SYNTHESIS AND NOVEL SALT FORMS OF (R)-5-((E)-2-PYRROLIDIN-3-YLVINYL)PYRIMIDINE Russian patent published in 2019 - IPC C07D403/06 C07D207/06 

FIELD: chemistry.

SUBSTANCE: invention relates to stereospecific synthesis of (R)-5-((E)-2-(pyrrolidin-3-ylvinyl)pyrimidine and its salts. (R)-5-((E)-2-(pyrrolidin-3-ylvinyl)pyrimidine is an agonist of the neuronal nicotinic receptor (NNR), selective to nicotine subtype α4β2, and can be used in treating and preventing CNS and pain disorders. Method of producing includes steps of a) treating compound 1 with methanesulphonyl chloride to obtain compound 2; (b) treating compound 2 with diethyl malonate and a suitable base to obtain compound 3; (c) hydrolysis of compound 3 to obtain compound 4; (d) decarboxylation of compound 4 to obtain compound 5; (e) reducing compound 5 to obtain compound 6;

(f) treating compound 6 with methanesulphonyl chloride to obtain compound 7; (g) reacting compound 7 with sodium iodide to obtain compound 8; (h) treating compound 8 with potassium tert-butoxide to form compound 9-tert-butyl-(R)-3-vinylpyrrolidine-1-carboxylate; (i) reacting compound 9 with 5-bromo-pyridine to obtain compound 10 and (j) removing the protective group from compound 10 to obtain compound 11 - (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine

.

Method of producing (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine salt involves the following steps: (i) mixing a free base or a (R)-5-((E)-2-(pyrrolidin-3-ylvinyl)pyrimidine in a suitable solvent, with an acid in pure form or in form of an acid solution in a suitable solvent; (ii) (a) cooling the obtained salt solution to cause precipitation to occur; or (ii) (b) adding a suitable anti-solvent to cause precipitation; or (ii) (c) evaporating the first solvent and adding a novel solvent and repeating step (ii) (a) or (ii) (b); and (iii) filtration to extract (R)-5-((E)-2-pyrrolidin-3-ylvinyl) pyrimidine salt.

EFFECT: method simplifies the process owing to use of novel intermediate compounds, does not require the use of chromatography and enables to obtain an end product of high quality (purity of 99 %).

16 cl, 8 dwg, 33 ex