Zentiva K.s.

Zentiva, A.s.

Josef Hajicek

Ondrej Dammer

Hana Stepankova

Jan Kalivoda

Miroslav Veverka

Stefan Vodny

Eva Veverkova

Marketa Slavikova

Stanislav Simek

Igor Cerna

Mokhtar Kebbati

Patrik Hosek

Racemization of the R(&#x2212;) isomer of the (2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester (Formula II) (also called R clopidogrel) is performed via conversion of a portion thereof to the S(+)isomer and it takes place in an organic solvent selected from alcohols, esters, ketones or ethers, or in their mixtures, in the presence of a base selected from substances of formula R1R2R3R4N+OH&#x2033; wherein R1, R2, R3 and R4 are identical or different substituents selected from C1-C5 alkyls or C5, C6 cycloalkyls or aryls, C7-C9 alkyl-cycloalkyls or alkyl-aryls, the molar ratio of the base to the starting substance being 1:1 to 1:10., OMe Cl I Cl&#x3c;VOMe II. 

Method of racemization of the R(&#x2212;) isomer of the (2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester

A method for manufacturing hydrogen sulphate (alpha S) of the alpha-(2-chlorophenyl)-6,7dihydrothieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester (clopidogrel hydrogen sulphate) of formula I, in crystalline Form I, wherein the compound of formula is separated out of a solution of clopidogrel in the form of the free base or salt in a solvent selected from the series of primary, secondary or tertiary C1-C5 alcohols, their esters with C1-C4 carboxylic acids, or optionally of mixtures thereof. 

Method for manufacturing crystalline form I of clopidogrel hydrogen sulphate

A method of preparation of (R)-(&#x2212;)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide of formula I and its use for production tamsulosin. A protective group is introduced to N-[(1R)-2(4-methoxyphenyl)-1-methylethyl]-N-[(1R)-1-phenylethyl)]amine and the resulting amide of formula IX is chlorosulfonated and the resulting sulfochloride is converted to a sulfonamide of formula X, from which the compound of formula I is obtained by hydrogenation.

Method of preparation of (R)-(&#x2212;)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide

The compound of formula (III), optionally its alkaline salt, is reacted with a compound of formula VII, wherein X is a leaving group, resulting in (S)-rivastigmine of formula II, which is then optionally converted into (S)-rivastigmine hydrogentartrade of formula I. 

Method of production of (&#x2212;)-(S)-3-[1-(dimethylamino)ethyl]phenyl-N-ethyl-N-methylcarbamate

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Prague, Czechia

Josef Hajicek