Rhone-Poulenc Sante

Rhone-Poulenc Rorer S.a.

Viviane Massonneau

Michel Mulhauser

Albert Buforn

Jean-Manuel Mas

Patrick Leon

Xavier Radisson

Noel Rouy

Isidore Le Fur

Bernadette Mandard-Cazin

Bernard Botannet

Claude Bonnamas

This invention relates to a method of preparing taxane derivatives of general formula (I) by esterification of protected baccatine III or 10-deacetylbaccatine III by means of an acid of general formula (VII), elimination of protection groupings of the ester obtained, and acylation of the amine function of the side chain. In formulae (I) and (VII): Ar stands for aryl, R is hydrogen or acetyl, R.sub.1 is benzoyl or R.sub.2 -CO--O- in which R.sub.2 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl, R.sub.3 and R.sub.4 may be the same or different and represent hydrogen, alkyl, alkenyl, aralkyl, aryl or alkoxy, and R.sub.5 is an alkyl radical substituted by one or more chlorine atoms (2,2,2-trichloroethyl, 2-trichloromethylisopropyl). ##STR1##

Process for preparing taxane derivatives

Disclosed is a compound of formula VII: ##STR1## where Ar represents an optionally substituted phenyl or .alpha.- or .beta.-naphthyl radical; R.sub.3 represents hydrogen, a C.sub.1-4 alkyl radical, a C.sub.2-4 alkenyl radical, an aralkyl radical, or an aryl radical; and R.sub.4 represents hydrogen, a C.sub.1-4 alkyl radical, a C.sub.2-4 alkenyl radical, an aralkyl radical, or an aryl radical; or alternatively R.sub.3 and R.sub.4, together with the carbon atom to which they are linked, form a 4- to 7-membered ring; and R.sub.5 represents an C.sub.1-4 alkyl radical substituted with at least one chlorine atom. The compound of formula VI may be used to manufacture a compound of formula VIII: ##STR2## where Ar, R.sub.3, R.sub.4 and R.sub.5 are defined above; G.sub.1 represents a group protecting the hydroxyl function; and where appropriate, G.sub.2 represents a group protecting the hydroxyl function.

Method of preparing taxane derivatives

Process for the preparation of derivatives of 3,5-dihydroxypentanoic acid

Hydroxyalkylating agents of formula: ##STR1## in which R denotes alkyl, n is 2 or 3, R.sub.1 denotes hydrogen or alkyl and R.sub.2 denotes alkyl an unsubstituted or substituted phenyl or ##STR2## are useful inter alia for the preparation of 1-(hydroxyalkyl)imidazoles. They are made by reaction of a sulphonic acid or dimethyl sulphate with a corresponding decarboxylate ester.

Process for preparing hydroxyalkylating agents, the agents so obtained,

A process for the preparation of an aromatic ether of general formula: ##STR1## by the action of 3-chloro-1,2-propanediol sulfate on a phenol of general formula:

Process for the preparation of aromatic ethers

Process for preparing 1-alkyl-5-nitroimidazoles of formula: ##STR1## which comprises reacting an alkyl sulphate with an imidazole derivative of general formula: ##STR2## in an organic solvent, and then hydrolyzing or alcoholyzing the product obtained. In the formulae (I) and (II), R denotes hydrogen, unsubstituted or substituted alkyl, aryl or cycloalkyl. In the formula (I), R.sub.1 denotes alkyl. In the formula (II), X denotes a group which can be removed by hydrolysis or alcoholysis.

Process for preparing 1-alkyl-5-nitroimidazoles

Process for preparing 1-(hydroxyalkyl)nitroimidazoles of formula: ##STR1## which comprises reacting a sulphite or diacetate of an alkylenediol of formula:

Process for preparing 1-hydroxyalkyl-2-methyl-5-nitroimidazoles

Process for preparing 1-hydroxyalkyl-5-nitroimidazole

Process for preparing 1-(hydroxyalkyl)nitroimidazoles of formula: ##STR1## which comprises reacting an alkylene sulphate of formula: ##STR2## with an imidazole derivative of formula: ##STR3## followed by hydrolyzing or alcoholyzing the product obtained. In the formulae (I) and (II), n is 2 or 3; in the formulae (I) and (III), R denotes hydrogen or hydrocarbon radical; and in the formula (III), X denotes hydrogen or a radical that can be removed by hydrolysis or alcoholysis.

Process for preparing 1-hydroxyalkyl-5-nitroimidazoles

Cyclic sulphates of formula ##STR1## in which R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6, which are identical or different, each denote hydrogen, halogen, alkyl, alkoxy, aryloxy or alkoxycarbonyl and n is 0 or 1, are prepared by rapid reaction, at a temperature of 150.degree. to 250.degree. C., of concentrated sulphuric acid with a glycol of formula ##STR2##

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Ecully, France

Viviane Massonneau