Synlett 2020; 31(09): 911-915
DOI: 10.1055/s-0039-1691743
letter
© Georg Thieme Verlag Stuttgart · New York

Convenient Synthesis of Furo[3,2-b]quinolin-4(1H)-ones

a  Department of Organic Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, 771 46 Olomouc, Czech Republic   Email: [email protected]
,
Miroslav Soural
a  Department of Organic Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, 771 46 Olomouc, Czech Republic   Email: [email protected]
b  Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 5, 779 00, Olomouc, Czech Republic
,
Radim Horák
a  Department of Organic Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, 771 46 Olomouc, Czech Republic   Email: [email protected]
,
Pavel Hradil
a  Department of Organic Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, 771 46 Olomouc, Czech Republic   Email: [email protected]
› Author Affiliations
This work was supported by the Ministry of Industry and Trade (project FV20250) and Palacky University (Grant Number IGA_PrF_2019_027).
Further Information

Publication History

Received: 19 December 2019

Accepted after revision: 10 February 2020

Publication Date:
26 February 2020 (online)


Abstract

In this work, we report the simple synthesis of furo[3,2-b]quinolin-4(1H)-ones from readily available 4-ethynyl-[1,3]dioxolo[4,5-c]quinolone as the key starting material. After Sonogashira (hetero)arylation, formation of the furoquinoline scaffold was accomplished using methanesulfonic acid and metal-free conditions. Although the cyclization was affected by the substitution of reaction intermediates, the method allowed the preparation of derivatives varying at the C3-position.

