公开(公告)号：US20180371013A1

公开(公告)日：2018-12-27

申请号：US15775581

申请日：2016-11-11

Applicant: API CORPORATION

Inventor： Masaki NAGAHAMA

IPC: C07K5/062 ,  C07C231/12 ,  C07C231/20 ,  C07B57/00

Abstract: The present invention provides a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Adopting a particular isomerization-crystallization condition makes it possible to a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Additionally, an intermediate efficacious for producing lacosamide is provided.

公开(公告)号：US20210078940A1

公开(公告)日：2021-03-18

申请号：US17050255

申请日：2019-04-26

Applicant: API CORPORATION

Inventor： Masaki NAGAHAMA ,  Hideki OOMIYA ,  Daiki OKADO ,  Hirotsugu TANIIKE

IPC: C07C253/20 ,  C07C51/06

Abstract: 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：US20160347718A1

公开(公告)日：2016-12-01

申请号：US15116861

申请日：2015-02-06

Applicant: API CORPORATION

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

IPC: C07D239/42 ,  C12P17/12

CPC classification number: C07D239/42 ,  C12N9/0006 ,  C12P17/12

Abstract: 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.

Abstract translation: 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：US20240391860A1

公开(公告)日：2024-11-28

申请号：US18681328

申请日：2022-08-26

Applicant: API CORPORATION

Inventor： Hirotsugu TANIIKE ,  Shunsuke TSUJI ,  Masaki NAGAHAMA ,  Yurie KOBA

IPC: C07C51/367 ,  C07C51/47

Abstract: Salicylic acid is produced with high productivity by reacting 2-halogenated benzoic acid in an aqueous solvent at a reaction temperature of 155° C. or higher and 300° C. or lower in the presence of a copper source and a ligand. Preferably, the method further includes a purification step A in which the obtained salicylic acid is brought into contact with a styrene-based synthetic adsorbent and/or a purification step B in which the obtained salicylic acid is brought into contact with zeolite. The compound is led to raw materials for various pharmaceuticals or intermediates thereof (for example, acetylsalicylic acid).

公开(公告)号：US20240351978A1

公开(公告)日：2024-10-24

申请号：US18738245

申请日：2024-06-10

Applicant: API CORPORATION

Inventor： Masaki NAGAHAMA ,  Hideki OOMIYA ,  Daiki OKADO ,  Hirotsugu TANIIKE

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

CPC classification number: C07C253/20 ,  C07C51/06 ,  C07C57/38 ,  C07C255/33 ,  C07C2602/10

Abstract: 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：US20190315696A1

公开(公告)日：2019-10-17

申请号：US16442770

申请日：2019-06-17

Applicant: API CORPORATION

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

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

Abstract: 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

Applicant: API CORPORATION

Inventor： Naoyuki WATANABE ,  Takanobu IURA ,  Hideki OOMIYA ,  Masaki NAGAHAMA

IPC: C07D215/14 ,  C12P17/12

Abstract: 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：US20240158328A1

公开(公告)日：2024-05-16

申请号：US18277158

申请日：2022-02-15

Applicant: API CORPORATION

Inventor： Masaki NAGAHAMA ,  Hirotsugu TANIIKE ,  Jun INOUE

IPC: C07C45/67 ,  C07C45/65 ,  C07C67/313

CPC classification number: C07C45/67 ,  C07C45/65 ,  C07C67/313 ,  C07C2601/16

Abstract: A method for producing a cyclohexenone compound, comprising: an isomerization step of bringing a reaction raw material including the compound represented by the following formula (4) into contact with an isomerization catalyst in a solvent to obtain the compound represented by the following formula (3). Preferably, an addition step of reacting the compound (1) and methyl vinyl ketone in a solvent in the presence of a base to obtain compound (2); a cyclization step of reacting compound (2) in a solvent in the presence of a strong acid to obtain compound (3); and an isomerization step of bringing compound (4) contained as an impurity in the reaction product of the cyclization step into contact with an isomerization catalyst in a solvent are performed in order.

公开(公告)号：US20220281806A1

公开(公告)日：2022-09-08

申请号：US17824393

申请日：2022-05-25

Applicant: API CORPORATION

Inventor： Masaki NAGAHAMA ,  Daiki OKADO ,  Hirotsugu TANIIKE

IPC: C07C253/22

Abstract: The present invention provides high purity 2-naphthylacetonitrile with fewer impurities that is useful as a starting material or intermediate for the synthesis of 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, including the following step 1 and step 2: step 1: a step of 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; step 2: a step of reacting the 2-naphthylacetic acid obtained in step 1, 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：US20220009880A1

公开(公告)日：2022-01-13

申请号：US17295222

申请日：2020-10-28

Applicant: API CORPORATION

Inventor： Masaki NAGAHAMA ,  Daiki OKADO ,  Hirotsugu TANIIKE

IPC: C07C253/22

Abstract: 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.