Chemagis Ltd.

Bio-dar Ltd.

Oded Arad

Joseph Kaspi

Vladimir Naddaka

Shady Saeed

Eyal Klopfer

Mohammed Alnabari

Elena Ostrovsky

Yana Sery

Ofer Sharon

Stephen Cherkez

Michael Brand

Guy Davidi

Oded Friedman

Lior Zelikovitch

Edna Danon

Shen Jingshan

Boris Freger

Olga Etlin

Dionne Montviliski

Guo Hongli

Moty Shookrun

Avner Rotman

Yoav Blatt

Ori Lerman

Itai Adin

David Cohen

Alexander Weisman

Moshe Bentolila

Rika Pinto

Shadi Saeed

Eugene Kimelman

Yana Seryi

Tamir Fizitzki

Julia Ditkovitch

Iosef Manascu

David Sondack

Eliezer Adar

Orna Kurlat

Meital Shiffer

Ada Salman

Irina Gribun

Carmen Iustain

The present invention provides an improved method of chromatographically separating the isomers of (1R,rR)-atracurium salts by high-performance liquid chromatography (HPLC), in the absence of a strong acid. The separation is preferably performed on a silica gel HPLC column using an eluent containing an organic solvent, a polar aprotic co-solvent and a weak organic acid.

(1R, 1'R)-atracurium salts separation process

The present invention provides an improved method for obtaining cisatracurium besylate, which preferably chromatographically separating cisatracurium besylate from a mixture of (1R,1'R)-atracurium isomers via flash chromatography.

(1R,1'R)-atracurium salts separation process

The present invention provides novel isoquinolinium compounds, methods of producing the isoquinolinium compounds, and methods for converting them into cisatracurium, e.g., cisatracurium besylate. The isoquinolinium compounds of the present invention can be obtained in the form of solids, which can be purified using simple techniques and can be used to afford pure cisatracurium besylate without HPLC purification.

Isoquinolinium compounds useful in the preparation of cisatracurium and associated intermediates

The present invention provides R,R'-atracurium salts, processes for producing and purifying such salts, and methods of using such salts to produce highly pure cisatracurium besylate.

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The present invention provides processes for producing isoquinolinium compounds, and for converting them into cisatracurium salts, e.g., cisatracurium besylate

Process for producing cisatracurium compounds and associated intermediates

Provided is a process for producing highly pure 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline (imiquimod), which includes reacting 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline with a non-gaseous amine precursor. Also provided are methods for isolating highly pure imiquimod. Further provided are intermediates useful in the production of imiquimod, methods for producing such intermediates, and methods for obtaining imiquimod from such intermediates.

Imiquimod production process

Derivatives of 1,2-benzisoxazole-3-methanesulfonic acid, which are non-hygroscopic and non-hydrated and their use as intermediates from the preparation of zonisamide are disclosed. Further disclosed are processes of preparing zonisamide from these 1,2-benzisoxazole-3-methanesulfonic acid derivatives, processes of preparing exemplary 1,2-benzisoxazole-3-methanesulfonic acid derivatives and crystalline forms of exemplary 2-benzisoxazole-3-methanesulfonic acid derivatives. A novel process of preparing zonisamide is also disclosed.

Derivatives of 1,2-benzisoxazole-3-methane sulfonic acid as novel intermediates for the synthesis of zonisamide

The present invention provides a process for preparing highly pure 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline (imiquimod). The process preferably includes heating 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline of formula (II) with ammonia in a polar aprotic solvent at relatively moderate pressure to produce imiquimod, and optionally purifying the imiquimod. The process of the present invention can produce highly pure imiquimod in high yield.

The present invention provides a process for preparing highly pure Temozolomide base which includes recovery from the purification mother liquors by using an anionic exchange resin. By treating Temozolomide hydrochloride with a mixture of an organic acid, a water miscible organic solvent, and water, Temozolomide free base is obtained in an acidic medium. Due to the high sensitivity of Temozolomide to basic pH values the recovery-including process is especially advantageous because it enables obtaining high yields of highly pure Temozolomide base in acidic conditions. The process for producing Temozolomide base includes hydrolysis of the starting material 8-cyano-3-methyl-[3H]-imidazo[5,1-d]-tetrazin-4-one in acidic medium to obtain highly pure Temozolomide hydrochloride in high yield.

Process for preparing temozolomide

The present invention provides a crystalline donepezil maleate, which is used as an intermediate in the preparation of donepezil hydrochloride. Also provided are novel processes for producing same in substantially pure form and a process for producing pharmaceutically pure amorphous donepezil hydrochloride therefrom.

Use of purified donepezil maleate for preparing pharmaceutically pure amorphous donepezil hydrochloride

A novel process for preparing (2&#x3b2;,3&#x3b1;,5&#x3b1;,16&#x3b2;,17&#x3b2;)-17-acetoxy-3-hydroxy-2-(4-morpholinyl)-16-(1-pyrrolidinyl) androstane, a known intermediate in the synthesis of the skeletal muscle relaxant rocuronium bromide, is disclosed.

Processes for the preparation of rocuronium bromide and intermediates thereof

An amorphous form of montelukast sodium and a montelukast sodium lactose co-precipitate, processes for producing same, pharmaceutical compositions containing same and methods of treatment utilizing same are disclosed.

Stable amorphous forms of montelukast sodium

Provided is a method for preparing letrozole, which includes reacting an activated bis-(4-cyanophenyl)-methane with a triazole to produce letrozole, and, optionally, purifying the letrozole. Also provided are highly pure letrozole, and a method of purifying letrozole, which method includes precipitating letrozole, e.g., by selective precipitation from a reaction mixture and/or by subjecting the letrozole to one or more crystallizations.

Letrozole production process

The present invention provides a process for preparing highly pure montelukast and salts thereof by reacting the side-chain precursor 1-(mercaptomethyl)-cyclopropaneacetic acid with 2-(2-(3S)-(3-(7-chloro-2-quinolinyl)-ethenyl)phenyl)-3-(methanesulfonyloxypropyl)phenyl-2-propanol in a solvent mixture containing a base.

Process for preparing montelukast and salts thereof

A novel process for preparing highly pure cilostazol, effected by reacting 6-hydroxy-3,4-dihydroquinolinone and 5-(4-chlorobutyl)-1-cyclohexyl-1H-tetrazole in the presence of a hydrated inorganic base, is disclosed. Further disclosed is highly pure cilostazol, and particularly highly pure cilostazol that is substantially free of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-1-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butyl ]-3,4-dihydro-1H-quinolin-2-one.

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Rehovot, Israel

Oded Arad