公开(公告)号：US07759501B2

公开(公告)日：2010-07-20

申请号：US10523287

申请日：2003-07-15

申请人： Kenji Kogami ,  Noriyuki Hayashizaka ,  Syuzo Satake ,  Ichiro Fuseya ,  Hirokazu Kagano

发明人： Kenji Kogami ,  Noriyuki Hayashizaka ,  Syuzo Satake ,  Ichiro Fuseya ,  Hirokazu Kagano

IPC分类号： C07D333/20 ,  C07D333/22

CPC分类号： C07D333/22 ,  C07D333/20

摘要： The present invention provides a process for producing an N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine represented by General Formula (2): wherein R is C1-4 alkyl, comprising the step of reducing (Z)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine represented by General Formula (1): wherein R is as defined above. According to the present invention, an N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine which is for use as an intermediate for various pharmaceuticals can be produced in an industrially inexpensive and easy manner.

摘要翻译： 本发明提供了制备由通式（2）表示的N-单烷基-3-羟基-3-（2-噻吩基）丙胺的方法：其中R是C 1-4烷基，包括还原（Z） - 由通式（1）表示的N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺：其中R如上所定义。 根据本发明，用作各种药物的中间体的N-单烷基-3-羟基-3-（2-噻吩基）丙胺可以以工业上便宜且容易的方式制备。

公开(公告)号：US20090137823A1

公开(公告)日：2009-05-28

申请号：US11989100

申请日：2006-08-01

申请人： Syuzo Satake ,  Noriyuki Hayashizaka ,  Ichiro Fuseya ,  Muneaki Tanaka ,  Hirokazu Kagano

发明人： Syuzo Satake ,  Noriyuki Hayashizaka ,  Ichiro Fuseya ,  Muneaki Tanaka ,  Hirokazu Kagano

IPC分类号： C07D333/22

CPC分类号： C07D333/22

摘要： The present invention provides a process for producing (E)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine represented by Formula (1); wherein R is a C1-4 alkyl, the method comprising the steps of: maintaining a solution containing (Z)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine dissolved therein at 25° C. or below to deposit crystals and separating crystals having a particle diameter of 100 μm or less from the deposited crystals; and a process for producing (E,Z)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine comprising the steps of: reacting an alkali metal salt of β-oxo-β-(2-thienyl)propanal with a monoalkylamine compound; adding a water-insoluble organic solvent to the resulting reaction mixture; adding seed crystals containing (E)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine to an organic layer obtained by conducting separation; and keeping the resulting mixture at 25° C. or below.

摘要翻译： 本发明提供由式（1）表示的（E）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的制备方法。 其中R是C 1-4烷基，所述方法包括以下步骤：在25℃以下溶解含有（Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的溶液， 从沉积的晶体中沉积晶体并分离出粒径为100μm以下的晶体; 和（E，Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙胺的制备方法，包括以下步骤：使β-氧代-β-（2-噻吩基）丙醛的碱金属盐 与单烷基胺化合物; 向所得反应混合物中加入水不溶性有机溶剂; 将含有（E）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的晶种加入到通过分离获得的有机层中; 并将所得混合物保持在25℃或更低。

公开(公告)号：US08183392B2

公开(公告)日：2012-05-22

申请号：US11989100

申请日：2006-08-01

申请人： Syuzo Satake ,  Noriyuki Hayashizaka ,  Ichiro Fuseya ,  Muneaki Tanaka ,  Hirokazu Kagano

发明人： Syuzo Satake ,  Noriyuki Hayashizaka ,  Ichiro Fuseya ,  Muneaki Tanaka ,  Hirokazu Kagano

IPC分类号： C07D333/22

CPC分类号： C07D333/22

摘要： The present invention provides a process for producing (E)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine represented by Formula (1); wherein R is a C1-4 alkyl, the method comprising the steps of: maintaining a solution containing (Z)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine dissolved therein at 25° C. or below to deposit crystals and separating crystals having a particle diameter of 100 μm or less from the deposited crystals; and a process for producing (E,Z)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine comprising the steps of: reacting an alkali metal salt of β-oxo-β-(2-thienyl)propanal with a monoalkylamine compound; adding a water-insoluble organic solvent to the resulting reaction mixture; adding seed crystals containing (E)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine to an organic layer obtained by conducting separation; and keeping the resulting mixture at 25° C. or below.

