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1. 发明申请

WO2007120538A1 NARCOTINE PURIFICATION PROCESS 审中-公开
标题翻译： NARCOTINE净化过程
公开(公告)号：WO2007120538A1
公开(公告)日：2007-10-25
申请号：PCT/US2007/008205
申请日：2007-03-28
申请人： MALLINCKRODT INC. , TOMAZI, Keith, G. , LOVE JR., Leroy , HAAR JR., Joseph P.
发明人： TOMAZI, Keith, G. , LOVE JR., Leroy , HAAR JR., Joseph P.
IPC分类号： C07D473/04
CPC分类号： C07D473/04
摘要： A process for purifying Narcotine to remove color and impurities to form Noscapine. The process includes forming an aqueous isopropanol solution with the Narcotine product wherein the isopropanol concentration of the solution is about 20% to about 70% by volume; and adjusting the pH of the solution with a strong base to a pH of about 10 to about 14, wherein impurities are removed from the Narcotine product.
摘要翻译：净化麻黄碱以除去颜色和杂质以形成诺斯卡品的方法。该方法包括用硝基异丁酸产物形成异丙醇水溶液，其中溶液的异丙醇浓度为约20％至约70％体积; 并用强碱将溶液的pH调节至约10至约14的pH，其中杂质从所述Narcotine产物中除去。

2. 发明申请

WO2008048254A1 HIGHLY PURE CRYSTALLINE BENZPHETAMINE HYDROCHLORIDE AND PROCESSES FOR PREPARING 审中-公开
标题翻译：高纯度结晶苯并苯胺氢氯化物及其制备方法
公开(公告)号：WO2008048254A1
公开(公告)日：2008-04-24
申请号：PCT/US2006/040415
申请日：2006-10-17
申请人： MALLINCKRODT INC. , TOMAZI, Keith, G. , NICHOLS, Gary, A. , MENZE, Michelle, R. , KALOTA, Dennis, J.
发明人： TOMAZI, Keith, G. , NICHOLS, Gary, A. , MENZE, Michelle, R. , KALOTA, Dennis, J.
IPC分类号： C07C209/84 , C07C211/27
CPC分类号： C07C211/27
摘要： A highly pure crystalline form of benzphetamine hydrochloride and methods for the purification and crystallization of benzphetamine hydrochloride in high yield are disclosed.
摘要翻译：公开了一种高纯度的苯并菲胺盐酸盐结晶形式以及以高产率纯化和结晶盐酸苯丙胺的方法。

3. 发明申请

WO2006057778A3 PROCESS FOR THE PURIFICATION OF BENZPHETAMINE HYDROCHLORIDE 审中-公开
标题翻译：纯化盐酸苯丙胺的方法
公开(公告)号：WO2006057778A3
公开(公告)日：2006-08-10
申请号：PCT/US2005039468
申请日：2005-11-02
申请人： MALLINCKRODT INC , TOMAZI KEITH G
发明人： TOMAZI KEITH G
IPC分类号： C07C209/84 , C07C211/27
CPC分类号： C07C209/84 , C07C211/27
摘要： The present invention relates to the economical and separation of benzphetamine hydrochloride and methamphetamine by liquid extraction. An extraction process employing a suitable organic solvent and water at a pH in the range of from about 6 to about 8 provides excellent removal of the methamphetamine by dissolution in the water phase while the benzphetamine dissolves in the organic phase. Simple separation of the two phases results in separation of the two amines.
摘要翻译：本发明涉及通过液体萃取经济和分离盐酸苄非他明和甲基苯丙胺。使用适合的有机溶剂和pH为约6至约8的水的萃取方法提供了通过溶解在水相中而甲基苯丙胺的优异去除，而苄非他明溶解于有机相中。两相的简单分离导致两种胺的分离。

4. 发明申请

WO2010039218A1 METHOD OF PURIFYING CRUDE NOSCAPINE 审中-公开
标题翻译：净化剂的方法
公开(公告)号：WO2010039218A1
公开(公告)日：2010-04-08
申请号：PCT/US2009/005373
申请日：2009-09-29
申请人： MALLINCKRODT INC. , MARSHALL, Benjamin, M. , TOMAZI, Keith, G.
发明人： MARSHALL, Benjamin, M. , TOMAZI, Keith, G.
IPC分类号： C07D491/048
CPC分类号： C07D491/048
摘要： The invention provides a method for separating noscapine from an opium source without substantially changing the color of the noscapine.
摘要翻译：本发明提供了一种从鸦片来源分离诺斯卡品而不显着改变诺斯卡品的颜色的方法。

