METHODS OF PRODUCTION ISOQUINOLINONES AND SOLID FORMS ISOQUINOLINONES

FIELD: chemistry.SUBSTANCE: invention relates to new polymorphic forms of the compounds of formula (I), having inhibitory action against phosphoinositide 3-kinase (PI3K). The compounds may be used to treat cancer, such as leukemia, lymphoma, inflammatory disease and autoimmune disease. The polymorphic forms of the compound of formula (I)is the polymorphic form C of the hydrate of the compound of formula (I), which has characteristic peaks in the x-ray powder diffraction pattern (XRPD) 2θ=10.4°(±0.2°), 13.3°(±0.2°) and 24.3°(±0.2°); Polymorph A, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=9.6°(±0.2°), 12.2°(±0.2°), and 18.3°(±0.2°); Polymorph B, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=7.9°(±0.2°), 13.4°(±0.2°), and 23.4°(±0.2°); polymorphic form D, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=11.4°(±0.2°), 17.4°(±0.2°), and 22.9°(±0.2°); polymorphic form E, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=6.7°(±0.2°), 9.3°(±0.2°) and 24.4°(±0.2°); Polymorphic form F, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=9.6°(±0.2°), 17.3°(±0.2°), and 24.6°(±0.2°); Polymorphic form G which is the solvate of the tert-butyl methyl ether of the compound of formula (I) and has characteristic peaks in the powder XRPD pattern 2θ=6.7°(±0.2°), 9.5°(±0.2°) and 19.0°(±0.2°); Polymorphic form H, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=8.9°(±0.2°), 9.2°(±0.2°) and 14.1°(±0.2°); Polymorphic Form I, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=9.7°(±0.2°), 19.3°(±0.2°), and 24.5°(±0.2°), and the polymorphic form J, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=9.1°(±0.2°), 17.3°(±0.2°) and 18.3°(±0.2°). The invention also relates to a process of preparing form C. For example, mentioned process comprising (i) exposure of the medium containing water, a composition comprising at least one polymorphic form, not a form of a compound of formula (I), for a period time sufficient for the transformation, preferably for 18-24 hours, at least 50% of the total amount of the polymorphic form (s) a non-form C; and (ii) recovering mentioned polymorph form C.EFFECT: high effectiveness of compounds.84 cl, 31 dwg, 16 tbl, 42 ex Изобретение относится к новым полиморфным формам соединения формулы (I), обладающим