公开(公告)号：US20160347718A1

公开(公告)日：2016-12-01

申请号：US15116861

申请日：2015-02-06

申请人： API CORPORATION

发明人： Naoyuki WATANABE ,  Yasumasa DEKISHIMA ,  Masaki NAGAHAMA ,  Tomoko MAEDA ,  Takashi OHTANI ,  Kosuke ITO ,  Hiroshi KAWABATA

IPC分类号： C07D239/42 ,  C12P17/12

CPC分类号： C07D239/42 ,  C12N9/0006 ,  C12P17/12

摘要： An object of the present invention is to provide a novel method capable of producing rosuvastatin calcium and intermediates therefor efficiently, inexpensively and with high purity. The present invention provides a method of efficiently producing rosuvastatin calcium and intermediates therefor having a high purity at an industrial scale, without using an extremely low temperature reaction or a special asymmetric catalyst.

摘要翻译： 本发明的目的是提供能够高效，低成本且高纯度地生产瑞舒伐他汀钙及其中间体的新方法。 本发明提供了在不使用极低温反应或特殊的不对称催化剂的情况下，有效地生产工业规模的高纯度的瑞舒伐他汀钙及其中间体的方法。

公开(公告)号：US20240351978A1

公开(公告)日：2024-10-24

申请号：US18738245

申请日：2024-06-10

申请人： API CORPORATION

发明人： Masaki NAGAHAMA ,  Hideki OOMIYA ,  Daiki OKADO ,  Hirotsugu TANIIKE

IPC分类号： C07C253/20 ,  C07C51/06 ,  C07C57/38 ,  C07C255/33

CPC分类号： C07C253/20 ,  C07C51/06 ,  C07C57/38 ,  C07C255/33 ,  C07C2602/10

摘要： The present invention provides a method for industrially producing a highly pure aromatic nitrile compound and a highly pure aromatic carboxylic acid compound safely and highly efficiently at low costs. Compound (2) is subjected to Willgerodt reaction in the presence of an additive as necessary, and the obtained amide compound (3) is hydrolyzed and neutralized to give carboxylic acid compound (4). Carboxylic acid compound (4) is reacted with a halogenating agent in the presence of a catalyst as necessary in an organic solvent, and further reacted with an amidating agent, and the obtained amide compound (5) or (6) is reacted with a dehydrating agent to give nitrile compound (1). Alternatively, carboxylic acid compound (4) is reacted with a halogenating agent and a compound represented by the formula R6SO2R7 in the presence of a catalyst as necessary in an organic solvent to give nitrile compound (1). Np is a naphthyl group optionally having substituent(s), R5 is an alkylene group having 1-3 carbon atoms, and other symbols are as described in the DESCRIPTION.

公开(公告)号：US20240002340A1

公开(公告)日：2024-01-04

申请号：US18243409

申请日：2023-09-07

申请人： API CORPORATION

发明人： Masato MURAI ,  Jun TAKEHARA ,  Daiki OKADO

IPC分类号： C07D211/60

CPC分类号： C07D211/60

摘要： A method for producing a compound represented by the formula (1):




wherein LG is a leaving group, PG1 is an amino-protecting group, and R is a hydrocarbon group having 1-8 carbon atoms and optionally having substituent(s), comprising



reacting a compound represented by the formula (6):








with an amino group protecting agent to obtain a compound represented by the formula (7):




or a salt thereof;



reacting the aforementioned compound represented by the formula (7) with a lactonization agent to obtain a compound represented by the formula (8):










reacting the aforementioned compound represented by the formula (8) with an esterification agent to obtain a compound represented by the formula (9):








and



reacting the aforementioned compound represented by the formula (9) with a leaving group introduction agent.

公开(公告)号：US11643386B2

公开(公告)日：2023-05-09

申请号：US17295222

申请日：2020-10-28

申请人： API CORPORATION

发明人： Masaki Nagahama ,  Daiki Okado ,  Hirotsugu Taniike

IPC分类号： C07C253/22

CPC分类号： C07C253/22

摘要： High purity 2-naphthylacetonitrile with fewer impurities can be used as a starting material or intermediate for synthesizing various pharmaceutical products, agricultural chemicals, and chemical products, and a production method thereof. A high purity 2-naphthylacetonitrile having an HPLC purity of 2-naphthylacetonitrile of not less than 95 area %, and containing naphthalene compounds represented by the formulas (a)-(j) at a content of a predetermined area % or below. A method for producing high purity 2-naphthylacetonitrile, may include: subjecting 2′-acetonaphthone to a Willgerodt reaction in the presence of an additive where necessary, and hydrolyzing the obtained amide compound to give 2-naphthylacetic acid; and reacting the 2-naphthylacetic acid obtained in the subjecting, a halogenating agent and sulfamide in the presence of a catalyst as necessary in an organic solvent to give 2-naphthylacetonitrile.

