Citation: Yong Li, Jie Lei, Jia Xu, Dian-Yong Tang, Zhong-Zhu Chen, Jin Zhu, Chuan Xu. A facile method for building fused quinoxaline-quinolinones via an acidless post-Ugi cascade reaction[J]. Chinese Chemical Letters, ;2017, 28(3): 541-545. doi: 10.1016/j.cclet.2016.10.027 shu

A facile method for building fused quinoxaline-quinolinones via an acidless post-Ugi cascade reaction

Yong Li ^a,b ,
Jie Lei ^a,b ,
Jia Xu ^a,b ,
Dian-Yong Tang ^b ,
Zhong-Zhu Chen ^b,, ,
Jin Zhu ^a,b ,
Chuan Xu ^c,,

a.
Key Laboratory for Asymmetric Synthesis and Chiral Technology of Sichuan Province Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
b.
Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, Chongqing 402160, China
c.
Department of Oncology, Chengdu Military General Hospital, Chengdu 610083, China

Corresponding author: Zhong-Zhu Chen, 18883138277@163.com Chuan Xu, 1535486239@qq.com
Received Date: 8 August 2016
Revised Date: 11 October 2016
Accepted Date: 14 October 2016
Available Online: 26 March 2016

Figures(4)

A series of quinolino[3, 4-b]quinoxalin-6(5H)-ones have been synthesized using an Ugi/deprotection/cyclization (UDC) strategy, followed by a nucleophilic aromatic substitution reaction. This facile microwave-assisted method provided good yields and could potentially be used for the construction of a diverse library of quinolino[3, 4-b]quinoxalin-6(5H)-ones for high-throughput screening in medicinal chemistry.
- Quinoxaline,
- Quinolino[3, 4-b]quinoxalin-6(5H)-one,
- Ugi/deprotection/cyclization (UDC) strategy,
- Nucleophilic substitution reaction,
- One-pot
1. [1]
  (a) E. Ruijter, R. Scheffelaar, R.V. Orru, Multicomponent reaction design in the quest for molecular complexity and diversity, Angew. Chem. Int. Ed. 50(2011) 6234-6246;
  (b) R.K. Li, Q.L. Yang, Y. Liu, et al., A novel and green synthesis of indolone-Namino acid derivatives via the Passerini three-component reactions in water, Chin. Chem. Lett. 27(2016) 345-348.
2. [2]
  (a) C.G. Neochoritis, J. Zhang, A. Dömling, Leuckart-Wallach approach to sugar isocyanides and its iMCRs, Synthesis 47(2015) 2407-2413;
  (b) Z. Hossaini, Solvent-free synthesis of substituted five membered heterocycles:one-pot reaction of primary amine and alkyl propiolate or isothiocyanate in the presence of oxalyl chloride, Chin. Chem. Lett. 25(2014) 159-162;
  (c) U.K. Sharma, N. Sharma, D.D. Vachhani, E.V.V. Eycken, Metal-mediated post-Ugi transformations for the construction of diverse heterocyclic scaffolds, Chem. Soc. Rev. 44(2015) 1836-1860;
  (d) G. Koopmanschap, E. Ruijter, R.V. Orru, Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics, Beilstein J. Org. Chem. 10(2014) 544-598.
3. [3]
  (a) B.H. Rotstein, S. Zaretsky, V. Rai, A.K. Yudin, Small heterocycles in multicomponent reactions, Chem. Rev. 114(2014) 8323-8359;
  (b) Z. Hossaini, F. Rostami-Charati, S. Seyfi, M. Ghambarian, Multicomponent reactions for the synthesis of functionalized 1, 4-oxathiane-3-thiones under microwave irradiation in water, Chin. Chem. Lett. 24(2013) 376-378;
  (c) G.R. Kuethe, J.T. Kuethe, Practical methodologies for the synthesis of indoles, Chem. Rev. 106(2006) 2875-2911.
