CRYSTALLINE FORM OF COMPOUND OF PYRIMIDO [6, 1-a] ISOQUINOLIN-4-ONE Russian patent published in 2016 - IPC C07D471/04 A61K31/519 A61P17/00 A61P11/06 A61P11/00 A61P27/02 A61P37/00 A61P27/14 

FIELD: chemistry.

SUBSTANCE: present invention relates to a novel crystalline Polymorph of N-{2-[(2E)-2-(mezitilimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]isoquinoline-3(4H)-yl]ethyl}urea. Said compound can be used in treating asthma, allergic asthma, bronchitis, chronic obstructive pulmonary disease (COPD) or respiratory distress syndrome. Crystalline structure of said Polymorph has x-ray powder diffraction diffractogram containing characteristic peaks in units 2θ, at 10.1°, 12.9°, 15.3° and 17.6°, and following structural parameters, obtained by single crystal analysis

Temperature 123 (2) K Wave length 0.71073 Å Crystalline circuit triclinic Spatial group P-1

Dimensions of elementary cell

a = 8.1246 (4) Å α = 91.583(4)°. b = 11.4573 (5) Å β = 90,299(4)°. c = 13.2398 (6) Å γ = 99.628(4)°. volume 1214.56 (10) Å ³ Z 2

At that, at least 95 % of polymorph is in thermodynamically stable polymorphic form. Invention also relates to method of producing said crystalline polymorph. Method involves (a) combining N-{2-[(2E)-2-(mezitilimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a] isoquinoline-3(4H)-yl]ethyl}urea with solvent to form mixture, (b) heating mixture at temperature in range of 45-121 °C during time, suitable for formation of said polymorph, and slow cooling to temperature in range of 30-40 °C, under conditions suitable for formation of said polymorph; and (c) filtering and drying. Method may further include stage of mixture filtration after step (a). As solvent DMSO, ethanol, methanol, isopropyl alcohol, hexanes, pentane, ethyl acetate, dichloromethane or chloroform can be used.

EFFECT: said mixture is retained at or above temperature of about 50 °C for about 24-96 hours.

19 cl, 22 dwg, 15 tbl, 13 ex