公开(公告)号：US07807426B2

公开(公告)日：2010-10-05

申请号：US10586337

申请日：2005-01-19

申请人： Akira Nishiyama ,  Naoaki Taoka ,  Narumi Kishimoto ,  Nobuo Nagashima

发明人： Akira Nishiyama ,  Naoaki Taoka ,  Narumi Kishimoto ,  Nobuo Nagashima

IPC分类号： C12P7/18 ,  C12P7/00

CPC分类号： C12P17/10 ,  C07C303/28 ,  C12P7/18 ,  C12P11/00 ,  C07C309/66

摘要： The present invention relates to a process for producing an optically active 1,4-pentanediol by asymmetrically reducing 5-hydroxy-2-pentanone, which is easily available at low cost. The present invention also relates to a process for producing an optically active 1-substituted 2-methylpyrrolidine including sulfonylating the optically active 1,4-pentanediol to convert it to an optically active sulfonate compound, and reacting the compound with an amine. According to the processes of the present invention, an optically active 1,4-pentanediol and an optically active 1-substituted 2-methylpyrrolidine, which are useful as an intermediate for medicines and an intermediate for agricultural chemicals, can be simply produced from an inexpensive starting material.

摘要翻译： 本发明涉及通过不对称地还原5-羟基-2-戊酮来制备光学活性的1,4-戊二醇的方法，该方法容易以低成本获得。 本发明还涉及一种光学活性1-取代的2-甲基吡咯烷的制备方法，其包括使光学活性的1,4-戊二醇磺酰化以将其转化成光学活性的磺酸盐化合物，并使该化合物与胺反应。 根据本发明的方法，用作药物中间体和农药中间体的光学活性的1,4-丁二醇和光学活性的1-取代的2-甲基吡咯烷可以简便地从廉价的 起始材料

公开(公告)号：US20070292926A1

公开(公告)日：2007-12-20

申请号：US10586337

申请日：2005-01-19

申请人： Akira Nishiyama ,  Naoaki Taoka ,  Narumi Kishimoto ,  Nobuo Nagashima

发明人： Akira Nishiyama ,  Naoaki Taoka ,  Narumi Kishimoto ,  Nobuo Nagashima

IPC分类号： C12P7/18 ,  C07C31/20 ,  C07D207/04

CPC分类号： C12P17/10 ,  C07C303/28 ,  C12P7/18 ,  C12P11/00 ,  C07C309/66

摘要： The present invention relates to a process for producing an optically active 1,4-pentanediol by asymmetrically reducing 5-hydroxy-2-pentanone, which is easily available at low cost. The present invention also relates to a process for producing an optically active 1-substituted 2-methylpyrrolidine including sulfonylating the optically active 1,4-pentanediol to convert it to an optically active sulfonate compound, and reacting the compound with an amine. According to the processes of the present invention, an optically active 1,4-pentanediol and an optically active 1-substituted 2-methylpyrrolidine, which are useful as an intermediate for medicines and an intermediate for agricultural chemicals, can be simply produced from an inexpensive starting material.

摘要翻译： 本发明涉及通过不对称地还原5-羟基-2-戊酮来制备光学活性的1,4-戊二醇的方法，该方法容易以低成本获得。 本发明还涉及一种光学活性1-取代的2-甲基吡咯烷的制备方法，其包括使光学活性的1,4-戊二醇磺酰化以将其转化成光学活性的磺酸盐化合物，并使该化合物与胺反应。 根据本发明的方法，用作药物中间体和农药中间体的光学活性的1,4-丁二醇和光学活性的1-取代的2-甲基吡咯烷可以简便地从廉价的 起始材料

公开(公告)号：US20100048909A1

公开(公告)日：2010-02-25

申请号：US12227788

申请日：2007-05-22

申请人： Kohei Mori ,  Akira Nishiyama ,  Naoaki Taoka ,  Daisuke Moriyama ,  Nobuo Nagashima

发明人： Kohei Mori ,  Akira Nishiyama ,  Naoaki Taoka ,  Daisuke Moriyama ,  Nobuo Nagashima

IPC分类号： C07D263/12 ,  C07D303/38 ,  C07C237/06

CPC分类号： C07B53/00 ,  C07B2200/07 ,  C07C67/31 ,  C07C231/18 ,  C07C237/04 ,  C07C237/22 ,  C07C2601/02 ,  C07D263/16 ,  C07D301/24 ,  C07D303/16 ,  C07D303/48 ,  C12P7/42 ,  C12P13/02 ,  C12P41/002 ,  C07C69/675

