Patent ID: 8207355
Filing Date: 2012-06-26
Classification: C07D

Abstract:
1. A process for synthesizing azetidine derivatives represented by formula (I), comprising the steps of: a) a ketone of formula (VIII) is condensed with 3-amino-1,2-propanediol, in the presence or absence of a solvent, in the presence or absence of an acidic or a basic catalyst, at a temperature of between 0° C. and 150° C. so as to form an imine diol of formula (VII); b) the imine diol of formula (VII) which is optionally not isolated, is reduced with a borohydride or hydrogen gas, in the presence of a metal catalyst in a solvent so as to form an amine diol of formula (VI); c) the amine diol of formula (VI) which is optionally not isolated, is activated with a sulphonylating agent in the presence of a base, in a solvent and optionally a cosolvent at a temperature ranging from −78° C. to 40° C. so as to form a sulphonic ester of formula (V), which is optionally not isolated; d) the sulphonic ester of formula (V) is cyclized by heating in a solvent in the presence or absence of a base, between 0° C. and 130° C., so as to form an azetidinol of formula (IV), which is optionally isolated in the form of a salt; e) the azetidinol of formula (IV) or the salt thereof, is converted to a sulphonate of formula (II) through the action of a sulphonylating agent in the presence of a base, in a solvent, at a temperature of between −78° and +40° C.; f) the sulphonate of formula (II) is condensed with a sulphonamide of formula (III) in the presence of a base, in the same solvent as that used in step e), so as to form a compound of formula (I); wherein in formulae (I), (II), (III), (IV), (V), (VI), (VII) and (VIII), R, R′ and R″ represent, one or more moieties independently selected from the group consisting of hydrogen, halogen, cyano or nitro radicals, linear or branched alkyl radicals containing from 1 to 6 carbon atoms, linear or branched alkoxy radicals containing from 1 to 6 carbon atoms, linear or branched alkyl carboxylate radicals wherein the alkyl contains from 1 to 6 carbon atoms, and trifluoromethyl or trifluoromethoxy radicals; R″′ represents a linear or branched alkyl or perfluoroalkyl group containing from 1 to 6 carbon atoms or an aryl group optionally substituted with one or more R″ radicals; and R1 represents a methyl group, CF