Synthesis of a New Polyfunctionalised Pyrimidine-4-carboxylate and Its Application for the Construction of a Series of Pyrimidine Derivatives

Abstract

The synthesis of a new and versatile polyfunctionalised pyrimidine-4-carboxylate, along with the study of its reactivity against 1,2-dinucleophiles and 1,4-dinucleophiles, is reported. These simple and efficient methodologies allowed for the synthesis of novel pyrimidine derivatives such as pyrimido[4,5-d]pyridazin-8-one-5-carboxylates and their corresponding carbohydrazides and N-acylhydrazone (NAH) derivatives, pyrimido[4,5-d][1,2]oxazin-8-one and its corresponding carbohydrazide derivative, and 3-pyrimidinylquinoxaline-2-one and its corresponding carbohydrazide. Furthermore, pyrimidine hydroxyimino derivatives were also prepared.

Key words

pyrimidine-4-carboxylate - 2,4,5-trisubstituted pyrimidine - pyrimido[4,5-d]pyridazinone - pyrimido[4,5-d]oxazinone - quinoxalinone

• References

• 1 Majumdar CK, Ponra S, Ghosh D. Synthesis 2011; 1132
• 2 Balzarini J, Mcguigan C. J. Antimicrob. Chemother. 2002; 50: 5
• 3 Vega S, Alonso J, Diaz JA, Junquera F. J. Heterocycl. Chem. 1990; 27: 269
• 4 Hill DM, Movassaghi M. Chem. Eur. J. 2008; 14: 6836
• 5 Eicher T, Hauptmann S. The Chemistry of Heterocycles . 2nd ed. Wiley-VCH; Weinheim: 2003
• 6 Matsushita A, Yoshii K, Oue M, Nakamura T, Yamada S. Patent US 20030055252 A1, 2003 ; Chem. Abstr. 2003, 138, 238198
• 7 Zanatta N, Fortes AS, Bencke CE, Marangoni MA, Camargo AF, Fantinel CA, Bonacorso HG, Martins MA. P. Synthesis 2015; 47: 827
• 8 Kidemet D, Ivaylo E, Vesna P. Synlett 2005; 2531
• 9 Schenone P, Sansebastino L, Mosti L. J. Heterocycl. Chem. 1990; 27: 295
• 10 Rosa FA, Machado P, Fiss GF, Vargas PS, Fernandes TS, Bonacorso HG, Zanatta NZ, Martins MA. P. Synthesis 2008; 3639
• 11 Berber H, Soufyane M, Santillana-Hayatc M, Miranda C. Tetrahedron Lett. 2002; 43: 9233
• 12 Silva MJ. V, Silva RG. M, Melo UZ, Gonçalves DS, Back DF, Moura S, Pontes RM, Basso EA, Gauze GF, Rosa FA. RSC Adv. 2016; 6: 290
• 13 Koza G, Keskin S, Ozer MS, Cengiz B, Sahin E, Balci M. Tetrahedron 2013; 69: 395
• 14 Liu Z, Wang R, Guo R, Hu J, Li R, Zhao Y, Gong P. Bioorg. Med. Chem. 2014; 22: 3642
• 15 Feng X.-Q, Zeng Z.-S, Liang Y.-H, Chen F.-E, Pannecouque C, Balzarini J, De Clercq E. Bioorg. Med. Chem. 2010; 18: 2370
• 16 Yuan H, Li X, Qu X, Sun L, Xu W, Wei T. Med. Chem. Res. 2009; 18: 671
• 17 Mlostoń G, Pieczonka AM, Wróblewska A, Linden A, Heimgartner H. Tetrahedron: Asymmetry 2012; 23: 795
• 18a Abdalla MS. M, Hegab MI, Taleb NA. A, Hasabelnaby SM, Goudah A. Eur. J. Med. Chem. 2010; 45: 1267
• 18b Vicini P, Zani F, Cozzini P, Doytchinova I. Eur. J. Med. Chem. 2002; 37: 553
• 18c Terzioglu N, Gürsoy A. Eur. J. Med. Chem. 2003; 38: 781
• 18d Ergeq N, Giinaya NS, Demirdamarb R. Eur. J. Med. Chem. 1998; 33: 143
• 19a Silva GA, Costa LM. M, Brito FC. F, Miranda AL. P. M, Barreiro EJ, Fraga CA. M. Bioorg. Med. Chem. 2004; 12: 3149
• 19b Duarte CD, Tributino JL, Lacerda DI, Martins MV, Alexandre-Moreira MS, Dutra F, Bechara EJ. H, De-Paula FS, Goulart MO. F, Ferreira J, Calixto JB, Nunes MP, Bertho AL, Miranda AL, Barreiro EJ, Fraga CA. M. Bioorg. Med. Chem. 2007; 15: 2421
• 20 Fraga CA. M, Barreiro E. J. Curr. Med. Chem. 2006; 13: 167
• 21 Sugiura M, Kobayashi S. Angew. Chem. Int. Ed. 2005; 44: 5176
• 22 Dev D, Palakurthy NB, Kumar N, Mandal B. Tetrahedron Lett. 2013; 54: 4397
• 23 Sun RS, Wang Y, Xia P. Chin. Chem. Lett. 2008; 19: 791
• 24 Hanzlowsky A, Jelencic B, Recnick S, Svete J, Golobic A, Stanovnik B. J. Heterocycl. Chem. 2003; 40: 487
• 25 CCDC 1444548 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 26 Chen P, Barrish JC, Iwanowicz E, Lin J, Bednarz MS, Chen B.-C. Tetrahedron Lett. 2001; 42: 4293
• 27 Abd Alla MS. M, Hegab MI, Taleb NA. A, Hasabelnaby SM, Goudah A. Eur. J. Med. Chem. 2010; 45: 1267
• 28 Jakobsen P, Horneman AM, Persson E. Bioorg. Med. Chem. 2000; 8: 2803
• 29 Perrin DD, Armarego LF. Purification of Laboratory Chemicals . 3rd ed. Pergamon Press; New York: 1996
• 30 Sheldrick GM. Acta Crystallogr. 2008; A64: 112
• 31 Farrugia LJ. J. Appl. Crystallogr. 1997; 30: 565