ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis of positional isomer and analogues of neostigmine methylsulfate: an anticholinesterase agent

Chilamkurthi Suresh, Dharmasoth Rama Devi, Keloth Basavaiah, K. V. V. Prasada rao, Balakrishna Aegurla, Guduri Anil Kumar, Dinesh Bhalerao, and Aaramadaka Sunil Kumar Reddy

Chemical Research Department, APL Research Centre-II, Aurobindo Pharma Ltd., Sangareddy District, India

E-mail: sureshchilamkurthi86@gmail.com

Received: 18 December 2022  Accepted: 25 May 2023

Abstract:

The present research paper describes the origin, synthesis and characterization of a positional isomer and analogues of Neostigmine methylsulfate namely Benzenaminium, 2-[[(dimethylamino)carbonyl]oxy]-N,N,N-trimethyl- (o-isomer), Benzenaminium, 3-[[(diethylamino)carbonyl]oxy]-N,N,N-trimethyl-, methyl sulfate (Diethyl analog) and Benzenaminium, 3-[[(ethylmethylamino)carbonyl]oxy]-N,N,N-trimethyl-,methyliodide (Ethylmethyl analog). The key starting material (m-Anisidine) contains traces of o-Anisidine and the other raw material (Dimethylcarbamoyl chloride) contains traces of N,N-diethylcarbamoyl chloride & N-Ethyl-N-methylcarbamoyl chloride, these traces of compounds generate the impurities 2, 3 & 4 in Neostigmine methylsulfate. Multistep synthesis (viz: alkylation, elimination, hydrolysis and carbamoylation) and characterisation data of these three compounds is presented in detail. These three process related impurities are very essential in the generic pharmaceutical industry to develop the analytical methods for Neostigmine methylsulfate.

Keywords: Neostigmine methylsulfate; Neostigmine methylsulfate o-isomer; Diethyl neostigmine methylsulfate or diethyl analog; Ethylmethyl neostigmine methyliodide or ethylmethyl analog

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-023-02891-4

Chemical Papers 77 (10) 5713–5719 (2023)