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Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Review Article

Recent Progress in the Synthesis of Pyrimidine Heterocycles: A Review

Author(s): Pradip Kumar Maji*

Volume 24, Issue 10, 2020

Page: [1055 - 1096] Pages: 42

DOI: 10.2174/1385272824999200507123843

Price: $65

Abstract

Pyrimidine heterocycles are proven to be biologically active heterocycles, found in many biological systems, displaying a broad spectrum of biological activities including anticancer, anxiolytic, antioxidant, antiviral, antifungal, anticonvulsant, antidepressant and antibacterial activities. Recently, various synthetic approaches, synthetic strategy, the variation of substrates and study devoted towards the evaluation of biological activities for the pyrimidine heterocycles have been reported in the literature. This review article describes the synthesis of various biologically interesting pyrimidine heterocyclic ring systems using various nitrogen building blocks.

Keywords: Pyrimidine, ammonium acetate, nitrile, amidine, guanidine, Biginelli reaction, dihydropyrimidones, cycloaddition reaction.

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Graphical Abstract
[1]
(a) Chai, B.; Wang, S.; Yu, W.; Li, H.; Song, C.; Xu, Y.; Liu, C.; Chang, J. Synthesis of novel strobilurin-pyrimidine derivatives and their antiproliferative activity against human cancer cell lines. Bioorg. Med. Chem. Lett., 2013, 23(12), 3505-3510.
[http://dx.doi.org/10.1016/j.bmcl.2013.04.045] [PMID: 23664877]
(b) Lee, S.; Lim, D.; Lee, E.; Lee, N.; Lee, H.G.; Cechetto, J.; Liuzzi, M.; Freitas-Junior, L.H.; Song, J.S.; Bae, M.A.; Oh, S.; Ayong, L.; Park, S.B. Discovery of carbohybrid-based 2-aminopyrimidine analogues as a new class of rapid-acting antimalarial agents using image-based cytological profiling assay. J. Med. Chem., 2014, 57(17), 7425-7434.
[http://dx.doi.org/10.1021/jm5009693] [PMID: 25137549]
(c) Zhang, J-Q.; Luo, Y-J.; Xiong, Y-S.; Yu, Y.; Tu, Z-C.; Long, Z-J.; Lai, X-J.; Chen, H-X.; Luo, Y.; Weng, J.; Lu, G. Design, synthesis, and biological evaluation of substituted pyrimidines as potential phosphatidylinositol 3-kinase (PI3K) inhibitors. J. Med. Chem., 2016, 59(15), 7268-7274.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00235] [PMID: 27427973]
(d) Balakrishnan, P.; Shanmugam, S.; Lee, W.S.; Lee, W.M.; Kim, J.O.; Oh, D.H.; Kim, D-D.; Kim, J.S.; Yoo, B.K.; Choi, H-G.; Woo, J.S.; Yong, C.S. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. Int. J. Pharm., 2009, 377(1-2), 1-8.
[http://dx.doi.org/10.1016/j.ijpharm.2009.04.020] [PMID: 19394413]
(e) Webb, M.E.; Marquet, A.; Mendel, R.R.; Rébeillé, F.; Smith, A.G. Elucidating biosynthetic pathways for vitamins and cofactors. Nat. Prod. Rep., 2007, 24(5), 988-1008.
[http://dx.doi.org/10.1039/b703105j] [PMID: 17898894]
(f) Parent, A.A.; Gunther, J.R.; Katzenellenbogen, J.A. Blocking estrogen signaling after the hormone: pyrimidine-core inhibitors of estrogen receptor-coactivator binding. J. Med. Chem., 2008, 51(20), 6512-6530.
[http://dx.doi.org/10.1021/jm800698b] [PMID: 18785725]
[2]
(a) Guo, W.; Zhao, M.; Tan, W.; Zheng, L.; Tao, K.; Fan, X. Developments towards synthesis of N-heterocycles from amidines via C–N/C–C bond formation. Org. Chem. Front., 2019, 6, 2120-2141.
[http://dx.doi.org/10.1039/C9QO00283A]
(b) Mahfoudh, M.; Abderrahim, R.; Leclerc, E. Campagne, J.-M. Recent approaches to the synthesis of pyrimidine derivatives. Eur. J. Org. Chem., 2017, 2017(20), 2856-2865.
[http://dx.doi.org/10.1002/ejoc.201700008]
(c) Aparna, E.P.; Devaky, K.S. Advances in the solid-phase synthesis of pyrimidine derivatives. ACS Comb. Sci., 2019, 21(2), 35-68.
[http://dx.doi.org/10.1021/acscombsci.8b00172] [PMID: 30607935]
(d) Hill, M.D.; Movassaghi, M. New strategies for the synthesis of pyrimidine derivatives. Chemistry, 2008, 14(23), 6836-6844.
[http://dx.doi.org/10.1002/chem.200800014] [PMID: 18384023]
(e) Radi, M.; Schenone, S.; Botta, M. Recent highlights in the synthesis of highly functionalized pyrimidines. Org. Biomol. Chem., 2009, 7(14), 2841-2847.
[http://dx.doi.org/10.1039/b906445a] [PMID: 19582291]
(f) Dar, A.M.; Uzzaman, S. Pathways for the synthesis of pyrimidine and pyran based heterocyclic derivatives: a concise review. Eur. Chem. Bull., 2015, 4(5), 249-259.
[http://dx.doi.org/10.17628/ecb.2015.4.249-259]
(g) Gore, R.P.; Rajput, A.P. A review on recent progress in multicomponent reactions of pyrimidine synthesis. Drug Invention Today, 2013, 5, 148-152.
[http://dx.doi.org/10.1016/j.dit.2013.05.010]
(h) Maji, P.K. Synthesis of pyrimidine-annulated five-membered heterocycles: an overview. Curr. Org. Chem., 2019, 23, 2204-2269.
[http://dx.doi.org/10.2174/1385272823666191019111627]
[3]
(a) Kantevari, S.; Vuppalapati, S.V.N.; Biradar, D.O.; Nagarapu, L. Highly efficient, one-pot, solvent-free synthesis of tetrasubstituted imidazoles using HClO4–SiO2 as novel heterogeneous catalyst. J. Mol. Catal. Chem., 2007, 266, 109-113.
[http://dx.doi.org/10.1016/j.molcata.2006.10.048]
(b) Heravi, M.M.; Zakeri, M.; Pooremamy, S.; Oskooie, H.A. Clean and efficient synthesis of polyhydroquinoline derivatives under solvent-free conditions catalyzed by morpholine. Synth. Commun., 2011, 41, 113-120.
[http://dx.doi.org/10.1080/00397910903531862]
(c) Samai, S.; Nandi, G.C.; Kumar, R.; Singh, M.S. Multicomponent one-pot solvent-free synthesis of functionalized unsymmetrical dihydro-1H-indeno[1,2-b]pyridines. Tetrahedron Lett., 2009, 50, 7096-7098.
[http://dx.doi.org/10.1016/j.tetlet.2009.10.022]
(d) Sanchez, L.M.; Sathicq, A.G.; Jios, J.L.; Baronetti, G.T.; Thomas, H.J.; Romanelli, G.P. Solvent-free synthesis of functionalized pyridine derivatives using Wells-Dawson heteropolyacid as catalyst. Tetrahedron Lett., 2011, 52, 4412-4416.
[http://dx.doi.org/10.1016/j.tetlet.2011.06.048]
(e) Zolfigol, M.A.; Safaiee, M. Synthesis of 1,4-dihydropyridines under solvent-free conditions. Synlett, 2004, 2004(5), 827-828.
[http://dx.doi.org/10.1055/s-2004-820010]
(f) Shen, L.; Cao, S.; Wu, J.; Li, H.; Zhang, J.; Wu, M.; Qian, X.K 2CO3-assisted one-pot sequential synthesis of 2-trifluoromethyl-6-difluoromethylpyridine-3,5-dicarboxylates under solvent-free conditions. Tetrahedron Lett., 2010, 51, 4866-4869.
[http://dx.doi.org/10.1016/j.tetlet.2010.07.041]
(g) Wu, P.; Cai, X-M.; Wang, Q-F.; Yan, C-G. One-pot multicomponent condensation reaction of aldehydes with cyclic ketones. Synth. Commun., 2011, 41, 841-850.
[http://dx.doi.org/10.1080/00397911003706990]
(h) Fassihi, A.; Abedi, D.; Saghaie, L.; Sabet, R.; Fazeli, H.; Bostaki, G.; Deilami, O.; Sadinpour, H. Synthesis, antimicrobial evaluation and QSAR study of some 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives. Eur. J. Med. Chem., 2009, 44(5), 2145-2157.
[http://dx.doi.org/10.1016/j.ejmech.2008.10.022] [PMID: 19056147]
(i) Kumar, S.; Sharma, P.; Kapoor, K.K.; Hundai, M.S. An efficient, catalyst- and solvent-free, four-component and one-pot synthesis of polyhydroquinolines on grinding. Tetrahedron, 2008, 64, 536-542.