摘要： An objective of the present application is to provide an industrially practicable method for producing an optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof from an inexpensive easily-available starting material. The derivative or salt thereof is useful as an intermediate for a medicine. It is also intended by the present application to provide a useful intermediate of the derivative. The objective is attained by the following method. First, an easily-available 2-halo-3-oxopropionic acid derivative is asymmetrically reduced, and then epoxidated to produce an optically-active epoxycarboxylic acid derivative. Next, the derivative is converted into an optically-active epoxyamide derivative by reaction with cyclopropylamine, and then reacted with a nitrile to obtain an optically-active oxazolinamide derivative. Subsequently, selective acid solvolysis of the oxazoline skeleton gives the optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof.

公开(公告)号：US07834190B2

公开(公告)日：2010-11-16

申请号：US12227788

申请日：2007-05-22

申请人： Kohei Mori ,  Akira Nishiyama ,  Naoaki Taoka ,  Daisuke Moriyama ,  Nobuo Nagashima

发明人： Kohei Mori ,  Akira Nishiyama ,  Naoaki Taoka ,  Daisuke Moriyama ,  Nobuo Nagashima

IPC分类号： C07D263/08 ,  C07D303/02

CPC分类号： C07B53/00 ,  C07B2200/07 ,  C07C67/31 ,  C07C231/18 ,  C07C237/04 ,  C07C237/22 ,  C07C2601/02 ,  C07D263/16 ,  C07D301/24 ,  C07D303/16 ,  C07D303/48 ,  C12P7/42 ,  C12P13/02 ,  C12P41/002 ,  C07C69/675

摘要： An objective of the present application is to provide an industrially practicable method for producing an optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof from an inexpensive easily-available starting material. The derivative or salt thereof is useful as an intermediate for a medicine. It is also intended by the present application to provide a useful intermediate of the derivative. The objective is attained by the following method. First, an easily-available 2-halo-3-oxopropionic acid derivative is asymmetrically reduced, and then epoxidated to produce an optically-active epoxycarboxylic acid derivative. Next, the derivative is converted into an optically-active epoxyamide derivative by reaction with cyclopropylamine, and then reacted with a nitrile to obtain an optically-active oxazolinamide derivative. Subsequently, selective acid solvolysis of the oxazoline skeleton gives the optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof.

摘要翻译： 本申请的目的是提供从便宜的廉价起始材料制备光学活性3-氨基-2-羟基丙基环丙基酰胺衍生物或其盐的工业上可行的方法。 其衍生物或其盐可用作药物的中间体。 本申请还希望提供衍生物的有用中间体。 目的是通过以下方法实现。 首先，容易获得的2-卤代-3-氧代丙酸衍生物被不对称地还原，然后环氧化以产生光学活性的环氧羧酸衍生物。 接下来，通过与环丙胺反应将衍生物转化为光学活性的环氧酰胺衍生物，然后与腈反应，得到光学活性的恶唑啉酰胺衍生物。 随后，恶唑啉骨架的选择性酸溶剂解产生光学活性3-氨基-2-羟基丙基丙烯酰胺衍生物或其盐。

公开(公告)号：US07408084B2

公开(公告)日：2008-08-05

申请号：US10516469

申请日：2003-06-02

申请人： Akira Nishiyama ,  Narumi Kishimoto ,  Nobuo Nagashima

发明人： Akira Nishiyama ,  Narumi Kishimoto ,  Nobuo Nagashima

IPC分类号： C07C211/05 ,  C07C213/08

CPC分类号： C07C49/84 ,  C07B2200/07 ,  C07C45/63 ,  C07C213/00 ,  C07C215/28 ,  C07C221/00 ,  C07C215/30 ,  C07C225/16

摘要： A process for easily producing an optically active β-amino alcohol useful as a pharmaceutical intermediate from an inexpensive, readily available starting material is provided. A readily available α-substituted ketone is reacted with an optically active amine to yield a diastereomer mixture of an optically active α-substituted aminoketone. One of the diastereomers is isolated optionally after the diastereomers are converted to salts with an acid. The optically active α-substituted aminoketone or a salt thereof thus isolated was stereoselectively reduced to yield an optically active β-substituted amino alcohol. The optically active β-substituted amino alcohol is subjected to hydrogenolysis to produce an optically active β-amino alcohol or a salt thereof.

