Studies on some 1-substituted heterocyclic isoquinoline derivatives by Bischler-Napieralski reaction. II. Syntheses of isoquinoline derivatives of pyridine series

Abstract

Synthesis of isoquinolines possessing 2-picolyl in 1-position was carried out, in order to see if it were possible to effect cyclization of the acid amide compounds by the Bischler-Napieralski reaction and to examine pharmacological activity of the synthesized isoquinolines. Starting with 2-picoline, ethyl 2-pyridineacetate (I) was prepared and (I) was derived through the hydrazide (II) to its azide (III). Condensation of this azide (III) and an amine (IV) afforded the acid amide (V) whose cyclization with phosphoryl chloride alone did not furnish the desired isoquinoline compound (VI). Condensation of the ester (I) and the amine (IV) was attempted by their direct fusion and N-(α-methyl-β-methoxy-3, 4-methylenedioxyphenethyl)-2-(2-pyridyl) acetamide (V) was obtained. Isoquinoline cyclization of this amide (V) by the Bischler-Napieralski reaction using phosphoryl chloride alone finally afforded the desired 1-(2-pyridylmethyl)-3-methyl-6, 7-methylenedioxyisoquinoline (VI).