NEW METHOD FOR PRODUCING ANTIFOLATE AGENTS HAVING GLUTAMIC ACID FRAGMENT IN ITS STRUCTURE Russian patent published in 2015 - IPC C07D475/08 

FIELD: chemistry.

SUBSTANCE: invention refers to a new method for producing antifolate agents having a glutamic acid fragment in their structure, or their salts of the general formula (I). The method involves carrying out a reaction of a compound of formula (I) and an acid or a base in a solution. The compounds of formula (II) are produced by carrying out a reaction of N-substituted glutamic acids or their salts with chloroacetonitrile. In formula (I), M means a monovalent or bivalent cation specified in a group consisting of Na⁺, K⁺, 1/2Ca⁺⁺ or 1/2Mg⁺⁺; R means a group . In the above group, R₁ represents a carbonyl group; R₂ and R₃ are identical or different and specified in linear or branched, saturated or unsaturated C₁-C₂₀-heteroalkyl groups, which can be optionally substituted by amino groups; aromatic or aliphatic C₃-C₁₈-hydrocarbon rings, which can be optionally substituted by one or more substitutes specified in a group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, amine, nitro, thiol, sulphoxy, sulphonic groups; aromatic or aliphatic C₃-C₁₈-heterocycles, which can be optionally substituted by one or more substitutes, specified in a group consisting of alkyl, alkenyl, alkynyl,carboxy, hydroxy, amine, nitro, thiol, sulphoxy, sulphonic groups; together R₂ and R₃ can both form a phenyl or thiophen ring, which can be substituted by an alkyl group or an alkyl group containing heteroatoms; and the alkyl groups can be additionally substituted by bicyclic or heterocyclic ring systems containing such structures, as purines or pyrimidines. In formula (II), R has the value as specified in formula (I).

EFFECT: method enables producing the high-yield antifolate agents of formula (I) with high analytical and optical purity.

14 cl, 4 ex