Otsuka Pharmaceutical Company, Limited

Masahiro Sota

Hiroshi Yamashita

Satoshi Aoki

Kenji Nakaya

Masashi Ishigami

Tetsuya Sato

Takayuki Nakamura

Nobuaki Ito

Yusuke Hoshika

Takuya Minowa

Hidekazu Toyofuku

Shuuji Kawano

Ryohei Eto

Takuma Ikebuchi

Kei Moriyama

Naoto Utsumi

Koichi Shinhama

Tetsuya Yamaguchi

Shin Ogasawara

Tatsuya Yamaguchi

Shigeo Fujieda

An object of the present invention is to provide a compound that can be used as a more superior therapeutic agent for central nervous system diseases. The present invention provides a dihydrate of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or of a salt thereof, and a process for producing the same.

Dihydrate of benzothiophene compound or of a salt thereof, and process for producing the same

The present invention provides a method for producing a compound of Formula (4): wherein Ris a hydrogen atom etc. by reacting a compound of Formula (2): wherein Xis a leaving group, with a compound of Formula (3): wherein Ris as defined above, in the presence of (a) a palladium compound and a tertiary phosphine or (b) a palladium carbene complex, in an inert solvent or without a solvent. The present invention can produce the compound of Formula (4), with high purity and high yield, and by a simple operation. 

Method for producing benzo[b]thiophene compound

The present invention provides a tetomilast crystal that is industrially easily produced in a large volume. (1) a tetomilast hydrate crystal having a power X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (2) an anhydrous tetomilast type A crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (3) an anhydrous tetomilast type C crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (4) a tetomilast acetonitrile solvate crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIGS.; and (5) a mixture consisting of the above anhydrous tetomilast type A crystal and an anhydrous tetomilast type B crystal. These crystals are stable towards heat and moisture, and are also excellent in terms of the disintegration property and dissolution property of tablets. Accordingly, these crystals are preferably used as pharmaceutical compositions.

Tetomilast polymorphs

The present invention provides a tetomilast crystal that is industrially easily produced in a large volume. (1) a tetomilast hydrate crystal having a power X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (2) an anhydrous tetomilast type A crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (3) an anhydrous tetomilast type C crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (4) a tetomilast acetonitrile solvate crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; and (5) a mixture consisting of the above anhydrous tetomilast type A crystal and an anhydrous tetomilast type B crystal. These crystals are stable towards heat and moisture, and are also excellent in terms of the disintegration property and dissolution property of tablets. Accordingly, these crystals are preferably used as pharmaceutical compositions.

The present invention provides a tetomilast crystal that is industrially easily produced in a large volume. (1) a tetomilast hydrate crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (2) an anhydrous tetomilast type A crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (3) an anhydrous tetomilast type C crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; (4) a tetomilast acetonitrile solvate crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG.; and (5) a mixture consisting of the above anhydrous tetomilast type A crystal and an anhydrous tetomilast type B crystal. These crystals are stable towards heat and moisture, and are also excellent in terms of the disintegration property and dissolution property of tablets. Accordingly, these crystals are preferably used as pharmaceutical compositions.

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Osaka, Japan

Masahiro Sota