METHOD FOR OBTAINING OF 1-R-INDOLE-3-YLSULFANYLACETATES OF (2-HYDROXYETHYL)AMMONIUM Russian patent published in 2018 - IPC C07D209/30 

FIELD: pharmacology.

SUBSTANCE: invention relates to a method for the preparation of indole-1-H-, 1-methyl-, 1-benzylindole-3-ylsulfanylacetate of (2-hydroxyethyl)ammonium heterocyclic compounds that have a broad spectrum of action, for example, selective erythropoiesis and immunomodulators with a minimum potential for undesirable effects on various body systems, and can be used to prevent and treat immune-dependent lesions that occur with anaemia, cancer and inflammatory diseases, complications with organs and bone marrow transplantation, protection against cardiogenic shock, stresses, etc. The method consists in the reaction of 1-R-indole-3-ylsulfanyl acetic acids with (2-hydroxyethyl)amines - triethanolamine, methyldiethanolamine, dimethylethanolamine without solvent upon heating to 60-65°C for 0.5-1 hour, with washing of the resulting salt with ether. The yield is 92-99%. The initial 1-R-indole-3-ylsulfanyl acetic acids (compounds 2) are obtained for this reaction from 1-H- or 1-methyl-or 1-benzylindole with thiourea, bromine, potassium bromide, taken in the molar ratios of 1:2:1:1, respectively, in a water medium at a temperature of 30-40°C for 3 h in inert gas, with subsequent processing of the reaction mass by an aqueous solution of sodium hydroxide, then an aqueous solution of monochloroacetic acid taken in the molar ratios of indole, sodium hydroxide, acid 1:(4-5):(1-1.2), heating of the reaction mixture at 90-100°C for 3 h at a pH of 9-10 with subsequent acidification with hydrochloric acid until pH=1 with a yield of 92-95%. Purity is 98.7-99.7. Replacement of scarce and expensive iodine and potassium iodide in alcohol solution with a more accessible aqueous solution of bromine and sodium bromide, excluding toxic hydrazine hydrate and toxic solvent (alcohol) from the process leads to a decrease in product cost and an increase in environmental fire safety, since the reaction is carried out in an aquatic environment. , R=H, CH³, CH₂C₆H₅; R¹, R²=H, CH₃, CH₂CH₂OH; n=1-3.

EFFECT: increased efficiency of compounds application.

2 cl, 2 dwg, 8 ex