SOLID FORMS OF EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR Russian patent published in 2018 - IPC C07D403/12 A61K31/506 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to the crystalline form of compound 1, which is a free base and can be solvated. Compound has the properties of an epidermal growth factor receptor (EGFR) kinase inhibitor and can be used to treat diseases associated with cell proliferation mediated by said activity of the compound. Crystalline form of compound 1 in the form of a free base is characterised by one or more peaks in the X-ray powder diffraction pattern, selected from peaks at 6.73±0.3, 18.30±0.3, 18.96±0.3 and 25.48±0.3 degrees 2-theta (form A), or peaks in the X-ray powder diffraction pattern, selected from the peaks at 10.67±0.3, 12.21±0.3, 18.11±0.3, 19.24±0.3 and 21.53±0.3 degrees 2-theta. (form B). Crystalline form of the free base of compound 1 can also be a crystalline solvated form with dimethylformamide and is characterised by one or more peaks in the X-ray powder diffraction pattern selected from the peaks at 16.32±0.3, 18.82±0.3, 20.26±0.3, 22.58±0.3 and 25.36±0.3 degrees 2-theta (Form C), or is a solvate with 1,4-dioxane, which is characterised by peaks in the X-ray powder diffraction pattern, selected from the peaks at 18.40±0.3, 19.31±0.3, 20.14±0.3, 20.53±0.3 and 25.25±0.3 degrees 2-theta (Form D), or a methyl ethyl ketone solvate characterised by peaks in the X-ray powder diffraction pattern selected from peaks at 5.78±0.3, 12.57±0.3, 15.34±0.3, 19.10±0.3 and 24.80±0.3 degrees 2-theta (Form E), a solvate with N-methyl-2-pyrrolidone, wherein said crystalline form is characterised by one or more peaks in the X-ray powder diffraction pattern, selected from the peaks at 15.51±0.3, 16.86±0.3, 18.80±0.3, 20.97±0.3 and 23.32±0.3 degrees 2-theta (Form F), or peaks in the X-ray powder diffraction pattern, selected from the peaks at 6.79±0.3, 17.86±0.3, 19.43±0.3, 19.98±0.3 and 22.35±0.3 degrees 2-theta (Form G). Compound 1 may be a hydrate, where the said crystalline form is characterised by one or more peaks in the X-ray powder diffraction pattern selected from peaks at 10.82±0.3, 11.08±0.3, 18.45±0.3, 22.85±0.3 and 25.06±0.3 degrees 2-theta (Form H), or peaks in the X-ray powder diffraction pattern selected from the peaks at 6.13±0.3, 12.22±0.3, 15.91±0.3, 18.35±0.3, 18.88±0.3 and 21.90±0.3 degrees 2-theta (Form I).

EFFECT: solid forms of the epidermal growth factor receptor kinase inhibitor are disclosed.

32 cl, 63 dwg, 4 tbl, 10 ex