Synthesis of 4-Tetrazolyl-Substituted 3,4-Dihydroquinazoline Derivatives with Anticancer Activity via a One-Pot Sequential Ugi-Azide/Palladium-Catalyzed Azide-Isocyanide Cross-Coupling/Cyclization Reaction

  • J Org Chem. 2022 Aug 5;87(15):9488-9496. doi: 10.1021/acs.joc.2c00382.
Jun Xiong  1 ,  Hui-Ting He  1 ,  He-Yu Yang  1 ,  Zhi-Gang Zeng  2 ,  Cheng-Ran Zhong  1 ,  Hang Shi  1 ,  Meng-Ling Ouyang  1 ,  Yuan-Yuan Tao  1 ,  Yong-Long Pang  1 ,  Yang-Hong Zhang  1 ,  Bo Hu  1 ,  Zi-Xiang Fu  1 ,  Xiao-Lei Miao  1 ,  Hai-Li Zhu  3 ,  Gang Yao  1
Affiliations
  • 1. School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, Hubei, P. R. China.
  • 2. School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, P. R. China.
  • 3. School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, P. R. China.
PMID: 35881945 DOI: 10.1021/acs.joc.2c00382
Abstract

A new one-pot preparation of 4-tetrazolyl-3,4-dihydroquinazolines has been reported. The Ugi-azide reactions of 2-azidobenzaldehydes, amines, trimethylsilyl azide, and isocyanides produced azide intermediates without separation, which were treated with isocyanides to give 4-tetrazolyl-3,4-dihydroquinazoline derivatives through a sequential Palladium-catalyzed azide-isocyanide cross-coupling/cyclization reaction in moderate to good yields. The biological evaluation demonstrated that compound 6c inhibited breast Cancer cells well and displayed broad applications for synthesis and medicinal chemistry.

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