SUBSTITUTED METHYL(2-{4-[3-(3-METHANESULFONYLAMINO-2-FLUORO-5-CHLORO-PHENYL)-1H-PYRAZOL-4-YL]PYRIMIDIN-2-YLAMINO}ETHYL) CARBAMATES, PROCESS FOR THEIR PREPARATION AND APPLICATION Russian patent published in 2017 - IPC C07D403/04 C07D405/14 A61K31/506 A61P35/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to new substituted methyl (2-{4-[3-(3-methanesulfonylamino-2-fluoro-5-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-ethyl) carbamates of general formula 1 and pharmaceutically acceptable salts thereof, having the properties of BRAF-kinase inhibitor. The compounds may find application for prevention and/or treatment of cancer, such as malignant melanoma. In general formula 1 , R¹ represents C₁-C₄alkyl_, 3-oxetanyl; R² and R³ together with the carbon atom to which they are attached form a C₃-C₆cycloalkyl_, with one atom possibly replaced by an oxygen atom. The invention also relates to an intermediate compound of general formula 4 where R1, R² and R³ are as defined above, Hal is a halogen selected from Cl, Br or I. The invention also relates to a process for formula 1 compound preparation. The method comprises reacting formula 2 reacting with amine 3 in the presence of a base, subsequent reaction of compound 4 with a suitable aryl boronic ester, in the presence of a palladium catalyst, tert-butyloxycarbonyl protecting group removal from compound 5 , and resulting amine 6 reacting with mesyl chloride in the presence of a base. The process is carried out according to Scheme 1 .

EFFECT: increased efficiency of compounds application.

13 cl, 5 ex, 2 dwg