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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Letter Article

Synthesis of trans N-Substituted Pyrrolidine Derivatives Bearing 1,2,4- triazole Ring

Author(s): Tangella Nagendra Prasad, Yeruva Pavankumar Reddy, Poorna Chandrasekhar Settipalli, Vadiga Shanthi Kumar, Eeda Koti Reddy, Shaik Firoj Basha and Shaik Anwar*

Volume 19, Issue 5, 2022

Published on: 08 April, 2022

Page: [578 - 582] Pages: 5

DOI: 10.2174/1570179419666211230094334

Price: $65

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Abstract

Background: 1,2,4-triazoles scaffolds display significant biological activities due to hydrogen bonding, solubility, dipole character, and rigidity.

Objective: The core motif of 1,2,4-triazoles plays a vital role in clinical drugs such as Rizatriptan (antimigraine), Ribavirin (antiviral), anastrozole (anticancer), etizolam (anxiolytic), estazolam (anticonvulsant), alprazolam (anti-hypnotic), letrozole (aromatase inhibitor), loreclezole (anticonvulsant), trazadone (antidepressant) etc.

Methods: Epoxide ring opening of tert-butyl 6-oxa-3-azabicyclo [3.1.0] hexane-3-carboxylate followed by methylation under basic conditions and de-protection gave the corresponding trans 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole hydrochloride salt as the precursor. This precursor on reaction with substituted benzoyl chlorides and benzyl bromides gave the desired amide and amine products.

Results: A library of 14 N-substituted pyrrolidine derivatives i.e. trans3-methoxy-4-(1H-1,2,4-triazol- 1-yl) pyrrolidin-1-yl) (phenyl)methanone and trans 1-benzyl-4-methoxypyrrolidin-3-yl)-1H-1,2,4- triazole were prepared.

Conclusion: Eight novel amides (6a-h) and six amines (8a-f) derivatives were synthesized using 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole 4 salt with substituted benzoyl chlorides and benzyl bromides.

Keywords: Ring opening, epoxide, N-substituted pyrrolidine, trans-1-(4-methoxypyrrolidin-3-yl)-1H-1, 2, 4-triazole, trans 3- methoxy-4-(1H-1, 4-triazol-1-yl) pyrrolidin-1-yl) (phenyl) methanone, trans 1-(benzyl-4-methoxypyrrolidin-3-yl)-1H-1, 4- triazole.

