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Synlett 2016; 27(10): 1547-1550
DOI: 10.1055/s-0035-1561577
letter
© Georg Thieme Verlag Stuttgart · New York

Rapid and Convenient Synthesis of Original 5-Substituted Quinolino[3,4-b]quinoxalin-6(5H)-ones under Eco-Friendly Conditions

Omar Khoumeri
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   eMail: patrice.vanelle@univ-amu.fr
,
François-Xavier Vanelle
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   eMail: patrice.vanelle@univ-amu.fr
,
Maxime D. Crozet
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   eMail: patrice.vanelle@univ-amu.fr
,
Thierry Terme
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   eMail: patrice.vanelle@univ-amu.fr
,
Patrice Vanelle*
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   eMail: patrice.vanelle@univ-amu.fr
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Publikationsverlauf

Received: 17. Dezember 2015

Accepted after revision: 15. Februar 2016

Publikationsdatum:
09. März 2016 (online)

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Abstract

We report herein the synthesis of 5-(substituted)quinolino[3,4-b]quinoxalin-6(5H)-one derivatives from ethyl 3-(2-bromophenyl)quinoxaline-2-carboxylate under one-pot Buchwald–Hartwig coupling–lactamization reaction.

Key words

quinoxaline - aromatic anilines - Buchwald–Hartwig reaction - lactamization reaction

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561577.
  • Supporting Information
 

  • References and Notes

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  • 17 Ethyl 3-(2-Bromophenyl)quinoxaline-2-carboxylate (3) To a mixture of ethyl 3-chloroquinoxaline-2-carboxylate (1 g, 4.22 mmol) and 2-bromophenylboronic acid (0.93 g, 4.64 mmol) in MeCN (30 mL), was added Pd(PPh3)4 (0.097 g, 0.084 mmol) and 2 M aq Na2CO3 solution (10 mL). The resulting mixture was stirred at 100 °C for 5 h. After cooling the mixture was diluted with CH2Cl2 and washed three times with H2O and dried over MgSO4. After filtration and evaporation of the solvent, the crude product was purified by silica gel chromatography with CH2Cl2 as eluent to furnish the product 3 as a yellow solid; yield 1.1 g (73%); mp 100 °C. 1H NMR (250 MHz, CDCl3): δ = 1.19 (t, J = 7.1 Hz, 3 H, CH3), 4.33 (q, J = 7.1 Hz, 2 H, CH2), 7.33–7.40 (m, 1 H, HAr), 7.45–7.85 (m, 2 H, HAr), 7.67 (d, J = 8.0 Hz, 1 H, HAr), 7.89–7.93 (m, 2 H, HAr), 8.19–8.23 (m, 1 H, HAr), 8.31–8.35 (m, 1 H, HAr). 13C NMR (62.5 MHz, CDCl3): δ = 13.7, 62.3, 122.1, 127.6, 129.3, 130.0, 130.3, 130.5, 131.0, 132.1, 132.3, 139.8, 140.4, 142.0, 144.4, 153.2, 164.7. Anal. Calcd for C17H13BrN2O2: C, 57.16; H, 3.67; N, 7.84. Found: C, 57.61; H, 3.61; N, 7.86.
  • 18 General Procedure for One-Pot Buchwald–Hartwig–Lactamization Reactions for the Synthesis of Compounds 5a–l A mixture of ethyl 3-(2-bromophenyl)quinoxaline-2-carboxylate (3, 50 mg, 0.14 mmol), aniline 4a (0.21 mmol, 1.5 equiv) in toluene (3 mL), Cs2CO3 (100 mg, 0.3 mmol), Pd(OAc)2 (6.2 mg, 0.028 mmol), and BINAP (14 mg, 0.021 mmol) was added to a 4 mL vial and the vial sealed. The resulting mixture was stirred at 110 °C for 5 h. After cooling the mixture was diluted with CH2Cl2, washed with H2O (3 × 40 mL) and dried over MgSO4. After filtration and evaporation, the crude product was purified by silica gel chromatography (CH2Cl2–Et2O, 97:3). 5-Phenylquinolino[3,4-b]quinoxalin-6(5H)-one (5a) Yield 97%; yellow solid; mp 240 °C. 1H NMR (250 MHz, CDCl3): δ = 6.73 (d, J = 7.9 Hz, 1 H, HAr), 7.38–7.46 (m, 4 H, HAr), 7.59–7.70 (m, 3 H, HAr), 7.87–8.01 (m, 2 H, HAr), 8,33 (d, J = 8.4 Hz, 1 H, HAr), 8.48 (d, J = 8.5 Hz, 1 H, HAr), 9.05–9.08 (m, 1 H, HAr). 13C NMR (62.5MHz, CDCl3): δ = 116.9, 119.6, 123.5, 125.8, 129.0, 129.2, 130.4, 130.4, 130.7, 131.0, 131.9, 132.9, 137.6, 140.5, 143.1, 144.5, 145.7, 160.3. Anal. Calcd for C21H13N3O: C, 78.00; H, 4.05; N, 13.00. Found: C, 78.12; H, 4.00; N, 12.91.