4. [4]
  (a) A. Dömling, I. Ugi, Multicomponent reactions with isocyanides, Angew. Chem. Int. Ed. 39(2000) 3168-3210;
  (b) A. Dömling, Recent developments in isocyanide based multicomponent reactions in applied chemistry, Chem. Rev. 106(2006) 17-89.
5. [5]
  Patil P., Zhang J., Kurpiewska K., Kalinowska-Tłuścik J., Dömling A.. Hydrazine in the Ugi tetrazole reaction[J]. Synthesis, 2016,48:1122-1130. doi: 10.1055/s-00000084
6. [6]
  Dömling A., Wang W., Wang K.. Chemistry and biology of multicomponent reactions[J]. Chem. Rev., 2012,112:3083-3135. doi: 10.1021/cr100233r
7. [7]
  Sharma N., Li Z., Sharma U.K., Van der Eycken E.V.. Facile access to functionalized spiro[indoline-3, 2'-pyrrole]-2, 5'-diones via post-Ugi domino Buchwald-Hartwig/Michael reaction[J]. Org. Lett., 2014,16:3884-3887. doi: 10.1021/ol5019079
8. [8]
  Kalinski C., Umkehrer M., Schmidt J.. A novel one-pot synthesis of highly diverse indole scaffolds by the Ugi/Heck reaction[J]. Tetrahedron Lett., 2006,47:4683-4686. doi: 10.1016/j.tetlet.2006.04.127
9. [9]
  Xu Z., De Moliner F., Cappelli A.P., Hulme C.. Aldol reactions in multicomponent reaction based domino pathways:a multipurpose enabling tool in heterocyclic chemistry[J]. Org. Lett., 2013,15:2738-2741. doi: 10.1021/ol401068u
10. [10]
  Xu Z., De Moliner F., Cappelli A.P., Hulme C.. Ugi/aldol sequence:expeditious entry to several families of densely substituted nitrogen heterocycles[J]. Angew. Chem. Int. Ed., 2012,51:8037-8040. doi: 10.1002/anie.v51.32
11. [11]
  Kumar A., Li Z., Sharma S.K., Parmar V.S., Van der Eycken E.V.. An expedient route to imidazo[1, 4] diazepin-7-ones via a post-Ugi gold-catalyzed heteroannulation[J]. Org. Lett., 2013,15:1874-1877. doi: 10.1021/ol400526a
12. [12]
  Nicholas B.V., Bai F., Perez C.. Phenazine antibiotic inspired discovery of potent bromophenazine antibacterial agents against Staphylococcus aureus and Staphylococcus epidermidis[J]. Org. Biomol. Chem., 2014,12:881-886. doi: 10.1039/c3ob42416b
13. [13]
  Conda-Sheridan M., Marler L., Park E.J.. Potential chemopreventive agents based on the structure of the lead compound 2-bromo-1-hydroxyphenazine, isolated from streptomyces species, strain CNS284[J]. J. Med. Chem., 2010,53:8688-8699. doi: 10.1021/jm1011066
14. [14]
  Zeghida W., Debray J., Chierici S., Dumy P., Demeunynck M.. Concise synthesis of 2-amino-4(3H)-quinazolinones from simple (hetero) aromatic amines[J]. J. Org. Chem., 2008,73:2473-2475. doi: 10.1021/jo7026883
15. [15]
  Shekhar A.C., Rao P.S., Narsaiah B., Allanki D.A., Sijwali P.S.. Emergence of pyrido quinoxalines as new family of antimalarial agents[J]. Eur. J. Med. Chem., 2014,77:280-287. doi: 10.1016/j.ejmech.2014.03.010
16. [16]
  Pendergast W., Johnson J.V., Dickerson S.H.. Benzoquinazoline inhibitors of thymidylate synthase:enzyme inhibitory activity and cytotoxicity of some 3-amino-and 3-methylbenzo[f]quinazolin-1(2H)-ones[J]. J. Med. Chem., 1993,36:2279-2291. doi: 10.1021/jm00068a004