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[1]
Láinez, M.J.A. Rizatriptan in the treatment of migraine. Neuropsychiatr. Dis. Treat., 2006, 2(3), 247-259.
[http://dx.doi.org/10.2147/nedt.2006.2.3.247] [PMID: 19412472]
[2]
Loustaud-Ratti, V.; Debette-Gratien, M.; Jacques, J.; Alain, S.; Marquet, P.; Sautereau, D.; Rousseau, A.; Carrier, P. Ribavirin: Past, present and future. World J. Hepatol., 2016, 8(2), 123-130.
[http://dx.doi.org/10.4254/wjh.v8.i2.123] [PMID: 26807208]
[3]
Chen, R.; Cui, J.; Wang, Q.; Li, P.; Liu, X.; Hu, H.; Wei, W. Antiproliferative effects of anastrozole on MCF-7 human breast cancer cells in vitro are significantly enhanced by combined treatment with testosterone undecanoate. Mol. Med. Rep., 2015, 12(1), 769-775.
[http://dx.doi.org/10.3892/mmr.2015.3427] [PMID: 25738971]
[4]
Gupta, S.; Garg, B. A case of etizolam dependence. Indian J. Pharmacol., 2014, 46(6), 655-656.
[http://dx.doi.org/10.4103/0253-7613.144943] [PMID: 25538342]
[5]
Vogel, G.W.; Morris, D. The effects of estazolam on sleep, performance, and memory: a long-term sleep laboratory study of elderly insomniacs. J. Clin. Pharmacol., 1992, 32(7), 647-651.
[http://dx.doi.org/10.1002/j.1552-4604.1992.tb05776.x] [PMID: 1640005]
[6]
Ait-Daoud, N.; Hamby, A.S.; Sharma, S.; Blevins, D. A Review of alprazolam use, misuse, and withdrawal. J. Addict. Med., 2018, 12(1), 4-10.
[http://dx.doi.org/10.1097/ADM.0000000000000350] [PMID: 28777203]
[7]
Kar, S. Current evidence supporting “letrozole” for ovulation induction. J. Hum. Reprod. Sci., 2013, 6(2), 93-98.
[http://dx.doi.org/10.4103/0974-1208.117166] [PMID: 24082649]
[8]
Sanna, E.; Murgia, A.; Casula, A.; Usala, M.; Maciocco, E.; Tuligi, G.; Biggio, G. Direct activation of GABAA receptors by loreclezole, an anticonvulsant drug with selectivity for the beta-subunit. Neuropharmacology, 1996, 35(12), 1753-1760.
[http://dx.doi.org/10.1016/S0028-3908(96)00138-4] [PMID: 9076754]
[9]
Jaffer, K.Y.; Chang, T.; Vanle, B.; Dang, J.; Steiner, A.J.; Loera, N.; Abdelmesseh, M.; Danovitch, I.; Ishak, W.W. Trazodone for insomnia: A systematic review. Innov. Clin. Neurosci., 2017, 14(7-8), 24-34.
[PMID: 29552421]
[10]
Peyton, L.R.; Gallagher, S.; Hashemzadeh, M. Triazole antifungals: a review. Drugs Today (Barc), 2015, 51(12), 705-718.
[PMID: 26798851]
[11]
Russell, P.E. A century of fungicide evolution. J. Agric. Sci., 2005, 143, 11-25.
[http://dx.doi.org/10.1017/S0021859605004971]
[12]
Carling, R.W.; Moore, K.W.; Street, L.J.; Wild, D.; Isted, C.; Leeson, P.D.; Thomas, S.; Connor, D.; McKernan, R.M.; Quirk, K.; Cook, S.M.; Atack, J.R.; Wafford, K.A.; Thompson, S.A.; Dawson, G.R.; Ferris, P.; Castro, J.L. 3-Phenyl-6-(2-pyridyl) methyloxy-1,2,4-triazolo[3,4-a] phthalazines and analogues: high-affinity gaminobutyric acid-A benzodiazepine receptor ligands with a2, a3, and a5-subtype binding selectivity over a1. J. Med. Chem., 2004, 47, 1807-1822.
[http://dx.doi.org/10.1021/jm031020p] [PMID: 15027873]
[13]
Kaproń B.; Czarnomysy, R.; Wysokiński, M.; Andrys, R.; Musilek, K.; Angeli, A.; Supuran, C.T.; Plech, T. 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy. J. Enzyme Inhib. Med. Chem., 2020, 35(1), 993-1002.
