DERIVATIVES OF 2,2-DIMETHYL-1,2-DIHYDRO-4H-PYRANO-[4,3D]-FURO-[2,3-B]-PYRIDINE SHOWING ANTITUMOR ACTIVITY Russian patent published in 1995 - IPC

FIELD: organic chemistry. SUBSTANCE: product: derivatives of 2,2-dimethyl-1,2-dihydro-4H-pyrano-[4,3-d] -furo-[2,3-b] -pyridine of the general formula where at R-CH₃, R₁=R₂-H; R₁-n-Br and R₂-H, R₁-H and R₂-C(O)-CH-CH= CH-O; where at R-C₆H₅, R₁=R₂-H; R₁-n-Br and R₂-H; R₁-H and R₂-C(O)-C=CH-CH=CH-O; R₁-n-Br and R₂-C(O)CH₃; R₁-n-Br and R₂-C(O)CCl₃. Maximal tolerated dose above >2500 mg/kg, degree of sarcoma 45 inhibition by 41-45% Walker carcinosarcoma by 30-43% Reagent 1: 3-phenacyloxy-5,6-dihydro-6,6-dimethyl-1-phenyl(methyl)-4-cyano-8H-pyrano-[3,4-c] -pyridine. Reagent 2: KOH. Reagent 3: phenacyl bromide. Conditions: boiling for 30 min in ethanol, ethanol distilling for drying, addition of reagent 3 and boiling in acetonitrile for 2 h. Reagent 4: C₂H₅ONa.. Reagent 5: 3-phenacyloxy-5,6-dihydro-6,6-dimethyl-1-phenyl(methyl)-4-cyano-8H-pyrano-[3,4-c] -pyridine. Conditions: cyclization at boiling for 1 h, and compounds I-IV were obtained. Compounds I-VII were synthesized by conversion of compounds I-IV to the corresponding amides by carboxylic acid chloroanhydrides at boiling in dioxane for 25-30 h. Synthesized compounds where used in medicine as antitumor agents. EFFECT: improved method of synthesis. 3 tbl