丙二醇和L - （+） - α-苯基甘氨醇盐。它还包括Montelukast的新型盐，特别是三（羟甲基）氨基甲烷，L - （+） - 高-2-氨基-1-苯基-1,3-丙二醇和L - （+） - α-苯基甘氨醇盐。

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