[http://dx.doi.org/10.1016/j.tet.2007.11.008]
(j) Sapkal, S.B.; Shelke, K.F.; Shingate, B.B.; Shingare, M.S. Nickel nanoparticle-catalyzed facile and efficient one-pot synthesis of polyhydroquinoline derivatives via Hantzsch condensation under solvent-free conditions. Tetrahedron Lett., 2009, 50, 1754-1756.
[http://dx.doi.org/10.1016/j.tetlet.2009.01.140]
(k) Rad-Moghadam, K.; Samavi, L. One‐pot three‐component synthesis of 2‐substituted 4‐aminoquinazolines. J. Heterocycl. Chem., 2006, 43, 913-916.
[http://dx.doi.org/10.1002/jhet.5570430415]
(l) Bagley, M.C.; Dale, J.W.; Bower, J. A new one-pot three-component condensation reaction for the synthesis of 2,3,4,6-tetrasubstituted pyridines. Chem. Commun. (Camb.), 2002, 2002(16), 1682-1683.
[http://dx.doi.org/10.1039/b203900a] [PMID: 12196948]
(m) Zhao, L.; Liang, F.; Bi, X.; Sun, S.; Liu, Q. Efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines by a double annulation strategy from α-alkenoyl-α-carbamoyl ketene-(S,S)-acetals. J. Org. Chem., 2006, 71(3), 1094-1098.
[http://dx.doi.org/10.1021/jo0522106] [PMID: 16438526]
(n) Risitano, F.; Grassi, G.; Foti, F.; Moraci, S. A novel efficient three-component one-pot synthesis of 1,3-diazabicyclo[3.1.0]hex-3-ene system under microwave irradiation. Synlett, 2005, 2005(10), 1633-1635.
[http://dx.doi.org/10.1055/s-2005-869859]
(o) Matsuoka, Y.; Ishida, Y.; Sasaki, D.; Saigo, K. Synthesis of enantiopure 1-substituted, 1,2-disubstituted, and 1,4,5-trisubstituted imidazoles from 1,2-amino alcohols. Tetrahedron, 2006, 62, 8199-8206.
[http://dx.doi.org/10.1016/j.tet.2006.05.079]
(p) Deng, X.; Mani, N.S. An efficient route to 4-aryl-5-pyrimidinylimidazoles via sequential functionalization of 2,4-dichloropyrimidine. Org. Lett., 2006, 8(2), 269-272.
[http://dx.doi.org/10.1021/ol052663x] [PMID: 16408892]
[4]
(a) Xia, J.J.; Wang, G.W. One-Pot synthesis and aromatization of 1,4-dihydropyridines in refluxing water. Synthesis, 2005, 2005(14), 2379-2383.
[http://dx.doi.org/10.1055/s-2005-870022]
(b) Fan, X.S.; Li, Y.Z.; Zhang, X.Y.; Qu, G.R.; Wang, J.J.; Hu, X.Y. an efficient and green synthesis of 1,4‐dihydropyridine derivatives through multi‐component reaction in ionic liquid. heteroatom chem. 2006, 17, 382-388.
[http://dx.doi.org/10.1002/hc.20221]
(c) Yadav, L.D.S.; Rai, V.K. three-component coupling strategy for the expeditious synthesis of novel 4-aminobenzoxazinone n-nucleosides. tetrahedron lett. 2006, 47, 395-397.
[http://dx.doi.org/10.1016/j.tetlet.2005.11.006]
[5]
Sasada, T.; Kobayashi, F.; Sakai, N.; Konakahara, T. An unprecedented approach to 4,5-disubstituted pyrimidine derivatives by a ZnCl2-catalyzed three-component coupling reaction. Org. Lett., 2009, 11(10), 2161-2164.
[http://dx.doi.org/10.1021/ol900382j] [PMID: 19371078]
[6]
Rakhi, C.; Ramesh, K.; Darbem, M.P.; Branquinho, T.A.; de Oliveira, A.R.; Manjari, P.S.; Domingues, N.L.C. Novel multi-component syntheses of pyrimidines using β-CD in aqueous medium. Tetrahedron Lett., 2016, 57, 1656-1660.
[http://dx.doi.org/10.1016/j.tetlet.2016.02.106]
[7]
Upare, A.; Sathyanarayana, P.; Kore, R.; Sharma, K.; Bathula, S.R. Catalyst free synthesis of mono- and disubstituted pyrimidines from O-acyl oximes. Tetrahedron Lett., 2018, 59, 2430-2433.
[http://dx.doi.org/10.1016/j.tetlet.2018.05.023]
[8]
Wang, P.; Zhang, X.; Liu, Y.; Chen, B. Synthesis of pyrimidines with ammonium acetate as nitrogen source under solvent-free conditions. Asian J. Org. Chem., 2019, 8, 1122-1127.
[http://dx.doi.org/10.1002/ajoc.201900248]
[9]
Chena, J.; Meng, H.; Zhang, F.; Xiao, F.; Deng, G-J. Transition-metal-free selective pyrimidines and pyridines formation from aromatic ketones, aldehydes and ammonium salts. Green Chem., 2019, 21, 5201-5206.
[http://dx.doi.org/10.1039/C9GC02077B]
[10]
Khatri, C.K.; Potadar, S.M.; Chaturbhuj, G.U. A reactant promoted solvent free synthesis of 3, 4-dihydropyrimidin-2 (1H)-thione analogues using ammonium thiocyanate. Tetrahedron Lett., 2017, 58, 1778-1780.
[http://dx.doi.org/10.1016/j.tetlet.2017.03.070]
[11]
(a) Sedenkova, K.N.; Averina, E.B.; Grishin, Y.K.; Kutateladze, A.G.; Rybakov, V.B.; Kuznetsova, T.S.; Zefirov, N.S. Three-component heterocyclization of gem-bromofluorocyclopropanes with NOBF4: access to 4-fluoropyrimidine N-oxides. J. Org. Chem., 2012, 77(21), 9893-9899.
[http://dx.doi.org/10.1021/jo301880m] [PMID: 23078111]
(b) Sedenkova, K.N.; Averina, E.B.; Grishin, Y.K.; Kuznetsova, T.S.; Zefirov, N.S. A novel and effective approach to 4-fluoropyrimidines. Tetrahedron Lett., 2014, 55, 483-485.
[http://dx.doi.org/10.1016/j.tetlet.2013.11.070]
(c) Sedenkova, K.N.; Averina, E.B.; Grishin, Y.K.; Bacunov, A.B.; Troyanov, S.I.; Morozov, I.V.; Deeva, E.B.; Merkulova, A.V.; Kuznetsova, T.S.; Zefirov, N.S. Nitronium salts as novel reagents for the heterocyclization of gem-bromofluorocyclopropanes into pyrimidine derivatives. Tetrahedron Lett., 2015, 56, 4927-4930.
[http://dx.doi.org/10.1016/j.tetlet.2015.06.089]
[12]
Lang, J.; Wei, Y. Difunctionalization of the isocyano group. Atom-economic synthesis of pyrimidinediones. Synlett, 2018, 30(3), 252-256.
[http://dx.doi.org/10.1055/s-0037-1610348]
[13]
Karumanchi, K.; Nangi, G.B.S.; Danda, S.R.; Chavakula, R.; Korupolu, R.B.; Bonige, K.B. A facile synthesis of Raltegravir potassium-an HIV integrase inhibitor. J. Heterocycl. Chem., 2019, 56, 2683-2690.
[http://dx.doi.org/10.1002/jhet.3663]
[14]
Karad, S.N.; Liu, R-S. Regiocontrolled gold-catalyzed [2+2+2] cycloadditions of ynamides with two discrete nitriles to construct 4-aminopyrimidine cores. Angew. Chem. Int. Ed. Engl., 2014, 53(34), 9072-9076.
[http://dx.doi.org/10.1002/anie.201405312] [PMID: 24989674]
[15]
Low, C.H.; Rosenberg, J.N.; Lopez, M.A.; Agapie, T. Oxidative coupling with Zr(IV) supported by a noninnocent anthracene-based ligand: application to the catalytic cotrimerization of alkynes and nitriles to pyrimidines. J. Am. Chem. Soc., 2018, 140(38), 11906-11910.
[http://dx.doi.org/10.1021/jacs.8b07418] [PMID: 30153728]
[16]
Su, L.; Sun, K.; Pan, N.; Liu, L.; Sun, M.; Dong, J.; Zhou, Y.; Yin, S-F. Cyclization of ketones with nitriles under base: a general and economical synthesis of pyrimidines. Org. Lett., 2018, 20(11), 3399-3402.