摘要翻译： 提供了一种从便宜的，容易获得的起始材料中容易地生产用作药物中间体的光学活性β-氨基醇的方法。 将容易获得的α-取代的酮与光学活性胺反应，得到光学活性的α-取代的氨基酮的非对映异构体混合物。 在非对映异构体与酸转化成盐之后，任选地分离非对映异构体之一。 将如此分离的光学活性α-取代的氨基酮或其盐立体选择性地还原，得到光学活性的β-取代的氨基醇。 将光学活性的β-取代氨基醇进行氢解以产生光学活性的β-氨基醇或其盐。

公开(公告)号：US20050277791A1

公开(公告)日：2005-12-15

申请号：US10516469

申请日：2003-06-02

申请人： Akira Nishiyama ,  Narumi Kishimoto ,  Nobuo Nagashima

发明人： Akira Nishiyama ,  Narumi Kishimoto ,  Nobuo Nagashima

IPC分类号： C07C45/63 ,  C07C49/84 ,  C07C213/00 ,  C07C215/28 ,  C07C215/30 ,  C07C221/00 ,  C07C225/16 ,  C07C29/06

CPC分类号： C07C49/84 ,  C07B2200/07 ,  C07C45/63 ,  C07C213/00 ,  C07C215/28 ,  C07C221/00 ,  C07C215/30 ,  C07C225/16

摘要： A process for easily producing an optically active β-amino alcohol useful as a pharmaceutical intermediate from an inexpensive, readily available starting material is provided. A readily available α-substituted ketone is reacted with an optically active amine to yield a diastereomer mixture of an optically active α-substituted aminoketone. One of the diastereomers is isolated optionally after the diastereomers are converted to salts with an acid. The optically active α-substituted aminoketone or a salt thereof thus isolated was stereoselectively reduced to yield an optically active β-substituted amino alcohol. The optically active β-substituted amino alcohol is subjected to hydrogenolysis to produce an optically active β-amino alcohol or a salt thereof.

摘要翻译： 提供了一种从便宜的，容易获得的起始材料中容易地生产用作药物中间体的光学活性β-氨基醇的方法。 将容易获得的α-取代的酮与光学活性胺反应，得到光学活性的α-取代的氨基酮的非对映异构体混合物。 在非对映异构体与酸转化成盐之后，任选地分离非对映异构体之一。 将如此分离的光学活性α-取代的氨基酮或其盐立体选择性地还原，得到光学活性的β-取代的氨基醇。 将光学活性的β-取代氨基醇进行氢解以产生光学活性的β-氨基醇或其盐。

公开(公告)号：US08338142B2

公开(公告)日：2012-12-25

申请号：US12449645

申请日：2008-02-18

申请人： Kohei Mori ,  Masutoshi Nojiri ,  Akira Nishiyama ,  Naoaki Taoka

发明人： Kohei Mori ,  Masutoshi Nojiri ,  Akira Nishiyama ,  Naoaki Taoka

IPC分类号： C12P17/12

CPC分类号： C07D211/60 ,  C07B57/00 ,  C07D211/56 ,  C12P17/12 ,  C12P41/006

摘要： The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing.

摘要翻译： 本发明涉及一种光学活性3-氨基哌啶或其盐的制备方法。 在该方法中，外消旋的丙内酰胺立体选择性地水解，得到光生活性的哌甲酰胺和光学活性的啮齿二甲酸，在衍生自生物体的酶源存在下，然后将光学活性的哌甲酰胺衍生成光学活性的氨基哌啶或其盐 通过酰化，Hofmann重排，氨基脱保护和进一步去保护; 或通过用BOC，霍夫曼重排和进一步去保护的选择性保护将光学活性的哌甲酰胺衍生成光学活性氨基哌啶或其盐。 通过本发明可以通过适用于工业制造的容易的方法从廉价且容易获得的原料中制备用作药物中间体的光学活性3-氨基哌啶或其盐。

公开(公告)号：US20100105917A1

公开(公告)日：2010-04-29

申请号：US12449645

申请日：2008-02-18

申请人： Kohei Mori ,  Masutoshi Nojiri ,  Akira Nishiyama ,  Naoaki Taoka

发明人： Kohei Mori ,  Masutoshi Nojiri ,  Akira Nishiyama ,  Naoaki Taoka

IPC分类号： C07D211/98 ,  C12P17/12 ,  C07D211/60

CPC分类号： C07D211/60 ,  C07B57/00 ,  C07D211/56 ,  C12P17/12 ,  C12P41/006

摘要： The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing.

