METHOD FOR PREPARING (E)-N-METHYL-N-(1-NAPHTHYLMETHYL)-6,6-DIMETHYLHEPT-2- ENE-4-INYL-1-AMINE OR ITS ACID-ADDITIVE SALT Russian patent published in 2003 - IPC

FIELD: organic chemistry, chemical technology, pharmacy. SUBSTANCE: invention relates to new method for preparing (E)-N-methyl-N-(1-naphthylmethyl)-6,6-dimethylhept-2-ene-4-inyl-1-amine of the formula (I) or its acid-additive salt. Compound of the formula (I) has international name "terbinafine" and used in medicine as an antifungal agent, preferably against mycosis caused by dermaphitones damaging skin and nails. Method involves reaction of secondary alcohol of the formula (IV) with hydrochloric acid taken usually in the amount 3-7 moles, preferably 5-5.5 moles, as concentrated aqueous solution. Prepared as result compound of the formula (IIIb) as mixture of E- and Z-isomers in the ratio = (3.3-3.4):1 is subjected for interaction with secondary amine of the formula (II) in solvent type of aliphatic ketone, for example methylisobutyl ketone, in the presence of a base, preferably, N,N-diisopropylethylamine, usually at temperature 20-80 C for 0-16 h, preferably, at 70-80 C for 305 h and optionally hydroiodic acid salt as catalyst, for example, in the amount 1-10% mole of hydroiodic acid salt, preferably, 5-7% mole of tetrabutylammonium-iodide. Then the prepared compound of the formula (I) as a base in solution, for example, methylisobutyl ketone in the ratio of isomers = (3.3- 3.4): 1 is converted to hydrochloride directly using hydrochloric acid aqueous solution, usually using 5- 37% hydrochloric acid at pH = 1-3 at temperature 10-30 C, preferably, using 20-37% hydrochloric acid at pH = 1.5-2.0. Precipitated E-isomer hydrochloride is separated if necessary and isolated as a base or converted to pharmaceutically acceptable acid-additive salt. Method provides preparing the end isomer with high purity and to use its in large-scale production. EFFECT: improved and simplified preparing method. 6 cl, 1 tbl, 6 ex