Sanofi-synthelabo

K&aacute;lm&aacute;n Simon

Istv&aacute;n Hermecz

Lajos T Nagy

Gergely H&eacute;ja

Gy&ouml;rgyn&eacute; Szvoboda

Csaba G&ouml;nczi

Andrea S&aacute;nt&aacute;n&eacute; Csutor

Tiborn&eacute; Szomor

&Eacute;va Csik&oacute;s

F&eacute;lix Hajd&uacute;

Judit Hal&aacute;sz

&Aacute;gota Smelk&oacute;n&eacute; Esek

Attila Simon

T&uuml;nde Er&ouml;sn&eacute; Tak&aacute;csy

Gergelyn&eacute; H&eacute;ja

L&aacute;szl&oacute; Kis

P&eacute;ter S&aacute;rosi

Andrea Gy&ouml;rbir&oacute;

Gyula Farkas

Anna Szab&oacute;

&Aacute;rp&aacute;dn&eacute; Vasv&aacute;ri

Csilla Majl&aacute;th

&Aacute;rp&aacute;d Ill&aacute;r

The invention relates to a process for the preparation of a compound of formula (I) and the salts thereof by reacting the compound of formula (II) with the compound of formula (III), which comprises carrying out the reaction in dimethyl sulfoxide, at a temperature between 10&deg; C. and 40&deg; C., preferably at room temperature and transforming the resulting base of formula (I), if desired, into its salt by a method known per se.

PROCESS FOR THE PREPARATION OF N-(1,1-DIMETHYLETHYL)-4-&lsqb;&lsqb;5&prime;-ETHOXY-4-CIS&lsqb;2-(4-MORPHOLINO)ETHOXY&rsqb;-2&prime;-OXOSPIRO&lsqb;CYCLOHEXAN-1,3&prime;&lsqb;H&rsqb;INDOL&rsqb;1&prime;(2&prime;-H)-YL&rsqb;-SULFONYL&rsqb;-3-METHOXYBENZAMIDE AND ITS SALTS

The invention relates to a process for the preparation of spiro &lsqb;(4-cyclohexanone)-&lsqb;3H&rsqb;indol&rsqb;-2&prime;&lsqb;1&prime;H&rsqb;-one derivatives of general formula I&mdash;wherein R and R independently stand for hydrogen, C alkyl, C alkoxy, C alkylthio, C polyfluoroalkyl, C polyfluoroalkoxy, C cycloalkyloxy, C cycloalkylthio, phenoxy, benzyloxy or nitro group&mdash;, characterized by reacting an indolin-2-one derivative of general formula II&mdash;wherein R and R are as defined above&mdash;with a compound capable for introducing a protective group, coupling the compound of general formula III, thus obtained&mdash;wherein R and R are as defined above and A stands for a protective group&mdash;with acrylic acid C ester; cyclizing the resulting compound of general formula IV&mdash;wherein R and R are as defined above&mdash;with a compound capable for introducing a protective group, coupling the compound of formula III thus obtained,&mdash;wherein R and R are as defined above and A stands for a protective group&mdash;with an acrylic acid C ester, cyclizing the resulting compound of formula IV&mdash;wherein R and R are as defined above R stands for C alkyl and A stands for a protective group&mdash;, eliminating the&mdash;COOR group and the A protective group of the keto-ester of general formula V&mdash;wherein R and R are as defined above, R stands for C alkyl and A stands for a protective group&mdash;, optionally without isolation of the compounds of general formulae IV and/or V and/or VI.

Process for the preparation of spiro&lsqb;(4-cyclohexanone)-&lsqb;3H&rsqb;indol&rsqb;-2&prime;&lsqb;1&prime;H&rsqb;-one derivatives

The invention relates to a process for the preparation of 2-methoxy-4-(N-t-butylaminocarbonyl)benzenesulfonyl chloride by sulfonating m-hydroxybenzoic acid, methylating the hydroxy group of the resulting sulfonic acid or its salt, transforming the carboxylic acid group and the sulfonic acid group to acid chloride groups and reacting the 4-chlorosulfonyl-3-methoxy-benzoyl chloride with t-butylamine, which comprises carrying out the sulfonation of the 3-methoxy-benzoic acid of general formula (II) with 96% sulfuric acid, separating the resulting 3-hydroxy-4-sulfobenzoic acid of general formula (III) in the form of its salt of general formula (IV), wherein Z stands for alkali metal or ammonium group, methylating the compound of general formula (IV) in the presence of a phase transfer catalyst at a pH value of about 11.5, transforming the 3-methoxy-4-sulfobenzoic acid mono salt of general formula (V), wherein the meaning of Z is as defined above, to the acid chloride of general formula (VI), and reacting the compound of general formula (VI) with t-butylamine used in equimolar amount or in a small excess, in the presence of an acid binding agent, in aprotic solvent, at low temperature.

Method for the preparation of 2-methoxy-4-(N-t-butylamino-carbonyl)-benzenesulfonyl chloride

The invention relates to a process for the preparation of spiro&lsqb;cis-4-(&bgr;-hydroxyethyloxy)cyclohexane-&lsqb;3H&rsqb;indol&rsqb;-2&prime;&lsqb;1&prime;H&rsqb;-one derivatives of the formula (I) wherein R and R are as defined herein, by reduction of a dispiro&lsqb;(1,3-dioxolane)-2,4&prime;-cyclohexane-1&prime;3&prime;-&lsqb;3H&rsqb;indol&rsqb;-2&Prime;&lsqb;1&Prime;H&rsqb;-one derivative of general formula (II), wherein R and R are as defined herein, which comprises carrying out the reduction (a) with sodium cyanoborohydride in the presence of a Lewis acid, or (b) with sodium borohydride in the presence of a strong acid.

Process for the preparation of spiro&lsqb;cis-4-(&bgr;-hydroxyethyloxy)cyclohexane-&lsqb;3h&rsqb;indol&rsqb;-2&prime;&lsqb;1&prime;H&rsqb;one derivatives

The invention relates to a process for the preparation of Fumagillin by liberation from its salt characterized by reacting Fumagillin dicyclohexylamine salt with an organic acid in alcoholic medium. According to the process Fumagillin can be produced in high yield and pure condition and with higher stability than products obtained by other preparation methods

Process for the preparation of fumagillin

Growing community of inventors

Budapest, Hungary

Kálmán Simon

Growing community of inventors

Budapest, Hungary

K&aacute;lm&aacute;n Simon

Kálmán Simon