[http://dx.doi.org/10.1021/acs.orglett.8b01324] [PMID: 29790759]
[17]
Lane, T.K.; Nguyen, M.H.; D’Souza, B.R.; Spahn, N.A.; Louie, J. The iron-catalyzed construction of 2-aminopyrimidines from alkynenitriles and cyanamides. Chem. Commun. (Camb.), 2013, 49(70), 7735-7737.
[http://dx.doi.org/10.1039/c3cc44422h] [PMID: 23877441]
[18]
Xie, L.G.; Niyomchon, S.; Mota, A.J.; González, L.; Maulide, N. Metal-free intermolecular formal cycloadditions enable an orthogonal access to nitrogen heterocycles. Nat. Commun., 2016, 7, 1-9.
[http://dx.doi.org/10.1038/ncomms10914] [PMID: 26975182]
[19]
You, X.; Yu, S.; Liu, Y. Reactions of zirconocene butadiyne or monoyne complexes with nitriles: straightfoward synthesis of functionalized pyrimidines. Organometallics, 2013, 32, 5273-5276.
[http://dx.doi.org/10.1021/om400880r]
[20]
Bagley, M.C.; Lin, Z.; Pope, S.J.A. Barium manganate in microwave-assisted oxidation reactions: synthesis of solvatochromic 2,4,6-triarylpyrimidines. Tetrahedron Lett., 2009, 50, 6818-6822.
[http://dx.doi.org/10.1016/j.tetlet.2009.09.116]
[21]
Lin, M.; Chen, Q-Z.; Zhu, Y.; Chen, X-L.; Cai, J-J.; Pan, Y-M.; Zhan, Z-P. Copper(II)-catalyzed synthesis of pyrimidines from propargylic alcohols and amidine: a propargylation–cyclization–oxidation tandem reaction. Synlett, 2011, 2011(8), 1179-1183.
[http://dx.doi.org/10.1055/s-0030-1259954]
[22]
Guo, W.; Liu, D.; Liao, J.; Ji, F.; Wu, W.; Jiang, H. Cu-Catalyzed intermolecular [3 + 3] annulation involving oxidative activation of an unreactive C(sp3)–H bond: access to pyrimidine derivatives from amidines and ketones. Org. Chem. Front., 2017, 4, 1107-1111.
[http://dx.doi.org/10.1039/C6QO00842A]
[23]
Zhou, Y.; Tang, Z.; Song, Q. Lewis acid‐mediated [3+3] annulation for the construction of substituted pyrimidine and pyridine derivatives. Adv. Synth. Catal., 2017, 359, 952-958.
[http://dx.doi.org/10.1002/adsc.201601386]
[24]
Stonehouse, J.P.; Chekmarev, D.S.; Ivanova, N.V.; Lang, S.; Pairaudeau, G.; Smith, N.; Stocks, M.J.; Sviridov, S.I.; Utkina, L.M. One-pot four-component reaction for the generation of pyrazoles and pyrimidines. Synlett, 2008, 2008(1), 100-104.
[http://dx.doi.org/10.1055/s-2007-1000839]
[25]
Deibl, N.; Ament, K.; Kempe, R. A sustainable multicomponent pyrimidine synthesis. J. Am. Chem. Soc., 2015, 137(40), 12804-12807.
[http://dx.doi.org/10.1021/jacs.5b09510] [PMID: 26414993]
[26]
Yuan, J.; Li, J.; Wang, B.; Sun, S.; Cheng, J. Base-promoted formal [4+1+1] annulation of aldehyde, N-benzyl amidine and DMSO toward 2,4,6-triaryl pyrimidines. Tetrahedron Lett., 2017, 58, 4783-4785.
[http://dx.doi.org/10.1016/j.tetlet.2017.11.020]
[27]
Vadagaonkar, K.S.; Kalmode, H.P.; Prakash, S.; Chaskar, A.C. Greener [3+3] tandem annulation-oxidation approach towards the synthesis of substituted pyrimidines. New J. Chem., 2015, 39, 3639-3645.
[http://dx.doi.org/10.1039/C4NJ02345E]
[28]
Guirado, A.; Alarcon, E.; Vicente, Y.; Andreu, R. A new improved method for the synthesis of 2,4-diarylpyrimidines starting from 2,2,2-trichloroethylideneacetophenones. Tetrahedron Lett., 2013, 54, 5115-5117.
[http://dx.doi.org/10.1016/j.tetlet.2013.07.075]
[29]
Zhichkin, P.; Fairfax, D.J.; Eisenbeis, S.A. A general procedure for the synthesis of 2-substituted pyrimidine-5-carboxylic esters. Synthesis, 2002, 2002(6), 720-722.
[http://dx.doi.org/10.1055/s-2002-25767]
[30]
Karpov, A.S.; Müller, T.J.J. Straightforward novel one-pot enaminone and pyrimidine syntheses by coupling-addition-cyclocondensation sequences. Synthesis, 2003, 35(18), 2815-2826.
[http://dx.doi.org/10.1055/s-2003-42480]
[31]
(a) Chu, X-Q.; Cao, W-B.; Xu, X-P.; Ji, S-J. Iron catalysis for modular pyrimidine synthesis through β-ammoniation/cyclization of saturated carbonyl compounds with amidines. J. Org. Chem., 2017, 82(2), 1145-1154.
[http://dx.doi.org/10.1021/acs.joc.6b02767] [PMID: 28032761]
(b) Zhan, J-L.; Wu, M-W.; Chen, F.; Han, B. Cu-Catalyzed [3 + 3] annulation for the synthesis of pyrimidines via β-C(sp3)-H functionalization of saturated ketones. J. Org. Chem., 2016, 81(23), 11994-12000.
[http://dx.doi.org/10.1021/acs.joc.6b02181] [PMID: 27805404]
[32]
Bluhm, U.; Boucher, J-L.; Clement, B.; Girreser, U.; Heber, D.; Ramassamy, B.; Wolschendorf, U. Synthesis, characterization and NO synthase inhibition testing of 2-aryl-5-aroyl-3,4,5,6-tetrahydropyrimidinium chlorides. J. Heterocycl. Chem., 2015, 52, 24-39.
[http://dx.doi.org/10.1002/jhet.1925]
[33]
Hu, M.; Wu, J.; Zhang, Y.; Qiu, F.Yu.Y. Synthesis of polysubstituted 5-aminopyrimidines from α-azidovinyl ketones and amidines. Tetrahedron, 2011, 67, 2676-2680.
[http://dx.doi.org/10.1016/j.tet.2011.01.062]
[34]
Vidal, M.; Arriagada, M.G.; Rezende, M.C.; Domínguez, M. Ultrasoundpromoted synthesis of 4-pyrimidinols and their tosyl derivatives. Synlett, 2016, 48(23), 4246-4252.
[http://dx.doi.org/10.1055/s-0035-1562788]
[35]
(a) Ho, S.L.; Cho, C.S. Microwave-assisted copper-powder-catalyzed synthesis of pyrimidinones from β-bromo α, β-unsaturated carboxylic acids and amidines. Synlett, 2013, 24(20), 2705-2708.
[http://dx.doi.org/10.1055/s-0033-1340283]
(b) Jiao, Y.; Ho, S.L.; Cho, C.S. Copper-powder-catalyzed synthesis of pyrimidines from β-bromo α, β-unsaturated ketones and amidine hydrochlorides. Synlett, 2015, 26(8), 1081-18084.
[http://dx.doi.org/10.1055/s-0034-1380410]
[36]
Reddy, L.S.; Reddy, T.R.; Reddy, N.C.G.; Mohan, R.B.; Lingappa, Y. One-pot, three-component synthesis of novel 4-phenyl-2-[3-(alkynyl/alkenyl/aryl)phenyl]pyrimidine libraries via Michael addition, cyclization, and C–C coupling reactions: a new MCR strategy. Synthesis, 2013, 45(45), 75-84.
[http://dx.doi.org/10.1055/s-0032-1316814]
[37]
Saikia, P.; Gogoi, S.; Boruah, R.C. A facile synthesis of steroidal and nonsteroidal pyrimidines under microwave irradiation. Tetrahedron Lett., 2015, 56, 2106-2109.
[http://dx.doi.org/10.1016/j.tetlet.2015.03.027]
[38]
Poly, S.S.; Siddiki, S.M.A.H.; Touchy, A.S.; Ting, K.W.; Toyao, T.; Maeno, Z.; Kanda, Y.; Shimizu, K. Acceptorless dehydrogenative synthesis of pyrimidines from alcohols and amidines catalyzed by supported platinum nanoparticles. ACS Catal., 2018, 8, 11330-11341.
[http://dx.doi.org/10.1021/acscatal.8b02814]
[39]
(a) Deibl, N.; Kempe, R. Manganese-catalyzed multicomponent synthesis of pyrimidines from alcohols and amidines. Angew. Chemie-Int. Ed., 2017, 56(6), 1663-1666.