[http://dx.doi.org/10.1080/14756366.2020.1748026] [PMID: 32253957]
[14]
Bekircan, O. Menteşe, E.; Ülker, S.; Kucuk, C. Synthesis of some new 1,2,4-triazole derivatives starting from 3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol with anti-lipase and anti-urease activities. Arch. Pharm. (Weinheim), 2014, 347(6), 387-397.
[http://dx.doi.org/10.1002/ardp.201300344] [PMID: 24532369]
[15]
Chu, X.M.; Wang, C.; Wang, W.L.; Liang, L.L.; Liu, W.; Gong, K.K.; Sun, K.L. Triazole derivatives and their antiplasmodial and antimalarial activities. Eur. J. Med. Chem., 2019, 166, 206-223.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.047] [PMID: 30711831]
[16]
Pokuri, S.; Singla, R.K.; Bhat, V.G.; Shenoy, G.G. Insights on the antioxidant potential of 1, 2, 4-triazoles: synthesis, screening & QSAR studies. Curr. Drug Metab., 2014, 15(4), 389-397.
[http://dx.doi.org/10.2174/1389200215666140908101958] [PMID: 25204824]
[17]
Cao, X.; Wang, W.; Wang, S.; Bao, L. Asymmetric synthesis of novel triazole derivatives and their in vitro antiviral activity and mechanism of action. Eur. J. Med. Chem., 2017, 139, 718-725.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.057] [PMID: 28858766]
[18]
Li, Y.S.; Tian, H.; Zhao, D.S.; Hu, D.K.; Liu, X.Y.; Jin, H.W.; Song, G.P.; Cui, Z.N. Synthesis and bioactivity of pyrazole and triazole derivatives as potential PDE4 inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(15), 3632-3635.
[http://dx.doi.org/10.1016/j.bmcl.2016.06.002] [PMID: 27289320]
[19]
Liao, L.; Jiang, C.; Chen, J.; Shi, J.; Li, X.; Wang, Y.; Wen, J.; Zhou, S.; Liang, J.; Lao, Y.; Zhang, J. Synthesis and biological evaluation of 1,2,4-triazole derivatives as potential neuroprotectant against ischemic brain injury. Eur. J. Med. Chem., 2020, 190, 112114.
[http://dx.doi.org/10.1016/j.ejmech.2020.112114] [PMID: 32061962]
[20]
Saghier, A.M.; Mohamed, M.A.; Abd-Allah, O.A.; Kadry, A.M.; Ibrahim, T.M.; Bekhit, A.A. Green synthesis, antileishmanial activity evaluation, and in silico studies of new amino acid-coupled 1,2,4-triazoles. Med. Chem. Res., 2019, 28, 169-181.
[http://dx.doi.org/10.1007/s00044-018-2274-x]
[21]
Rodrigues, L.D.; Sunil, D.; Chaithra, D.; Bhagavath, P. 1,2,3/1,2,4-Triazole containing liquid crystalline materials: an up-to-date review of their synthetic design and mesomorphic behavior. J. Mol. Liq., 2020, 297, 111-909.
[http://dx.doi.org/10.1016/j.molliq.2019.111909]
[22]
Nicolas, R.L.; Raul, P.; Eduardo, B.; Ignacio, A.; Jose, M.B.; Santiago, G.G.; Vicente, G.; Vicente, V.L.; Eduardo, G.V.; Vicente, G.F. Enantiopure Triazolium Salts: Chemoenzymatic Synthesis and Applications in Organocatalysis. ChemCatChem, 2011, 3, 1921-1928.
[http://dx.doi.org/10.1002/cctc.201100218]
[23]
Kuang, R.; Ganguly, A.K.; Chan, T.M.; Pramanik, B.N.; Blythin, D.J.; McPhail, A.T.; Saksena, A.K. Enantioselective syntheses of carbocyclic ribavirin and its analogs: linear versus convergent approaches. Tetrahedron Lett., 2000, 41, 9575-9579.
[http://dx.doi.org/10.1016/S0040-4039(00)01704-4]
[24]
(a) Periasamy, M.; Anwar, S.; Reddy, M.N. Simple and convenient methods for synthesis, resolution and application of aminonaphthols. Indian J. Chem., 2009, 48B, 1261-1273.
