# Chain Extension of Piperazine in Ethanol: Synthesis of 2-(4-(2-(Phenylthio)ethyl)piperazinyl)acetonitriles and ACAT-1 Inhibitors

## TL;DR

A new method for synthesizing acetonitriles using ethanol and less-odor disulfides is developed, leading to effective ACAT-1 inhibitors.

## Contribution

A novel, efficient, and environmentally friendly synthesis method for ACAT-1 inhibitors using ethanol and less-odor disulfides.

## Key findings

- The three-component reaction proceeds via an SN2 mechanism.
- The synthesized compounds show good activity for ACAT-1 inhibition.
- The method uses ethanol and less-odor disulfides with a simple purification process.

## Abstract

A base-induced synthesis of 2-(4-(2-(phenylthio)ethyl)piperazinyl) acetonitriles by reaction of disulfides, 1-(chloromethyl)-4-aza-1-azonia bicyclo[2.2.2]octane chloride and trimethylsilyl cyanide is reported. The scope of the method is demonstrated with 30 examples. The reaction mechanism research indicates that the three-component reaction would be a SN2 reaction. The products exhibit good activities towards advanced synthesis of aqueous soluble acyl-CoA: cholesterol O-acyltransferase-1 (ACAT-1) inhibitors. Our work is superior as it uses less-odor disulfides as carbon sources and EtOH as solvent in a water and dioxygen insensitive reaction system, followed by a simple purification process.