One‐Pot Two‐Step Synthesis of 1,4,5,6‐Tetrahydropyridazines Through a Three‐Component Reaction of 2,5‐Dimethoxytetrahydrofuran, Hydrazides, and Aromatic Nucleophiles

A one‐pot two‐step method for the synthesis of heteroaryl‐substituted 1,4,5,6‐tetrahydropyridazines was developed using 2,5‐dimethoxytetrahydrofuran (2,5‐DMTHF), hydrazides, and arene nucleophile as substrates. In the first step, condensation of 2,5‐DMTHF and tosyl hydrazide generates a 2‐tosyl‐2,3,4,5‐tetrahydropyridazin‐3‐ol intermediate, which undergoes in the second step a nucleophilic substitution with indole, with the aid of Al(OTf) 3 catalyst, to give an (indol‐3‐yl)‐substituted tosyl‐tetrahydropyridazine in good yield. Thiophenes and electron‐rich benzenes can also be used as nucleophiles in the synthesis. This operationally simple and efficient protocol offers a straightforward route to access 6‐heteroaryl‐substituted 1,4,5,6‐tetrahydropyridazines.