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

Synthesis and characterization of related compounds of Bisoprolol fumarate: a β-blocker agent

Santhosh Reddy Pindi, Venkateswara Rao Gollapalli, Paul Douglas Sanasi, Ramadas Chavakula, and Sukumar Nandi

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

E-mail: psanthoshreddy007@gmail.com

Received: 26 April 2023  Accepted: 27 September 2023

Abstract:

Bisoprolol is a beta blocker used for the treatment of high blood pressure. During the synthesis and scale up of Bisoprolol, several related compounds will be generated. In this article we have disclosed a facile preparative access to the chemical synthesis of five related compounds of Bisoprolol, namely, 3,3′-((methylenebis(4,1-phenylene))bis(oxy))bis(1-(isopropylamino) propan-2-ol) (2),(Bisoprolol Ph.Eur impurity-C), 3,3′-(((oxybis(methylene))bis(4,1-phenylene)) bis(oxy))bis(1-(isopropyl amino)propan-2-ol) (3), (Bisoprolol Ph.Eur impurity-D), (±) 2-(4-((2-isopropoxyethoxy)methyl)phenoxy)-3-(isopropylamino)propan-1-ol (4), (Bisoprolol Ph.Eur impurity-F), (±) 4-((3-isopropyl-2-oxooxazolidin-5-yl)methoxy)benzaldehyde (17) (Bisoprolol Ph.Eur impurity-T), (±) 5-((4-(hydroxymethyl)phenoxy)methyl)-3-isopropyloxazolidin-2-one (18) (Bisoprolol Ph.Eur impurity-U). These related compounds were listed in Pharmacopoeias and hence these impurities were synthesized and their structure was well established by modern analytical techniques like ¹H-NMR, ¹³C-NMR, HRMS. These synthetic methodologies will be useful in the future for the synthesis of other related compounds and analogues of the Bisoprolol.

Graphical abstract

Keywords: Bisoprolol; Ph. Eur impurity; β-blocker; Bisoprolol Ph. Eur impurity-C; Bisoprolol Ph. Eur impurity-D; Bisoprolol Ph Eur impurity-F; Bisoprolol Ph. Eur impurity-T; Bisoprolol Ph. Eur impurity-U

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-023-03118-2

Chemical Papers 78 (2) 1335–1345 (2024)