Synlett, Table of Contents Synlett 2014; 25(07): 935-938DOI: 10.1055/s-0033-1340860 letter © Georg Thieme Verlag Stuttgart · New YorkMicrowave-Assisted Synthesis of 4-Substituted 2-Methylthiopyrimidines Andreas Thomann a Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany Fax: +49(681)30270308 Email: rolf.hartmann@helmholtz-hzi.de , Carsten Börger b PharmBioTec GmbH, Saarland University, Science Park 1, 66123 Saarbrücken, Germany , Martin Empting a Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany Fax: +49(681)30270308 Email: rolf.hartmann@helmholtz-hzi.de , Rolf W. Hartmann* a Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany Fax: +49(681)30270308 Email: rolf.hartmann@helmholtz-hzi.de c Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany› Author AffiliationsRecommend Article Abstract Buy Article All articles of this category Abstract Typically, SNAr reactions at 4-chloro-2-methylthiopyrimidine are carried out employing DMF and sodium hydride under inert gas as well as prolonged reaction times. Herein, we describe a mild and rapid microwave-assisted synthesis to achieve 4-substituted 2-methylthiopyrimidnes from the corresponding chlorine precursor. Moderate to excellent yields were obtained in a green chemistry fashion requiring only few minutes of reaction time. Key words Key wordsgreen chemistry - pyrimidine - combinatorial chemistry - medicinal chemistry - nucleophilic aromatic substitution Full Text References References 1 Goldstein DM, Gong L, Michoud C, Palmer WS, Sidduri A. US Patent WO 2008028860 (A1), 2008 2 Goulet Joung L, Holmes MA, Hunt JA, Mills SG, Parsons WH, Sinclair PJ, Zaller D. US Patent WO 0100207 (A1), 2001 3 Beresis RT, Goulet JL, Hermes JD, Holmes MA, Hong XJ, Hunt JA, Kovacs E, Mills SG, Park Y.-W, Ruzek RD, Salowe SP, Sinclair PJ, Sonatore LM, Wong F, Woods A, Wu L, Zaller DM. Bioorg. Med. Chem. Lett. 2009; 19: 5440 4 Balitza AE, Bilodeau MT, Coll KE, Hartman GD, Manley PJ, McFall RC, Rickert KW, Rodman LD, Thomas KA. Bioorg. Med. Chem. Lett. 2003; 13: 1673 5 Kim M.-H, Lee J, Jung K, Kim M, Park Y.-J, Ahn H, Kwon Y, Hah J.-M. Bioorg. Med. Chem. 2013; 21: 2271 6 Borowski T, Mokrosz MJ, Krol M, Broclawik E, Baranowski TC, Strekowski L. J. Med. Chem. 2000; 43: 1901 7 Ikeda M, Maruyama K, Okabe S, Nobuhara Y, Yamada T. Chem. Pharm. Bull. 1997; 45: 549 8 Lukasik PM, Elabar S, Lam F, Shao H, Liu X, Abbas AY, Wang S, Lam F, Wang S. Eur. J. Med. Chem. 2012; 57: 311 9 Chung JY, Hah J.-M, Kim H, Lee J, Oh C.-H, Sim T, Yoo KH, Yu H. Bioorg. Med. Chem. Lett. 2010; 20: 1573 10a Kennedy GL. Drug Chem. Toxicol. 1986; 9: 147 10b Massmann W. Brit. J. Ind. Med. 1956; 13: 51 11 Vera-Luque P, Alajarin R, Alvarez-Builla J, Vaquero JJ. Org. Lett. 2006; 8: 415 12 Kappe CO. Angew. Chem. Int. Ed. 2004; 43: 6250 13 de la Hoz ADiaz-Ortiz A. Moreno A. Chem. Soc. Rev. 2005; 164 14 Vorobiov AN, Gaponik PN, Petrov PT, Ivashkevich OA. Synthesis 2006; 1307 15 Su W.-K, Hong Z, Shan W.-G, Zhang X.-X. Eur. J. Org. Chem. 2006; 2723 16 Ouali A, Taillefer M, Xia N. Angew. Chem. Int. Ed. 2007; 46: 934 17 Wright JB. Chem. Rev. 1951; 48: 397 18 Larinaa LI, Milatab V. Magn. Reson. Chem. 2009; 47: 142 19 Jouvin K, Coste A, Bayle A, Legrand F, Karthikeyan G, Tadiparthi K, Evano G. Organometallics 2012; 31: 7933 20 Bentin T, Hamzavi R, Salomonsson J, Roy H, Ibba M, Nielsen PE. J. Biol. Chem. 2004; 279: 19839 21 Barlin GB, Batterham TF. J. Chem. Soc. B 1967; 516 22 Hurst DT, Johnson M. Heterocycles 1985; 23: 611 23 He H, Jin C, Fu L, Liang Y.-J. Eur. J. Med. Chem. 2011; 46: 429 24 List B, Castello C. Synlett 2001; 1687 Supplementary Material Supplementary Material Supporting Information
