Synthetic route optimization of Sumepirin antiepileptic drug candidate

M S Dzyurkevich,Y G Shtyrlin,N V Shtyrlin

doi:10.15826/chimtech.2020.7.4.04

Abstract

In this work we describe the transformation of synthetic route of the antiepileptic drug candidate Sumepirin starting from discovery stage. Initial method included six step process requiring two steps of purification using colon chromatography and has poor overall yield of target compound. The process developed is convenient, scalable, technological and meet the most of conditions of green chemistry. The overall yield was increased up to 62.5% in four steps without colon chromatography purification which allows to obtain the target compound with purity of 99.5+% which is especially important for the active ingredient.

Highlights

The social and medical significance of epilepsy is determined by its high prevalence
Synthesis of (5‐hydroxy-3,4‐bis(hydroxymethyl)-6‐methylpyridin-2‐yl)methanesulfonic acid (11) starting from 6-(hydroxymethyl)-3,3,8‐trimethyl-1,5‐dihydro-[1,3]dioxepino[5,6‐c] pyridin-9‐ol (4). 15 liter glass reactor equipped with anchor-type stirrer, reflux condenser, heating jacket, thermometer and pH-meter is loaded with 1565 g (6540 mmol) of compound 4 and solution of 1262 g (9810 mmol) if sodium sulfite in 5.5 liters of distilled water
Synthesis of sodium (5‐hydroxy3,4-bis(hydroxymethyl)-6-methylpyridin2-yl)methanesulfonate (1) starting from (5-hydroxy-3,4‐bis(hydroxymethyl)6‐methylpyridin-2‐yl)methanesulfonic acid (11). 15 liter glass reactor equipped with anchor-type stirrer is loaded with 1343 g (5100 mmol) of compound 11 and solution of 204 g (5100 mmol) of sodium hydroxide in 2.5 liters of water

Summary

Introduction

The social and medical significance of epilepsy is determined by its high prevalence. The precipitate formed is filtered off, washed 3 times with the 100 ml of distilled water and dried to obtain 154 g (94%) of compound 4 as pale yellow solid; m.p. 182–183 °C. In the 100 ml round bottom flask equipped with mechanical stirring bar a solution of 1.0 g (3.34 mmol) of compound 6 in 20 ml of dichloromethane and solution of 0.8 g (6.67 mmol) of sodium sulfite in 30 ml of water were added.

Results

Conclusion