Synthesis and antiviral activity of 5-methoxybenzofurans

Abstract

)propionic acid with PC15 in chloroform in the presence of dimethylformamide (DMF) gave the acid chloride, which was treated without further purification with diethylamine to give (2-methyl-5-methoxy-3benzofuryl)propionir diethylamide (V). Reaction of the acid chloride with ammonia failed to give the unsubstituted amide. (2-Methyl-5-methoxy-3-benzofuryl )propionamide (VI) was obtained by reducing the hydrazide (II) over Raney nickel. Amides (IV-VI) were reduced with LiAIH, to the amines, 3-y-hydroxyethyl aminopropyl- (VII), 3-y-diethylaminopropyl- (VIII), and 3-y-aminopropyl- (IX) 2-methyl-5-methoxybenzofurans. 2Methyl-3-y-piper idinopropyl-5-methoxybenzofuran (X) was obtained by replacing the hydroxygroup in (III) by the piperidine residue in the presence of a skeletal nickel catalyst. In addition to 3-aminopropyl derivatives of 5-hydroxybenzofurar~ we have obtained some 3aminoethyl derivatives. 2-Methyl-3-aminoethyl-5-methoxybenzofuran (XIII) has been obtained from the hydrazide (II) via 2-methyl-3-B-ethoxycarbonylaminoethyl-5-methoxybenzofuran (XI) and 2-methyl-3-(B,phthalimidoethyl)5-methoxybenzofuran (XII). Some of the above reactions were also carried out with (2-methyl-5-methoxy-3-benzofuryl )butyric acid. Esterification of ~he acid gave the ethyl ester (XIV). This served as the starting material for the preparation of (2-methyl-5-methoxy-3-benzofuryl )butyrohydrazide (XV) and (2-methyl-5-methoxy-3-benzofuryl )-butyric 8-hydroxyethylamide (XVI). In addition to the 3-aminoalkyl derivatives, we have obtained some 2-aminoalkyl-5methoxybenzofurans. The key intermediate in the preparation of these compounds was 2-bromo