Efficient Synthesis of Functionalized Pyrido[2,3-c]coumarin Derivatives by a One-Pot Three-Component Reaction

Abstract

A methanesulfonic acid promoted three-component reaction has been developed for the synthesis of functionalized pyrido[2,3-c]coumarin derivatives from ketones, aromatic aldehydes, and 3-aminocoumarin. In this simple and efficient protocol, products were obtained in moderate to good yields (28 examples). The reaction proceeds by an asynchronous [4+2] cycloaddition (inverse-electron-demand Diels–Alder reaction).

Key words

multicomponent reactions - pyridocoumarins - ketones - aldehydes - cycloaddition reactions

• References and Notes

• 1a Murray RD. H. Nat. Prod. Rep. 1995; 12: 477
• 1b Estévez-Braun A, González AG. Nat. Prod. Rep. 1997; 14: 465
• 1c Vermeer C, Schurgers LJ. Hematol. Oncol. Clin. North Am. 2000; 14: 339
• 1d Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS. Arch. Intern. Med. 2005; 165: 1095
• 1e Isambert N, Lavilla R. Chem. Eur. J. 2008; 14: 8444
• 1f Touré BB, Hall DG. Chem. Rev. 2009; 109: 4439
• 2a Badran MM, Ismail MM, El-Hakeem A. Egypt. J. Pharm. Sci. 1992; 33: 1081
• 2b El-Farargy AF. Egypt. J. Pharm. Sci. 1991; 32: 625
• 2c Nofal ZM, El-Masry H, Fahmy HH, Sarhan I. Egypt. J. Pharm. Sci. 1997; 38: 1
• 2d Nofal ZM, El-Zahar MI, Abd-El-Karim SS. Molecules 2000; 5: 99
• 2e Vijaykumar PR, Reddy RV, Rao VR. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2003; 42: 1738
• 2f Venugopala KN, Jayashree BS. Indian J. Heterocycl. Chem. 2003; 12: 307
• 2g Vaccaro W, Yang BV, Kim S.-H, Huynh T, Tortolani DR, Leavitt K, Li W, Doweyko AM, Chen X.-T, Doweyko L. WO 2004009017, 2004
• 3 Kulkarni YD, Srivastava D, Bishnoi A, Dua PR. J. Indian Chem. Soc. 1996; 73: 173
• 4 Marcu MG, Schulte TW, Neckers L. J. Natl. Cancer Inst. 2000; 92: 242
• 5 Melagraki G, Afantitis A, Igglessi-Markopoulou O, Detsi A, Koufaki M, Kontogiorgis C, Hadjipavlou-Litina DJ. Eur. J. Med. Chem. 2009; 44: 3020
• 6 Kolotilo NV, Sinitsa AA, Rassukana YuV, Onys’ko PP. Zh. Obshch. Khim. 2006; 76: 1260 ; Chem. Abstr. 2006, 146, 316980
• 7a Rodighiero G, Antonello C. Boll. Chim. Farm. 1958; 97: 592
• 7b Irgolic KJ In Houben–Weyl . Klamann D. Thieme; Stuttgart: 1990. 4th ed., Vol. E12b, 150
• 8a Hammond PR, Atkins RL. J. Heterocycl. Chem. 1978; 12: 1061
• 8b Atkins RL, Bliss DE. J. Org. Chem. 1978; 43: 1975
• 8c Grandberg II, Denisov LK, Popova OA. Khim. Geterotsikl. Soedin. 1987; 2: 147
• 9 Fujimoto A, Sakurai A, Iwase E. Bull. Chem. Soc. Jpn. 1976; 49: 809
