公开(公告)号：JP2013209424A

公开(公告)日：2013-10-10

申请号：JP2013127772

申请日：2013-06-18

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： MORI KOHEI ,  NISHIYAMA AKIRA ,  TAOKA NAOAKI ,  MORIYAMA DAISUKE ,  NAGASHIMA NOBUO

IPC: C07D263/16 ,  C07B53/00 ,  C07C67/31 ,  C07C69/675 ,  C07C237/06 ,  C07D303/48 ,  C12P41/00

CPC classification number: 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

Abstract: PROBLEM TO BE SOLVED: To provide a practical process for industrial production of an optically active 3-amino-2-hydroxypropionic acid cyclopropylamide derivative or a salt thereof useful as an intermediate of a medicine from a low cost and easily obtainable raw material, and useful intermediates thereof.SOLUTION: At first, an optically active epoxycarboxylic acid derivative is produced by an asymmetric reduction of an easily available 2-halo-3-oxopropionic acid derivative, followed by epoxidation of the resulting substance. Then, the optically active epoxycarboxylic acid derivative is reacted with cyclopropylamine to convert it into an optically active epoxyamide derivative, which derivative is then reacted with a nitrile to produce an optically active oxazolinamide derivative. Subsequently, an optically active 3-amino-2-hydroxypropionic acid cyclopropylamide derivative or a salt thereof is produced by a selective acid solvolysis of the oxazoline skeleton.

Abstract translation: 要解决的问题：提供从低成本和容易获得的原料中用作药物中间体的光学活性3-氨基-2-羟基丙酸环丙基酰胺衍生物或其盐的工业生产的实用方法，并且可用 其中间体。解决方案：首先，通过不容易获得的2-卤代-3-氧代丙酸衍生物的不对称还原产生光学活性环氧羧酸衍生物，然后进行所得物质的环氧化。 然后，将光学活性环氧羧酸衍生物与环丙胺反应，将其转化为光学活性环氧酰胺衍生物，然后将该衍生物与腈反应，生成光学活性的恶唑啉酰胺衍生物。 随后，通过恶唑啉骨架的选择性酸溶剂解产生光学活性3-氨基-2-羟基丙酸环丙基酰胺衍生物或其盐。

公开(公告)号：JP2012036093A

公开(公告)日：2012-02-23

申请号：JP2008318070

申请日：2008-12-15

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： MORI KOHEI ,  NISHIYAMA AKIRA

IPC: C07D217/10

CPC classification number: C07D217/10

Abstract: PROBLEM TO BE SOLVED: To inexpensively and efficiently produce (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline useful as an intermediate for a medicine and having high optical purity.SOLUTION: The (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline having the high optical purity can be produced by forming a salt from the easily available (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline having low optical purity and an inexpensive acid such as acetic acid and p-toluenesulfonic acid, and crystallizing the salt.

Abstract translation: 待解决的问题：为了廉价和有效地制备可用作药物中间体并具有高光学纯度的（S）-1-苯基-1,2,3,4-四氢异喹啉。 解决方案：具有高光学纯度的（S）-1-苯基-1,2,3,4-四氢异喹啉可以通过从容易获得的（S）-1-苯基-1,2 具有低光学纯度的3,4-四氢异喹啉和廉价的酸如乙酸和对甲苯磺酸，并使盐结晶。 版权所有（C）2012，JPO＆INPIT

公开(公告)号：JP2006022045A

公开(公告)日：2006-01-26

申请号：JP2004201784

申请日：2004-07-08

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： MORI KOHEI ,  NISHIYAMA AKIRA ,  NAGASHIMA NOBUO

IPC: C07D207/14 ,  B01D9/02 ,  C07B57/00

Abstract: PROBLEM TO BE SOLVED: To provide a method for isolating and purifying an optically active 1-t-butoxycarbonyl-3-aminopyrrolidine salt, by which the highly pure optically active 1-t-butoxycarbonyl-3-aminopyrrolidine salt can be obtained in a high yield and by which the production of the salt can simply and efficiently be performed in a commercial scale.
SOLUTION: This method for isolating and purifying the optically active 1-t-butoxycarbonyl-3-aminopyrrolidine salt is characterized by forming a salt from the optically active 1-t-butoxycarbonyl-3-aminopyrrolidine and an acid, crystallizing the salt, and isolating the optically active 1-t-butoxycarbonyl-3-aminopyrrolidine salt as the crystals to leave contaminated impurities such as enantiomer and 1-t-butoxycarbonyl-3-t-butoxycarbonyl-aminopyrrolidine in the mother liquor.
COPYRIGHT: (C)2006,JPO&NCIPI