5. 发明申请

WO2006060099A1 CRYSTALLIZATION METHOD FOR BENZPHETAMINE 审中-公开
标题翻译：苯并咪唑的结晶方法
公开(公告)号：WO2006060099A1
公开(公告)日：2006-06-08
申请号：PCT/US2005/039448
申请日：2005-11-02
申请人： MALLINCKRODT INC. , KALOTA, Dennis, J. , TOMAZI, Keith, G.
发明人： KALOTA, Dennis, J. , TOMAZI, Keith, G.
IPC分类号： C07C209/84 , C07C211/27
CPC分类号： C07C209/84 , C07C211/27
摘要： There is disclosed a method for the crystallization of benzphetamine hydrochloride from an organic medium by the steps of removing water from the system to a very low level and then reducing the temperature of the organic medium to provide crystallization of the acid salt. In the event that crystallization does not occur upon lowering the temperature of the medium, it has been discovered that gentle heating of the organic medium results in crystallization of the acid salt. It has also been discovered that higher temperature crystallization has been provided by removal of methamphetamine from the composition. The crystalline benzphetamine hydrochloride can then be isolated by typical liquid/solid separation means such as filtration or centrifugation.
摘要翻译：公开了通过以下步骤从有机介质中结晶苯并特苯胺盐酸盐的方法：将水从体系中除去至非常低的水平，然后降低有机介质的温度以提供酸盐的结晶。在降低介质温度时不发生结晶的情况下，发现有机介质的温和加热导致酸盐的结晶。还已经发现，通过从组合物中除去甲基苯丙胺已经提供了较高温度的结晶。然后可以通过典型的液体/固体分离方法如过滤或离心分离结晶苯并特苯胺盐酸盐。

6. 发明申请

WO2005123743A1 EXTRACTION OF ALKALOIDS FROM OPIUM 审中-公开
标题翻译：从OPIUM提取碱性物质
公开(公告)号：WO2005123743A1
公开(公告)日：2005-12-29
申请号：PCT/US2005/016512
申请日：2005-05-06
申请人： MALLINCKRODT INC. , TOMAZI, Keith, G.
发明人： TOMAZI, Keith, G.
IPC分类号： C07D489/02
CPC分类号： C07D489/02 , C07D217/20 , C07D221/22 , C07D491/04
摘要： A method for extracting at least one alkaloid from opium that includes dissolving opium in a solvent, heating the dissolved opium solution, cooling the dissolved opium solution, adjusting the pH of the dissolved opium solution with at least one first weak acid, filtering the dissolved opium solution to recover a filtrate; and then separating and purifying at least one alkaloid in the filtrate. Preferably, this includes an additional step of chilling the opium solution after adjusting the pH of the dissolved opium solution with at least one first acid. The preferred method for separating and purifying at least one alkaloid in the filtrate includes utilizing preparative liquid chromatography, however, solvent extraction and filtration can also be utilized.
摘要翻译：一种从鸦片中提取至少一种生物碱的方法，包括将鸦片溶解在溶剂中，加热溶解的鸦片溶液，冷却溶解的鸦片溶液，用至少一种第一弱酸调节溶解的鸦片溶液的pH，过滤溶解的鸦片溶液回收滤液; 然后分离和纯化滤液中的至少一种生物碱。优选地，这包括在用至少一种第一酸调节溶解的鸦片溶液的pH后冷却鸦片溶液的另外的步骤。用于分离和纯化滤液中至少一种生物碱的优选方法包括采用制备型液相色谱法，然而也可以使用溶剂萃取和过滤。

7. 发明申请

WO2012037309A3 IMPROVED PROCESS FOR THE PREPARATION OF SUFENTANIL BASE AND RELATED COMPOUNDS 审中-公开
标题翻译：改进的苏芬太尼碱及其相关化合物的制备方法
公开(公告)号：WO2012037309A3
公开(公告)日：2012-05-10
申请号：PCT/US2011051695
申请日：2011-09-15
申请人： MALLINCKRODT LLC , ORR BRIAN , HAAR JR JOSEPH , KLEMM GEORGE H , TOMAZI KEITH G
发明人： ORR BRIAN , HAAR JR JOSEPH , KLEMM GEORGE H , TOMAZI KEITH G
IPC分类号： C07D409/06
CPC分类号： C07D409/06
摘要： The present disclosure generally related to an improved process for the preparation of various piperidine derivatives. More particularly, the present disclosure related to an improved process for preparing sufentanil base (1) and related compounds, which advantageously utilizes more cost effective and/or less hazardous reagents, including a dispersion comprising between about 50% and about 70% by weight (based on the total weight of the dispersion) of an alkali metal hydride, such as sodium hydride, as well as eliminates the need for expensive and/or time consuming purification techniques.
摘要翻译：本公开总体上涉及制备各种哌啶衍生物的改进方法。更具体地说，本公开涉及用于制备舒芬太尼碱（1）和相关化合物的改进方法，其有利地使用更具成本效益和/或危害更小的试剂，包括含有约50重量％至约70重量％基于分散体的总重量）的碱金属氢化物如氢化钠，并且消除了对昂贵和/或耗时的纯化技术的需要。