17. [17]
  Chern J.W., Tao P.L., Wang K.C.. Studies on quinazolines and 1, 2, 4-benzothiadiazine 1. 1-dioxides. 8.1, 2 Synthesis and pharmacological evaluation of tricyclic fused quinazolines and 1, 2, 4-benzothiadiazine 1, 1-dioxides as potential alpha1-adrenoceptor antagonists[J]. J. Med. Chem., 1998,41:3128-3141. doi: 10.1021/jm970159v
18. [18]
  Grosso J.A., Nichols E.D., Kohli J.D., Glock D.. Synthesis of 2-(alkylamino)-5, 6-and -6, 7-dihydroxy-3, 4-dihydroquinazolines and evaluation as potential dopamine agonists[J]. J. Med. Chem., 1982,25:703-708. doi: 10.1021/jm00348a018
19. [19]
  Song G., Li S., Yang Z.. Microwave-assisted synthesis of fused piperazinebenzimidazoles via a facile, one-pot procedure[J]. Tetrahedron Lett., 2015,56:4616-4618. doi: 10.1016/j.tetlet.2015.06.035
20. [20]
  Ou T., Lu Y., Tan J.. G-quadruplexes:targets in anticancer drug design[J]. ChemMedChem, 2008,3:690-713. doi: 10.1002/(ISSN)1860-7187
21. [21]
  L. El Kaïm, L. Grimaud, Isocyanide Chemistry:Ugi and Passerini Reactions with Carboxylic Acid Surrogates, Wiley-VCH, Weinheim, 2012, pp. 159-194.
22. [22]
  Avaz M., Martinez-Ariza G., Hulme C.. A robust protocol for the synthesis of quinoxalines and 5H-benzo[e][1, 4] di-azepines via the acidless Ugi reaction[J]. Synlett, 2014,25:1680-1684. doi: 10.1055/s-00000083
23. [23]
  Pan S., List B.. Catalytic three-component Ugi reaction[J]. Angew. Chem. Int. Ed., 2008,47:3622-3625. doi: 10.1002/(ISSN)1521-3773
24. [24]
  Chen Z., Zhang J., Tang D., Xu Z.. Synthesis of fused benzimidazole-quinoxalinones via UDC strategy and following the intermolecular nucleophilic substitution reaction[J]. Tetrahedron Lett., 2014,55:2742-2744. doi: 10.1016/j.tetlet.2014.03.063
25. [25]
  Xu Z., De Moliner F., Cappelli A.P., Hulme C.. Aldol reactions in multicomponent reaction based domino pathways:a multipurpose enabling tool in heterocyclic chemistry[J]. Org. Lett., 2013,15:2738-2741. doi: 10.1021/ol401068u
26. [26]
  Bhattacharya D., Mitra S., Chattopadhyay P.. A rapid one pot synthetic approach towards imidazole fused benzodiazepinone using Ugi reaction strategy[J]. Synthesis, 2015,47:2294-2298. doi: 10.1055/s-00000084
1. [1]
  Xiaochun Liu , Gaoyan Chen , Xiaodong Yue , Chaoyue Wang , Xue-Xin Zhang , Xuecheng Ran , Yingxiao Zong , Junke Wang , Xicun Wang . A novel N-stable Co₂P nano-catalyst for the synthesis of quinoxalines by annulation of alkynes and 1,2-diaminobenzenes. Chinese Chemical Letters, 2025, 36(8): 110707-. doi: 10.1016/j.cclet.2024.110707
2. [2]
  Ren Shen , Yanmei Fang , Chunxiao Yang , Quande Wei , Pui-In Mak , Rui P. Martins , Yanwei Jia . UV-assisted ratiometric fluorescence sensor for one-pot visual detection of Salmonella. Chinese Chemical Letters, 2025, 36(4): 110143-. doi: 10.1016/j.cclet.2024.110143
3. [3]
