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Synlett 2016; 27(12): 1888-1892
DOI: 10.1055/s-0035-1561610
DOI: 10.1055/s-0035-1561610
letter
Efficient Synthesis of Functionalized Pyrido[2,3-c]coumarin Derivatives by a One-Pot Three-Component Reaction
Further Information
Publication History
Received: 30 December 2015
Accepted after revision: 20 March 2016
Publication Date:
18 April 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201612/lookinside/thumbnails/st-2015-w1005-l_10-1055_s-0035-1561610-1.jpg)
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 reactionsSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561610.
- Supporting Information
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References and Notes
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- 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.