2-(CHROMENO[4,3-D]PYRIMIDIN-5-YL)ACETIC ACID DERIVATIVES AND A METHOD FOR PRODUCTION THEREOF Russian patent published in 2020 - IPC C07D491/52 C09B57/00 G01N33/52 G01N33/533 

FIELD: chemistry.

SUBSTANCE: invention relates to novel 2-(chromeno[4,3-d]pyrimidin-5-yl)acetic acid derivative of general formula I and a method for production thereof. In general formula I (a-aa)

R¹=Cl, R²=H, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ia); or R¹=H, R²=H, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ib); or R¹=CH₃, R²=H, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ic); or R¹⁼Br, R²=H, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Id); or R¹=F, R²=H, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ie); or R¹=NO₂, R²=H₅ R³=H, R⁴=CH₃, EWG=COOC₂H₅ (If); or R¹=CH₃O R²=H, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ig); or R¹=OH, R²=H, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ih); or R¹=H, R²=CH₃, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ii); or R¹=H, R²=OH, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ij); or R¹=CH₃, R²=CH₃, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Ik); R¹=F, R²=F, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Il); R¹=CH₃, R²=H, R³=Br, R⁴=CH₃, EWG=COOC₂H₅ (Im); R¹=CH₃, R²=H, R³=NO₂, R⁴=CH₃, EWG=COOC₂H₅ (In); or R¹=Br, R²=CH₃O, R³=H, R⁴=CH₃, EWG=COOC₂H₅ (Io); or R¹=Cl, R²=H, R³=H, R⁴=H, EWG=COOC₂H₅ (Ip); R¹=Cl, R²=H, R³=H, R⁴=Ph, EWG=COOC₂H₅ (Iq); or R¹=Cl, R²=H, R³=H, R⁴=4-CH₃Ph, EWG=COOC₂H₅ (Ir); or R¹=Cl, R²=H, R³=H, R⁴=NH₂, EWG=COOC₂H₅ (Is); or R¹=Cl, R²=H, R³=H, R⁴=CH₃O, EWG=COOC₂H₅ (It); or R¹=Cl, R²=H, R³=H, R⁴=CH₃S, EWG=COOC₂H₅ (Iu); or R¹=Cl, R²=H, R³=H, R⁴=BnS, EWG=COOC₂H₅ (Iv); or R¹=Cl, R²=H, R³=H, R⁴=CH₃, EWG=COOH (Iw); or R¹=Cl, R²=H, R³=H, R⁴=CH₃, EWG=CONH₂ (Ix); or R¹=Cl, R²=H, R³=H, R⁴=CH₃, EWG=CON(C₂H₅)₂ (Iy); or R¹=Cl, R²=H, R³=H, R⁴=CH₃, EWG=COC₄H₈N₂CH₃ (Iz); or R¹=Cl, R²=H, R³=H, R⁴=CH₃, EWG=CN (Iaa). Method of producing a compound of general formula I is carried out by reacting 3-substituted chromone with a binucleophilic reagent, wherein 3-substituted chromone used is electron-deficient 3-vinylchromone selected from the group: ethyl-3-(6-chloro-4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(6-methyl -4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(6-bromo-4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(6-fluoro-4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(6-nitro-4-oxo-4H-chromene-3-yl)acrylate, ethyl-3-(6-methoxy-4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(6-hydroxy-4-oxo-4H-chromene-3-yl)acrylate, ethyl-3-(7-methyl-4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(7-hydroxy -4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(6,7-dimethyl-4-oxo-4H-chromene-3-yl)acrylate, ethyl-3-(6,7-difluoro-4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(8-bromo-6-methyl-4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(6-methyl-8-nitro-4-oxo-4H-chromen-3-yl)acrylate, ethyl-3-(6-bromo-6-methoxy-4-oxo-4H-chromene-3-yl)acrylate, ethyl-3-(6-chloro-4-oxo-4H-chromene-3-yl)acrylate, 3-(6-chloro-4-oxo-4H-chromen-3-yl)acrylic acid, 3-(6-chloro-4-oxo-4H-chromen-3-yl)acrylamide, N,N-diethyl-3-(6-chloro-4-oxo-4H-chromen-3-yl)acrylamide, 3-(6-chloro-4-oxo-4H-chromen-3-yl)-1-(4-methylpiperazin-1-yl)prop-2-en-1-one, 3-(6-chloro-4-oxo- 4H-chromen-3-yl)acrylonitrile, and corresponding 1,3-N,N-binucleophilic reagent is selected from amidine, guanidine or isourea derivative, which is generated directly in reaction mass from its salt – chloride or sulphate, under action of strong base – sodium ethylate, sodium hydroxide, 1,8-diazabicyclo[5.4.0]undec-7-ene. Process is carried out in ethanol at temperature of 15–25 °C, and the end product is extracted in the form of a precipitate by pouring the reaction mixture into 1M hydrochloric acid or water.

EFFECT: compound has fluorescence in the violet-blue spectrum of 390–455 nm and can be used as fluorescent dyes and / or probes in biochemical studies.

2 cl, 1 tbl, 27 ex