Synthetic Versatility of β-Alkoxyvinyl Trichloromethyl Ketones for Obtaining [1,2,4]Triazolo[1,5-a]pyrimidines

Abstract

The synthetic versatility of 4-alkoxy-4-alkyl/aryl-1,1,1-trichloroalk-3-en-2-ones (enones) for the synthesis of [1,2,4]triazolo[1,5-a]pyrimidines, in which the trichloromethyl group is either maintained or eliminated from the product by simply controlling the reaction medium, is reported. These enones react with 3-amino-1H-1,2,4-triazoles under acidic conditions to furnish exclusively 7-(trichloromethyl)-[1,2,4]triazolo[1,5-a]pyrimidines, whereas under basic conditions [1,2,4]triazolo[1,5-a]pyrimidin-5/7(1H)-ones are obtained with elimination of the trichloromethyl group. The regioselectivity of the reactions performed under basic conditions is highly influenced by the substituents present in the starting enones. Twenty-one examples are synthesized using these two methodologies, with yields of up to 86%.

Key words

triazolopyrimidines - triazolopyrimidinones - trichloromethyl ketones - trichloromethyl enones - cyclocondensation reaction

• References

• 1 Federico S. Ciancetta A. Porta N. Redenti S. Pastorin G. Cacciari B. Klotz KN. Moro S. Spalluto G. J. Med. Chem. 2014; 57: 6210
• 2 Lou K. Yao Y. Hoye AT. James MJ. Cornec A.-S. Hyde E. Gay B. Lee VM.-Y. Trojanowski JQ. Smith AB. III. Brunden KR. Ballatore C. J. Med. Chem. 2014; 57: 6116
• 3 Cornec A.-S. James MJ. Kovalevich J. Trojanowski JQ. Lee VM.-Y. Smith AB. III. Ballatore C. Brunden KR. Bioorg. Med. Chem. Lett. 2015; 25: 4980
• 4 Deng X. Kokkonda S. El Mazouni F. White J. Burrows JN. Kaminsky W. Charman SA. Matthews D. Rathod PK. Phillips MA. J. Med. Chem. 2014; 57: 5381
• 5 Wang H. Lee M. Peng Z. Blázquez B. Lastochkin E. Kumarasiri M. Bouley R. Chang M. Mobashery S. J. Med. Chem. 2015; 58: 4194
• 6 Zhu X. Zhang M. Liu J. Ge J. Yang G. J. Agric. Food Chem. 2015; 63: 3377
• 7 Łakomska I. Hoffmann K. Muzioł T. Sitkowski J. J. Mol. Struct. 2014; 1056–1057: 146
• 8 Łakomska I. Hoffmann K. Wojtczak A. Sitkowski J. Maj E. Wietrzyk J. J. Inorg. Biochem. 2014; 141: 188
• 9 Caballero AB. Marín C. Rodríguez-Diéguez A. Ramírez-Macías I. Barea E. Sánchez-Moreno M. Salas JM. J. Inorg. Biochem. 2011; 105: 770
• 10 Chernyshev VM. Pyatakov DA. Astakhov AV. Sokolov AN. Fakhrutdinov AN. Rybakov VB. Chernyshev VV. Tetrahedron 2015; 71: 6259
• 11 Büyükafşar K. Yazar A. Düşmez D. Öztürk H. Polat G. Levent A. Pharmacol. Res. 2001; 44: 321
• 12 Zhong M. Wang T. Hu J. Environ. Monit. Assess. 2015; 187: 390
• 13 Martins MA. P. Cunico W. Pereira CM. P. Sinhorin AP. Flores AF. C. Bonacorso HG. Zanatta N. Curr. Org. Synth. 2004; 1: 391
• 14 Kuznetsova OA. Filyakova VI. Pashkevich KI. Ulomskii EN. Plekhanov PV. Rusinov GL. Kodess MI. Rusinov VL. Russ. Chem. Bull. 2003; 52: 1190
• 15 Lipson VV. Desenko SM. Orlov VD. Shishkin OV. Shirobokova MG. Chernenko VN. Zinov’eva LI. Chem. Heterocycl. Compd. 2000; 36: 1329
• 16 Chernyshev VM. Astakhov AV. Starikova ZA. Tetrahedron 2010; 66: 3301
• 17 Emelina EE. Petrov AA. Russ. J. Org. Chem. 2009; 45: 417
• 18 Frizzo CP. Scapin E. Marzari MR. B. München TS. Zanatta N. Bonacorso HG. Buriol L. Martins MA. P. Ultrason. Sonochem. 2014; 21: 958
• 19 Martins MA. P. Bastos GP. Bonacorso HG. Zanatta N. Flores AF. C. Siqueira GM. Tetrahedron Lett. 1999; 40: 4309
• 20 Mittersteiner M. Linshalm BL. Vieira AP. F. Brondani PB. Scharf DR. de Jesus PC. Chirality 2018; 30: 106
• 21 Gonçalves HA. Pereira BA. Teixeira WK. O. Moura S. Flores DC. Flores AF. C. J. Fluorine Chem. 2016; 187: 40
• 22 Dos Santos JM. Da Silveira AS. Souza LA. Lobo MM. Bonacorso HG. Martins MA. P. Zanatta N. Synthesis 2015; 47: 3947
• 23 Fesenko AA. Shutalev AD. Tetrahedron 2010; 66: 7219