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：US5071966A

公开(公告)日：1991-12-10

申请号：US576499

申请日：1990-09-10

申请人： Kazunori Kan ,  Hiroshi Murakami ,  Nobuo Nagashima ,  Noboru Ueyama ,  Takehisa Ohashi

发明人： Kazunori Kan ,  Hiroshi Murakami ,  Nobuo Nagashima ,  Noboru Ueyama ,  Takehisa Ohashi

IPC分类号： C07F7/02 ,  C07F7/18

CPC分类号： C07F7/186 ,  C07F7/1852

摘要： A process for preparing an enol silyl ether compound from a diazoacetoacetic acid ester having the general formula (IV): ##STR1## wherein R.sup.1 is a lower alkyl group having 1 to 6 carbon atoms, phenyl group, a substituted phenyl group, an aralkyl group or allyl group, and R.sup.2, R.sup.3 and R.sup.4 are the same or mutually different and each is a lower alkyl group having 1 to 6 carbon atoms, which comprises reacting a diazoacetoacetic acid ester having the general formula (I): ##STR2## wherein R.sup.1 is the same as defined above, with a trialkylsilyl chloride having the general formula (II): ##STR3## wherein R.sup.2, R.sup.3 and R.sup.4 are the same as defined above, in an inert solvent in the presence of an organic base and an alkali halide having the general formula (III):MX (III)wherein M is an alkaline metal and X is bromine atom or iodine atom. The desired compound is useful as an intermediate for synthesis of carbapenem .beta.-lactam antibiotics.

摘要翻译： PCT No.PCT / JP90 / 00038 Sec。 371 1990年9月10日第 102（e）1990年9月10日PCT 1990年1月12日PCT PCT。 公开号WO90 / 08149 日本时间1990年7月26日。一种由具有通式（IV）的重氮乙酰乙酸酯制备烯醇甲硅烷基醚化合物的方法：其中R 1为具有1至6个碳原子的低级烷基，苯基 基团，取代的苯基，芳烷基或烯丙基，R 2，R 3和R 4相同或相互不同，各自为具有1至6个碳原子的低级烷基，其包括使具有一般性基团的重氮乙酰乙酸酯 式（I）：其中R 1与上述定义相同，具有通式（II）的三烷基甲硅烷基氯：其中R2，R3和R4与上述定义相同 在有机碱和具有通式（III）的碱金属卤化物存在下，在惰性溶剂中反应：其中M是碱金属，X是溴原子或碘原子的MX（III）。 所需化合物可用作合成碳青霉烯β-内酰胺抗生素的中间体。

公开(公告)号：US20110305595A1

公开(公告)日：2011-12-15

申请号：US13203102

申请日：2010-01-29

申请人： Saburo Matsuoka ,  Masao Hayakawa ,  Etsuo Takeuchi ,  Nobuo Nagashima

发明人： Saburo Matsuoka ,  Masao Hayakawa ,  Etsuo Takeuchi ,  Nobuo Nagashima

IPC分类号： C22C38/04 ,  C22C38/14 ,  C22C38/12 ,  C22C38/02 ,  C22C38/06

CPC分类号： H01M8/04208 ,  C21D8/005 ,  C21D9/14 ,  C21D2211/005 ,  C22C38/02 ,  C22C38/04 ,  C22C38/12 ,  C22C38/14 ,  H01M8/04201 ,  Y02P70/56

摘要： A ferritic steel having tensile properties and fatigue properties capable of withstanding use in a hydrogen environment and a method of manufacture thereof are provided. By adding one or more element selected from among vanadium (V), titanium (Ti) and niobium (Nb) so that the steel includes, together with at least ferrite grains in the structure, a carbide or carbides of one or more element selected from among V, Ti and Nb, the reduction of area and the fatigue crack propagation rate of the ferritic steel in a hydrogen environment are improved. The advantages of the invention were confirmed in cases where the ferrite grains are small grains of 1 μm or less in size, and in cases where the ferrite grains are coarse grains from several micrometers to 20 μm in size, and moreover in cases where the ferrite grains are coarse grains from several micrometers to 60 μm in size.