• 10 Khan MA, Gremal AL. J. Heterocycl. Chem. 1977; 14: 1009
• 11 Pavé G, Chalard P, Viaud-Massuard M.-C, Troin Y, Guillaumet G. Synlett 2003; 987
• 12 Majumdar KC, Chattopadhyay B, Taher A. Synthesis 2007; 3647
• 13a Kudale AA, Kendall J, Miller DO, Collins JL, Bodwell GJ. J. Org. Chem. 2008; 73: 8437
• 13b Kudale AA, Miller DO, Dawe LN, Bodwell GJ. Org. Biomol. Chem. 2011; 9: 7196
• 13c Khan AT, Das DK, Islam K, Das P. Tetrahedron Lett. 2012; 53: 6418
• 13d Belala M, Das DK, Khan AT. Synthesis 2015; 47: 1109
• 14a Dömling A, Wang W, Wang K. Chem. Rev. 2012; 112: 3083
• 14b Sadjadi S, Heravi MM. Tetrahedron 2011; 67: 2707
• 14c Wan J.-P, Liu Y.-Y. RSC Adv. 2012; 2: 9763
• 14d Isambert N, Lavilla R. Chem. Eur. J. 2008; 14: 8444
• 14e Touré BB, Hall DG. Chem. Rev. 2009; 109: 4439
• 15 Chen Z, Zhu Q, Su W. Tetrahedron Lett. 2011; 52: 2601
• 16 Chen Z, Bi J, Su WK. Chin. J. Chem. 2013; 31: 507
• 17 Chen Z. Yang X., Su W. 2015; 56: 2476
• 18 Kudale AA, Kendall J, Warford CC, Wilkins ND, Bodwell GJ. Tetrahedron Lett. 2007; 48: 5077
• 19a Gao Q, Liu S, Wu X, Zhang J, Wu A. J. Org. Chem. 2015; 80: 5984
• 19b Pottie IR, Nandaluru PR, Benoit WL, Miller DO, Dawe LN, Bodwell GJ. J. Org. Chem. 2011; 76: 9015
• 19c Dang AT, Miller DO, Dawe LN, Bodwell GJ. Org. Lett. 2008; 10: 233
• 20 Pyrido[2,3-c]coumarins 4; General Procedure A dry 25 mL flask was charged with 3-aminocoumarin (1a; 1 mmol), aromatic aldehyde 2 (1 mmol), ketone 3 (1 mmol), MsOH (1 mmol), and MeCN (5 mL). The mixture was stirred at the reflux temperature for 2.5−8 h until the reaction was complete (TLC) and then cooled to r.t. The crystalline solids were collected and washed with a little cold MeCN to give the pure product. 3-(3-Chlorophenyl)-1-phenyl-5H-chromeno[3,4-b]pyridin-5-one (4f) Pale-yellow powder; yield: 329 mg (86%); mp 241–243 °C; ¹H NMR (400 MHz, CDCl₃): δ = 8.16 (s, 1 H), 8.09–8.06 (m, 1 H), 7.90 (s, 1 H), 7.57–7.55 (m, 3 H), 7.45–7.38 (m, 4 H), 7.36–7.33 (m, 2 H), 7.04 (d, J = 8.0 Hz, 1 H), 6.89–6.85 (m, 1 H); ¹³C NMR (100 MHz, CDCl₃): δ = 158.9, 155.9, 151.0, 149.3, 139.6, 139.4, 138.9, 135.2, 130.8, 130.3, 129.8, 129.4, 128.9, 128.3, 127.9, 127.7, 127.5, 125.6, 123.9, 117.9, 117.2. HRMS-ESI: m/z [M + H]⁺ calcd for C₂₄H₁₅ClNO₂: 384.0786; found: 384.0794. 3-(1-Naphthyl)-1-phenyl-5H-chromeno[3,4-b]pyridin-5-one (4l) Pale-yellow powder; yield: 331 mg (83%); mp 237–239 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.24–8.23 (m, 1 H), 7.94–7.91 (m, 2 H), 7.84 (s, 1 H), 7.78–7.77 (m, 1 H), 7.53–7.46 (m, 8 H), 7.39 (d, J = 8.0 Hz, 2 H). 