Patent ID: 8680319

Claim:
A method for producing antifolate agents having a glutamic acid part in their structure or salt thereof with the general formula wherein M is a monovalent or divalent cation selected from group consisting of Na + , K + , ½Ca ++ or ½Mg ++ ; and R is with R 1 being a carbonyl group; and R 2 and R 3 being the same or different and being selected from the group consisting of (i) straight-chain or branched, saturated or unsaturated C 1 -C 20 -heteroalkyl groups, which can optionally be substituted with amino groups; and (ii) aromatic or aliphatic C 3 -C 18 -hydrocarbon rings, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups, which can optionally be substituted and/or form further rings; and (iii) aromatic or aliphatic C 3 -C 18 -heterocycles, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups, which can optionally be substituted and/or form further rings; whereby R 2 and R 3 together can form an aromatic or aliphatic C 3 -C 18 -heterocycle, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups, which can optionally be substituted and/or form further rings; comprising reacting a compound of the following formula wherein R is the same as in formula (I), with an acid or base in a solvent; and the compounds of formula (II) are obtained from reacting glutamic acid, N-substituted glutamic acids or their salts with chloroacetonitrile.