摘要翻译： 提供一种具有耐氢气环境中使用的拉伸性能和疲劳特性的铁素体钢及其制造方法。 通过添加选自钒（V​​），钛（Ti）和铌（Nb）中的一种或多种元素，使得钢至少与结构中的铁素体晶粒一起包含一种或多种元素的碳化物或碳化物， 在V，Ti和Nb中，在氢环境中铁素体钢的面积减小和疲劳裂纹扩展速率提高。 在铁素体晶粒尺寸小于1μm的小晶粒的情况下，在铁素体晶粒的尺寸为几微米至20μm的粗晶粒的情况下，在铁素体的情况下，在本发明的优点的情况下， 晶粒是尺寸从几微米到60μm的粗晶粒。

公开(公告)号：US20100197934A1

公开(公告)日：2010-08-05

申请号：US12757947

申请日：2010-04-09

申请人： Takahiro Ohishi ,  Hirokazu Nanba ,  Masanobu Sugawara ,  Masashi Izumida ,  Tatsuya Honda ,  Kohei Mori ,  Satohiro Yanagisawa ,  Nobuo Nagashima ,  Kenji Inoue

发明人： Takahiro Ohishi ,  Hirokazu Nanba ,  Masanobu Sugawara ,  Masashi Izumida ,  Tatsuya Honda ,  Kohei Mori ,  Satohiro Yanagisawa ,  Nobuo Nagashima ,  Kenji Inoue

IPC分类号： C12P17/10 ,  C12P13/12 ,  C07C321/00 ,  C07D233/02

CPC分类号： C12P13/12 ,  C07C319/06 ,  C07D233/76 ,  C12P17/04 ,  C12P17/10 ,  C12P41/009 ,  C07C323/58

摘要： The present invention provides a simple industrial process for producing an L- or D-optically active α-methylcysteine derivative or its salt, which is a useful pharmaceutical intermediate, from readily available, inexpensive raw materials. In a process for producing an L- or D-optically active α-methylcysteine derivative or its salt, a racemic N-carbamoyl-α-methylcysteine derivative or its salt is D-selectively cyclized with hydantoinase to produce a D-5-methyl-5-thiomethylhydantoin derivative or its salt and an N-carbamoyl-α-methyl-L-cysteine derivative or its salt, which are then subjected to deprotection of the amino group and the sulfur atom, and hydrolysis.

摘要翻译： 本发明提供了一种简单的工业方法，用于从容易获得的便宜的原料制备作为有用的药物中间体的L-或D-光学活性的α-甲基半胱氨酸衍生物或其盐。 在制备L-或D-光学活性α-甲基半胱氨酸衍生物或其盐的方法中，外消旋的N-氨基甲酰基-α-甲基半胱氨酸衍生物或其盐与乙内酰脲酶D选择性环化以产生D-5-甲基 - 5-硫代甲基乙内酰脲衍生物或其盐和N-氨基甲酰基-α-甲基-L-半胱氨酸衍生物或其盐，然后进行氨基和硫原子的脱保护和水解。

公开(公告)号：US20060089503A1

公开(公告)日：2006-04-27

申请号：US10540023

申请日：2003-12-10

申请人： Takahiro Ohishi ,  Kohei Mori ,  Koichi Kinoshita ,  Katsuji Maehara ,  Hiroaki Kawasaki ,  Nobuo Nagashima ,  Yoshihide Fuse

发明人： Takahiro Ohishi ,  Kohei Mori ,  Koichi Kinoshita ,  Katsuji Maehara ,  Hiroaki Kawasaki ,  Nobuo Nagashima ,  Yoshihide Fuse

IPC分类号： C07D305/12 ,  C07D405/02

CPC分类号： C07D305/12 ,  C07C319/14 ,  C07D317/60 ,  C07D407/06 ,  C07C323/56

摘要： The present invention provides a process for simply producing an optically active 2-thiomethyl-3-phenylpropionic acid derivative useful as an intermediate for medicines from inexpensive raw materials. An optically active 2-hydroxymethyl-3-phenylpropionic acid ester derivative which can be relatively easily obtained by asymmetric reduction reaction with an enzyme is cyclized to an optically active P-lactone derivative which is then reacted with a sulfur compound to produce an optically active 2-thiomethyl-3-phenylpropionic acid derivative in high yield.