  Min Fu , Ruihan Wang , Wenqiang Liu , Sen Zhou , Chunhong Zhong , Yaohao Li , Pan He , Xin Li , Shiying Shang , Zhongping Tan . Improved one-pot protein synthesis enabled by a more precise assessment of peptide arylthioester reactivity. Chinese Chemical Letters, 2025, 36(7): 110542-. doi: 10.1016/j.cclet.2024.110542
4. [4]
  Mengxing Liu , Jing Liu , Hongxing Zhang , Jianan Tao , Peiwen Fan , Xin Lv , Wei Guo . One-pot accessing of meso–aryl heptamethine indocyanine NIR fluorophores and potential application in developing dye-antibody conjugate for imaging tumor. Chinese Chemical Letters, 2025, 36(4): 109994-. doi: 10.1016/j.cclet.2024.109994
5. [5]
  Jun-Gang Wang , Bing-Yi Zhou , Yao-Luo Hu , Yong-Dong Du , Rong-He Wu , Chun-Yan Wu , Wen-Chao Yang , An-Xin Wu . Atom-swapping skeletal editing of benzo[c]oxepines for the construction of 2-benzodiazepines via a continuous manufacturing one-pot synthesis. Chinese Chemical Letters, 2026, 37(4): 111200-. doi: 10.1016/j.cclet.2025.111200
6. [6]
  Yu Pang , Min Wang , Ning-Hua Yang , Min Xue , Yong Yang . One-pot synthesis of a giant twisted double-layer chiral macrocycle via [4 + 8] imine condensation and its X-ray structure. Chinese Chemical Letters, 2024, 35(10): 109575-. doi: 10.1016/j.cclet.2024.109575
7. [7]
  Chun-Ying Xu , Xiao-Lin Luan , Yuan-Yuan Cui , Cheng-Xiong Yang . One-pot in situ doping synthesis of phenylboronic acid-functionalized magnetic-cyclodextrin microporous organic network for specific enrichment and detection of sulfonylurea herbicides. Chinese Chemical Letters, 2025, 36(9): 110937-. doi: 10.1016/j.cclet.2025.110937
8. [8]
  Feng Han , Fuxian Wan , Ying Li , Congcong Zhang , Yuanhong Zhang , Chengxia Miao . Comprehensive Organic Chemistry Experiment: Phosphotungstic Acid-Catalyzed Direct Conversion of Triphenylmethanol for the Synthesis of Oxime Ethers. University Chemistry, 2025, 40(3): 342-348. doi: 10.12461/PKU.DXHX202405181
9. [9]
  Bingbing Dong , Junmin Zhang , Xiang-Yu Ye , Xuan Huang , Yonggui Robin Chi . Catalytic construction of P-stereogenic center via phosphorus-centered nucleophilic substitution. Chinese Chemical Letters, 2025, 36(9): 111052-. doi: 10.1016/j.cclet.2025.111052
10. [10]
  Zhen Liu , Zhi-Yuan Ren , Chen Yang , Xiangyi Shao , Li Chen , Xin Li . Asymmetric alkenylation reaction of benzoxazinones with diarylethylenes catalyzed by B(C₆F₅)₃/chiral phosphoric acid. Chinese Chemical Letters, 2024, 35(5): 108939-. doi: 10.1016/j.cclet.2023.108939
11. [11]
  Shuang Zhao , Fei Jia , Kaibei Zhan , Rui-Xi Wang , Pengfei Tan , Lin Shen , Li-Ming Wu , Ling Chen . Amino substitution strategy achieves significant blue shift while preserving high optical anisotropy: A₂(H₃C₃N₄S₂)₂•H₂O (A =NH₄, K, Rb, Cs). Chinese Chemical Letters, 2026, 37(3): 110625-. doi: 10.1016/j.cclet.2024.110625
12. [12]
  Zhirong Yang , Shan Wang , Ming Jiang , Gengchen Li , Long Li , Fangzhi Peng , Zhihui Shao . One stone three birds: Ni-catalyzed asymmetric allenylic substitution of allenic ethers, hydroalkylation of 1,3-enynes and double alkylation of enynyl ethers. Chinese Chemical Letters, 2024, 35(8): 109518-. doi: 10.1016/j.cclet.2024.109518