摘要翻译： 本发明涉及一种光学活性3-氨基哌啶或其盐的制备方法。 在该方法中，外消旋的丙内酰胺立体选择性地水解，得到光生活性的哌甲酰胺和光学活性的啮齿二甲酸，在衍生自生物体的酶源存在下，然后将光学活性的哌甲酰胺衍生成光学活性的氨基哌啶或其盐 通过酰化，Hofmann重排，氨基脱保护和进一步去保护; 或通过用BOC，霍夫曼重排和进一步去保护的选择性保护将光学活性的哌甲酰胺衍生成光学活性氨基哌啶或其盐。 通过本发明可以通过适用于工业制造的容易的方法从廉价且容易获得的原料中制备用作药物中间体的光学活性3-氨基哌啶或其盐。

公开(公告)号：US07223859B2

公开(公告)日：2007-05-29

申请号：US10801141

申请日：2004-03-16

申请人： Tatsuyoshi Tanaka ,  Masanobu Sugawara ,  Hirofumi Maeda ,  Akira Nishiyama ,  Yoshihiko Yasohara ,  Nobuo Nagashima

发明人： Tatsuyoshi Tanaka ,  Masanobu Sugawara ,  Hirofumi Maeda ,  Akira Nishiyama ,  Yoshihiko Yasohara ,  Nobuo Nagashima

IPC分类号： C07D205/02 ,  C07C233/00

CPC分类号： C07D205/08 ,  C07C231/02 ,  C07C309/66 ,  C07C309/73

摘要： The present invention provides a method for easily producing an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative useful for an intermediate for pharmaceutical products, particularly an inhibitor of a cholesteryl ester transfer protein (CETP) from easily available raw materials. In the present invention, (S)-N-[4-(trifluoromethyl)phenyl]-3-hydroxypentanoic acid amide prepared from easily available raw materials leads a production of (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone to give (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide. Furthermore, (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone is reacted with a carbamic acid ester to give an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative.

摘要翻译： 本发明提供了一种容易地制备用于药物产品中间体（特别是胆固醇酯转移蛋白（CETP）抑制剂）的（R）-3- [4-（三氟甲基）苯基氨基] - 戊酸酰胺衍生物的方法， 容易获得的原料。 在本发明中，由容易获得的原料制备的（S）-N- [4-（三氟甲基）苯基] -3-羟基戊酸酰胺导致（R）-4-乙基-1- [4-（三氟甲基） ）苯基] -2-氮杂环丁酮，得到（R）-3- [4-（三氟甲基）苯基氨基] - 戊酸酰胺。 此外，将（R）-4-乙基-1- [4-（三氟甲基）苯基] -2-氮杂环丁酮与氨基甲酸酯反应，得到（R）-3- [4-（三氟甲基）苯基氨基] - 戊酸 酰胺衍生物。

公开(公告)号：US07986014B2

公开(公告)日：2011-07-26

申请号：US12654490

申请日：2009-12-22

申请人： Reika Ichihara ,  Yoshinori Tsuchiya ,  Masato Koyama ,  Akira Nishiyama

发明人： Reika Ichihara ,  Yoshinori Tsuchiya ,  Masato Koyama ,  Akira Nishiyama

IPC分类号： H01L29/76 ,  H01L29/94 ,  H01L31/062 ,  H01L31/113 ,  H01L31/119

CPC分类号： H01L21/823857 ,  H01L21/823462

摘要： A semiconductor device includes a semiconductor substrate, an nMISFET formed on the substrate, the nMISFET including a first dielectric formed on the substrate and a first metal gate electrode formed on the first dielectric and formed of one metal element selected from Ti, Zr, Hf, Ta, Sc, Y, a lanthanoide and actinide series and of one selected from boride, silicide and germanide compounds of the one metal element, and a pMISFET formed on the substrate, the pMISFET including a second dielectric formed on the substrate and a second metal gate electrode formed on the second dielectric and made of the same material as that of the first metal gate electrode, at least a portion of the second dielectric facing the second metal gate electrode being made of an insulating material different from that of at least a portion of the first dielectric facing the first metal gate electrode.