A J C SIAN OURNAL OF HEMISTRY A J C SIAN OURNAL OF HEMISTRY https://doi.org/10.14233/ajchem.2020.22565 INTRODUCTION Design and synthesis of molecules possessing value as human therapeutic agents is one of the main objectives of drug discovery. Compounds containing heterocyclic ring systems have being receiving great attention as they belong to a class of compounds with proven beneficial in medicinal chemistry [1]. Thiazolidine-2,4-dione (TZD) is a derivative from thia- zolidine which belongs to an important heterocyclic group. Thiazolidinedione possesses different types of biological activities like anticonvulsant activity, hypnotic activity, antitubercular activity, antibacterial activity antimicrobial, antidiabetic, anticancer and anti-inflammatory, etc. [2-5]. Anti- diabetic activity of this moiety is very well established and numbers of drugs are available in market based on this moiety (Fig. 1). In 1980’s, antihyper glycaemia activity of thiazolidine- 2,4-diones were studied extensively. Ciglitazone was the first active compound of this class, whereas other derivatives viz. pioglitazone, troglitazone, englitazone and rosiglitazone (Fig. 1) were reported soon after this. Various derivatives of thiazo- lidinedione have been reported for their diverse biological activities apart from synthetic interests [6-8]. Biological/thera- peutically activities such as hypoglycaemic, cardiovascular, antibacterial, anti-inflammatory, antilipidimic and various other activities have been reported [9]. Thiazolidine-2,4-dione derivatives have been studied extensively and found to have Design, Synthesis and Characterization of Pyrimidine based Thiazolidinedione Derivatives VIJAY KUMAR SHARMA 1,2 , ANUP BARDE 2,* and SUNITA RATTAN 1,* 1 Amity Institute of Applied Sciences, Amity University Uttar Pradesh, Noida-201313, India 2 Integral Bio Sciences Pvt. Ltd. C-64, Hosiery Complex, Phase-II, Noida-201306, India *Corresponding authors: E-mail: srattan@amity.edu; anup.barde@ibs.net.in Received: 1 December 2019; Accepted: 11 January 2020; Published online: 29 April 2020; AJC-19842 Novel thiazolidine-2,4-dione (TZD) based pyrimidine derivatives have been synthesized by Knoevenagel condensation reaction between thiazolidine-2,4-dione and amino pyrimidinyl aliphatic aldehydes followed by heterogeneous metal reduction. Synthetic strategy involved nucleophillic substitution of hydroxyl protected six membered aliphatic chain on 4,6-dichloropyrimidine followed by Suzuki coupling. This approach is regioselective, efficient and versatile for synthesis of such analogs. Keywords: Thiazolidine-2,4-dione, Suzuki coupling, Knoevenagel condensation. Asian Journal of Chemistry; Vol. 32, No. 5 (2020), 1101-1108 This is an open access journal, and articles are distributed under the terms of the Attribution 4.0 International (CC BY 4.0) License. This license lets others distribute, remix, tweak, and build upon your work, even commercially, as long as they credit the author for the original creation. You must give appropriate credit, provide a link to the license, and indicate if changes were made. diverse chemical reactivities along with broad spectrum of biological activities [10-14]. Literature provides ample indica- tions that varying the substitutions on the thiazolidine ring results in modulation of the biological activities [15]. 2,4-Thiazolidinedione derivatives with aliphatic chain up to five carbon chain was reported as insulin sensitizers with antidiabetic activities [16]. Keeping in mind further scope for thiazolidinedione, a series of pyrimidine based thiazolidine- dione with C-linked aromatic substituents and amine substi- tuted six membered aliphatic chain with terminal thiazolidine- 2,4-dione group were designed. Suzuki partners for C-C bond formation are chosen based on their potential to influence the SAR. EXPERIMENTAL 1 H and 13 C NMR spectra were recorded at 400 and 101 MHz instruments, respectively and spectral data were reported in ppm relative to tetramethylsilane (TMS) as the internal standard. UPLC-LCMS were recorded in UPLC coupled with Single quadruple mass spectrometer using electrospray ionization (ESI). Step-1: Synthesis of compound 3: To a solution of 6-aminohexanol (1) (1 eq.) in DCM (500 mL) was added DMAP (0.1 eq.) at ambient temperature and reaction mixture was cooled to 0 °C. Triethyl amine (1.5 eq.) and tert-butyldimethyl-