[http://dx.doi.org/10.1002/anie.201611318]
(b) Mastalir, M.; Glatz, M.; Pittenauer, E.; Allmaier, G.; Kirchner, K. Sustainable synthesis of quinolines and pyrimidines catalyzed by manganese PNP pincer complexes. J. Am. Chem. Soc., 2016, 138(48), 15543-15546.
[http://dx.doi.org/10.1021/jacs.6b10433] [PMID: 27934004]
[40]
Sokolenko, L.V.; Yagupolskii, Y.L.; Kumanetska, L.S.; Marrot, J.; Magnier, E.; Lipetskij, V.O.; Kalinin, I.V. CF3S(O)n-containing enaminones as precursors for the synthesis of pyrimidine-4(3H)-ones. Tetrahedron Lett., 2017, 58, 1308-1311.
[http://dx.doi.org/10.1016/j.tetlet.2017.02.046]
[41]
Schmitt, E.; Commare, B.; Panossian, A.; Vors, J-P.; Pazenok, S.; Leroux, F.R. Synthesis of mono- and bis(fluoroalkyl)pyrimidines from FARs, fluorinated acetoacetates, and malononitrile provides easy access to novel highvalue pyrimidine scaffolds. Chemistry, 2018, 24(6), 1311-1316.
[http://dx.doi.org/10.1002/chem.201703982] [PMID: 28992385]
[42]
(a) Duerfeldt, A.S.; Boger, D.L. Total syntheses of (-)-pyrimidoblamic acid and P-3A. J. Am. Chem. Soc., 2014, 136(5), 2119-2125.
[http://dx.doi.org/10.1021/ja412298c] [PMID: 24410439]
(b) Anderson, E.D.; Boger, D.L. Inverse electron demand Diels-Alder reactions of 1,2,3-triazines: pronounced substituent effects on reactivity and cycloaddition scope. J. Am. Chem. Soc., 2011, 133(31), 12285-12292.
[http://dx.doi.org/10.1021/ja204856a] [PMID: 21736324]
(c) Anderson, E.D.; Boger, D.L. Scope of the inverse electron demand Diels-Alder reactions of 1,2,3-triazine. Org. Lett., 2011, 13(9), 2492-2494.
[http://dx.doi.org/10.1021/ol2007428] [PMID: 21488676]
(d) Glinkerman, C.M.; Boger, D.L. Cycloadditions of 1,2,3-triazines bearing c5-electron donating substituents: Robust pyrimidine synthesis. Org. Lett., 2015, 17(16), 4002-4005.
[http://dx.doi.org/10.1021/acs.orglett.5b01870] [PMID: 26172042]
[43]
Jiang, M.; Nie, Q.; Cai, M. Heterogeneous gold(I)-catalyzed cyclization between ynals and amidines: an efficient and practical synthesis of 2,4-disubstituted pyrimidines. Synth. Commun., 2019, 49, 2488-2500.
[http://dx.doi.org/10.1080/00397911.2019.1631347]
[44]
Fandrick, D.R.; Reinhardt, D.; Desrosiers, J-N.; Sanyal, S.; Fandrick, K.R.; Ma, S.; Grinberg, N.; Lee, H.; Song, J.J.; Senanayake, C.H. General and rapid pyrimidine condensation by addressing the rate limiting aromatization. Org. Lett., 2014, 16(11), 2834-2837.
[http://dx.doi.org/10.1021/ol500886a] [PMID: 24818876]
[45]
Guo, W.; Li, C.; Liao, J.; Ji, F.; Liu, D.; Wu, W.; Jiang, H. Transition metal free intermolecular direct oxidative C-N bond formation to polysubstituted pyrimidines using molecular oxygen as the sole oxidant. J. Org. Chem., 2016, 81(13), 5538-5546.
[http://dx.doi.org/10.1021/acs.joc.6b00867] [PMID: 27275869]
[46]
Liu, D.; Guo, W.; Wu, W.; Jiang, H. Base-mediated three-component tandem reactions for the synthesis of multisubstituted pyrimidines. J. Org. Chem., 2017, 82(24), 13609-13616.
[http://dx.doi.org/10.1021/acs.joc.7b02113] [PMID: 29161041]
[47]
(a) Chu, X-Q.; Xie, T.; Li, L.; Ge, D.; Shen, Z-L.; Loh, T-P. Combining fluoroalkylation and defluorination to enable formal [3 + 2 + 1] heteroannulation by using visible-light photoredox organocatalysis. Org. Lett., 2018, 20(9), 2749-2752.
[http://dx.doi.org/10.1021/acs.orglett.8b00963] [PMID: 29683679]
(b) Chu, X-Q.; Cheng, B-Q.; Zhang, Y-W.; Ge, D.; Shen, Z-L.; Loh, T-P. Copper-catalyzed three-component cyclization of amidines, styrenes, and fluoroalkyl halides for the synthesis of modular fluoroalkylated pyrimidines. Chem. Commun. (Camb.), 2018, 54(21), 2615-2618.
[http://dx.doi.org/10.1039/C7CC09571F] [PMID: 29479589]
[48]
Wang, S.; Luo, N.; Li, Y.; Wang, C. DBU-Mediated cyclization of acylcyclopropanecarboxylates with amidines: access to polysubstituted pyrimidines. Org. Lett., 2019, 21(12), 4544-4548.
[http://dx.doi.org/10.1021/acs.orglett.9b01436] [PMID: 31184171]
[49]
Guo, W.; Liao, J.; Liu, D.; Li, J.; Ji, F.; Wu, W.; Jiang, H. A four-component reaction strategy for pyrimidine carboxamide synthesis. Angew. Chem. Int. Ed. Engl., 2017, 56(5), 1289-1293.
[http://dx.doi.org/10.1002/anie.201608433] [PMID: 27966816]
[50]
Liu, F.; Zhang, X.; Qian, Q.; Yang, C. a concise and efficient approach to 2,6-disubstituted 4-fluoropyrimidines from α-cf3 aryl ketones. synlett 2020, 52(2), 273-280.
[http://dx.doi.org/10.1055/s-0039-1690248 273-280.]
[51]
Leenders, R.; van de Sande, M.; Bonfanti, J-F. A novel pyrimidine forming cyclization. Tetrahedron Lett., 2020, 61151369
[http://dx.doi.org/10.1016/j.tetlet.2019.151369]
[52]
(a) Shen, J.; Meng, X. Selective synthesis of pyrimidines from cinnamyl alcohols and amidines using the heterogeneous OMS-2 catalyst. Cat. Coummn., 2019, 138105846
[http://dx.doi.org/10.1016/j.catcom.2019.105846]
(b) Zheng, L-Y.; Guo, W.; Fan, X-L. Metal‐free, TBHP‐mediated, [3+2+1]‐type intermolecular cycloaddition reaction: synthesis of pyrimidines from amidines, ketones, and DMF through C(sp3)−H activation. Asian J. Org. Chem., 2017, 6, 837-840.
[http://dx.doi.org/10.1002/ajoc.201700105]
[53]
Wu, P.; Zhang, X.; Chen, B. Direct synthesis of 2,4,5-trisubstituted imidazoles and di/tri-substituted pyrimidines via cycloadditions of α, β-unsaturated ketones/aldehydes and N-hydroxyl imidamides. Tetrahedron Lett., 2019, 60, 1103-1107.
[http://dx.doi.org/10.1016/j.tetlet.2019.03.025]
[54]
Stepaniuk, O.O.; Rudenko, T.V.; Vashchenko, B.V.; Matvienko, V.O.; Kondratov, I.S.; Tolmachev, A.A.; Grygorenko, O.O. Reaction of β-alkoxyvinyl α-ketoesters with acyclic NCN binucleophiles - Scalable approach to novel functionalized pyrimidines. Tetrahedron, 2019, 75, 3472-3478.
[http://dx.doi.org/10.1016/j.tet.2019.05.005]
[55]
Iaroshenko, V.O.; Dudkin, S.; Sosnovskikh, V.Y.; Villinger, A.; Langer, P. (β‐D‐Ribofuranosyl)formamidine in the design and synthesis of 2‐(β‐D‐Ribofuranosyl)pyrimidines, including RF‐containing derivatives. Eur. J. Org. Chem., 2013, 13(15), 3166-3173.
[http://dx.doi.org/10.1002/ejoc.201300107]
[56]
Reddy, M.L.C.; Khan, F.R.N.; Saravanan, V. Synthesis of new sulfoximine-tethered alkynones and further extension towards metal-free synthesis of pyrimidines, amino pyrimidines, pyrazoles and isoxazoles. ChemistrySelect, 2019, 4, 9573-9577.
[http://dx.doi.org/10.1002/slct.201902774]
[57]
Komkov, A.V.; Potapova, T.V.; Zuev, M.I.; Baranin, S.V.; Bubnov, Y.N. Synthesis of new trichloromethyl- and alkoxy-substituted pyrido[2,3-d]pyrimidine derivatives. Russ. Chem. Bull. Int. Ed., 2019, 68, 365-373.
