Eisai R&d Management Co., Ltd.

Masabumi Takahashi

Francis Gerard Fang

Mitsuo Nagai

Kazuhiro Yoshizawa

Yuzo Watanabe

Masayuki Omori

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 A&#x3b2; 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.

Method for producing 5-(difluoromethyl)pyrazine-2-carboxylic acid and production intermediate thereof

A method for producing a compound or a salt thereof represented by a formula (I), comprising reacting a compound or a salt thereof represented by a formula (II) and an aniline derivative represented by a formula (III) in water or a mixed solvent of water and an organic solvent in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and substantially in the absence of a base is disclosed, wherein Ris a 4-[3-(dimethylamino)azetidin-1-yl]piperidin-1-yl group, a 4-(4-methylpiperazin-1-yl)piperidin-1-yl group, a 3-hydroxyazetidin-1-yl group or a methyl(1-methylpiperidin-4-yl)amino group, R, R, Rand Rmay be the same or different and are each a hydrogen atom or a fluorine atom, and Ris a hydrogen atom or a halogen atom.

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Kamisu, Japan

Masabumi Takahashi