(b) Settipalli, P.C.; Reddy, Y.P.; Gudise, V.B.; Anwar, S. Knoeve-nagel-Friedel-Crafts-Hemiketalization Triple Cascade Reaction: A Diastereoselective Formal [1+2+3] Cyclization Towards Indenonaphthopyran Scaffolds. ChemistrySelect, 2021, 6, 47-51.
[http://dx.doi.org/10.1002/slct.202004619]
(c) Kumar, V.S.; Gudise, V.B.; Settipalli, P.C.; Reddy, E.K.; Basha, S.F.; Reddy, Y.P.; Srinivasadesikan, V.; Lee, S-L.; Anwar, S. Understanding the mechanism of SN2′ vs. SN2 in cascade reaction of β-naphthol and nitrostyrene derived MBH acetates. ChemistrySelect, 2020, 5, 3080-3081.
[http://dx.doi.org/10.1002/slct.201904618]
(d) Basha, S.F.; Prasad, T.N.; Gudise, V.B. kumar, V. S.; Mulakayala, N.; Anwar, S. An efficient, multicomponent, green protocol to access 4,7-dihydrotetrazolo [1,5-a] pyrimidines and 5,6,7,9-tetrahydrotetrazolo [5,1-b] quinazolin-8(4H)-ones using PEG-400 under microwave irradiation. Synth. Commun., 2019, 49, 3181-3190.
[http://dx.doi.org/10.1080/00397911.2019.1659973]
(e) Huang, W.Y.; Anwar, S.; Chen, K. Morita-Baylis-Hillman (MBH) Reaction derived nitroallylic alcohols, acetates and amines as synthons in organocatalysis and heterocycle synthesis. Chem. Rec., 2017, 17(3), 363-381.
[http://dx.doi.org/10.1002/tcr.201600075] [PMID: 27701816]
(f) Gudise, V.B.; Settipalli, P.C.; Reddy, E.K.; Anwar, S. Oxa-Michael Michael Reaction of MBH Alcohol and 2-Arylidene1,3-indanedione: regioselective formal [4+2] cycloaddition towards tetrahydrospiropyran scaffolds. Eur. J. Org. Chem., 2019, 2019, 2234-2242.
[http://dx.doi.org/10.1002/ejoc.201801709]
(g) Reddy, Y.P.; Gudise, V.B.; Settipalli, P.C.; Anwar, S. Synthesis of multisubstituted indanedione based spiropyrans via Oxa-Michael/michael cascade reaction. ChemistrySelect, 2021, 6, 4456-4460.
[http://dx.doi.org/10.1002/slct.202100915]
(h) Cheng, Y.S.; Anwar, S.; Chen, K. Organocatalytic synthesis of spirocarbocycles. Mini Rev. Org. Chem., 2018, 15, 364-373.
[http://dx.doi.org/10.2174/1570193X15666171228145726]
(i) Reddy, E.K.; Remya, C.; Sajith, A.M.; Dileep, K.V.; Sadsivan, C.; Anwar, S. Functionalised dihydroazo pyrimidine derivatives from Morita-Baylis-Hillman Acetates: synthesis and studies against acetylcholinesterase as its inhibitors. RSC Advances, 2016, 6, 77431-77439.
[http://dx.doi.org/10.1039/C6RA12507G]
(j) Reddy, E.K.; Remya, C.; Mantosh, K.; Sajith, A.M.; Omkumar, R.V.; Sadasivan, C.; Anwar, S. Novel tacrine derivatives exhibiting improved acetylcholinesterase inhibition: Design, synthesis and biological evaluation. Eur. J. Med. Chem., 2017, 139, 367-377.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.013] [PMID: 28810188]
(k) Prasad, T.N.; Reddy, E.K.; Gudise, V.B.; Basha, S.F.; Anwar, S. Design, synthesis and biological evaluation of substituted 2-amino-1,3-thiazine derivatives as antituberculosis and anti-cancer agents. Synth. Commun., 2019, 49, 1277-1285.
[http://dx.doi.org/10.1080/00397911.2019.1597125]
(l) Reddy, E.K.; Battula, S.; Anwar, S.; Sajith, A.M. Drug Re-purposing Approach and potential therapeutic strategies to treat COVID-19. Mini Rev. Med. Chem., 2021, 21(6), 704-723.
[http://dx.doi.org/10.2174/1389557520666201113105940] [PMID: 33185159]

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