公开(公告)号：US20210024905A1

公开(公告)日：2021-01-28

申请号：US17043339

申请日：2019-03-29

申请人： API CORPORATION

发明人： Toyokazu YOSHIDA ,  Koichi ISHIDA ,  Ryoma MIYAKE ,  Takanobu IURA ,  Hiroshi KAWABATA

IPC分类号： C12N9/18 ,  C12P41/00 ,  C12P7/62

摘要： The present invention provides a novel hydrolase that can industrially produce optically highly pure (1S,2S)-1-alkoxycarbonyl-2-vinylcyclopropane carboxylic acid with high efficiency at low costs, and a production method using the hydrolase.

公开(公告)号：US20190315696A1

公开(公告)日：2019-10-17

申请号：US16442770

申请日：2019-06-17

申请人： API CORPORATION

发明人： Naoyuki WATANABE ,  Tomoko MAEDA ,  Yasumasa DEKISHIMA ,  Hiroshi KAWABATA ,  Masaki NAGAHAMA

IPC分类号： C07D239/42 ,  C12N9/04 ,  C12P17/12

摘要： An object of the present invention is to provide a novel method capable of producing rosuvastatin calcium and intermediates therefor efficiently, inexpensively and with high purity. The present invention provides a method of efficiently producing rosuvastatin calcium and intermediates therefor having a high purity at an industrial scale, without using an extremely low temperature reaction or a special asymmetric catalyst.

公开(公告)号：US20180222865A1

公开(公告)日：2018-08-09

申请号：US15749377

申请日：2016-08-05

申请人： API CORPORATION

发明人： Naoyuki WATANABE ,  Takanobu IURA ,  Hideki OOMIYA ,  Masaki NAGAHAMA

IPC分类号： C07D215/14 ,  C12P17/12

摘要： Production of pitavastatin calcium safely on an industrial scale with a high yield and high selectivity at low cost. A method of producing pitavastatin calcium including step (i) for acetalizing a compound represented by the formula (1) to give a compound represented by the formula (3), step (ii) for reacting a compound represented by the formula (3) with an acid to give a compound represented by the formula (4), and step (iii) for hydrolyzing a compound represented by the formula (4) and reacting same with a calcium compound.

公开(公告)号：US09790181B2

公开(公告)日：2017-10-17

申请号：US15108141

申请日：2014-12-26

申请人： API CORPORATION

发明人： Jun Takehara ,  Masato Murai ,  Takashi Ohtani ,  Tomoko Maeda ,  Tsugihiko Hidaka

IPC分类号： C07D211/16 ,  C07D498/08 ,  C07D211/60 ,  C07C309/66 ,  C07C233/47

CPC分类号： C07D211/60 ,  C07C233/47 ,  C07C309/66 ,  C07D498/08 ,  Y02P20/55

摘要： A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by formula (10) below: the method including removing the protecting group from the hydroxyl group in a compound represented by formula (7) below: (wherein P represents a protecting group, R3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms) to synthesize a compound represented by formula (8) below: (wherein R3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms).

公开(公告)号：US20160083341A1

公开(公告)日：2016-03-24

申请号：US14888576

申请日：2014-05-01

申请人： API Corporation

发明人： Yuuki Asuma ,  Hisatoshi Uehara ,  Tomoko Maeda ,  Yasuyo Saito ,  Ryoma Miyake ,  Hiroshi Kawabata

IPC分类号： C07C319/06 ,  C07C323/52 ,  C12P13/12 ,  C07C323/58 ,  C07D277/14 ,  C07C319/14 ,  C07C319/20 ,  C07C323/60

CPC分类号： C07C319/06 ,  C07C319/02 ,  C07C319/14 ,  C07C319/20 ,  C07C323/52 ,  C07C323/58 ,  C07C323/60 ,  C07D277/14 ,  C12P13/12 ,  C07C323/12 ,  C07C323/03