摘要翻译： 本发明提供简单地生产用作廉价原料的药物中间体的光学活性2-硫代甲基-3-苯基丙酸衍生物的方法。 可以通过与酶的不对称还原反应相对容易地获得的光学活性的2-羟甲基-3-苯基丙酸酯衍生物环化成光学活性的P-内酯衍生物，然后与硫化合物反应以产生光学活性2 硫代甲基-3-苯基丙酸衍生物。

公开(公告)号：US06515179B2

公开(公告)日：2003-02-04

申请号：US10148877

申请日：2002-06-11

申请人： Nobuo Nagashima

发明人： Nobuo Nagashima

IPC分类号： C07D20716

CPC分类号： C07D207/416 ,  C07C209/62 ,  C07C213/02 ,  C07C227/18 ,  C07C269/04 ,  C07D205/04 ,  C07C211/27 ,  C07C229/36 ,  C07C271/20

摘要： A 2- or 4-nitrobenzenesulfonamide is allowed to react with an alkali metal alkoxide to remove a nitrobenzenesulfonyl group to thereby obtain an amine corresponding to the amide. Furthermore, a method for producing an amine derivative by allowing the resulting amine without isolation to react with an activated, substituted oxycarbonyl compound or an activated acyl compound is provided. According to this method, a corresponding free amine and its substituted derivative can be produced easily and industrially advantageously from the 2- or 4-nitrobenzenesulfonamide without using a thiol compound.

摘要翻译： 使2-或4-硝基苯磺酰胺与碱金属醇盐反应以除去硝基苯磺酰基，从而得到对应于酰胺的胺。 此外，提供了通过使得到的胺不经分离而与活化的取代的氧羰基化合物或活化的酰基化合物反应来制备胺衍生物的方法。 根据该方法，可以在不使用硫醇化合物的情况下，容易且工业上有利地从2-或4-硝基苯磺酰胺制备相应的游离胺及其取代的衍生物。

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：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：US07109352B2

公开(公告)日：2006-09-19

申请号：US10716430

申请日：2003-11-20

申请人： Masanobu Sugawara ,  Akio Fujii ,  Kazumi Okuro ,  Yasuhiro Saka ,  Nobuo Nagashima ,  Kenji Inoue ,  Toshihiro Takeda ,  Koichi Kinoshita ,  Tadashi Moroshima ,  Yoshihide Fuse ,  Yasuyoshi Ueda

发明人： Masanobu Sugawara ,  Akio Fujii ,  Kazumi Okuro ,  Yasuhiro Saka ,  Nobuo Nagashima ,  Kenji Inoue ,  Toshihiro Takeda ,  Koichi Kinoshita ,  Tadashi Moroshima ,  Yoshihide Fuse ,  Yasuyoshi Ueda

IPC分类号： C07D203/02 ,  C07D203/08

CPC分类号： C07D203/08 ,  C07B2200/07 ,  C07C227/10 ,  C07C227/32 ,  C07C227/42 ,  C07C229/30 ,  C07C303/36 ,  C07D203/20 ,  C07D203/24 ,  C07C311/19 ,  C07C229/26

摘要： An optically active amino acid derivative is produced by N-protecting an optically active 3-haloalanine derivative followed by cyclization, or cyclizing this derivative followed by N-protection to thereby give an optically active N-protected-aziridine-2-carboxylic acid derivative which is protected by a benzenesulfonyl group substituted by nitro at the 2- and/or 4-positions and then treating this product with an organic metal reagent, or by N-protecting an optically active 3-haloalanine derivative to thereby give N-protected-aziridine-2-carboxylic acid which is protected by a benzenesulfonyl group substituted by nitro at the 2- and/or 4-positions and then treating this product with an organic metal reagent. According to this process, natural and unnatural optically active amino acids can be produced from inexpensive materials by using simple procedures.

摘要翻译： 光学活性氨基酸衍生物是通过N-保护光学活性3-卤代丙氨酸衍生物进行环化，或环化该衍生物进行N-保护而得到光学活性N-保护的氮丙啶-2-羧酸衍生物 在2-和/或4-位被硝基取代的苯磺酰基保护，然后用有机金属试剂处理该产物，或通过N-保护光学活性3-卤代丙氨酸衍生物，由此得到N-保护的氮丙啶 -2-羧酸，其在2-和/或4-位被硝基取代的苯磺酰基保护，然后用有机金属试剂处理该产物。 根据该方法，可以通过简单的方法从便宜的材料制备天然和非天然旋光氨基酸。

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。