METHOD OF PRODUCING CREATINE AMIDES Russian patent published in 2016 - IPC C07C277/08 C07C279/14 C07K5/06 

FIELD: chemistry.

SUBSTANCE: invention relates to pharmaceutical chemistry, in particular to a process for preparing creatine amides of general formula shown below, which exhibit anti-ischemic activity. In formula R denotes amino acid residue of amino acid; Y denotes OR¹, NR²R³, where R¹ is H, CH₂Ph, alkyl C₁-C₃, R², R³ - H, alkyl C₁-C₄; X - low-molecular C₁-C₄ organic acid or mineral acid, or water. Method involves treating creatine para-toluenesulphonic acid in dimethyl formamide, followed by reacting obtained complex with derivatives of amino acids in presence of a condensing agent and a base. Condensing agent used is formic acid monoester chloride, wherein condensing agent and base are added simultaneously. Then an alkali metal acetate is added to obtained mixture, followed by distilling not less than 80 % of dimethyl formamide, extracting active ingredient with a aprotic polar solvent containing at least one ingredient from a group including acetone, tetrahydrofuran, methyl ethyl ketone and acetonitrile. Further, solvent was distilled off, residue is dissolved in a polar aprotic solvent containing at least one ingredient from a group consisting of water, ethanol and isopropyl alcohol, acetic and formic acid, p-toluenesulphonic acid is removed by anion-exchange chromatography on a sorbent. Solvent is removed in presence of low molecular weight C₁-C₄ organic acid or inorganic acid and alcohol at not more than pH 4.5, then treated with a solvent containing at least one ingredient from A group consisting of acetone, tetrahydrofuran, methyl ethyl ketone, ethyl acetate and acetonitrile. Active ingredient is extracted with a solvent containing at least one ingredient from a group consisting of ethyl and methyl alcohols are distilled off at least 70 % of solvent and treated with a solvent containing at least one ingredient from a group consisting of acetone, tetrahydrofuran, methyl ethyl ketone, acetonitrile, and acetate.

EFFECT: disclosed method increases output and purity of end product.

22 cl, 1 tbl, 25 ex

NH=C(NH₂)-N(CH₃)-CH₂-CO-RY*X