Sanofi-synthelabo

Sanofi-aventis

Attila Supic

Zsolt Dombrády

Istv&aacute;n M&eacute;sz&aacute;ros

Zolt&aacute;n Makovi

Antal Gaj&aacute;ry

Csaba Husz&aacute;r

Attila Kis-Tam&aacute;s

Attila N&eacute;meth

P&eacute;ter Aranyosi

K&aacute;roly Gy&uuml;re

Katalin Dubovszki

Lajosn&eacute; P&aacute;li

Endre Koll&aacute;r

&Aacute;gnes Kunsztn&eacute; K&aacute;r&aacute;sz

Erzs&eacute;bet Bogn&aacute;r

Zsuzsanna N&aacute;d

Zsuzsanna Csetrin&eacute; H&aacute;ri

Bertrand Castro

Zsolt Párkányi

Sándor Viktor Szabó

Mátyás Aradi

József Ugrics

Ferenc Kovács

Antal Gajáry

István Gyöngyösi

Ilona Dervalicsn&eacute; Zr&iacute;nyi

Ilona Dervalicsne Zrinyi

Zsolt Dombr&aacute;dy

Andrea Major

Erika Máténé Török

László Schultz

Erzsébet Szalay

József Zsiga

Mária Bakonyi

Tiborné Bai

Katalin Gáspár

Ferenc Bakos

M&aacute;ria Bakonyl

Katalin G&aacute;sp&aacute;r

Tiborn&eacute; Bai

Matyas Aradi

Istvan Gyoengyoesi

Erika Matene Toeroek

Laszlo Schultz

Sandor Szabo

Jozsef Zsiga

Ferenc Kovacs

Jozsef Ugrics

The process according to the invention relates to the preparation of 2-chloromethyl-thiophene of the formula (I). During this process thiophene is chloromethylated in the presence of one or more compounds containing keto group and optionally it is transformed into the compound of the formula (II). Compounds of formula (I) and (II) are intermediates of several pharmaceutically active ingredients.

Chloromethylation of thiophene

The invention relates to the racemization process of the optically active [2-(2-thienyl)ethylamino](2-halogenophenyl)acetamides of general formula (VII) by using basic compounds. The resulting racemic compounds of general formula (VII) can thus be recycled into synthesis of the therapeutically useful compounds of general formula (VI).

Process for racemization

Process for the preparation of compounds of formula (I) wherein R means hydrogen atom, or C,alkyl group, or C,aralkyl group or phenyl group, characterised in that: a) the compound of formula (III) is reacted with a compound of formula (IV) wherein X means halogen atom or C,alkoxy group or hydroxyl group and the resulting compound of formula (II) is transformed in the presence of an oxidising agent in a reaction medium with pH above 7, into the compound of formula (I), or b) the compound of formula (III) is reacted with an anhydride of general formula (V) and the resulting compound of formula (II) transformed in the presence of an oxidising agent, in a reaction medium with pH above 7, into the compound of formula (I), or c) a compound of formula (II) is transformed in the presence of an oxidising agent, in a reaction medium with pH above 7, into the compound of formula (I), and if desired, the resulting compounds of formula (I), before or after isolation, are transformed into acid addition salts, or the compounds of formula (I) are liberated from their acid addition salts. Thus a process for the preparation of intermediates useful in synthesis of angiotensin II antagonists is disclosed.

Process for the preparation of 1,3-diaza-spiro (4.4) non-1-en-4-one derivatives and 1-cyano-1-acylamino-cyclopentane intermediates

Process for the preparation of compounds of formula (I) wherein R means hydrogen atom, or C,alkyl group, or C,aralkyl group or phenyl group, characterised in that a) the compound of formula (III) is reacted with a compound of formula (IV) wherein X means halogen atom or C,alkoxy group or hydroxyl group, and the resulting compound of formula (II) is transformed, in a reaction medium with pH above 7, into the compound of formula (I) or b) the compound of formula (III) is reacted with an anhydride of general formula (V) and the resulting compound of formula (II) transformed, in a reaction medium with pH above 7, into the compound of formula (I), or c) a compound of formula (II) is transformed, in a reaction medium with pH above 7, into the compound of formula (I), and if desired, the resulting compounds of formula (I), before or after isolation, are transformed into acid addition salts, or the compounds of formula (I) are liberated from their acid addition salts. Thus a process for the preparation of intermediates useful in synthesis of angiotensin II antagonists is disclosed.

Process for the preparation of 1,3-diaza-spiro (4.4) non-1-en-4-one derivatives and 1-cyano-1-acylaminocyclopentane intermediates

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Budapest, Hungary

Attila Supic