Eisai Company, Limited

Eisai Chemical Co., Ltd.

Eisai R&d Management Co., Ltd.

Masahiko Tsujii

Yoshio Urawa

Akihiko Shimotani

Takeo Kanai

Takashi Sato

Hiroshi Yoshino

Yutaka Tsuchiya

Keizo Takayanagi

Akio Kayano

Yoshihiko Hisatake

Atsushi Koiwa

Masayuki Konishi

Nobuo Niikawa

Mikio Uchiyama

Shigeharu Nochi

Hiroshi Kuroda

Naoyuki Shimomura

Yasuyuki Suzuki

Kazuhide Ashizawa

Manabu Sasho

Ken Furukawa

Kazuhiro Yoshizawa

Taiju Nakamura

Hiroyuki Chiba

Hiroyuki Saito

Hirofumi Kuroda

Takako Yoshiba

Shin Sakurai

Eiichi Yamamoto

Masahiro Sakurai

Ikuo Kushida

Hiroyuki Ishizuka

Astsushi Koiwa

Yoshikazu Furusawa

Katsuhiko Hirota

Yukio Morita

Process for producing sulfoxide derivatives or salts thereof in the amorphous state, characterized by heat-drying solvated crystals of a sulfoxide derivative or a salt thereof represented by the general formula (I): wherein Rrepresents a hydrogen atom, a methoxy group, or a difluoromethoxy group; Rrepresents a methyl group or a methoxy group; Rrepresents a 3-methoxypropoxy group, a methoxy group, or a 2,2,2-trifluoroethoxy group; Rrepresents a hydrogen atom or a methoxy group; and B represents a hydrogen atom, an alkali metal or &#xbd; alkaline earth metal.

Process for production of sulfoxide derivatives or salts thereof in the amorphous state

In the present invention, the methods of producing a fluorinated cyclic benzamidine derivative (A), or a salt thereof, comprise the step of reacting a specific novel compound with ammonia or imide. The methods of this invention for producing a morpholine-substituted phenacyl derivative (B), or a salt thereof, comprise reaction of a specific novel compound with morpholine, reaction of the product with a halogenating reagent, and deketalization of the product. The methods of this invention for a producing cyclic benzamidine derivative (C), or a salt thereof, comprise the step of coupling compound (A), or a salt thereof, with compound (B), or a salt thereof, in the presence of an ether or a hydrocarbon. The methods of this invention for recrystallizing a cyclic benzamidine derivative (C), or a salt thereof, comprise the steps of dissolving compound (C), or the salt thereof, in a mixed solvent comprising an alcohol and water, or a mixed solvent comprising an ether and water, and after dissolution, adding additional water to precipitate crystals of compound (C), or the salt thereof.

Methods for producing cyclic benzamidine derivatives

The present invention provides carbapenem hydrochloride trihydrate crystals, which are chemically stable, easily purified and useful as antimicrobial agents, a process for producing them, and a powdery charged preparation for injection containing them. That is, it provides carbapenem hydrochloride trihydrate crystals having a powdery X-ray diffraction pattern containing lattice distances (d) of 9.0, 4.1 and 2.8 &#x212b;, a process for producing them, and a powdery charged preparation for injection containing them.

Carbapenem compound crystals and interjection preparations

Sulfoxide compounds and acetone complexes, and a process for producing the same

Described is a protected aminothiazolylacetic acid derivative represented by the following formula (I): ##STR1## wherein A represents a nitrogen atom or a methine group, R.sup.1 and R.sup.2 may be the same or different and individually represent a hydrogen atom, a lower alkyl group or a substituted or unsubstituted aryl group, R.sup.3 represents a lower alkoxy group, a halogenated lower alkoxy group, a triphenylmethoxy group, a lower alkyl group or an acyloxy group, and R.sup.4 represents a halogen atom, a hydroxy group, a lower alkoxy group or a substituted or unsubstituted amino group; and salts thereof; as well as processes for the preparation thereof. The protected aminothaizolylacetic acid derivative according to the present invention is an useful intermediate for introducing a 2-(2-aminothiazol-4-yl)-2-alkoxyiminoacetyl group or a 2-(2-aminotiazol-4-yl)-2-alkenoyl group into a cephem skeleton.

Protected aminothiazolylacetic acid derivatives

Disclosed herein is a purification method of a crude product by column chromatography on silica gel or on a vinyl alcohol copolymer. Methanol-containing n-hexane and/or n-hexane-containing methanol is used as an eluent to elute the crude product, thereby obtaining an intended product with high purity and good yield. The solvents recovered from the effluent can be regenerated without any trouble such as rectification and a great cost by mixing them under stirring and then separating the resulting upper and lower layer from each other. The column used can also be reused again and again by washing with methanol. The separation and purification method is excellent in separation efficiency, operation efficiency and economical efficiency.

Purification method of crude product

Purified secretin is obtained by subjecting crude secretin to reversed-phase high-performance liquid chromatography using, as an eluant, a solvent mixture of an acid or salt thereof and an organic solvent.

Process for purifying secretin

A heptacosapeptide having the following structural formula:

Heptacosapeptide

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Chiba, Japan

Masahiko Tsujii