Medicinal Chemistry Research

, Volume 24, Issue 5, pp 1777–1788 | Cite as

Synthesis and cytotoxic evaluation for some new 2,5-disubstituted pyrimidine derivatives for anticancer activity

  • Onteddu Surendranatha Reddy
  • Ch. Venkata Suryanarayana
  • K. J. P. Narayana
  • V. Anuradha
  • B. Hari BabuEmail author
Review Article


An efficient synthetic approach for 2,5-disubstituted pyrimidines has been reported. The desired 2,5-substituted pyrimidines were obtained by Suzuki coupling of 2-substituted benzyloxy-5-bromopyrimidines with various aryl boronic acids in the presence catalytic amount of PdCl2(PPh3)2 with 0.5 M aqueous Na2CO3 in water at 80 °C. 2-Benzyloxy-5-bromopyrimidines were synthesized, in turn by the reaction of 2-chloro-5-bromopyrimidine with substituted benzyl alcohols in the presence of Cs2CO3 in CH3CN:DMF (1:1). Some of the 2,5-disubstituted pyrimidines have shown moderate in vitro cytotoxic activity against HeLa cell line.

Graphical Abstract


2-Chloro-5-bromopyrimidine Cesium carbonate Green synthesis HeLa cell line PdCl2(PPh3)2 



The authors are highly thankful to Department of Chemistry, Acharya Nagarjuna University, Nagarjunanagar, Guntur, and Andhra Pradesh, India for constant encouragement.

Supplementary material

44_2014_1276_MOESM1_ESM.docx (2.4 mb)
Copies of 1H and 13C NMR spectra for all the new compounds


