DERIVATIVES OF N-(2,4- OR 2,5-DISUBSTITUTED TETRAHYDROFURYLALKYL)-N-(PHENYLETHYL--OL)-AMINE IN RACEMIC OR ENANTIOMERIC FORM, OR THEIR PHARMACEUTICALLY ACCEPTABLE SALT, METHOD OF THEIR SYNTHESIS AND PHARMACEUTICAL COMPOSITION

摘要

FIELD: organic chemistry, medicine as agonists of b-adrenergic receptors. SUBSTANCE: product: derivatives of N-(2,4- or 2,5-disubstituted tetrahydrofurylalkyl)-N-(phenylethyl-b-ol)-amine in racenic or enantiomeric form of the formula (I) given in description text where R - b-alkyl, pyridyl, thienyl or unsubstituted phenyl or that substituted with halogen atom, C₁-C₁₀-alkoxy-group, or C₁-C₅-alkylsulfonyl group; n= 1-10, or their pharmaceutically acceptable salts, method of their synthesis and pharmaceutical composition prepared on their base. Reagent 1: substituted benzylamine of the formula (III) indicated in description text. Reagent 2: methyl-5-bromoacetylsalicylate. Process conditions: in the medium of protonic solvent or acetonitrile in the presence of triethylamine, at temperature from the room one to the boiling point of reaction mixture, for 2-18 hr. Reagent 3: compound of the formula (IV) indicated in description text. Reagent 4: sodium hydride as a reductant. Process conditions: in inert atmosphere, at temperature from 0 C to the room one, for 2-8 hr followed by debenzylation of synthesized compound of the formula (V) indicated in description text by hydrogenation in the presence of catalyst Pd/C or C₁-C₅, under pressure 2-5.5 bars, at the range of temperature from the room one to 40 C, for from 10 min to 5 hr. EFFECT: improved method of synthesis. 6 cl, 3 tbl