7.11 (d, J = 8.0 Hz, 1 H) 6.92 – 6.88 (m, 1 H), ¹³C NMR (100 MHz, CDCl₃): δ = 159.4, 158.6, 150.8 , 148.2, 139.2, 139.1, 136.1, 133.7, 131.9, 130.8, 130.3, 129.7, 129.3, 128.9, 128.3, 128.2, 128.0, 127.6, 126.8, 125.9, 125.0, 124.9, 123.5, 117.6, 116.9. HRMS-ESI: m/z [M + H]⁺ calcd for C₂₈H₁₈NO₂: 400.1332; found: 400.1327. 3-Phenyl-1-(4-tolyl)-5H-chromeno[3,4-b]pyridin-5-one (4m) Pale-yellow powder; yield: 283 mg (78%); mp 208–210 °C. ¹H NMR (400 MHz,CDCl₃): δ = 8.18–8.15 (m, 2 H), 7.90 (s, 1 H), 7.49–7.41 (m, 3 H), 7.35–7.29 (m, 6 H), 7.11 (d, J = 8.0 Hz, 1 H) 6.90–6.86 (m, 1 H), 2.49 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 158.7, 157.1, 150.7, 148.8, 139.0, 138.9, 136.9, 136.6, 130.0, 129.9, 129.9, 128.6, 128.1, 127.9, 127.5, 127.4, 127.1, 123.4, 117.5, 117.1, 21.4. HRMS-ESI: m/z [M + H]⁺ calcd for C₂₅H₁₈NO₂: 364.1332; found: 364.1316. 1-(4-Fluorophenyl)-3-phenyl-5H-chromeno[3,4-b]pyridin-5-one (4p) White powder; yield: 315 mg (86%); mp 278–280 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.31–8.29 (m, 2 H), 8.22 (s, 1 H), 7.63–7.59 (m, 2 H), 7.57–7.51 (m, 3 H), 7.46–7.40 (m, 4 H), 7.02–6.94 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 164.2, 161.8, 158.6, 157.4, 150.8, 147.6, 139.2, 136.9, 135.6, 130.4, 130.1, 130.0, 128.8, 128.0, 127.4, 127.3, 127.2, 123.6, 117.8, 116.9, 116.7, 116.5. HRMS-ESI: m/z [M + H]⁺ calcd for C₂₄H₁₅FNO₂: 368.1081; found: 368.1065. 8-Phenyl-9,10,11,12-tetrahydro-6H-chromeno[3,4-c]isoquinolin-6-one (4v) Pale-yellow powder; yield: 277 mg (85%); mp 217–219 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.25 (d, J = 8.4 Hz, 1 H), 7.52–7.32 (m, 8 H), 3.36 (s, 2 H), 2.85 (s, 2 H), 1.88 (s, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 160.6, 159.1, 150.7, 144.9, 139.3, 137.0, 135.7, 129.8, 129.6, 128.8, 128.1, 128.0, 127.8, 123.7, 118.0, 117.8, 31.7, 28.9, 22.5, 21.6. HRMS-ESI: m/z [M + H]⁺ calcd for ­C₂₂H₁₈NO₂: 328.1332; found: 328.1323. 2-Methyl-1,3-diphenyl-5H-chromeno[3,4-b]pyridin-5-one (4x) Pale-yellow powder; yield: 268 mg (74%); mp 228–230 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.68–7.50 (m, 8 H), 7.40–7.35 (m, 4 H), 6.86–6.83 (m, 1 H), 6.63–6.61 (m, 1 H), 2.09 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 160.8, 158.9, 150.9, 147.8, 139.3, 138.6, 136.2, 129.9, 129.2, 128.6, 128.5, 128.1, 127.3, 123.5, 117.6, 117.3, 19.3. HRMS-ESI: m/z [M + H]⁺ calcd for C₂₅H₁₈NO₂: 364.1332; found: 364.1315.