Synthesis of 7-Arylpurines from Substituted Pyrimidines

Abstract

A simple three-step approach for the synthesis of substituted N7-arylpurines with an overall yield of the whole sequence from 40% to 71% is described. N7-Arylpurines were constructed by de novo synthesis from commercially available substituted 4-chloropyrimidine-5-amines. Different substituents at purine C2 and C6 were obtained by changing the corresponding substituents of the starting pyrimidine. Further, heteroaromatic, electron-deficient, and electron-rich aromatic groups were attached to the exocyclic amino group by iodane reagents under copper catalysis. This moiety is prepared to become purine N7 position after the ring closure. Finally, purine C8 substitution was varied during the last step of the developed sequence by employing different reagents for the purine ring closing reactions or post functionalization.

Key words

purines - pyrimidines - copper-catalyzed arylation - iodanes - de novo synthesis - imidazole ring closing

Publication History

Received: 09 June 2022

Accepted after revision: 13 July 2022

Accepted Manuscript online:
13 July 2022

Article published online:
13 September 2022

• References

• 1a Seley-Radtke KL, Yates MK. Antiviral Res. 2018; 154: 66
• 1b Zhou D, Xie D, He F, Song B, Hu D. Bioorg. Med. Chem. Lett. 2018; 28: 2091
• 1c CLL Trialists’ Collaborative Group 2012; 97: 428
• 1d Shelton J, Lu X, Hollenbaugh JA, Cho JH, Amblard F, Schinazi RF. Chem. Rev. 2016; 116: 14379
• 1e Jordheim LP, Durantel D, Zoulim F, Dumontet C. Nat. Rev. Drug Discov. 2013; 12: 447
• 2 Yates MK, Seley-Radtke KL. Antiviral Res. 2019; 162: 5
• 3a Idris M, Kapper SC, Tadle AC, Batagoda T, Ravinson DS. M, Abimbola O, Djurovich PI, Kim J, Coburn C, Forrest SR, Thompson ME. Adv. Optical Mater. 2021; 9: 2001994
• 3b Yun B.-S, Kim J.-H, Kim S.-Y, Son H.-J, Cho DW, Kang SO. Phys. Chem. Chem. Phys. 2019; 21: 7155
• 3c Sebris A, Traskovskis K, Novosjolova I, Turks M. Chem. Heterocycl. Compd. 2021; 57: 560
• 3d Traskovskis K, Sebris A, Novosjolova I, Turks M, Guzauskas M, Volyniuk D, Bezvikonnyi O, Grazulevicius J, Mishnev A, Grzibovskis R, Vembris A. J. Mater. Chem. C 2021; 9: 4532
• 3e Sebris A, Novosjolova I, Traskovskis K, Kokars V, Tetervenoka N, Vembris A, Turks M. ACS Omega 2022; 7: 5242
• 4a Chen S, Graceffa RF, Boezio AA. Org. Lett. 2015; 18: 16
• 4b Stanovnik B, Tišler M, Hribar A, Barlin GB, Brown DJ. Aust. J. Chem. 1981; 34: 1729
• 4c Lambertucci C, Cristalli G, Dal Ben D, Kachare DD, Bolcato C, Klotz K.-N, Spalutto G, Volpini R. Purinergic Signal. 2007; 3: 339
• 4d Česnek M, Masojídková M, Holý A, Šolínová V, Koval D, Kašička V. Collect. Czech. Chem. Commun. 2006; 71: 1303
• 4e Toyota A, Katagiri N, Kaneko C. Synth. Commun. 1993; 23: 1295
• 5a Kotek V, Chudíková N, Tobrman T, Dvořák D. Org. Lett. 2010; 24: 5724
• 5b Aarhus TI, Fritze UF, Hennum M, Gundersen L.-L. Tetrahedron Lett. 2014; 55: 5748
• 5c Liu J, Dang Q, Wei Z, Shi F, Bai X. J. Comb. Chem. 2006; 8: 410
• 5d Fu H, Lam Y. J. Comb. Chem. 2005; 7: 734
• 6a Verkoyen C, Golovinsky E, Müller G, Kölbel M, Norpoth K. Liebigs Ann. Chem. 1987; 957
• 6b Gruner M, Rehwald M, Eckert K, Gewald K. Heterocycles 2000; 53: 2363
• 7a Bredereck H, Effenberger F, Rainer G. Justus Liebigs Ann. Chem. 1964; 673: 82