Supporting Information

 
  • References and Notes

  • 1 Adamska-Szewczyk A, Glowniak K, Baj T. Curr. Issues Pharm. Med. Sci. 2016; 29: 33
  • 2 Scala A, Cordaro M, Risitano F, Colao I, Venuti A, Sciortino MT, Primerano P, Grassi G. Mol. Divers. 2012; 16: 325
  • 3 Wang B, Li Q, Shi W, Chen L, Sun J. Chem. Biol. Drug Des. 2018; 91: 957
  • 4 Akula M, Yogeeswari P, Sriram D, Jha M, Bhattacharya A. RSC Adv. 2016; 6: 46073
  • 5 Xiao Z, Waters NC, Woodard CL, Li Z, Li P.-K. Bioorg. Med. Chem. Lett. 2001; 11: 2875
  • 6 Yamaguchi S, Tsuzuki K, Sannomiya Y, Oh-Hira Y, Kawase Y. J. Heterocycl. Chem. 1989; 26: 285
  • 7 Sun N, Du R.-L, Zheng Y.-Y, Huang B.-H, Guo Q, Zhang R.-F, Wong K.-Y, Lu Y.-J. Eur. J. Med. Chem. 2017; 135: 1
  • 8 Zhao M, Kamada T, Takeuchi A, Nishioka H, Kuroda T, Takeuchi Y. Bioorg. Med. Chem. Lett. 2015; 25: 5551
  • 9 Bierer DE, Dubenko LG, Zhang P, Lu Q, Imbach PA, Garofalo AW, Phuan P.-W, Fort DM, Litvak J, Gerber RE, Sloan B, Luo J, Cooper R, Reaven GM. J. Med. Chem. 1998; 41: 2754
  • 10 Lu YJ, Sun N, Huang ZS, Gu LQ. Chin. Chem. Lett. 2008; 19: 518
  • 11 Rádl S, Konvička P, Váchal P. J. Heterocycl. Chem. 2000; 37: 855
  • 12 Sundstrom TJ, Wright DL. Synlett 2010; 2875
  • 13 Beccalli EM, Broggini G, Martinelli M, Paladino G, Zoni C. Eur. J. Org. Chem. 2005; 2091
  • 14 Radchatawedchakoon W, Promthong N, Sakee U. Lett. Org. Chem. 2013; 10: 640
  • 15 Patil MD, Liu R.-S. Org. Biomol. Chem. 2019; 17: 4452
  • 16 Jean A, Rouden J, Maddaluno J, De Paolis M, Blanchet J. ­Tetrahedron Lett. 2019; 60: 534
  • 17 Gharpure SJ, Nanda SK, Shelke YG. Chem. Eur. J. 2017; 23: 10007
  • 18 Horak R, Koristek K, Samsulova V, Slaninova L, Grepl M, Kvapil L, Funk P, Hradil P, Soural M. J. Heterocycl. Chem. 2020; DOI: 10.1002/jhet.3886.
  • 19 Verma AK, Choudhary D, Saunthwal RK, Rustagi V, Patel M, Tiwari RK. J. Org. Chem. 2013; 78: 6657
  • 20 Tang J, Xu B, Mao X, Yang H, Wang X, Lv X. J. Org. Chem. 2015; 80: 11108
  • 21 Widner DL, Knauf QR, Merucci MT, Fritz TR, Sauer JS, Speetzen ED, Bosch E, Bowling NP. J. Org. Chem. 2014; 79: 6269
  • 22 Yue D, Yao T, Larock RC. J. Org. Chem. 2006; 71: 62
  • 23 Li J.-H, Zhang X.-D, Xie Y.-X. Synthesis 2005; 804
  • 24 Hamm DC, Braun LA, Burazin AN, Gauthier AM, Ness KO, Biebel CE, Sauer JS, Tanke R, Noll BC, Bosch E, Bowling NP. Dalton Trans. 2013; 42: 948
  • 25 Heidenreich RG, Kohler K, Krauter JG. E, Pietsch J. Synlett 2002; 1118
  • 26 Novák Z, Szabó A, Répási J, Kotschy A. J. Org. Chem. 2003; 68: 3327
  • 27 To a solution of alkyne 1 (200 mg, 0.54 mmol) in DMAC/H2O (9.5/0.5; 950 μL/50 μL), 10% Pd/C (0.05 equiv, 0.027 mmol, 29 mg), PPh3 (0.1 equiv, 0.054 mmol, 14 mg), CuI (0.1 equiv, 0.054 mmol, 10 mg), and DIPEA (3 equiv, 210 μL) were added. The reaction mixture was flushed with nitrogen, followed by addition of aryl or heteroaryl iodide (1 equiv). The reaction was heated to 70–75 °C and was monitored by TLC (hexane/EtOAc, 4:1). Upon completion (2–4 h), the reaction mixture was diluted with DCM and filtered through glass filter. Dark brown solution was evaporated, and the product was purified by column chromatography (hexane/EtOAc, 4:1 → EtOAc).Representative Product: 4-(Phenylethynyl)-[1,3]dioxolo[4,5-c]quinoline (2)Yield: 46%; mp 120–121 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 7.96 (d, J = 8.7 Hz, 1 H), 7.83 (d, J = 8.2 Hz, 1 H), 7.67 (td, J = 7.7, 1.7 Hz, 3 H), 7.56–7.60 (m, 1 H), 7.49–7.53 (m, 3 H), 6.48 (s, 2 H). 13C NMR (101 MHz, DMSO-d 6): δ = 149.1, 145.3, 142.1, 131.8, 129.9, 129.0, 128.9, 128.7, 127.3, 126.1, 120.9, 119.8, 115.1, 104.0, 93.4, 84.1. HRMS: m/z calcd for C18H11NO2 [M + H]: 274.0863; found: 274.0863.
  • 28 To a solution of alkyne 1 (1 equiv, 200 mg, 0.54 mmol) in acetonitrile (HPLC quality, 2 mL), PdCl2(PPh3)2 (0.02 equiv, 0.01 mmol, 7.6 mg), CuI (0.01 equiv, 0.005 mmol, 1 mg), and Et3N (3 equiv, 225 μL) were added. The reaction mixture was flushed with nitrogen, followed by addition of aryl or heteroaryl bromide/iodide (1 equiv). The reaction was heated to 50–55 °C and was monitored by TLC (hexane/EtOAc, 4:1). Upon completion (2–4 h), the reaction mixture was diluted with DCM and filtered through the glass filter. The dark brown solution was evaporated, and the product was purified by column chromatography (hexane/EtOAc, 4:1 → EtOAc).
  • 29 To a solution of quinoline 1 (50 mg, 1 equiv) in dioxane (0.5 mL), methanesulfonic acid (5 equiv) and water in volume ratio 1:2 were added. The reaction mixture was heated to 85–90 °C in the pressurized tube until the disappearance of starting material (monitored by LC–MS). After that, the reaction mixture was quenched by water (4 mL), and pH was adjusted on 6–7 by 10% NaOH. The precipitated solid was filtered off, washed with water, and dried. The crude product was purified by stirring in chloroform.Furo[3,2-b]quinolin-9(4H)-one (21)Yield 60%, mp 180–183 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 12.12 (s, 1 H), 8.24 (d, J = 8.2 Hz, 1 H), 8.14 (s, 1 H), 7.55–7.65 (m, 2 H), 7.26 (t, J = 7.3 Hz, 1 H), 6.86 (s, 1 H). 13C NMR (101 MHz, DMSO-d 6): δ = 164.0, 149.9, 139.6, 137.9, 137.5, 131.3, 125.4, 124.5, 121.4, 117.9, 102.3. HRMS: m/z calcd for C11H7NO2 [M + H]: 186.0550; found: 186.0551.
  • 30 Alabugin VI, Gonzalez-Rodriguez E, Kawade KR, Stepanov AA, Vasilevsky FS. Molecules 2019; 24: 1036