Cenes Limited

Isp Investments Inc.

Finetech Laboratories Ltd.

Lev Yudovitch

Arie L Gutman

Genadi Nisnevitch

Gennady Nisnevich

Boris Pertsikov

Marina Etinger

Igor Zaltzman

Igor Rokhman

Igor Rochman

Gennadi Nisnevich

The present invention provides, according to an aspect thereof, a novel process for the preparation of dronedarone [1] and pharmaceutically acceptable salts thereof. According to a preferred embodiment, the process comprises N-acetylating of p-anisidine or p-phenetidine with acetic anhydride, reacting of the obtained N-(4-alkoxyphenyl)acetamide with 2-bromohexanoyl chloride or bromide in the presence of aluminum chloride or bromide to obtain N-[3-(2-bromohexanoyl)-4-hydroxyphenyl]acetamide [6], converting the compound [6] into 2-butyl-5-benzofuranamine hydrochloride [12] and subsequently converting [12] into [1] or pharmaceutically acceptable salts thereof. In accordance with another aspect of this invention, there are provided novel intermediates, inter alia the novel compounds [6] and [12]. The novel intermediates of the present invention are stable, solid compounds, obtainable in high yields, which can be easily purified by crystallization and stored for long periods of time.

Process for the preparation of dronedarone

The present invention provides a new and effective process for the synthesis of 17-phenyl-18,19,20-trinor-PGFand its derivatives, including the anti-glaucoma drugs Bimatoprost and Latanoprost. The benefit of the present invention rises inter alia from the fact that a major intermediate involved in the synthesis of the above compounds may be isolated from a mixture containing also an undesired isomer, by crystallization. In addition, the undesired isomer may be oxidized to give the starting compound, which is then recycled.

Process for the preparation of 17-phenyl-18,19,20-thinor-pgf 2a and its derivatives

Conjugation of 4,5-Epoxymorphinan-6-ols with Bromoglucuronides in the presence of Zinc containing compounds as activator under conditions capable of forming 4,5-Epoxymorphinan-6-oxyglucuronides is disclosed. This novel approach provides an efficient method for preparation of both anomers of 4,5-Epoxymorphinan-6-oxyglucuronides. The deprotected end products are useful as analgesic agents.

Process for preparation of 4,5-epoxymorphinan-6-oxyglucuronides

Glycosidation of 4,5-Epoxymorphinan-6-ols with a Thioglycoside as a glycoside donor is disclosed. The process comprises reacting a 4,5-Epoxymorphinan-6-ol and a Thioglycoside in the presence of a thiophilic promoter under conditions capable of forming 4,5-Epoxymorphinan-6-glycosides. This novel approach was used for preparation of pharmaceutically important 4,5-Epoxymorphinan-6-&bgr;-D-glucuronides. The process provides both high stereo-selectivity and high yields.

Glycosidation of 4,5-epoxymorphinan-6-ols

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Haifa, Israel

Lev Yudovitch