  1. Bardhan S, Wacharasindhu S, Wan Z-K, Mansour TS (2009) Heteroaryl ethers by oxidative palladium catalysis of pyridotriazol-1-yloxy pyrimidines with arylboronic acids. Org Lett 11:2511–2514CrossRefPubMedGoogle Scholar
  2. Berber H, Soufyane M, Santillana-Hayat M, Mirand C (2002) Unexpected synthesis of (trifluroethyl)pyrimidines from the heterocyclisation of α-trifluoroacetylpropanenitriles. Tetrahedron Lett 43:9233–9235CrossRefGoogle Scholar
  3. Boyd HF, Hammond B, Hickey DMB, Ife RJ, Leach CA, Lewis VA, Macphee CH, Milliner KJ, Pinto IL, Smith SA, Stansfield IG, Theobald CJ, Whittaker CM (2001) The identification of a potent water soluble inhibitor of lipoprotein-associated phosphopase A2. Bioorg Med Chem Lett 11:701–704CrossRefPubMedGoogle Scholar
  4. Brown DJ (1962) The chemistry of heterocyclic compounds. In: The pyrimidines, vol 16. Wiley-Inter scienceGoogle Scholar
  5. García-Valverde M, Torroba T (2005) Special issue: sulfur-nitrogen heterocycles. Molecules 10:318–320CrossRefGoogle Scholar
  6. Herrera A, Martíez-Álvarez R, Chioua M, Chioua R, Sánchez Á (2002) On the regioselectivity in the reaction of aliphatic ketones and Aromatic nitriles. Regiospecific synthesis of alkylarylpyrimidines. Tetrahedron 58:10053–10058CrossRefGoogle Scholar
  7. Isley NA, Gallou F, Lipshutz BH (2013) Transforming Suzuki-Miyaura cross-couplings of MIDA boronates into a green technology: no organic solvents. J Am Chem Soc 135(47):17707–17710CrossRefPubMedCentralPubMedGoogle Scholar
  8. Jain KS, Chitre TS, Miniyar PB, Kathiravan MK, Bendre VS, Veer VS, Shahane SR, Shishoo CJ (2006) Biological and medicinal significance of pyrimidines. Curr Sci 90:793–803Google Scholar
  9. Joule JA, Mills K (2010) Heterocyclic chemistry, 5th edn. Wiley-BlackwellGoogle Scholar
  10. Kappe CO (1993) 100 years of the biginelli dihydropyrimidine synthesis. Tetrahedron 49:6937–6963CrossRefGoogle Scholar
  11. Lagoja IM (2005) Pyrimidine as constituent of natural biologically active compounds. Chem Biodivers 2:1–50CrossRefPubMedGoogle Scholar
  12. Leadbeater NE, Marco M (2002) Ligand-free palladium catalysis of the Suzuki reaction in water using microwave heating. Org Lett 4:2973–2976CrossRefPubMedGoogle Scholar
  13. Li S, Lin Y, Cao J, Zhang S (2007) Guanidine/Pd(OAc)2 - catalyzed room temperature Suzuki cross-coupling reaction in aqueous media under aerobic conditions. J Org Chem 72(11):4067–4072CrossRefPubMedGoogle Scholar
  14. Lipshutz BH, Abela AR (2008) Micellar catalysis of Suzuki-Miyaura cross-couplings with heteroaromatics in water. Org Lett 10(23):5329–5332CrossRefPubMedGoogle Scholar
  15. Liu L, Zhang Y, Wang Y (2005) Phosphine-free palladium acetate catalyzed Suzuki reaction in water. J Org Chem 70:6122–6125CrossRefPubMedGoogle Scholar
  16. Miyaura N, Suzuki A (1995) Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem Rev 95:2457–2483CrossRefGoogle Scholar
  17. Morgentin R, Jung F, Lamorlette M, Maudet M, Menard M, Ple P, Pasquet G, Renaud F (2009) An efficient large-scale synthesis of alkyl 5-hydroxy-pyridine- and pyrimidin-2-yl- acetate. Tetrahedron 65(4):757–764CrossRefGoogle Scholar
  18. Nencka R, Votruba I, Hřebabecký H, Jansa P, Tloušt’ová E, Horská K, Masojídková M, Holý A (2007) Discovery of 5-substituted-6-chlorouracils as efficient inhibitors of human thymidine phosphorylase. J Med Chem 50:6016–6023CrossRefPubMedGoogle Scholar
  19. Parry PR, Wang C, Batsanov AS, Bryce MR, Tarbit B (2002) Functionalized pyridylboronic acids and their Suzuki cross-coupling reactions to yield novel heteroarylpyridines. J Org Chem 67:7541–7543CrossRefPubMedGoogle Scholar
  20. Plumb JA, Milroy R, Kaye SB (1989) Effects of the pH dependence of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan absorption on chemosensitivity determined by a novel tetrazolium-based assay. Cancer Res 49(16):4435–4440PubMedGoogle Scholar
  21. Saygili N, Batsanov AS, Bryce MR (2004) 5-Pyrimidylboronic acid and 2-methoxy-5-pyrimidyl boronic acid: new heteroarylpyrimidine derivatives via Suzuki cross-coupling reactions. Org Biomol Chem 2(6):852–857CrossRefPubMedGoogle Scholar
  22. Schomaker JM, Delia TJ (2001) Arylation of halogenated pyrimidines via a Suzuki coupling reaction. J Org Chem 66:7125–7128CrossRefPubMedGoogle Scholar
  23. Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M, Kaupmann K (2003) N, N′-Dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) and structurally related compounds: novel allosteric enhancers of gamma-aminobutyric acidB receptor. J Pharmacol Exp Ther 307(1):322–330CrossRefPubMedGoogle Scholar
  24. Xie F, Zhao H, Li D, Chen H, Quan H, Shi X, Lou L, Hu Y (2011) Syntheisis and Biological Evalution of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors. J Med Chem 54:3200–3205CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Onteddu Surendranatha Reddy
    • 1
  • Ch. Venkata Suryanarayana
    • 2
  • K. J. P. Narayana
    • 3
  • V. Anuradha
    • 2
  • B. Hari Babu
    • 1
    Email author
  1. 1.Department of ChemistryAcharya Nagarjuna UniversityGunturIndia
  2. 2.Department of ChemistryVignan School of P.G. StudiesGunturIndia
  3. 3.Department of MicrobiologyAcharya Nagarjuna UniversityGunturIndia

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