Antitumer evaluation of some newly synthesized Mannich bases derived from benzofuran derivatives

Treatment of [4-methoxy-6-hydroxybenzofuran-5-yl]methyl ketone (1) with 2-aminothiazol in presence of formaldehyde gave [4-methoxy-5-acetyl-6-hydroxy-7-(thiazol-2-ylamino)methyl)]benzofuran(2) which reacted with 3,4-dimethoxybenzaldehyde or p-bromobenzaldehyde in ethanolic sodium hydroxide to give the corresponding chalcone (3a,b) respectively. Cyclization of chalcone 3a with thiosemicarbazide in ethanolic acetic acid mixture yielded thioamidopyrazoline derivative (4) which reacted with each one of 3-aminophenthylbromide or ethylchloroacetate to produce 5,6 respectively. In addition, compound 3a,b reacted with thiourea in alcoholic potassium hydroxide to give 4,6-disubstituted pyrimidin-2-thione (7a,b). Methylation of 7b with methyliodide led to the formation of 2-methylthiopyrimidine derivative (8). Also, treatment of 7b with C-ethoxycarbonyl-N-(p-tolyl) hydrazonyl-chloride gave triazolino[4,3-a]pyrimidin-3-carboxylate (12). Moreover, interaction of 3a with acetylacetone in boiling ethanolic sodium ethoxide gave 6-acetyl-5-(3,4-dimethoxy phenyl)-3-[4-methoxy-6-hydroxy-7-((thiazol-2-ylamino)methyl) benzofuran-5-yl] cyclohex-2-en-1-one(13) which reacted with cyanoacetohydrazide in acid medium or base medium to give indazole derivative (15) and oxaquinoline derivative (17) respectively. On the other hand, when compound 2 treated with phosphorus oxychloride under Vilsmier-Haak reaction condition gave 4-methoxy-9-((thiazol-2-yl amino) methyl)-5H-furo[3,2-g]benzopyran-6-carboxaldehyd-5-one(18). Condensation of 18 with thiosemicarbazide gave thiocarbazone derivative (20). Similarly, treatment of 18 with cyanoacetohydrazide yielded cyanoacetohydrazone 21. Cyclization of the latter compound 21 with p-fluorobenzylidinmalononitrile gave 1,2,4-triazolopyridine derivative (23). Evaluation of some new compounds revealed remarkable antitumor activity against HEPG2(Hepatocellular carcinoma cells).