公开(公告)号：US10065930B2

公开(公告)日：2018-09-04

申请号：US15328166

申请日：2015-08-03

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Yuzo Watanabe

IPC: C07D239/34

CPC classification number: C07D239/34 ,  C07D239/36

Abstract: There are provided a method for producing 2,4-disubstituted pyrimidine-5-ol, and particularly, 2,4-dimethylpyrimidine-5-ol and an intermediate thereof used in industrial production. The production method according to the present invention includes a step of producing 2,4-disubstituted pyrimidine-5-ol according to a hydrolysis reaction of a 2,4-disubstituted-5-(4-(nitrophenyl)oxy)pyrimidine compound and is suitable for industrial production since an inexpensive and easily available starting material can be used, regioselectivity of a substituent group is easily controlled, impurities are easily controlled, and 2,4-disubstituted pyrimidine-5-ol can be produced without using reagents and intermediates causing health problems, risks and the like.

公开(公告)号：US20170204068A1

公开(公告)日：2017-07-20

申请号：US15328166

申请日：2015-08-03

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Yuzo Watanabe

IPC: C07D239/34

CPC classification number: C07D239/34 ,  C07D239/36

Abstract: There are provided a method for producing 2,4-disubstituted pyrimidine-5-ol, and particularly, 2,4-dimethylpyrimidine-5-ol and an intermediate thereof used in industrial production. The production method according to the present invention includes a step of producing 2,4-disubstituted pyrimidine-5-ol according to a hydrolysis reaction of a 2,4-disubstituted-5-(4-(nitrophenyl)oxy)pyrimidine compound and is suitable for industrial production since an inexpensive and easily available starting material can be used, regioselectivity of a substituent group is easily controlled, impurities are easily controlled, and 2,4-disubstituted pyrimidine-5-ol can be produced without using reagents and intermediates causing health problems, risks and the like.

公开(公告)号：US20220194925A1

公开(公告)日：2022-06-23

申请号：US17604527

申请日：2020-05-13

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Taichi Abe ,  Kazuhiro Yoshizawa ,  Yuzo Watanabe ,  Takeshi Miura ,  Yusuke Ayata ,  Yoshinori Yasuda

IPC: C07D401/12 ,  C07C41/09 ,  C07D239/34

Abstract: The present application discloses a method and a compound that are useful for preparation of a compound of Formula (XI). Furthermore, the present application discloses the compound of Formula (XI) comprising a small amount of impurities.

公开(公告)号：US09227942B2

公开(公告)日：2016-01-05

申请号：US14396261

申请日：2013-04-25

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Kazuhiro Yoshizawa ,  Masayuki Omori ,  Yuzo Watanabe ,  Mitsuo Nagai ,  Masabumi Takahashi ,  Francis G. Fang

IPC: C07D241/24

CPC classification number: C07D241/24

Abstract: 5-(Difluoromethyl)pyrazine-2-carboxylic acid, which is a raw material for the construction of 5-(difluoromethyl)pyrazine-2-carboxamide, which is a common partial structural motif of the compound having an Aβ production inhibitory action or a BACE1 inhibitory action, can be industrially advantageously produced by decarboxylating 5-[carboxy(difluoro)methyl]pyrazine-2-carboxylic acid, which is obtainable from 5-chloropyrazine-2-carboxylate.

Abstract translation: 5-（二氟甲基）吡嗪-2-甲酸，其是用于构建具有A＆bgr的化合物的常见部分结构基序的5-（二氟甲基）吡嗪-2-甲酰胺的原料。 产生抑制作用或BACE1抑制作用，可在工业上有利地由5-氯吡嗪-2-羧酸酯得到5- [羧基（二氟）甲基]吡嗪-2-羧酸脱羧产生。

公开(公告)号：US20150087836A1

公开(公告)日：2015-03-26

申请号：US14396261

申请日：2013-04-25

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Kazuhiro Yoshizawa ,  Masayuki Omori ,  Yuzo Watanabe ,  Mitsuo Nagai ,  Masabumi Takahashi ,  Francis G. Fang

IPC: C07D241/24

CPC classification number: C07D241/24

Abstract: 5-(Difluoromethyl)pyrazine-2-carboxilic acid, which is a raw material for the construction of 5-(difluoromethyl)pyrazine-2-carboxamide, which is a common partial structural motif of the compound having an A production inhibitory action or a BACE1 inhibitory action, can be industrially advantageously produced by decarboxylating 5-[carboxy(difluoro)methyl]pyrazine-2-carboxylic acid, which is obtainable from 5-chloropyrazine-2-carboxylate.

Abstract translation: 5-（二氟甲基）吡嗪-2-甲酸，其是用于构建5-（二氟甲基）吡嗪-2-甲酰胺的原料，其是具有A产生抑制作用的化合物的常见部分结构基序或 BACE1抑制作用可以在工业上有利地由5-氯吡嗪-2-羧酸酯可得5- [羧基（二氟）甲基]吡嗪-2-羧酸脱羧制得。