Abstract translation: 要解决的问题：提供一种用于分离和纯化光学活性1-叔丁氧基羰基-3-氨基吡咯烷盐的方法，通过该方法可以获得高纯度的光学活性1-叔丁氧基羰基-3-氨基吡咯烷酮盐 以高产率，通过其可以以商业规模简单有效地进行盐的生产。 解决方案：用于分离和纯化光学活性1-叔丁氧基羰基-3-氨基吡咯烷盐的方法的特征在于由光学活性1-叔丁氧基羰基-3-氨基吡咯烷和酸形成盐，使盐结晶 并分离出作为晶体的光学活性的1-叔丁氧基羰基-3-氨基吡咯烷盐，以在母液中留下污染的杂质如对映体和1-叔丁氧基羰基-3-叔丁氧基羰基 - 氨基吡咯烷。 版权所有（C）2006，JPO＆NCIPI

公开(公告)号：JP2013136632A

公开(公告)日：2013-07-11

申请号：JP2013060990

申请日：2013-03-22

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： MORI KOHEI ,  NOJIRI MASUTOSHI ,  NISHIYAMA AKIRA ,  TAOKA NAOAKI

IPC: C07D211/56 ,  C07D211/60 ,  C12P41/00

CPC classification number: C07D211/60 ,  C07B57/00 ,  C07D211/56 ,  C12P17/12 ,  C12P41/006

Abstract: PROBLEM TO BE SOLVED: To provide a method which can easily produce an optically active 3-amino piperidine or a salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material and is practical for industrial production thereof, and to provide the intermediate useful for producing the optically active 3-amino piperidine or the salt thereof.SOLUTION: The method for producing the optically active 3-aminopiperidine or salt thereof includes: a process of stereoselectively hydrolyzing a racemic nipecotamide to convert into an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from microorganism; and a process of subsequently subjecting the optically active nipecotamide to aroylation, Hofmann rearrangement, protection of amino groups and deprotection, and deriving the optically active nipecotamide into the optically active aminopiperidine or the salt thereof, or subjecting the optically active nipecotamide to selective protection with BOC (t-botoxycarbonyl), Hofmann rearrangement and deprotection and, thereby, deriving the optically active nipecotamide into the optically active aminopiperidine or the salt thereof. The optically active 3-aminopiperidine or the salt thereof useful as the pharmaceutical intermediate can be produced by an easy method applicable for industrial production from easily available starting material. Further, the intermediate useful for the production method is provided.

Abstract translation: 要解决的问题：提供一种可以从廉价且容易获得的原料容易地制备用作药物中间体的光学活性3-氨基哌啶或其盐的方法，并且其实用于其工业生产，并提供中间体 可用于制备光学活性3-氨基哌啶或其盐。解决方案：用于制备光学活性3-氨基哌啶或其盐的方法包括：立体选择性水解外消旋哌啶甲酰胺以转化为光学活性的夹螺旋体和光学上的方法 在源自微生物的酶源存在下的活性乳酸; 以及随后对光学活性的nipecotamide进行丙烯酰化，霍夫曼重排，保护氨基和去保护的步骤，以及将光学活性的nipecotamide导出到光学活性氨基哌啶或其盐中，或者使光学活性的哌啶甲酰胺与BOC （叔丁氧基羰基），霍夫曼重排和去保护，从而将光学活性的哌甲酰胺衍生成光学活性氨基哌啶或其盐。 可用作药物中间体的光学活性3-氨基哌啶或其盐可以通过易于获得的起始原料通过适用于工业生产的容易的方法制备。 此外，提供了可用于生产方法的中间体。

公开(公告)号：JP2010180186A

公开(公告)日：2010-08-19

申请号：JP2009027079

申请日：2009-02-09

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： MORI KOHEI ,  FUJII AKIO

IPC: C07D217/02 ,  C07B53/00 ,  C07D207/08 ,  C07F1/04 ,  C07F5/02

Abstract: PROBLEM TO BE SOLVED: To provide an asymmetric reducing agent capable of easily being prepared from inexpensive and easily available raw materials, and also a method for producing an optically active tetrahydroisoquinoline derivative or its salt useful as a medicinal intermediate in a high optical purity, inexpensively and simply, and suitable for an industrial production. SOLUTION: This asymmetric reducing agent is prepared by an organic carboxylic acid having a predetermined acidity, an optically active proline derivative and a metal borohydride. Also, by using the asymmetric reducing agent, 1,2-dihydroisoquinoline is reduced, to prepare the optically active tetrahydroisoquinoline derivative. COPYRIGHT: (C)2010,JPO&INPIT

Abstract translation: 要解决的问题：提供能够容易地由廉价且容易获得的原料制备的不对称还原剂，以及用于制备光学活性四氢异喹啉衍生物或其盐在高光学中有用的医药中间体的方法 纯度高，成本低廉，适合工业生产。 解决方案：该不对称还原剂由具有预定酸度的有机羧酸，光学活性脯氨酸衍生物和金属硼氢化物制备。 此外，通过使用不对称还原剂，还原1,2-二氢异喹啉，制备光学活性的四氢异喹啉衍生物。 版权所有（C）2010，JPO＆INPIT

