Method of preparing taxane derivatives

Claim 1

Process for preparing taxane derivatives of formula: ##STR16## in which: R represents a hydrogen atom or an acetyl radical, and R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents: an unbranched or branched alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted with at least one substituent selected from halogen atoms and hydroxyl radicals, alkyloxy radicals containing 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms, piperidino or morpholino radicals, 1-piperazinyl radicals (optionally substituted at position 4 with an alkyl radical containing 1 to 4 carbon atoms or with a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms), cycloalkyl radicals containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, phenyl, cyano or carboxyl radicals or alkyloxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, or a phenyl radical optionally substituted with at least one atom or radical selected from alkyl radicals containing 1 to 4 carbon atoms or alkyloxy radicals containing 1 to 4 carbon atoms, or a saturated or unsaturated 5- or 6-membered nitrogenous heterocyclic radical optionally substituted with at least one alkyl radical containing 1 to 4 carbon atoms, the cycloalkyl, cycloalkenyl or bicycloalkyl radicals can be optionally substituted with at least one alkyl radical containing 1 to 4 carbon atoms, and Ar represents a phenyl or α- or β-naphthyl radical optionally substituted with at least one atom or radical selected from halogen including fluorine, chlorine, bromine, iodine atoms and alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, dialkylcarbamoyl, cyano and trifluoromethyl radicals, the alkyl radicals and alkyl portions of the other radicals contain 1 to 4 carbon atoms, and that the alkenyl and alkynyl radicals contain 3 to 8 carbon atoms and the aryl radicals are phenyl or α- or β-naphthyl radicals, comprising esterifying a protected 10-deacetylbaccatin III or baccatin III derivative of formula: ##STR17## in which G 1 and, where appropriate, G 2 represent a group protecting the hydroxyl function, by means of an acid of formula: ##STR18## in which Ar is defined as above, R 3 and R 4 , which may be identical or different, represent a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms or an alkenyl radical containing 2 to 4 carbon atoms, or an aralkyl radical in which the alkyl portion contains 1 to 4 carbon atoms and the aryl portion represents a phenyl radical optionally substituted with at least one alkoxy radical containing 1 to 4 carbon atoms, or an aryl radical representing a phenyl radical optionally substituted with at least one alkoxy radical containing 1 to 4 carbon atoms, or alternatively R 3 and R 4 , together with the carbon atom to which they are linked, form a 4- to 7-membered ring, and R 5 represents an alkyl radical containing 1 to 4 carbon atoms substituted with at least one chlorine atom, or an activated derivative of this acid, to obtain a product of formula: ##STR19## in which Ar, R 3 , R 4 , R 5 , G 1 and G 2 are defined as above, b) replacing the groups protecting the hydroxyl and amino functions of the product obtained by hydrogen atoms to obtain a product of formula: ##STR20## in which Ar and R are defined as above, then c) treating the product thereby obtained with a reagent which enables a substituent R l to be introduced on the amino function, and d) isolating the product obtained.