CRYSTALS OF 6,7-UNSATURATED-7-CARBAMOYL MORPHINANE DERIVATIVE, AND METHOD FOR PRODUCING SAME Russian patent published in 2017 - IPC C07D489/08 C07D271/06 A61K31/485 A61P1/08 A61P1/10 

FIELD: chemistry.

SUBSTANCE: invention relates to salts of p-toluenesulphonic acid compound of formula (IA) or hydrate thereof, including crystalline forms thereof. Invention relates to form I of crystals of hydrate of salt of p-toluenesulphonic acid compound of formula (IA), where X-ray diffraction spectrum of powder of crystalline has peaks, corresponding to diffraction angles (2θ): 12.9°±0.2°, 17.6°±0.2°, 22.4°±0.2°, 25.4°±0.2° and 28.7°±0.2°. Invention also relates to form II of crystals of hydrate of salt of p-toluenesulphonic acid compound of formula (IA), where X-ray diffraction spectrum of powder of crystalline has peaks, corresponding to diffraction angles (2θ): 8.8°±0.2°, 17.5°±0.2°, 21.9°±0.2°, 23.7°±0.2° and 26.1°±0.2°. Crystalline forms of salts of p-toluenesulphonic acid compound of formula (IA) and hydrates thereof are intended for preparing a pharmaceutical composition, exhibiting agonistic activity with respect to opioid receptor. Crystalline form of salt of p-toluenesulphonic acid compound of formula (IA) or crystalline forms of hydrate of said salt of p-toluenesulphonic acid is obtained by adding p-toluenesulphonic acid to a compound of formula (IA) and crystallisation of salt of p-toluenesulphonic acid or hydrate thereof in a solvent. Method of producing crystalline form or crystalline form of hydrates of said salt of p-toluenesulphonic acid of formula (IA) can also be performed in following steps: 1) treating with a base compound of formula (IIE), where R^1a is hydrogen or protecting hydroxyl group, which can be removed by a base selected from a group, consisting of acetyl, formyl, benzoyl, chloroacetyl, pivaloyl, methyl carbonate, isobutyl carbonate, benzyl carbonate, vinyl carbonate, phenyl carbamate, mesyl and tosyl, 2) adding p-toluenesulphonic acid and 3) crystallisation of salt of p-toluenesulphonic acid in a solvent.

EFFECT: technical result is stable form of 6,7-unsaturated-7-carbamoyl morphinane.

14 cl, 19 tbl, 26 ex

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