2-Substituted thio carbapenem derivatives

Claim 1

A process for the preparation of a compound of the formula (I): ##STR59## or a pharmaceutically acceptable salt or in-vivo hydrolysable ester thereof wherein R 1 and R 2 are each independently hydrogen, alkyl of 1 to 10 carbon atoms, alkenyl of up to 10 carbon atoms, alkynyl of up to 10 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cycloalkylalkyl of 3 to 6 carbon atoms in the cycloalkyl ring and 1 to 6 carbon atoms in the alkyl moiety, alkylcycloalkyl of 1 to 6 carbon atoms in the alkyl moiety and 3 to 6 carbon atoms in the cycloalkyl ring, phenyl, phenylalkyl of 1 to 6 carbon atoms in the alkyl moiety or phenylalkynyl of up to 6 carbon atoms in the alkynyl moiety each of which is unsubstituted or substituted by amino, mono-, di or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxyl, alkoxyl of 1 to 6 carbon atoms, mercapto, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, phenylthio, sulfamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, cyano or carboxy, or one of R 1 and R 2 is hydrogen and the other is sulphonato-oxyethyl and R 3 is alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, phenyl, phenylalkyl of 1 to 6 carbon atoms in the alkyl moiety, alkanoyl of 1 to 6 carbon atoms, phenylalkanoyl of 1 to 6 carbon atoms in the alkyl moiety, phenylcarbonyl, heterocyclyl of 4 to 7 ring atoms up to 4 of which are selected from the group consisting of oxygen, sulphur and nitrogen, unsubstituted or substituted by one or more amino, alkanoylamino of 1 to 6 carbon atoms in the alkyl moiety, mono-, di- or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxyl, alkoxy of 1 to 6 carbon atoms, mercapto, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, phenylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxy, a carboxyl salt or a carboxyl ester, alkanoyloxy of 1 to 6 carbon atoms in the alkyl moiety or phenylcarbonyl; which process comprises reacting a compound of the formula (II): ##STR60## wherein R a is hydrogen, a salt moiety, RHU 1 and R 2 are as above defined, and R 4 is pyrimidinyl, with a compound of the formula (III): R.sup.3 --SH (III) wherein R 3 is as above defined, and thereafter if necessary: (i) removing any group R a , (ii) converting the product into a pharmaceutically acceptable salt or in-vivo hydrolysable ester.