[http://dx.doi.org/10.1007/s11172-019-2394-6]
[58]
Cheremnykh, K.P.; Savelyev, V.A.; Pokrovskii, M.A.; Baev, D.S.; Tolstikova, T.G.; Pokrovskii, A.G.; Shults, E.E. Design, synthesis, cytotoxicity, and molecular modeling study of 2,4,6-trisubstituted pyrimidines with anthranilate ester moiety. Med. Chem. Res., 2019, 28, 545-558.
[http://dx.doi.org/10.1007/s00044-019-02314-8]
[59]
Mahdavi, M.; Kianfard, H.; Saeedi, M.; Ranjbar, P.R.; Shafiee, A. Efficient synthesis of polyfunctionalized pyrimidine derivatives. Synlett, 2016, 27(11), 1689-1692.
[http://dx.doi.org/10.1055/s-0035-1561381]
[60]
Nishimura, Y.; Cho, H. Synthesis of 4-unsubstituted dihydropyrimidines having acyl and alkoxycarbonyl groups at 5- and 6-positions by cyclizationelimination reactions using 1,3-diaza-1,3-butadienes. Tetrahedron Lett., 2014, 55, 411-414.
[http://dx.doi.org/10.1016/j.tetlet.2013.11.038]
[61]
Nishimura, Y.; Kubo, T.; Okamoto, Y.; Cho, H. Convergent synthesis of 4,6-unsubstituted 5-acyl-2-phenyldihydropyrimidines by substitution reactions of Weinreb amide group of tetrahydropyrimidines. Tetrahedron Lett., 2016, 57, 4492-4495.
[http://dx.doi.org/10.1016/j.tetlet.2016.08.077]
[62]
(a) Guzmán, A.; Romero, M.; Talamás, F.X.; Villena, R.; Greenhouse, R.; Muchowski, J.M. 1,3-Diaza-1,3-butadienes. Synthesis and conversion into pyrimidines by [4π + 2π] cycloaddition with electron deficient acetylenes. Synthetic utility of 2-(trichloromethyl)pyrimidines. J. Org. Chem., 1996, 61, 2470-2483.
[http://dx.doi.org/10.1021/jo952106w]
(b) Resendiz, A.S.; Eduardo, H.L.; Flores, J.B.; Otero, D.M.; Ortega, M.R. Synthesis and crystal structures of stable 4-aryl-2-(trichloromethyl)-1,3-diaza-1,3-butadienes. Synthesis, 2016, 48(14), 2205-2212.
[http://dx.doi.org/10.1055/s-0035-1561936]
(c) Mercado, I.M.; Galicia, I.Z.; Olivo, H.F.; Orteg, M.R. 2-Trifluoromethyl-1,3-diazabutadienes as useful intermediates for the construction of 2-trifluoromethylpyrimidine derivatives. Synthesis, 2018, 50(20), 4133-4139.
[63]
Lagunas, M.L.T.; Mercado, I.M.; Galicia, I.Z.; Olivo, H.F.; Ortega, M.R. A synthesis of 4-chloro-2-(trichloromethyl)pyrimidines and their study in nucleophilic substitution. Synthesis, 2019, 51(2), 530-537.
[http://dx.doi.org/10.1055/s-0037-1610270]
[64]
Khan, K.M.; Iqbal, S.; Bashir, M.A.; Ambreen, N.; Perveen, S.; Voelter, V. An efficient and simple methodology for the synthesis of 2-amino-4-(Nalkyl/arylamino)-6-chloropyrimidines. Tetrahedron Lett., 2015, 56, 1179-1182.
[http://dx.doi.org/10.1016/j.tetlet.2015.01.153]
[65]
Yavari, I.; Nematpour, M. Copper-catalyzed tandem synthesis of tetrasubstituted pyrimidines from alkynes, sulfonyl azides, trichloroacetonitrile, and tetramethylguanidine. Synlett, 2013, 44(18), 165-168.
[http://dx.doi.org/10.1002/chin.201318150]
[66]
Yavari, I.; Malekafzali, A.; Keihan, R.E.; Skoulika, S.; Alivaisi, R. A one-pot synthesis of trichloromethylated pyrimidines from trichloroacetimidamides and acetylenic esters. Tetrahedron Lett., 2016, 57, 1733-1735.
[http://dx.doi.org/10.1016/j.tetlet.2015.12.066]
[67]
Yavari, I.; Amirahmadi, A.; Halvagar, M.R. A synthesis of functionalized thiazoles and pyrimidine-4(3H)-thiones from 1,1,3,3-tetramethylguanidine, acetylenic esters, and aryl isothiocyanates. Synlett, 2017, 28(19), 2629-2632.
[http://dx.doi.org/10.1055/s-0036-1590862]
[68]
Felluga, F.; Benedetti, F.; Berti, F.; Drioli, S.; Regini, G. Efficient Biginelli synthesis of 2-aminodihydropyrimidines under microwave irradiation. Synlett, 2018, 29(8), 1047-1054.
[http://dx.doi.org/10.1055/s-0036-1591900]
[69]
Holsworth, D.D.; Stier, M.; Edmunds, J.J.; He, W.; Place, S.; Maiti, S. An expeditious synthesis of 6-alkyl-5-(4′-amino-phenyl)-pyrimidine-2,4-diamines. Synth. Commun., 2003, 33, 3467-3475.
[http://dx.doi.org/10.1081/SCC-120024725]
[70]
Sharma, N.; Chundawat, T.S.; Mohapatra, S.C.; Bhagat, S. Synthesis of novel fluorinated multisubstituted pyrimidines and 1,5-benzodiazepines via fluorinated N,S-acetals. Synthesis, 2016, 48(24), 4495-4508.
[http://dx.doi.org/10.1055/s-0036-1588588]
[71]
Azzam, R.A. Tailored-design synthesis of sulfapyrimidine derivatives. J. Heterocycl. Chem., 2018, 56, 619-627.
[http://dx.doi.org/10.1002/jhet.3439]
[72]
Wang, R.; Guan, W.; Han, Z-B.; Liang, F.; Suga, T.; Bi, X.; Nishide, H. Ambient-light-promoted three-component annulation: synthesis of perfluoroalkylated pyrimidines. Org. Lett., 2017, 19(9), 2358-2361.
[http://dx.doi.org/10.1021/acs.orglett.7b00894] [PMID: 28414451]
[73]
(a) Nagarajaiah, H.; Mukhopadhyay, A.; Moorthy, J.N. Biginelli reaction: an overview. Tetrahedron Lett., 2016, 57, 5135-5149.
[http://dx.doi.org/10.1016/j.tetlet.2016.09.047]
(b) Jubeen, F.; Iqbal, S.Z.; Shafiq, N.; Khan, M.; Parveen, S.; Iqbal, M.; Nazir, A. Eco-friendly synthesis of pyrimidines and its derivatives: a review on broad spectrum bioactive moiety with huge therapeutic profile. synth. commun., 2018, 48, 601-625.
[http://dx.doi.org/10.1080/00397911.2017.1408840,]
(c) Patil, R.V.; Chavan, J.U.; Dalal, D.S.; Shinde, V.S.; Beldar, A.G. biginelli reaction: polymer supported catalytic approaches. acs comb. sci.,, 2019, 21(3), 105-148.
[http://dx.doi.org/10.1021/acscombsci.8b00120] [PMID: 30645098]
(d) Suresh, A.C.; Sandhu, J.S. past, present and future of the biginelli reaction: a critical perspective. arkivoc, 2012, 2012(1), 66-133.
[http://dx.doi.org/10.3998/ark.5550190.0013.103]
(e) Panda, S.S.; khanna, P.; khanna, L. biginelli reaction: a green perspective. curr. org. chem, 2012, 16(4), 507-520.
[http://dx.doi.org/10.2174/138527212799499859]
[74]
Chavan, S.S.; Degani, M.S. Ionic liquid mediated one-pot synthesis of 6-aminouracils. Green Chem., 2012, 14, 296-299.
[http://dx.doi.org/10.1039/C1GC15940B]
[75]
Barthakur, M.G.; Borthakur, M.; Devi, P.; Saikia, C.J.; Saikai, A.; Bora, U.; Chetia, A.; Boruah, R.C. A novel and efficient lewis acid catalysed preparation of pyrimidines: microwave-promoted reaction of urea and β-formyl enamides. Synlett, 2007, 2007(2), 223-226.
[http://dx.doi.org/10.1055/s-2007-968018]
[76]
Ren, Y-M.; Cai, C. Three-components condensation catalyzed by molecular iodine for the synthesis of 2,4,6-triarylpyridines and 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones under solvent-free conditions. Monatsh. Chem., 2009, 140, 49-52.