• 7b Laufer SA, Domeyer DM, Scior TR. F, Albrecht W, Hauser DR. J. J. Med. Chem. 2005; 48: 710
• 7c Castillo J.-C, Orrego-Hernández J, Portilla J. Eur. J. Org. Chem. 2016; 3824
• 8a McCoull KD, Rindgen D, Blair IA, Penning TM. Chem. Res. Toxicol. 1999; 12: 237
• 8b Xue W, Siner A, Rance M, Jayasimhulu K, Talaska G, Warshawsky D. Chem. Res. Toxicol. 2002; 15: 915
• 8c Stack DE, Li G, Hill A, Hoffman N. Chem. Res. Toxicol. 2008; 21: 1415
• 9 Keder R, Dvořáková H, Dvořák D. Eur. J. Org. Chem. 2009; 1522
• 10 Sun K, Zhu Z, Sun J, Liu L, Wang X. J. Org. Chem. 2016; 81: 1476 ; however, this paper provides disputable NMR data for the obtained N7 arylated product
• 11 Huang H, Strater ZM, Rauch M, Shee J, Sisto TJ, Nuckolls C, Lambert TH. Angew. Chem. Int. Ed. 2019; 58: 13318
• 12 Fang W.-P, Cheng Y.-T, Cheng Y.-R, Cherng Y.-J. Tetrahedron 2005; 61: 3107
• 13a Li S, Yang W, Ji M, Cai J, Chen J. J. Chem. Res. 2019; 43: 14
• 13b Daluge SM, Martin MT, Sickles BR, Livingston DA. Nucleosides Nucleotides Nucleic Acids 2000; 19: 297
• 13c Showalter HD. H, Bridges AJ, Zhou H, Sercel AD, McMichael A, Fry DW. J. Med. Chem. 1999; 42: 5464
• 13d Timoshenko VM, Nikloin YV, Chernega AN, Shermolovich YG. Eur. J. Org. Chem. 2002; 1619
• 13e Wang J, Li Y.-H, Pan S.-C, Li M.-F, Du W, Yin H, Li JH. Org. Process Res. Dev. 2020; 24: 146
• 14a Niu H.-Y, Xia C, Qu G.-R, Zhang Q, Jiang Yi, Mao R.-Z, Li D.-Y, Guo H.-M. Org. Biomol. Chem. 2011; 9: 5039
• 14b Jiang J, Li J. ChemistrySelect 2020; 5: 542
• 15 Manna S, Serebrennikova PO, Utepova IA, Antonchik AP, Chupakhin ON. Org. Lett. 2015; 17: 4588
• 16 Bielawski M, Zhu M, Olofsson B. Adv. Synth. Catal. 2007; 349: 2610
• 17 Purkait N, Kervefors G, Linde E, Olofsson B. Angew. Chem. Int. Ed. 2018; 57: 11427
• 18 Carroll MA, Wood RA. Tetrahedron 2007; 63: 11349
• 19 Ma C, Zeng Q, Wu X, Zhou L, Huang Y. New J. Chem. 2017; 41: 2873
• 20 Sharp PP, Garnier J.-M, Hatfaludi T, Xu Z, Segal D, Jarman KE, Jousset H, Garnham A, Feutrill JT, Cuzzupe A, Hall P, Taylor S, Walkley CR, Tyler D, Dawson MA, Czabotar P, Wilks AF, Glaser S, Huang DC. S, Burns CJ. ACS Med. Chem. Lett. 2017; 8: 1298
• 21 Matsuzaki K, Okuyama K, Tokunaga E, Saito N, Shiro M, Shibata N. Org. Lett. 2015; 17: 3038
• 22 Zhu M, Jalalian N, Olofsson B. Synlett 2008; 592
• 23 Sokolovs I, Lubriks D, Sūna E. J. Am. Chem. Soc. 2014; 136: 6920
• 24 Kasahara T, Jang YJ, Racicot L, Panagopoulos D, Liang SH, Ciufolini MA. Angew. Chem. Int. Ed. 2014; 53: 9637
• 25 Bielawski M, Malmgren J, Pardo LM, Wikmark Y, Olofsson B. ChemistryOpen 2014; 3: 19
• 26 Tibiletti F, Simonetti M, Nicholas KM, Palmisano G, Parravicini M, Imbesi F, Tollari S, Penoni A. Tetrahedron 2010; 66: 1280
• 27 Gordon MR, Lindell SD, Richards D. Synlett 2018; 29: 473
• 28 Canela M.-D, Liekens S, Camarasa M.-J, Priego EM, Pérez-Pérez M.-J. Eur. J. Med. Chem. 2014; 87: 421
• 29 Easter JA, Burrell RC, Bonacorsi SJ. Jr. J. Labelled Compd. Radiopharm. 2013; 56: 632
• 30 Šála M, Kögler M, Plačková P, Mejdrová I, Hřebabecký H, Procházková E, Strunin D, Lee G, Birkus G, Weber J, Mertlíková-Kaiserová H, Nencka R. Bioorg. Med. Chem. Lett. 2016; 26: 2706
• 31 Mahajan TR, Gundersen L.-L. Tetrahedron Lett. 2015; 56: 5899
• 32 Šála M, De Palma AM, Hřebabecký H, Dejmek M, Dračínský M, Leyssen P, Neyts J, Mertlíková-Kaiserová H, Nencka R. Bioorg. Med. Chem. Lett. 2011; 21: 4271