公开(公告)号：US20090176992A1

公开(公告)日：2009-07-09

申请号：US12280684

申请日：2006-08-31

申请人： Seong-Jin Kim ,  Chang Woo Jong ,  Hyun Bin Kang ,  Byung Hyun Moon ,  Long Guo Quan ,  Duk Kwon Won ,  Kyung Yong Jin

发明人： Seong-Jin Kim ,  Chang Woo Jong ,  Hyun Bin Kang ,  Byung Hyun Moon ,  Long Guo Quan ,  Duk Kwon Won ,  Kyung Yong Jin

IPC分类号： C07D209/88

CPC分类号： C07D209/88 ,  C07D263/24 ,  C07D413/12 ,  Y02P20/55

摘要： The present invention relates to a process for the efficient preparation of highly optical pure chiral carvedilol. According to the present invention, a chiral oxazolidin-2-one or oxazolidin-2-thione having formula 2, produced from the reaction of N-protected 2-(2-methoxyphenoxy)ethylamine with a chiral glycidol derivative is used as a key intermediate for the preparation of the chiral carvedilol. Specifically, the process for the preparation of the chiral carvedilol comprises a) reacting a compound of formula 2 with a halogenation agent, a sulfonation agent or a mitsunobu reagent to activate a hydroxyl group of the compound of formula 2, followed by nucleophilic substitution reaction with 9H-4-hydroxy carbazole to produce a compound of formula 7, and b) subjecting the obtained compound of formula 7 to a deprotection reaction in a presence of an inorganic base to produce the targeted chiral carvedilol. The process of the present invention can be accomplished in a mild condition. The process neither requires any extraordinary purification procedure, nor involves decrease of optical purity. Therefore, the process of the present invention provides highly optical pure chiral carvedilol in simple and efficient manner.

摘要翻译： 本发明涉及高效光学纯手性卡维地洛的高效制备方法。 根据本发明，由N-保护的2-（2-甲氧基苯氧基）乙胺与手性缩水甘醇衍生物的反应生成的具有式2的手性恶唑烷-2-酮或恶唑烷-2-硫酮用作关键中间体 用于制备手性卡维地洛。 具体地说，制备手性卡维西洛的方法包括：a）使式2的化合物与卤化剂，磺化剂或mitsunobu试剂反应以活化式2化合物的羟基，然后与 9H-4-羟基咔唑制备式7的化合物，和b）在无机碱的存在下使得到的式7的化合物进行脱保护反应，得到目标的手性卡维地洛。 本发明的方法可以在温和的条件下完成。 该方法既不需要任何非凡的纯化程序，也不涉及降低光学纯度。 因此，本发明的方法以简单有效的方式提供高光学纯手性卡维地洛。

公开(公告)号：US08101781B2

公开(公告)日：2012-01-24

申请号：US12280684

申请日：2006-08-31

申请人： Seong-Jin Kim ,  Chang Woo Jong ,  Hyun Bin Kang ,  Byung Hyun Moon ,  Long Guo Quan ,  Duk Kwon Won ,  Kyung Yong Jin

发明人： Seong-Jin Kim ,  Chang Woo Jong ,  Hyun Bin Kang ,  Byung Hyun Moon ,  Long Guo Quan ,  Duk Kwon Won ,  Kyung Yong Jin

IPC分类号： A61K31/403 ,  C07D209/88

CPC分类号： C07D209/88 ,  C07D263/24 ,  C07D413/12 ,  Y02P20/55

摘要： The present invention relates to a process for the efficient preparation of highly optical pure chiral carvedilol. According to the present invention, a chiral oxazolidin-2-one or oxazolidin-2-thione having formula 2, produced from the reaction of N-protected 2-(2-methoxyphenoxy)ethylamine with a chiral glycidol derivative is used as a key intermediate for the preparation of the chiral carvedilol. Specifically, the process for the preparation of the chiral carvedilol comprises a) reacting a compound of formula 2 with a halogenation agent, a sulfonation agent or a mitsunobu reagent to activate a hydroxyl group of the compound of formula 2, followed by nucleophilic substitution reaction with 9H-4-hydroxy carbazole to produce a compound of formula 7, and b) subjecting the obtained compound of formula 7 to a deprotection reaction in a presence of an inorganic base to produce the targeted chiral carvedilol. The process of the present invention can be accomplished in a mild condition. The process neither requires any extraordinary purification procedure, nor involves decrease of optical purity. Therefore, the process of the present invention provides highly optical pure chiral carvedilol in simple and efficient manner.

摘要翻译： 本发明涉及高效光学纯手性卡维地洛的高效制备方法。 根据本发明，由N-保护的2-（2-甲氧基苯氧基）乙胺与手性缩水甘醇衍生物的反应生成的具有式2的手性恶唑烷-2-酮或恶唑烷-2-硫酮用作关键中间体 用于制备手性卡维地洛。 具体地说，制备手性卡维西洛的方法包括：a）使式2的化合物与卤化剂，磺化剂或mitsunobu试剂反应以活化式2化合物的羟基，然后与 9H-4-羟基咔唑制备式7的化合物，和b）在无机碱的存在下使得到的式7的化合物进行脱保护反应，得到目标的手性卡维地洛。 本发明的方法可以在温和的条件下完成。 该方法既不需要任何非凡的纯化程序，也不涉及降低光学纯度。 因此，本发明的方法以简单有效的方式提供高光学纯手性卡维地洛。