[http://dx.doi.org/10.1007/s00706-008-0011-8]
[77]
Sathicq, A.G.; Ruiz, D.M.; Constantieux, T.; Rodriguez, J.; Romanelli, G.P. Preyssler heteropoly acids encapsulated in a silica framework for an efficient preparation of fluorinated hexahydropyrimidine derivatives under solvent-free conditions. Synthesis, 2014, 25(6), 881-883.
[http://dx.doi.org/10.1055/s-0033-1340845]
[78]
Fuchs, D.; Esfahani, M.N.; Diab, L.; Smejkal, T.; Breit, B. Tandem hydroformylation–Biginelli reaction. Synlett, 2013, 24(13), 1657-1662.
[http://dx.doi.org/10.1055/s-0033-1339298]
[79]
Rao, G.B.D.; Anjaneyulu, B.; Kaushik, M.P. A facile one-pot fivecomponent synthesis of glycoside annulated dihydropyrimidinone derivatives with 1,2,3-triazol linkage via transesterification/Biginelli/click reactions in aqueous medium. Tetrahedron Lett., 2014, 55, 19-22.
[http://dx.doi.org/10.1016/j.tetlet.2013.09.023]
[80]
Kolosov, M.A.; Kulyk, O.G.; Al-Ogaili, M.J.K.; Orlov, V.D. An effective Biginelli-type synthesis of 1-methoxy-3,4-dihydropyrimidin-2(1H)-ones. Tetrahedron Lett., 2015, 56, 4666-4669.
[http://dx.doi.org/10.1016/j.tetlet.2015.06.041]
[81]
Savanur, H.M.; Kalkhambkar, R.G.; Aridoss, G.; Laali, K.K. [bmim(SO3H)][OTf]/[bmim][X] and Zn(NTf2)2/[bmim][X] (X = PF6 and BF4); efficient catalytic systems for the synthesis of tetrahydropyrimidin-ones (-thiones) via the Biginelli reaction. Tetrahedron Lett., 2016, 57, 3029-3035.
[http://dx.doi.org/10.1016/j.tetlet.2016.05.103]
[82]
Chen, P.; Tu, M. Synthesis of 2-selenoxo DHPMs by Biginelli reaction with Hf(OTf)4 as catalyst. Tetrahedron Lett., 2018, 59, 987-990.
[http://dx.doi.org/10.1016/j.tetlet.2018.01.070]
[83]
Gonçalves, I.; Davi, L.; Rockenbach, L. das Neves, G.M.; Kagami, L.P.; Canto, R.F.S.; Figueiró, F.; Batastini, A.M.O.; Lima, V.L.E. Versatility of the Biginelli reaction: synthesis of new biphenyl dihydropyrimidin-2-thiones using different ketones as building blocks. Tetrahedron Lett., 2018, 59, 2759-2762.
[http://dx.doi.org/10.1016/j.tetlet.2018.06.006]
[84]
(a) Ryabukhin, S.V.; Plaskon, A.S.; Ostapchuk, E.N.; Volochnyuk, D.M.; Shishkin, O.V.; Shivanyuk, A.N.; Tolmachev, A.A. A one-step fusion of 1,3-thiazine and pyrimidine cycles. Org. Lett., 2007, 9(21), 4215-4218.
[http://dx.doi.org/10.1021/ol701782v] [PMID: 17850093]
(b) Ryabukhin, S.V.; Plaskon, A.S.; Ostapchuk, E.N.; Volochnyuk, D.M.; Tolmachev, A.A. N-Substituted ureas and thioureas in Biginelli reaction promoted by chlorotrimethylsilane: convenient synthesis of N1-alkyl-, N1-aryl-, and N1,N3-dialkyl-3,4-dihydropyrimidin-2(1H)-(thi)ones. Synthesis, 2007, 417-427.
[http://dx.doi.org/10.1055/s-2007-965881]
[85]
Sekhar, T.; Thriveni, P.; Krishna, M.H.; Ramesh, K.; Jasmine, S.M.; Allam, U.S. Synthesis and antibacterial activity of novel (4-fluorophenyl)(4-(naphthalen-2-yl)-6-aryl-2-thioxo-2,3-dihydropyrimidin-1(6H)-yl)methanone derivatives. J. Heterocycl. Chem., 2018, 56, 44-50.
[http://dx.doi.org/10.1002/jhet.3368]
[86]
(a) Zanatta, N.; Fortes, A.S.; Bencke, C.E.; Marangoni, M.A.; Camargo, A.F.; Fantinel, C.A.; Bonacorso, H.G.; Martins, M.A.P. Efficient syntheses of ethyl 2-methylthio- and ethyl 2-benzylthio-6-methyl(aryl)pyrimidine-4-carboxylates and their carboxylic acid derivatives. Synthesis, 2015, 47(6), 827-835.
[http://dx.doi.org/10.1055/s-0034-1379696]
(b)dos Santos, J.M.; da Silveira, A.S.; Souza, L.A.; Lobo, M.M.; Bonacorso, H.G.; Martins, M.A.P.; Zanatta, N. Highly regioselective synthesis of 3,6-disubstituted 2-(methylsulfanyl)pyrimidin-4(3H)-ones. Synthesis, 2015, 3947-3955.
[87]
Fard, M.A.D.; Ghafuri, H.; Rashidizadeh, A. Sulfonated highly ordered mesoporous graphitic carbon nitride as a super active heterogeneous solid acid catalyst for Biginelli reaction. Microporous Mesoporous Mater., 2019, 274, 83-93.
[http://dx.doi.org/10.1016/j.micromeso.2018.07.030]
[88]
Harikrishnan, P.S.; Rajesh, S.M.; Perumal, S.; Almansour, A.I. A microwave-mediated catalyst- and solvent-free regioselective Biginelli reaction in the synthesis of highly functionalized novel tetrahydropyrimidines. Tetrahedron Lett., 2013, 54, 1076-1079.
[http://dx.doi.org/10.1016/j.tetlet.2012.12.034]
[89]
Starcevich, J.T.; Laughlin, T.J.; Mohan, R.S. Iron(III) tosylate catalyzed synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones via the Biginelli reaction. Tetrahedron Lett., 2013, 54, 983-985.
[http://dx.doi.org/10.1016/j.tetlet.2012.12.032]
[90]
Sahoo, P.K.; Bose, A.; Mal, P. Solvent-free ball-milling Biginelli reaction by subcomponent synthesis. Eur. J. Org. Chem., 2015, 2015(32), 6994-6998.
[http://dx.doi.org/10.1002/ejoc.201501039]
[91]
Lillo, V.J.; Saá, J.M. Towards enzyme-like, sustainable catalysis: switchable, highly efficient asymmetric synthesis of enantiopure Biginelli dihydropyrimidinones or hexahydropyrimidinones. Chemistry, 2016, 22(48), 17182-17186.
[http://dx.doi.org/10.1002/chem.201604433] [PMID: 27669489]
[92]
Hang, Z.; Zhu, J.; Lian, X.; Xu, P.; Yu, H.; Han, S. A highly enantioselective Biginelli reaction using self-assembled methanoproline-thiourea organocatalysts: asymmetric synthesis of 6-isopropyl-3,4-dihydropyrimidines. Chem. Commun. (Camb.), 2016, 52(1), 80-83.
[http://dx.doi.org/10.1039/C5CC07880F] [PMID: 26498376]
[93]
Hu, X.; Zhang, R.; Xie, J.; Zhou, Z.; Shan, Z. Synthesis of a novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid and application to the asymmetric catalytic Biginelli reaction. Tetrahedron Asymmetry, 2017, 28, 69-74.
[http://dx.doi.org/10.1016/j.tetasy.2016.11.014]
[94]
Xu, D.; Li, H.; Wang, Y. Highly enantioselective Biginelli reaction catalyzed by a simple chiral primary amine catalyst: asymmetric synthesis of dihydropyrimidines. Tetrahedron, 2012, 68, 7867-7872.
[http://dx.doi.org/10.1016/j.tet.2012.07.027]
[95]
Ding, D.; Zhao, C.G. Primary amine-catalyzed Biginelli reaction for the enantioselective synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Eur. J. Org. Chem., 2010, 2010(20), 3802-3805.
[http://dx.doi.org/10.1002/ejoc.201000448] [PMID: 21188287]
[96]
Dughera, S.; Barbero, M.; Cadamuro, S. Brønsted acid catalysed enantioselective Biginelli reaction. Green Chem., 2017, 19, 1529-1535.
[http://dx.doi.org/10.1039/C6GC03274E]
[97]
An, D.; Fan, Y.S.; Gao, Y.; Zhu, Z-Q.; Zheng, L-Y.; Zhang, S-Q. Highly enantioselective Biginelli reaction catalyzed by double axially chiral bisphosphorylimides. Eur. J. Org. Chem., 2014, 2014(2), 301-306.