13. [13]
  Zhenguo Zhang , Lanyang Li , Xinlong Zong , Yongheng Lv , Shuanglei Liu , Liang Ji , Xuefei Zhao , Zhenhua Jia , Teck-Peng Loh . "Water" accelerated B(C₆F₅)₃-catalyzed Mukaiyama-aldol reaction: Outer-sphere activation model. Chinese Chemical Letters, 2025, 36(7): 110504-. doi: 10.1016/j.cclet.2024.110504
14. [14]
  Pan Gao , Qingzheng Kong , Ying Sun , Qian Ma , Qi Wang , Zeyu Guo , Ledi Li , Bingbing Li , Jingwei Xu , Xiaomei Jiang , Zhaolai Chen . One-dimensional (C12H12N)3Cu3I6 for high-performance direct X-ray detection. Chinese Journal of Structural Chemistry, 2026, 45(1): 100767-100767. doi: 10.1016/j.cjsc.2025.100767
15. [15]
  Yi-Kao Xu , Guo-Ping Luo , Liang-Bin Hu , Wei-Min He . Asymmetric Büchner reaction and arene cyclopropanation via copper-catalyzed controllable cyclization of diynes. Chinese Chemical Letters, 2025, 36(8): 111226-. doi: 10.1016/j.cclet.2025.111226
16. [16]
  Zhi-Long Li , Hao-Fei Ni , Bo Zhuang , Kun Ding , Da-Wei Fu , Qiang Guo , Meng-Meng Lun . Halogen substitution strategy for regulating the photoluminescence and dielectric response of ferroelastics. Chinese Chemical Letters, 2026, 37(4): 110755-. doi: 10.1016/j.cclet.2024.110755
17. [17]
  Linjie Ju , Zhongxi Huang , Qian Shen , Chan Fu , Shuanghe Li , Wenjie Duan , Chenfeng Xu , Weizhen An , Zhiqiang Zhai , Jifu Wei , Changmin Yu , Guoren Zhou . Glutathione depletion based Pt(Ⅳ) hybrid mesoporous organosilica delivery system to conquer cisplatin chemoresistance: A “one stone three birds” strategy. Chinese Chemical Letters, 2024, 35(10): 109450-. doi: 10.1016/j.cclet.2023.109450
18. [18]
  Lei Shen , Hongmei Liu , Ming Jin , Jinchao Zhang , Caixia Yin , Shuxiang Wang , Yutao Yang . “Three-in-one” strategy of trifluoromethyl regulated blood-brain barrier permeable fluorescent probe for peroxynitrite and antiepileptic evaluation of edaravone. Chinese Chemical Letters, 2024, 35(10): 109572-. doi: 10.1016/j.cclet.2024.109572
19. [19]
  Jun Huang , Jiangping Qin , Caijin Ban , Jingmei Yuan , Jing Yang , Guoping Yang . Visible-light induced cascade sulfonation/cyclization reaction in water towards sulfonated dihydroisoquinolino[1,2-b]quinazolinones. Chinese Chemical Letters, 2026, 37(2): 111379-. doi: 10.1016/j.cclet.2025.111379
20. [20]
  Fenglin Wang , Chengwei Kuang , Zhicheng Zheng , Dan Wu , Hao Wan , Gen Chen , Ning Zhang , Xiaohe Liu , Renzhi Ma . Noble metal clusters substitution in porous Ni substrate renders high mass-specific activities toward oxygen evolution reaction and methanol oxidation reaction. Chinese Chemical Letters, 2025, 36(6): 109989-. doi: 10.1016/j.cclet.2024.109989

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(1578)
HTML views(67)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142