摘要翻译： 本发明提供由式（1）表示的（E）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的制备方法。 其中R是C 1-4烷基，所述方法包括以下步骤：在25℃以下溶解含有（Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的溶液， 从沉积的晶体沉积晶体并分离出粒径为100μm以下的晶体; 和（E，Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的制备方法，包括以下步骤：使＆bgr-氧代 - （2-噻吩基） ）丙醛与单烷基胺化合物; 向所得反应混合物中加入水不溶性有机溶剂; 将含有（E）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的晶种加入到通过分离获得的有机层中; 并将所得混合物保持在25℃或更低。

公开(公告)号：US07659411B2

公开(公告)日：2010-02-09

申请号：US10579734

申请日：2004-12-13

申请人： Seiji Bando ,  Syuzo Satake ,  Hirokazu Kagano

发明人： Seiji Bando ,  Syuzo Satake ,  Hirokazu Kagano

IPC分类号： C07D333/28 ,  C07D333/22 ,  A61K31/38 ,  A01N43/06

CPC分类号： C07D333/22

摘要： The present invention provides a process for producing a 2-acylthiophene compound which has a low content of the 3-isomer generated as a by-product, the process comprising reacting a thiophene compound represented by formula (1): wherein R1is a hydrogen atom, a C1-6 alkyl group, a phenyl group, or a halogen atom, with at least one member selected from the group consisting of acid anhydrides represented by formula (2): wherein R2 is a C1-6 alkyl group or a phenyl group, and acid halides represented by formula (3): wherein R2 is as defined above and X is a halogen atom, in the presence of a solid acid catalyst at a temperature less than 75° C. in the absence of solvent, thus producing a 2-acylthiophene compound represented by formula (4): wherein R1 and R2 are as defined above.

摘要翻译： 本发明提供一种生产副产物3-异构体含量低的2-酰基噻吩化合物的方法，该方法包括使由式（1）表示的噻吩化合物：其中R 1为氢原子， C 1-6烷基，苯基或卤素原子，与选自由式（2）表示的酸酐中的至少一种：其中R2是C1-6烷基或苯基， 和式（3）表示的酰基卤：其中R 2如上所定义，X为卤素原子，在不存在溶剂的情况下，在固体酸催化剂存在下，在低于75℃的温度下，产生2 （4）表示的α-酰基噻吩化合物：其中R1和R2如上定义。

公开(公告)号：US20070149787A1

公开(公告)日：2007-06-28

申请号：US10579734

申请日：2004-12-13

申请人： Seiji Bando ,  Syuzo Satake ,  Hirokazu Kagano

发明人： Seiji Bando ,  Syuzo Satake ,  Hirokazu Kagano

IPC分类号： C07D333/22

CPC分类号： C07D333/22

摘要： The present invention provides a process for producing a 2-acylthiophene compound which has a low content of the 3-isomer generated as a by-product, the process comprising reacting a thiophene compound represented by formula (1): wherein R1is a hydrogen atom, a C1-6 alkyl group, a phenyl group, or a halogen atom, with at least one member selected from the group consisting of acid anhydrides represented by formula (2): wherein R2 is a C1-6 alkyl group or a phenyl group, and acid halides represented by formula (3): wherein R2 is as defined above and X is a halogen atom, in the presence of a solid acid catalyst at a temperature less than 75° C. in the absence of solvent, thus producing a 2-acylthiophene compound represented by formula (4): wherein R1 and R2 are as defined above.

摘要翻译： 本发明提供一种生产副产物3-异构体含量低的2-酰基噻吩化合物的方法，该方法包括使由式（1）表示的噻吩化合物：其中R 1 与氢原子，C 1-6烷基，苯基或卤原子具有至少一个选自酸式酸酐（式 2）：其中R 2是C 1-6烷基或苯基，和由式（3）表示的酰基卤：其中R 2， / SUP>如上所定义，X是卤素原子，在不存在溶剂的情况下，在固体酸催化剂存在下，在低于75℃的温度下，由式（4）表示的2-酰基噻吩化合物， ：其中R 1和R 2如上所定义。

公开(公告)号：US20120149917A1

公开(公告)日：2012-06-14

申请号：US13396972

申请日：2012-02-15

申请人： Syuzo SATAKE ,  Noriyuki Hayashizaka ,  Ichiro Fuseya ,  Muneaki Tanaka ,  Hirokazu Kagano

发明人： Syuzo SATAKE ,  Noriyuki Hayashizaka ,  Ichiro Fuseya ,  Muneaki Tanaka ,  Hirokazu Kagano

IPC分类号： C07D333/22

CPC分类号： C07D333/22

摘要： The present invention provides a process for producing (E)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine represented by Formula (1); wherein R is a C1-4 alkyl, the method comprising the steps of: maintaining a solution containing (Z)—N-monoalkyl-3-oxo-3-(2-thienyl)propenamine dissolved therein at 25° C. or below to deposit crystals and separating crystals having a particle diameter of 100 μm or less from the deposited crystals; and a process for producing (E,Z)—N-monoalkyl-3-oxo-3-(2-thienyl)propenamine comprising the steps of: reacting an alkali metal salt of β-oxo-β-(2-thienyl)propanal with a monoalkylamine compound; adding a water-insoluble organic solvent to the resulting reaction mixture; adding seed crystals containing (E)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine to an organic layer obtained by conducting separation; and keeping the resulting mixture at 25° C. or below.