8. 发明申请

WO2012037309A2 IMPROVED PROCESS FOR THE PREPARATION OF SUFENTANIL BASE AND RELATED COMPOUNDS 审中-公开
标题翻译：用于制备SUFENTANIL基础和相关化合物的改进方法
公开(公告)号：WO2012037309A2
公开(公告)日：2012-03-22
申请号：PCT/US2011/051695
申请日：2011-09-15
申请人： MALLINCKRODT LLC , ORR, Brian , HAAR, JR., Joseph , KLEMM, George H. , TOMAZI, Keith G.
发明人： ORR, Brian , HAAR, JR., Joseph , KLEMM, George H. , TOMAZI, Keith G.
IPC分类号： C07D409/06
CPC分类号： C07D409/06
摘要： The present disclosure generally related to an improved process for the preparation of various piperidine derivatives. More particularly, the present disclosure related to an improved process for preparing sufentanil base (1) and related compounds, which advantageously utilizes more cost effective and/or less hazardous reagents, including a dispersion comprising between about 50% and about 70% by weight (based on the total weight of the dispersion) of an alkali metal hydride, such as sodium hydride, as well as eliminates the need for expensive and/or time consuming purification techniques.
摘要翻译：本公开通常涉及用于制备各种哌啶衍生物的改进方法。更具体地说，本发明涉及一种制备舒芬太尼碱（1）和相关化合物的改进方法，其有利地利用更具成本效益和/或更不危险的试剂，包括包含约50重量％至约70重量％基于分散体的总重量）碱金属氢化物如氢化钠，并且不需要昂贵和/或耗时的纯化技术。

9. 发明申请

WO2010039220A1 PROCESSES FOR THE PRODUCTION OF BUPRENORPHINE WITH REDUCED IMPURITY FORMATION 审中-公开
标题翻译：生产具有减少形成的保护素的方法
公开(公告)号：WO2010039220A1
公开(公告)日：2010-04-08
申请号：PCT/US2009/005375
申请日：2009-09-29
申请人： MALLINCKRODT INC. , ALLEN, Brenda, E. , JARVI, Esa, T. , KALOTA, Dennis, J. , MEYER, James, R. , TOMAZI, Keith, G. , MANNINO, Anthony , ORR, Brian
发明人： ALLEN, Brenda, E. , JARVI, Esa, T. , KALOTA, Dennis, J. , MEYER, James, R. , TOMAZI, Keith, G. , MANNINO, Anthony , ORR, Brian
IPC分类号： C07D489/12
CPC分类号： C07D489/12
摘要： The present invention provides process for the production of opiate alkaloids. In particular, the present invention provides processes for the production of buprenorphine or a derivative of buprenorphine that minimizes the formation of impurities.
摘要翻译：本发明提供了生产阿片碱生物碱的方法。特别地，本发明提供生产丁丙诺啡或丁丙诺啡衍生物的方法，其使杂质的形成最小化。

10. 发明申请

WO2006057778A2 PROCESS FOR THE PURIFICATION OF BENZPHETAMINE HYDROCHLORIDE 审中-公开
标题翻译：苄基氢氯化物的纯化方法
公开(公告)号：WO2006057778A2
公开(公告)日：2006-06-01
申请号：PCT/US2005/039468
申请日：2005-11-02
申请人： MALLINCKRODT INC. , TOMAZI, Keith, G.
发明人： TOMAZI, Keith, G.
IPC分类号： C07C209/84 , C07C211/27
CPC分类号： C07C209/84 , C07C211/27
摘要： The present invention relates to the economical and separation of benzphetamine hydrochloride and methamphetamine by liquid extraction. An extraction process employing a suitable organic solvent and water at a pH in the range of from about 6 to about 8 provides excellent removal of the methamphetamine by dissolution in the water phase while the benzphetamine dissolves in the organic phase. Simple separation of the two phases results in separation of the two amines.
摘要翻译：本发明涉及通过液体萃取经济和分离盐酸苯丙胺和甲基苯丙胺。使用合适的有机溶剂和pH在约6至约8范围内的水的萃取方法提供了在苯甲酰胺溶解在有机相中溶解在水相中的甲基苯丙胺的极好的除去。两相的简单分离导致两种胺的分离。

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