摘要： According to the present invention, it becomes possible to perform a process for converting into an α-substituted cysteine represented by general formula (1) or a salt thereof at low cost and on an industrial scale by employing a process that is routed through a compound represented by general formula (3) to a compound represented by general formula (6). Particularly, by employing a process that is routed through a compound represented by general formula (7-2), it becomes possible to detach a tert-butyl protection group in a simple manner and to produce the compound represented by general formula (1) with high purity. Furthermore, by employing a process that is routed through tert-butylthiomethanol or a process that is routed through a compound represented by general formula (9), it becomes possible to produce a compound represented by general formula (2) without generating bischloromethylether that is an oncogenic substance. In the production of an α-substituted-D-cysteine or a salt thereof, it becomes possible to perform a process for converting the compound represented by general formula (2) into a compound represented by general formula (3S) in one step by allowing an enzyme or the like to act on the compound represented by general formula (2).

摘要翻译： 根据本发明，可以通过使用通过化合物的方法，以低成本和工业规模进行转化成由通式（1）表示的α-取代的半胱氨酸或其盐的方法 由通式（3）表示的化合物与通式（6）表示的化合物反应。 特别是通过使用通过通式（7-2）表示的化合物的方法，可以简单地分离叔丁基保护基，并制备通式（1）表示的化合物与 高纯度 此外，通过使用通过叔丁基硫醇的方法或通过通式（9）表示的化合物的方法，可以生成由通式（2）表示的化合物，而不产生作为 致癌物质。 在制备α-取代-D-半胱氨酸或其盐时，可以通过以下步骤进行将由通式（2）表示的化合物转化为通式（3S）表示的化合物的方法：允许 酶等作用于由通式（2）表示的化合物。

公开(公告)号：US20130096339A1

公开(公告)日：2013-04-18

申请号：US13579045

申请日：2011-02-16

申请人： Yuuki Asuma ,  Tatsuya Suzuki ,  Jun Takehara ,  Tsugihiko Hidaka ,  Kuniko Asada ,  Ryoma Miyake ,  Yasumasa Dekishima ,  Hiroshi Kawabata

发明人： Yuuki Asuma ,  Tatsuya Suzuki ,  Jun Takehara ,  Tsugihiko Hidaka ,  Kuniko Asada ,  Ryoma Miyake ,  Yasumasa Dekishima ,  Hiroshi Kawabata

IPC分类号： C07C67/343

CPC分类号： C07C67/343 ,  C07B53/00 ,  C07B57/00 ,  C07B2200/07 ,  C07C67/313 ,  C07C227/04 ,  C07C227/32 ,  C07C247/22 ,  C07C269/02 ,  C07C2601/02 ,  C12P7/62 ,  C12P41/005 ,  C07C69/743 ,  C07C229/48 ,  C07C271/24

摘要： It is an object of the present invention to provide a novel method for producing (1R,2S)/(1S,2R)-1-amino-1-alkoxycarbonyl-2-vinylcyclopropane which is useful as a synthetic intermediate of therapeutic agents for hepatitis C and a synthetic intermediate thereof. According to the present invention, when a trans-2-butene derivative having a leaving group at each of the 1- and 4-positions is reacted with a malonic ester in the presence of a base, a specific amount of an alkali metal alkoxide or an alkali metal hydride is used as the base, and further a specific amount of a malonic ester is used to produce a cyclopropane diester, and further, chiral or achiral 1-amino-1-alkoxy-carbonyl-2-vinylcyclopropane and a salt thereof are synthesized using the cyclopropane diester.

摘要翻译： 本发明的目的是提供一种制备（1R，2S）/（1S，2R）-1-氨基-1-烷氧基羰基-2-乙烯基环丙烷的新方法，其可用作肝炎治疗剂的合成中间体 C及其合成中间体。 根据本发明，当在碱存在下使具有1位和4位的离去基团的反式-2-丁烯衍生物与丙二酸酯反应时，将特定量的碱金属醇盐或 使用碱金属氢化物作为碱，进一步使用特定量的丙二酸酯来制备环丙烷二酯，此外，手性或非手性1-氨基-1-烷氧基 - 羰基-2-乙烯基环丙烷及其盐 使用环丙烷二酯合成。