[98]
Karthikeyan, P.; Aswar, S.A.; Muskawar, P.N.; Bhagat, P.R.; Kumar, S.S. Development and efficient 1-glycyl-3-methyl imidazolium chlorideecopper(II) complex catalyzed highly enantioselective synthesis of 3, 4-dihydropyrimidin- 2(1H)-ones. J. Organomet. Chem., 2013, 723, 154-162.
[http://dx.doi.org/10.1016/j.jorganchem.2012.06.022]
[99]
Xu, F.; Huang, D.; Lin, X.; Wang, Y. Highly enantioselective Biginelli reaction catalyzed by SPINOL-phosphoric acids. Org. Biomol. Chem., 2012, 10(22), 4467-4470.
[http://dx.doi.org/10.1039/c2ob25663k] [PMID: 22565820]
[100]
Cai, Y.; Yang, H.; Li, L.; Jiang, K.; Lai, G.; Jiang, J.; Xu, L. Cooperative and enantioselective nbcl5/primary amine catalyzed Biginelli reaction. Eur. J. Org. Chem., 2010, 2010(26), 4986-4990.
[http://dx.doi.org/10.1002/ejoc.201000894]
[101]
(a) Wang, Y.; Yang, H.; Yu, J.; Miao, Z.; Chen, R. Highly enantioselective biginelli reaction promoted by chiral bifunctional primary amine-thiourea catalysts: asymmetric synthesis of dihydropyrimidines. Adv. Synth. Catal., 2009, 351, 3057-3062.
[http://dx.doi.org/10.1002/adsc.200900597]
(b) Wang, Y.; Yu, J.; Miao, Z.; Chen, R. Bifunctional primary amine-thiourea-TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst: the asymmetric synthesis of dihydropyrimidines. Org. Biomol. Chem., 2011, 9(8), 3050-3054.
[http://dx.doi.org/10.1039/c0ob01268h] [PMID: 21394354]
[102]
Saha, S.; Moorthy, J.N. Enantioselective organocatalytic Biginelli reaction: dependence of the catalyst on sterics, hydrogen bonding, and reinforced chirality. J. Org. Chem., 2011, 76(2), 396-402.
[http://dx.doi.org/10.1021/jo101717m] [PMID: 21192642]
[103]
(a) Guo, Y.; Gao, Z.; Meng, X.; Huang, G.; Zhong, H.; Yu, H.; Ding, X.; Tang, H.; Zou, C. Highly enantioselective Biginelli reaction of aliphatic aldehydes catalyzed by chiral phosphoric acids. Synlett, 2017, 28(15), 2041-2045.
[http://dx.doi.org/10.1055/s-0036-1588853]
(b) Guo, Y.; Gao, Z.; Fan, C.; Chen, J.; Li, J.; Huang, Y.; Huang, G.; Yu, H.; Zou, C. Enantioselective Biginelli reaction of aliphatic aldehydes catalyzed by a chiral phosphoric acid: a key step in the synthesis of the bicyclic guanidine core of Crambescin A and Batzelladine A. Synthesis, 2018, 28(15), 2394-2406.
[http://dx.doi.org/10.1055/s-0036-1591567]
[104]
Pourshab, M.; Asghari, S.; Mohseni, M. Synthesis and antibacterial evaluation of novel spiro[indole‐pyrimidine]ones. J. Heterocycl. Chem., 2018, 55, 173-180.
[http://dx.doi.org/10.1002/jhet.3021]
[105]
Moradi, L.; Bahrami, C.; Mirzaei, A.; Zarehbin, M.R.; Yavari, I. A one-pot, catalyst-free synthesis of novel 2-thioxo-tetrahydropyrimidine derivatives via the three-component reaction of alkyl chloroglyoxalates, alkyl isocyanides, and thioureas. Tetrahedron Lett., 2015, 56, 1510-1512.
[http://dx.doi.org/10.1016/j.tetlet.2015.02.025]
[106]
Shao, Z.; Pan, Q.; Chen, J.; Yu, Y. Zhang, G. Synthesis of polysubstituted 5-aminopyrimidine-2(1H)-thiones from vinyl azides and thiourea. Tetrahedron, 2012, 68, 6565-6568.
[http://dx.doi.org/10.1016/j.tet.2012.05.057]
[107]
Dabholkar, V.V.; Ansari, F.Y. Ultrasound irradiated synthesis of bispyrimidine derivative in aqueous media. Synth. Commun., 2012, 42, 2423-2431.
[http://dx.doi.org/10.1080/00397911.2011.558970]
[108]
Dofe, V.S.; Sarkate, A.P.; Shaikh, Z.M.; Jadhav, C.K.; Nipte, A.S.; Gill, C.H. Ultrasound‐assisted synthesis of novel pyrazole and pyrimidine derivatives as antimicrobial agents. J. Heterocycl. Chem., 2018, 55, 756-762.
[http://dx.doi.org/10.1002/jhet.3105]
[109]
Abbass, S.A.; Moustafa, G.A.I.; Hassan, H.A.; Abuo-Rahma, G.E-D.A. Facile one-pot three-component synthesis of 4,6-diaryl-3,4dihydropyrimidine-2(1H)-thiones under ultrasonic irradiation. Synth. Commun., 2019, 49, 2995-3000.
[110]
(a) El-Ansary, A.K.E.; Mohamed, N.A.; Mohamed, K.O.; Abd-Elfattah, H.M.W.; El-Manawety, M.A. A simple and convenient synthesis of novel thiopyrimidine derivatives as anticancer agents. Res. J. Pharm. Biol. Chem. Sci., 2015, 6, 1745.
(b) El-serwy, W.S.; Mohamed, H.S.; El-serwy, W.S.; Mohamed, N.A.; Kassem, E.M.M.; Nossier, E.S.; Shalaby, A.S.G. Molecular docking study of newly synthesized thiopyrimidines as antimicrobial agents targeting DNA gyrasee enzyme. J. Heterocycl. Chem., 2019, 56, 2027-2035.
[http://dx.doi.org/10.1002/jhet.3583]
[111]
Okamura, H.; Becker, S.; Tiede, N.; Wiedemann, S.; Feldmann, J.; Carell, T. A one-pot, water compatible synthesis of pyrimidine nucleobases under plausible prebiotic conditions. Chem. Commun. (Camb.), 2019, 55(13), 1939-1942.
[http://dx.doi.org/10.1039/C8CC09435G] [PMID: 30681091]
[112]
Xiong, J.; Wei, X.; Ding, M-W. New facile synthesis of 2-alkylthiopyrimidin-4(3H)-ones by tandem aza-Wittig reaction starting from the Baylis–Hillman adducts. Synlett, 2017, 28(9), 1075-1078.
[113]
Harry, N.A.; Cherian, R.M.; Radhika, S.; Anilkumar, G. A novel catalystfree, ecofriendly, on water protocol for the synthesis of 2,3-dihydro-1hperimidines. Tetrahedron Lett., 2019, 60150946
[http://dx.doi.org/10.1016/j.tetlet.2019.150946]
[114]
Cao, H.; Wang, X.; Jiang, H.; Zhu, Q.; Zhang, M.; Liu, H. Development, scope and mechanisms of multicomponent reactions of asymmetric electron-deficient alkynes with amines and formaldehyde. Chemistry, 2008, 14(36), 11623-11633.
[http://dx.doi.org/10.1002/chem.200801471] [PMID: 19016558]
[115]
Dandia, A.; Jain, A.K.; Sharma, S. Indium triflate catalyzed one-pot multicomponent synthesis of spiro-hexahydropyrimidines explained by multiple covalent bond formation. Tetrahedron Lett., 2012, 53, 5270-5274.
[http://dx.doi.org/10.1016/j.tetlet.2012.07.079]
[116]
Mukhopadhyay, C.; Rana, S.; Butcher, R.J. FeCl3 catalysed two consecutive aminomethylation at the α-position of the β-dicarbonyl compounds: an easy access to hexahydropyrimidines and its spiro analogues. Tetrahedron Lett., 2011, 52, 4153-4157.
[http://dx.doi.org/10.1016/j.tetlet.2011.05.144]
[117]
Zhang, M.; Jiang, H-F. A new multicomponent reaction catalyzed by a lewis acid catalyst: convenient synthesis of polyfunctional tetrahydropyrimidines. Eur. J. Org. Chem., 2008, 2008(20), 3519-3523.
[http://dx.doi.org/10.1002/ejoc.200800289]
[118]
Jadhav, S.D.; Singh, A. Oxidative annulations involving DMSO and formamide: K2S2O8 mediated syntheses of quinolines and pyrimidines. Org. Lett., 2017, 19(20), 5673-5676.
[http://dx.doi.org/10.1021/acs.orglett.7b02838] [PMID: 28980820]
[119]
(a) Pieta, M.; Kedzia, J.; Janecki, T. An efficient synthesis of 1,3-disubstituted 5-diethoxyphosphoryluracils. Tetrahedron Lett., 2015, 56, 1891-1893.