摘要翻译： 本发明提供由式（1）表示的（E）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的制备方法。 其中R是C 1-4烷基，所述方法包括以下步骤：在25℃以下溶解含有（Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的溶液， 从沉积的晶体沉积晶体并分离出粒径为100μm以下的晶体; 和（E，Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的制备方法，包括以下步骤：使＆bgr-氧代 - （2-噻吩基） ）丙醛与单烷基胺化合物; 向所得反应混合物中加入水不溶性有机溶剂; 将含有（E）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的晶种加入到通过分离获得的有机层中; 并将所得混合物保持在25℃或更低。

公开(公告)号：US08722906B2

公开(公告)日：2014-05-13

申请号：US13396972

申请日：2012-02-15

申请人： Syuzo Satake ,  Noriyuki Hayashizaka ,  Ichiro Fuseya ,  Muneaki Tanaka ,  Hirokazu Kagano

发明人： Syuzo Satake ,  Noriyuki Hayashizaka ,  Ichiro Fuseya ,  Muneaki Tanaka ,  Hirokazu Kagano

IPC分类号： C07D333/22

CPC分类号： C07D333/22

摘要： The present invention provides a process for producing (E)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine represented by Formula (1); wherein R is a C1-4 alkyl, the method comprising the steps of: maintaining a solution containing (Z)—N-monoalkyl-3-oxo-3-(2-thienyl)propenamine dissolved therein at 25° C. or below to deposit crystals and separating crystals having a particle diameter of 100 μm or less from the deposited crystals; and a process for producing (E,Z)—N-monoalkyl-3-oxo-3-(2-thienyl)propenamine comprising the steps of: reacting an alkali metal salt of β-oxo-β-(2-thienyl)propanal with a monoalkylamine compound; adding a water-insoluble organic solvent to the resulting reaction mixture; adding seed crystals containing (E)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine to an organic layer obtained by conducting separation; and keeping the resulting mixture at 25° C. or below.

摘要翻译： 本发明提供由式（1）表示的（E）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的制备方法。 其中R是C 1-4烷基，所述方法包括以下步骤：在25℃以下溶解含有（Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的溶液， 从沉积的晶体沉积晶体并分离出粒径为100μm以下的晶体; 和（E，Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的制备方法，包括以下步骤：使＆bgr-氧代 - （2-噻吩基） ）丙醛与单烷基胺化合物; 向所得反应混合物中加入水不溶性有机溶剂; 将含有（E）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的晶种加入到通过分离获得的有机层中; 并将所得混合物保持在25℃或更低。

公开(公告)号：US20050240030A1

公开(公告)日：2005-10-27

申请号：US10523287

申请日：2003-07-15

申请人： Kenji Kogami ,  Noriyuki Hayashizaka ,  Syuzo Satake ,  Ichiro Fuseya ,  Hirokazu Kagano

发明人： Kenji Kogami ,  Noriyuki Hayashizaka ,  Syuzo Satake ,  Ichiro Fuseya ,  Hirokazu Kagano

IPC分类号： C07D333/20 ,  C07D333/22

CPC分类号： C07D333/22 ,  C07D333/20

摘要： The present invention provides a process for producing an N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine represented by General Formula (2): wherein R is C1-4 alkyl, comprising the step of reducing (Z)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine represented by General Formula (1): wherein R is as defined above. According to the present invention, an N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine which is for use as an intermediate for various pharmaceuticals can be produced in an industrially inexpensive and easy manner.

摘要翻译： 本发明提供一种制备由通式（2）表示的N-单烷基-3-羟基-3-（2-噻吩基）丙胺的方法：其中R是C 1-4烷基，包括 由通式（1）表示的还原（Z）-N-单烷基-3-氧代-3-（2-噻吩基）丙烯胺的步骤：其中R如上所定义。 根据本发明，用作各种药物的中间体的N-单烷基-3-羟基-3-（2-噻吩基）丙胺可以以工业上便宜且容易的方式制备。