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1. 发明公开

EP2915805A1 METHOD FOR PRODUCING OPTICALLY ACTIVE BICYCLIC UREA COMPOUND 审中-公开
标题翻译： VERFAHREN ZUR HERSTELLUNG EINER OPTISCH AKTIVEN BICYCLISCHEN HARNSTOFFVERBINDUNG
公开(公告)号：EP2915805A1
公开(公告)日：2015-09-09
申请号：EP13850807.2
申请日：2013-10-25
申请人： Kaneka Corporation
发明人： HIRAI, Yoshinori , NISHIYAMA, Akira
IPC分类号： C07D211/60 , C07D471/08 , C07D487/08 , C07B53/00 , C07B61/00
CPC分类号： C07D211/98 , C07B53/00 , C07D211/60 , C07D471/08 , C07D471/18 , C07D487/08
摘要： A problem to be solved by the present invention is to provide a process for producing an optically active bicyclic urea compound useful as an intermediate for β-lactamase inhibitor, in a simple and easy manner with high efficiency.
The present invention includes reacting a specific ester compound with a specific amine in the presence of a metal alkoxide and/or an alkaline earth metal salt to produce the corresponding amide compound, which is then reacted with phosgene or a phosgene equivalent, followed by, if necessary, treatment with an acid or a base, to produce an optically active bicyclic urea compound. This makes it possible to produce an optically active bicyclic urea compound in a simple and easy manner with high efficiency and in high optical purity, without using expensive reagents such as catalysts and condensation agents, and without passing through protection and deprotection steps.
摘要翻译：本发明要解决的问题是提供以简单且容易的方式高效率地生产用作β-内酰胺酶抑制剂的中间体的光学双环脲化合物的方法。本发明包括在金属醇盐和/或碱土金属盐的存在下使特定的酯化合物与特定的胺反应以产生相应的酰胺化合物，然后与光气或光气当量反应，然后如果必要时用酸或碱处理，以产生光学双环脲化合物。这使得可以以简单和容易的方式以高效率和高光学纯度生产光学活性双环脲化合物，而不使用昂贵的试剂如催化剂和缩合剂，并且不经过保护和脱保护步骤。

2. 发明公开

EP3060573A1 TETRAPEPTIDE COMPOUND AND METHOD FOR PRODUCING SAME 有权转让
标题翻译： TETRA肽化合物和方法及其生产
公开(公告)号：EP3060573A1
公开(公告)日：2016-08-31
申请号：EP14802957.2
申请日：2014-10-23
申请人： Kaneka Corporation , Stealth Peptides International, Inc.
发明人： HIRAI, Yoshinori , NISHIYAMA, Akira , MITSUDA, Masaru
IPC分类号： C07K5/11
CPC分类号： C07K5/1021 , A61K38/00 , C07B2200/13 , C07K5/1019
摘要： The present invention is to provide a method for the efficient production on an industrial scale of SS-31 (D-Arg-Dmt-Lys-Phe-NH2), which is an SS peptide. According to the present invention, the desired SS-31 is produced by efficiently synthesizing a tetrapeptide compound as a precursor of SS-31 and improving the tetrapeptide purity by crystallization.

3. 发明公开

EP2345733A1 PROCESS FOR PRODUCING N-PROTECTED AMINO ACID 审中-公开
标题翻译：生产N-保护的氨基酸的方法
公开(公告)号：EP2345733A1
公开(公告)日：2011-07-20
申请号：EP09823674.8
申请日：2009-10-29
申请人： Kaneka Corporation
发明人： HIRAI, Yoshinori , MAEHARA, Katsuji , MOROSHIMA, Tadashi , KANAMARU, Hiroyuki , IWASAKI, Akira
IPC分类号： C12P13/06
CPC分类号： C12P13/06 , C07C269/04 , C12P13/04 , C07C271/22
摘要： In the present invention, an N-protected amino acid is obtained by producing an amino acid using a biocatalyst such as a microorganism and enzyme; acidizing the reaction mixture containing the amino acid to adjust pH to not more than 4, without isolating the amino acid; and then protecting the amino group under a basic condition. As a result, a high-quality N-protected amino acid can be quantitatively and efficiently produced using a quantitative or slightly excessive protecting agent, even when the amino acid produced using a biocatalyst is directly protected without isolating the amino acid.
摘要翻译：在本发明中，N-保护的氨基酸通过使用生物催化剂如微生物和酶产生氨基酸而获得; 将含有氨基酸的反应混合物酸化以将pH调节至不超过4，而不分离氨基酸; 然后在碱性条件下保护氨基。结果，即使使用生物催化剂产生的氨基酸在不分离氨基酸的情况下直接被保护，使用定量或稍过量的保护剂也可以定量和有效地产生高质量的N-保护的氨基酸。

4. 发明授权

EP3060573B1 TETRAPEPTIDE COMPOUND AND METHOD FOR PRODUCING SAME 有权转让
公开(公告)号：EP3060573B1
公开(公告)日：2019-07-17
申请号：EP14802957.2
申请日：2014-10-23
申请人： Kaneka Corporation , Stealth BioTherapeutics Corp
发明人： HIRAI, Yoshinori , NISHIYAMA, Akira , MITSUDA, Masaru
IPC分类号： C07K5/11