[http://dx.doi.org/10.1016/j.tetlet.2015.02.094]
(b) Wang, C.; Xu, H.; Xie, Z.; Wang, X.; Zhang, Z.; Sun, Q. Chlorotrimethylsilane-promoted one-pot synthesis of steroidal[17,16-d]pyrimidines. Steroids, 2010, 75(12), 1033-1038.
[http://dx.doi.org/10.1016/j.steroids.2010.06.007] [PMID: 20600203]
[120]
(a) Movassaghi, M.; Hill, M.D. Single-step synthesis of pyrimidine derivatives. J. Am. Chem. Soc., 2006, 128(44), 14254-14255.
[http://dx.doi.org/10.1021/ja066405m] [PMID: 17076488]
(b) Ahmad, O.K.; Hill, M.D.; Movassaghi, M. Synthesis of densely substituted pyrimidine derivatives. J. Org. Chem., 2009, 74(21), 8460-8463.
[http://dx.doi.org/10.1021/jo9017149] [PMID: 19810691]
(c) Estrada, A.A.; Lyssikatos, J.P.; St-Jean, F.; Bergeron, P. Access to saturated fused pyrimidine derivatives via a flexible N-vinyl tertiary enamide synthesis. Synlett, 2011, 2011(16), 2387-2391.
[121]
Jeong, J.U.; Chen, X.; Rahman, A.; Yamashita, D.S.; Luengo, J.I. an efficient synthesis of 3-substituted 3h-pyrimidin-4-ones. org. lett., 2004, 6(6), 1013-1016.
[http://dx.doi.org/10.1021/ol049921v] [PMID: 15012088]
[122]
Gayon, E.; Szymczyk, M.; Gérard, H.; Vrancken, E.; Campagne, J-M. Stereoselective and catalytic access to β-enaminones: an entry to pyrimidines. J. Org. Chem., 2012, 77(20), 9205-9220.
[http://dx.doi.org/10.1021/jo301675g] [PMID: 23006434]
[123]
Sahtel, S.; Besbes, R.; Vrancken, E.; Campagne, J-M. Straightforward synthesis of various chiral pyrimidines bearing stereogenic center at the C2 position, including C-terminal peptide isosters. Beilstein J. Org. Chem., 2019, 2019(1), 134.
[http://dx.doi.org/10.3762/bxiv.2019.134.v1]
[124]
(a) Hirose, M.; Hagimori, M.; Shigemitsu, Y.; Mizuyama, N. Wang, B. C.; Tominaga, Y. One-pot synthesis of 6-substituted amino-2,4-diaminopyrimidine derivatives using ketene dithioacetals with amines and guanidine carbonate. Heterocycles, 2009, 78, 899-903.
[http://dx.doi.org/10.3987/COM-08-11587]
(b) Yan, S.; Niu, Y.; Chen, X.; Liu, Y.; Lin, J. Microwave‐assisted solvent‐free synthesis of highly functionalized pyrimidine derivatives. J. Heterocycl. Chem., 2012, 49, 877-882.
[http://dx.doi.org/10.1002/jhet.891]
[125]
Stopka, T.; Adler, P.; Hagn, G.; Zhang, H.; Tona, V.; Maulide, N. Electrophilic activation of amides for the preparation of polysubstituted pyrimidines. Synthesis, 2019, 51(1), 194-202.
[126]
Unger, L.; Accorsi, M.; Eidamshaus, C.; Reich, D.; Zimmer, R.; Reissig, H.U. Preparation and reactions of trichloromethyl-substituted pyridine and pyrimidine derivatives. Synthesis, 2018, 50(20), 4071-4080.
[127]
Xu, Y.; Chen, L.; Yang, Y.W.; Zhang, Z.; Yang, W. Vinylethylene carbonates as α,β-unsaturated aldehyde surrogates for regioselective [3 + 3] cycloaddition. Org. Lett., 2019, 21, 6674-6678.
[http://dx.doi.org/10.1021/acs.orglett.9b02266] [PMID: 31398047]
[128]
Yang, K.; Dang, Q.; Cai, P-J.; Gao, Y.; Yu, Z-X.; Bai, X. Reaction of aldehydes/ketones with electron-deficient 1,3,5-triazines leading to functionalized pyrimidines as Diels-Alder/Retro-Diels-Alder reaction products: reaction development and mechanistic studies. J. Org. Chem., 2017, 82(5), 2336-2344.
[http://dx.doi.org/10.1021/acs.joc.6b02570] [PMID: 28112917]
[129]
Zeng, Z.; Jin, H.; Song, X.; Wang, Q.; Rudolph, M.; Rominger, F.; Hashmi, A.S. Gold-catalyzed intermolecular cyclocarboamination of ynamides with 1,3,5-triazinanes: en route to tetrahydropyrimidines. Chem. Commun. (Camb.), 2017, 53(31), 4304-4307.
[http://dx.doi.org/10.1039/C7CC00789B] [PMID: 28288220]
[130]
Wu, Z.C.; Boger, D.L. Synthesis, characterization, and cycloaddition reactivity of a monocyclic aromatic 1,2,3,5-tetrazine. J. Am. Chem. Soc., 2019, 141(41), 16388-16397.
[http://dx.doi.org/10.1021/jacs.9b07744] [PMID: 31524389]
[131]
Babaoglu, E.; Harms, K.; Hilt, G. Indium-mediated blaise-type reaction of bromomalonates with nitriles and isocyanates. Synlett, 2016, 27(12), 1820-1823.
[132]
(a) Kiselyov, A.S. One-pot synthesis of polysubstituted pyrimidines. Tetrahedron Lett., 2005, 46, 1663-1665.
[http://dx.doi.org/10.1016/j.tetlet.2005.01.068]
(b) Vugts, D.J.; Jansen, H.; Schmitz, R.F.; de Kanter, F.J.J.; Orru, R.V.A. A novel four-component reaction for the synthesis of functionalised dihydropyrimidines. Chem. Commun. (Camb.), 2003, 2003(20), 2594-2595.
[http://dx.doi.org/10.1039/b308243a] [PMID: 14594297]
(c) Vugts, D.J.; Koningstein, M.M.; Schmitz, R.F.; de Kanter, F.J.J.; Groen, M.B.; Orru, R.V.A. Multicomponent synthesis of dihydropyrimidines and thiazines. Chemistry, 2006, 12(27), 7178-7189.
[http://dx.doi.org/10.1002/chem.200600168] [PMID: 16847990]
[133]
Glasnov, T.N.; Vugts, D.J.; Koningstein, M.M.; Desai, B.; Fabian, W.M.F.; Orru, R.V.A.; Kappe, C.O. Microwave‐assisted Dimroth rearrangement of thiazines to dihydropyrimidinethiones: synthetic and mechanistic aspects. qsar comb. sci, 2006, 25, 509-518.
[http://dx.doi.org/10.1002/qsar.200540210]
[134]
Avalos, M.; Babiano, R.; Cintas, P.; Hursthouse, M.B.; Jimenez, J.L.; Lerma, E.; Light, M.E.; Palacios, J.C. A one-pot domino reaction in constructing isoorotate bases and their nucleosides. Tetrahedron Lett., 2006, 47, 1989-1992.
[http://dx.doi.org/10.1016/j.tetlet.2006.01.057]
[135]
Nishimura, Y.; Cho, H. Synthesis of 4,6-unsubstituted 2-aminodihydropyrimidine-5-carboxylates through sequential Staudinger/Aza-Wittig/cyclization reactions. Synlett, 2015, 26(2), 233-237.
[http://dx.doi.org/10.1055/s-0034-1378932]
[136]
Pearson, M.S.M.; Robin, A.; Bourgougnon, N.; Meslin, J.C.; Deniaud, D. An efficient route to pyrimidine nucleoside analogues by [4 + 2] cycloaddition reaction. J. Org. Chem., 2003, 68(22), 8583-8587.
[http://dx.doi.org/10.1021/jo034709a] [PMID: 14575489]
[137]
Talhi, O.; Pinto, D.C.G.A.; Silva, A.M.S. Synthesis of 5-(2-hydroxybenzoyl)-1,3-disubstituted uracils. Synlett, 2013, 24(9), 1147-1149.
[http://dx.doi.org/10.1055/s-0033-1338932]
[138]
Kakiya, H.; Yagi, K.; Shinokubo, H.; Oshima, K. Reaction of α,α-dibromo oxime ethers with Grignard reagents: alkylative annulation providing a pyrimidine core. J. Am. Chem. Soc., 2002, 124(31), 9032-9033.
[http://dx.doi.org/10.1021/ja0269284] [PMID: 12148990]
[139]
Kalogirou, A.S.; Manoli, M.; Koutentis, P.A. Two-step conversion of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine into 4,5,6-trichloropyrimidine-2-carbonitrile. Tetrahedron Lett., 2017, 58, 2618-2621.
[http://dx.doi.org/10.1016/j.tetlet.2017.05.082]

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