INHIBITORS OF TYPE ErbB INHIBITORS Russian patent published in 2016 - IPC C07C335/20 C07D403/12 C07D413/14 C07D413/12 C07D417/12 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula 10 and method for production thereof. Compounds possess properties of receptor tyrosine kinase type I inhibitors and can be used in treating hyperproliferative disorders. Invention also relates to novel intermediate compounds of formula 8 and 9 and to method of producing compounds 9. Compounds 10 and 8 correspond to common formulas (8) (10), where each R⁶, R⁸ and R^8a are independently hydrogen or C₁-C₆alkyl, where said alkyl is optionally substituted OR¹⁵; or R⁸ and R^8a together with atom to which they are connected, three-six-Member carbocyclic ring is formed; and R¹⁵ is hydrogen or C₁-C₆alkyl. Connection 9 corresponds to general formula (9), where A represents O; E represents , where X is CH; D¹, D² and D³ independently represent N or CR¹⁹; D⁴ and D⁵ are independently N or CR¹⁹ and D⁶ represents O, S or NR²⁰, at least one of D⁴ and D⁵ is not CR¹⁹; D⁷, D⁸, D⁹ and D¹⁰ represent independently N or CR¹⁹, wherein at least one of D⁷, D⁸, D⁹ and D¹⁰ represents N; R¹ represents H or C₁-C₆alkyl; each R² independently represents halogen, cyano, trifluoromethyl, difluoromethyl, ftormetil or C₁-C₆alkyl; each R⁶, R⁸ and R^8a are independently hydrogen or C₁-C₆alkyl, where said alkyl is optionally substituted by OR¹⁵, or R⁸ and R^8a together with atom, to which they are bonded, 3-6-member carbocyclic ring is formed; R¹⁵ represents H or C₁-C₆alkyl; each R¹⁹ independently represents H, halogen or C₁-C₆alkyl; each R²⁰ is independently hydrogen or C₁-C₄alkyl, j is 0 and n represents 0, 1 or 2.

EFFECT: method of preparing compound of formula 10 involves condensation of compound of formula 8 with compound of formula 2 (2) in presence of acid in acceptable solvent, followed by thiourea of formula 9 cyclization, preferably in water solution of NaOH in tetrahydrofuran with addition of thozilchloride TsCl.

9 cl, 1 tbl, 281 ex