Synthesis of Difluoromethyl-Substituted Quinazolines through Selective Difluoromethylation

Abstract

A highly selective difluoromethylation of quinazolines has been achieved by using commercially available ethyl bromodifluoroacetate as difluorocarbene precursor, providing the corresponding difluoromethyl substituted quinazoline derivatives with up to 83% yield.

Key words

difluoromethylation - quinazoline - ethyl bromodifluoroacetate - difluoromethyl substituted quinazoline - difluorocarbene

Publication History

Received: 26 December 2020

Accepted after revision: 27 January 2021

Accepted Manuscript online:
27 January 2021

Article published online:
22 February 2021

• References

• 1a Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology. Wiley-Blackwell; Chichester: 2009
• 1b Kirsch P. Modern Fluoroorganic Chemistry: Synthesis Reactivity, Application. Wiley-VCH; Weinheim: 2013
• 1c Buer BC, Chugh J, Al-Hashimi HM, Marsh EN. G. Biochemistry 2010; 49: 5760
• 1d Nie J, Guo H.-C, Cahard D, Ma J.-A. Chem. Rev. 2011; 111: 455
• 1e Liu Q, Ni C, Hu J. Natl. Sci. Rev. 2017; 4: 303
• 1f Chen M.-W, Yang Q, Deng ZH, Ding QP, Peng YY. J. Org. Chem. 2019; 84: 10371
• 2a Zafrani Y, Yeffet D, Sod-Moriah G, Berliner A, Amir D, Marciano D, Gershonov E, Saphier S. J. Med. Chem. 2017; 60: 797
• 2b Sessler CD, Rahm M, Becker S, Goldberg JM, Wang F, Lippard SJ. J. Am. Chem. Soc. 2017; 139: 9325
• 3a Sorbera LA, Leeson PA, Castaner J. Drugs Future 2000; 25: 1261
• 3b Gomila I, Barceló B, Rosell A, Avella S, Sahuquillo L, Dastis M. J. Anal. Toxicol. 2017; 41: 760
• 4 Brahms DL. S, Dailey WP. Chem. Rev. 1996; 96: 1585
• 5 Nawrot E, Jonczyk A. J. Fluorine Chem. 2006; 127: 943
• 6 Thomoson CS, Dolbier WR. J. Org. Chem. 2013; 78: 8904
• 7a Hu J. J. Fluorine Chem. 2009; 130: 1130
• 7b Zheng J, Li Y, Hu J, Meuzelaar GJ, Federsel H.-J. Chem. Commun. 2007; 5149
• 8 Zhang L, Zheng J, Hu J. J. Org. Chem. 2006; 71: 9845
• 9a Ando M, Wada T, Sato N. Org. Lett. 2006; 8: 3805
• 9b Mehta VP, Greaney MF. Org. Lett. 2013; 15: 5036
• 10 Chen QY, Wu SW. J. Fluorine Chem. 1989; 44: 433
• 11 Zafrani Y, Sod-Moriah G, Segall Y. Tetrahedron 2009; 65: 5278
• 12a Xie Q, Ni C, Zhang R, Li L, Rong J, Hu J. Angew. Chem. Int. Ed. 2017; 56: 3206
• 12b Hu M, Ni C, Li L, Han Y, Hu J. J. Am. Chem. Soc. 2015; 137: 14496
• 13 Fier PS, Hartwig JF. Angew. Chem. Int. Ed. 2013; 52: 2092
• 14 Shen X, Zhou M, Ni C, Zhang W, Hu J. Chem. Sci. 2014; 5: 117
• 15 Miller TG, Thanassi JW. J. Org. Chem. 1960; 25: 2009
• 16a Liu J.-B, Yan H. Tetrahedron Lett. 2013; 54: 891
• 16b Lu H, Yang Q, Zhou YR, Guo YQ, Deng ZH, Ding QP, Peng YY. Org. Biomol. Chem. 2014; 12: 758
• 16c Zhang CY, Zhou YR, Deng ZH, Chen X, Peng YY. Eur. J. Org. Chem. 2015; 1735
• 16d Peng YY, Zeng MJ, Wang HM, Zhu J, Yang Q, Deng ZH, Yu CY. Tetrahedron 2015; 71: 9457
• 16e Liu J.-B, Zhou H.-P, Peng Y. -Y. Tetrahedron Lett. 2014; 55: 2872
• 16f Gao W, Ding Q, Yuan J, Mao X, Peng Y. Chin. J. Chem. 2017; 35: 1717
• 17 Sun X, Yu S. Org. Lett. 2014; 16: 2938
• 18 Polley A, Bairy G, Das P, Jana R. Adv. Synth. Catal. 2018; 360: 4161
• 19a Morimoto K, Makino K, Sakata G. J. Fluorine Chem. 1992; 59: 417
• 19b Ando M, Wada T, Sato N. Org. Lett. 2006; 8: 3805
• 19c Rakhimov AI, Kameneva IY, Navrotskii MB, Titova ES, Kudashev SV. Zh. Obshch. Khim. 2008; 78: 828
• 19d Fuchibe K, Koseki Y, Aono T, Sasagawa H, Ichikawa J. J. Fluorine Chem. 2012; 133: 52
• 19e Maiti S, Kim J, Park J.-H, Nam D, Lee JB, Kim Y.-J, Kee J.-M, Seo JK, Myung K, Rohde J.-U, Choe W, Kwon O.-H, Hong SY. J. Org. Chem. 2019; 84: 6737
• 20 Hour M.-J, Huang L.-J, Kuo S.-C, Yia Y, Bastow K, Nakanishi Y, Hamel E, Lee K.-H. J. Med. Chem. 2000; 43: 4479
• 21 Wei L.-S, He G.-X, Kong X.-F, Peng C.-X, Mo D.-L, Su G.-F. J. Org. Chem. 2018; 83: 6719
• 22 Zhang YG, Huang J, Deng ZH, Mao XC, Peng YY. Tetrahedron 2018; 74: 2330
• 23 Li H, He L, Neuman H, Beller M, Wu X.-F. Green Chem. 2014; 16: 1336