Eisai R&d Management Co., Ltd.

Eisai Company, Limited

Mamoru Miyazawa

Shigeto Negi

Atsushi Kamada

Manabu Sasho

Susumu Inoue

Koichi Ito

Naoyuki Shimomura

Keisuke Matsuyama

Kenji Hayashi

Jun Niijima

Masanobu Shinoda

Kohshi Ueno

Fumiyoshi Matsuura

Yuki Komatsu

Kaoru Murata

Naoki Ozeki

Katsutoshi Nishiura

Masaharu Gotoda

Teiji Takigawa

Keizo Sato

Kimihiro Matsuo

Manabu Shasho

Yoshihiko Hisatake

Atsushi Tsukuba Res Lab Eisai Co Ltd Kamada

Koichi Tsukuba Res Lab Eisai Co Ltd Ito

Naoyuki Tsukuba Res Lab Eisai Co Ltd Shimomura

It is possible to commercially advantageously prepare 1-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-y)ethyl]piperidin-4-yl}-N-methyl-1H-indole-6-carboxamide by coupling (7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)acetaldehyde, which is obtained by oxidizing 8-(2-hydroxyethyl)-7-methoxy-2,2-dimethylchroman-4-one, with N-methyl-1-(piperidin-4-yl)-1H-indole-6-carboxamide.

Method for producing indole derivative having piperidine ring

The present invention relates to calcium bis[(2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy) -2-fluoropropoxy]phenyl]-2-isopropoxypropionate] represented by formula (I), a hydrate thereof, a crystal of the compound of formula (I), and a crystal of the hydrate of the compound of formula (I) which are useful as pharmaceuticals, and to processes for producing the same, and intermediates therefore, and processes for production thereof. There is need for (2S)-3-[3-[(2S)-3-(4 -chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionic acid, in the form of a drug substance, purified so as to minimize a residual solvent content and having a uniformized specification and a highly favorable workability, and a process for producing the same. Crystalline calcium bis[(2S)-3-[3-[(2S)-3-(4 -chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionate], a calcium salt of (2S) -3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionic acid, solves the above problem.

Calcium bis [(2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl ]-2-isopropoxypropionate] and intermediate thereof

An object of the present invention is to provide a process, or the like, suitable for the industrialization of effective deprotection reaction without using a toxic solvent as well as to provide a process, or the like, for preparing a water-soluble azole prodrug effectively. The present invention provides a process for preparing a salt represented by Formula (I); (wherein X represents a fluorine atom bonded at position 4 or position 5 of a phenyl group) comprising the steps of: (a) carrying out a deprotection reaction of a compound represented by Formula (II); (wherein X represents a fluorine atom bonded at position 4 or position 5 of a phenyl group)in the presence of a carbocation scavenger.

Process for preparation of water-soluble azole prodrugs

Process for production of indole derivatives and intermediates therefor

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Kamisu, Japan

Mamoru Miyazawa