5. 发明授权

EP2650281B1 PROCESS FOR PREPARING CYCLIC AMINE COMPOUNDS 有权
标题翻译：用于生产环胺衍生物
公开(公告)号：EP2650281B1
公开(公告)日：2016-07-13
申请号：EP12762930.1
申请日：2012-03-28
申请人： KANEKA CORPORATION
发明人： HIRAI, Yoshinori , NISHIYAMA, Akira
IPC分类号： C07D211/60
CPC分类号： C07D211/60

6. 发明公开

EP2650281A1 PROCESS FOR PREPARING CYCLIC AMINE COMPOUNDS 有权
标题翻译： VERFAHREN ZUR HERSTELLUNG CYCLISCHER AMINVERBINDUNGEN
公开(公告)号：EP2650281A1
公开(公告)日：2013-10-16
申请号：EP12762930.1
申请日：2012-03-28
申请人： KANEKA CORPORATION
发明人： HIRAI, Yoshinori , NISHIYAMA, Akira
IPC分类号： C07D211/60
CPC分类号： C07D211/60
摘要： A cyclic amine compound having a prescribed configuration can be efficiently prepared by reducing an imine derivative in the presence of a sulfonic acid. Specifically, a cyclic amine compound which is substituted with an amino group and a carboxyl group in which both groups are arranged in the trans configuration can be prepared efficiently.
摘要翻译：通过在磺酸存在下还原亚胺衍生物可以有效地制备具有规定构型的环胺化合物。具体地说，可以有效地制备被两个基团排列成反式构型的被氨基和羧基取代的环胺化合物。

7. 发明公开

EP2460885A1 METHOD FOR PRODUCING OPTICALLY ACTIVE 3-SUBSTITUTED GLUTARIC ACID MONOAMIDE 审中-公开
标题翻译： HERSTELLUNGSVERFAHRENFÜROPTISCH AKTIVES 3-SUBSTITUIERTESGLUTARINSÄURE-MONOAMID
公开(公告)号：EP2460885A1
公开(公告)日：2012-06-06
申请号：EP10804093.2
申请日：2010-07-26
申请人： Kaneka Corporation
发明人： NOJIRI, Masutoshi , UEKITA, Ken , HIRAI, Yoshinori , NISHIYAMA, Akira , TAOKA, Naoaki
IPC分类号： C12P41/00
CPC分类号： C12P13/02 , C12P41/006
摘要： The present invention relates to a method for producing optically active 3-substituted glutaric acid monoamide, which comprises allowing an enzyme source having activity of asymmetrically hydrolyzing a prochiral 3-substituted glutaric acid diamide compound to act on the compound. According to the present invention, a method for producing optically active 3-substituted glutaric acid monoamide, which is a useful drug intermediate, at a high yield from an inexpensive and readily available starting material.
摘要翻译：本发明涉及一种光学活性3-取代戊二酸单酰胺的制造方法，其包括使具有不对称水解前手性3-取代戊二酸二酰胺化合物的酶源作用于该化合物。根据本发明，从廉价且容易获得的起始原料中以高产率制备作为有用药物中间体的光学活性3-取代戊二酸单酰胺的方法。

8. 发明公开

EP2423187A1 PROCESS FOR PRODUCTION OF N-ALKOXYCARBONYL-tert-LEUCINES 审中-公开
标题翻译： VERFAHREN ZUR HERSTELLUNG VON N-ALKOXYCARBONYL-TERT.-LEUCINEN
公开(公告)号：EP2423187A1
公开(公告)日：2012-02-29
申请号：EP09843676.9
申请日：2009-07-13
申请人： Kaneka Corporation
发明人： KAWASAKI, Hiroaki , MOROSHIMA, Tadashi , MAEHARA, Katsuji , HIRAI, Yoshinori
IPC分类号： C07C269/04 , C07C271/12
CPC分类号： C07C269/04 , C07C271/22
摘要： A high quality N-alcoxycarbonyl-tert leucine can be efficiently and stably produced with an easy procedure by reacting tert-leucine with an N-alcoxycarbonylating agent in the presence of water, wherein the use amount of the N-alcoxycarbonylating agent is not less than 0.90 times by mole and not more than 1.00 times by mole relative to the tert-leucine, with maintaining the pH of the reaction mixture in the range of not less than 9 and not more than 13 using a basic agent. In addition, an N-alcoxycarbonyl-tert-leucine can be efficiently extracted from the basic aqueous solution thereof under a mild condition using a water-immiscible solvent by mixing a hydroxide. Furthermore, the two crystal forms of N-butoxycarbonyl-tert-leucine can be controlled by adjusting the water amount in crystallization step, and the compound can be stably produced in an industrial production.
摘要翻译：通过在水存在下使叔亮氨酸与N-烷氧羰基化剂反应，可以通过简单的方法有效稳定地制备高质量的N-烷氧羰基 - 叔亮氨酸，其中N-烷氧基羰基化剂的用量不小于使用碱性试剂将反应混合物的pH保持在不小于9且不大于13的范围内，相对于叔亮氨酸为0.90倍摩尔，不大于1.00倍摩尔。此外，通过混合氢氧化物，可以在温和条件下使用水不混溶溶剂从其碱性水溶液中有效地提取N-烷氧基羰基 - 叔亮氨酸。此外，可以通过调节结晶步骤中的水量来控制N-丁氧基羰基 - 叔 - 亮氨酸的两种晶体形式，并且可以在工业生产中稳定地生产化合物。

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