A Facile Synthesis of Novel (Z)‐ethyl‐3‐(5‐substituted‐1‐alkyl/aryl‐1H‐indol‐3‐yl)‐2‐(1H‐tetrazol‐5‐yl)acrylate

Abstract

A novel route was developed for synthesis of high potential 1H‐tetrazoles by using conventional method. Tetrazole scaffold is a promising pharmacophore fragment, frequently used in the development of various novel drugs. Here, the novel (Z)‐3‐(N‐alkyl‐indol‐3‐yl)‐2‐(1H‐tetrazole‐5‐yl)acrylates 5 (a–i) have been synthesized from (Z)‐ethyl‐3‐(1H‐indol‐3‐yl)2‐(1H‐tetrazol‐5‐yl)acrylates 4 (a–c) by using various alkylating agents such as Dimethyl Sulphate (DMS), Diethyl Sulphate (DES), and benzyl chloride; 4 (a–c) were synthesized from sodium azide in the presence of copper sulfate in dimethylformamide; 3 (a–c) have been prepared by Knoevenagel condensation of indole‐3‐carbaldehyde 1 (a–c) and ethylcyanoacetate 2 in the presence of L‐Proline as a catalyst at room temperature in ethanol for an hour. This is an efficient and clean click chemistry method that has various advantages such as easy workup, higher yields, shorter reaction times, and more economical.