1 2 Original article 3 Meglumine catalyzed one-pot green synthesis of novel 4 4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-amines 5 Santhosh Govindaraju Q1 , Sumaiya Tabassum, Riyaz-ur-Rahaman Khan, 6 Mohamed Afzal Pasha * 7 Department of Studies in Chemistry, Central College Campus, Bangalore University, Bengaluru 560001, India 8 9 1. Introduction 10 Multicomponent reactions (MCRs) [1] are progressive trans- 11 formations [2] wherein the target is obtained from three or more 12 different substrates by reacting in a well-defined manner. These 13 coherent reactions are environmentally benign, versatile and atom 14 economic. They offer significant advantages over conventional 15 linear-step syntheses by reducing time, save money and raw- 16 materials; thus minimize the formation of waste [3]. MCRs 17 minimize the feeding of auxiliary substances and energy, which 18 can result in significant economic and environmental benefits. The 19 outcome of MCRs has proved to be very influential and efficient 20 bond-forming tools in organic, combinatorial and medicinal 21 chemistry [4]. 22 Pyridine containing scaffolds are ubiquitous heterocycles of 23 paramount significance to organic and medicinal research since 24 decades [5]. Amongst the vast scaffold, functionalized pyra- 25 zolo[3,4-b]pyridine system are a promising class of compounds 26 with intriguing biological properties [6] such as antitubercular, 27 antibacterial, antioxidant, antiviral [7], antimalarial [8], anti- 28 inflammatory [9] and antileishmanial [10] activities. They are 29 templates for drug discovery [11] and their applicability in the 30 treatment of bipolar disorder, Alzheimer’s disease, schizophrenia, 31 cancer, depression, diabetes, and dementia is well known 32 [12]. These derivatives are potent inhibitors of glycogen synthase 33 kinase-3 (GSK-3) [13], adenosine [14], blood platelet aggregation 34 [15], HIV reverse transcriptase [16], protein kinase [17] and cyclin 35 dependent kinase 1 (CDK1) [18]. In addition, they are often used as 36 luminophores, fluorescence standards in organic light-emitting 37 diodes [19] and corrosion inhibitors for metals and alloys [20]. 38 Owing to the aforementioned facts, we were prompted to 39 design these pharmacologically interesting class of motifs. A 40 detailed literature survey reveals that, many efforts were put in by 41 chemists towards their synthesis [21], but all these synthetic 42 methodologies have one or more shortcomings such as low yield, 43 drastic conditions, multistep reactions, cumbersome work up, use 44 of toxic reagents and solvents, longer reaction duration and 45 occurrence of several side reactions. Thus, the quest for green and 46 efficient routes for the facile access to this fused heterocycle is 47 highly desirable. 48 Today, considerable attention is directed towards the employ- 49 ment of harmless, safe, inexpensive and environmentally benign 50 reagents like biodegradable materials as they possess high 51 catalytic efficiency, nontoxic nature and recyclable properties 52 [22]. Meglumine, an organic compound with the molecular 53 formula C 7 H 17 NO 5 and IUPAC name (2R,3R,4R,5S)-6-(methylami- 54 no)hexane-1,2,3,4,5-pentol is an amino sugar derived from 55 sorbitol. It offers many advantages due to noncorrosive nature, 56 ready and commercial availability; it is inert, biodegradable, 57 reusable and stable to moisture and air. It has served as an efficient Chinese Chemical Letters xxx (2016) xxx–xxx A R T I C L E I N F O Article history: Received 12 June 2016 Received in revised form 20 July 2016 Accepted 26 August 2016 Available online xxx Keywords: One-pot five-component reaction Substituted phenylacetonitriles Meglumine Pyrazolopyridin-6-amines Ethanol A B S T R A C T Meglumine efficiently catalyzes the one-pot, five-component reaction of hydrazine, ethyl acetoacetate, aryl aldehydes, substituted phenylacetonitriles and ammonium acetate in ethanol at room temperature to afford novel 4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-amine derivatives. The present approach offers several advantages such as shorter reaction durations, low cost, excellent yields, milder reaction conditions, simple workup procedure and is environment friendly. All the synthesized derivatives are characterized by IR, 1 H NMR, 13 C NMR, HRMS and CHN analysis. ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved. * Corresponding Q2 author. E-mail address: m_af_pasha@ymail.com (M.A. Pasha). G Model CCLET 3830 1–5 Please cite this article in press as: S. Govindaraju, et al., Meglumine catalyzed one-pot green synthesis of novel 4,7-dihydro-1H- pyrazolo[3,4-b]pyridin-6-amines, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.09.013 Contents lists available at ScienceDirect Chinese Chemical Letters jo u rn al h om epag e: ww w.els evier.c o m/lo cat e/cc let http://dx.doi.org/10.1016/j.cclet.2016.09.013 1001-8417/ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. 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