公开(公告)号：JP2009292842A

公开(公告)日：2009-12-17

申请号：JP2009217497

申请日：2009-09-18

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： OISHI TAKAHIRO ,  NANBA HIRONORI ,  SUGAWARA MASANOBU ,  IZUMIDA SHOJI ,  HONDA TATSUYA ,  MORI KOHEI ,  YANAGISAWA YOSHIHIRO ,  NAGASHIMA NOBUO ,  INOUE KENJI

IPC: C07C319/06 ,  C07B61/00 ,  C07C273/18 ,  C07C275/16 ,  C07C319/28 ,  C07C323/58 ,  C07D233/76 ,  C12P13/12 ,  C12P17/04 ,  C12P17/10 ,  C12P41/00

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

Abstract: PROBLEM TO BE SOLVED: To provide a simple industrial method 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. SOLUTION: The method for producing an L- or D-optically active α-methylcysteine derivative or its salt, includes D-selectively cyclizing a racemic N-carbamoyl-α-methylcysteine derivative or its salt 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, and deprotecting the amino group and then the sulfur atom, and then hydrolyzing. COPYRIGHT: (C)2010,JPO&INPIT

Abstract translation: 要解决的问题：提供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α-甲基半胱氨酸衍生物或其盐的简单工业方法。 解决方案：用于制备L-或D-光学活性α-甲基半胱氨酸衍生物或其盐的方法包括将外消旋的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，并将氨基然后硫原子脱保护，然后水解。 版权所有（C）2010，JPO＆INPIT

公开(公告)号：JP2010088455A

公开(公告)日：2010-04-22

申请号：JP2009299437

申请日：2009-12-15

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： TAOKA NAOAKI ,  MORIYAMA DAISUKE ,  MORI KOHEI ,  OISHI TAKAHIRO

IPC: C12P7/62 ,  C07C67/313 ,  C07C69/67 ,  C07D317/60 ,  C12P17/04 ,  C12P41/00

CPC classification number: C12P7/62 ,  C07C67/313 ,  C07D317/60 ,  C12P17/04 ,  C12P41/002 ,  C07C69/716

Abstract: PROBLEM TO BE SOLVED: To provide a process for producing an optically active 3-hydroxypropionic ester derivative useful as an intermediate for a medicament. SOLUTION: The process for producing the optically active 3-hydroxypropionic ester derivative comprises synthesizing a 2-formylacetic ester derivative by using an acetic ester derivative available at low cost, a formic ester and a base, and then stereoselectively reducing the formyl group of the derivative by use of an enzymatic source capable of stereoselectively reducing the formyl group thereof. COPYRIGHT: (C)2010,JPO&INPIT

Abstract translation: 待解决的问题：提供一种制备用作药物中间体的光学活性3-羟基丙酸酯衍生物的方法。 解决方案：制备光学活性3-羟基丙酸酯衍生物的方法包括通过使用低成本获得的乙酸酯衍生物，甲酸酯和碱合成2-甲酰基乙酸酯衍生物，然后立体选择性还原甲酰基 的衍生物通过使用能够立体选择性还原其甲酰基的酶源。 版权所有（C）2010，JPO＆INPIT

公开(公告)号：JP2009161441A

公开(公告)日：2009-07-23

申请号：JP2007339114

申请日：2007-12-28

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： NISHIYAMA AKIRA ,  SUGAWARA MASANOBU ,  MORI KOHEI ,  KIZAKI NORIYUKI ,  NISHIYAMA TOZO ,  YASOHARA YOSHIHIKO

IPC: C07D205/08 ,  C07B61/00 ,  C12P13/02

Abstract: PROBLEM TO BE SOLVED: To provide a method for safely and efficiently producing optically active 1-phenyl-4-methyl-2-azetidinone useful as an intermediate for medicines and agrochemicals from an inexpensive and easily available raw material at a low cost. SOLUTION: This optically active 1-phenyl-4-methyl-2-azetidinone is produced from an inexpensive and easily available optically active N-aryl-3-sulfonyloxybutanoic acid amide derivative using inexpensive, easily available and safe sodium hydroxide or potassium hydroxide in a good yield. COPYRIGHT: (C)2009,JPO&INPIT

Abstract translation: 要解决的问题：提供一种以低成本从廉价且容易获得的原料中安全有效地制造用作药物和农药的中间体的光学活性1-苯基-4-甲基-2-氮杂环丁酮的方法 。 解决方案：该光学活性的1-苯基-4-甲基-2-氮杂环丁酮是由便宜且易于获得的光学活性N-芳基-3-磺酰氧基丁酸酰胺衍生物制备的，其使用便宜且容易获得且安全的氢氧化钠或钾 氢氧化物以良好的产率。 版权所有（C）2009，JPO＆INPIT