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Synlett 2018; 29(10): 1395-1399
DOI: 10.1055/s-0036-1591565
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© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed Cascade Synthesis of [1,2,4]-Triazoloquinazolinones

Zhenbang Lou
a   School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, P. R. of China   Email: fuhua@mail.tsinghua.edu.cn
b   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
,
Ningning Man
b   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
,
Haijun Yang
b   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
,
Changjin Zhu
a   School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, P. R. of China   Email: fuhua@mail.tsinghua.edu.cn
,
Hua Fu  *
a   School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, P. R. of China   Email: fuhua@mail.tsinghua.edu.cn
b   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
› Author AffiliationsFinancial support from the National Natural Science Foundation of China (Grant No. 21772108) is gratefully acknowledged.
Further Information

Publication History

Received: 04 February 2018

Accepted after revision: 12 March 2018

Publication Date:
20 April 2018 (online)

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Abstract

An efficient and practical method for the synthesis of 1,2,4-triazolo[5,1-b]quinazolin-9(3H)-ones has been developed via the copper-catalyzed domino reactions of readily available substituted N′-acetyl-2-bromobenzohydrazides with cyanamide. The protocol uses inexpensive CuI as the catalyst, and no other ligand or additive was required. The target products were prepared in good to excellent yields with tolerance of various functional groups.

Key words

copper - domino reactions - [1,2,4]-triazoloquinazolinones - cyanamide - synthetic method

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591565.
  • Supporting Information
 

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  • 15 General Procedures for the Preparation of Compounds 3a–w: A Schlenk tube was charged with a mixture of CuI (0.03 mmol, 5.7 mg), Cs2CO3 (0.3 mmol, 98 mg), substituted N′-acetyl-2-bromobenzohydrazide 1 (0.3 mmol), cyanamide (2; 0.45 mmol, 19 mg) and anhyd DMF (3.0 mL). After being evacuated and recharged with Ar for three times, the tube was sealed and the mixture was allowed to stir at 120 °C for 10–15 h. After completion of the reaction, the mixture was cooled to r.t., and H2O (20 mL) was added to the mixture. The solution was extracted with CH2Cl2–MeOH (10:1; 3 × 10 mL), and the combined organic layers were dried over anhyd Na2SO4. The solution was concentrated, and the residue was purified by silica gel column chromatography (CH2Cl2–MeOH = 30:1 or 20:1) providing the target product (3a–x). Three representative examples are shown as follows: 6-Methyl-2-phenyl-[1,2,4]triazolo[5,1-b]quinazolin-9(3H)-one (3e): eluent: CH2Cl2–MeOH = 30:1. Isolated yield: 85% (70.4 mg); white solid; mp 352–353 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 8.16 (d, J = 6.5 Hz, 2 H), 8.11 (d, J = 8.2 Hz, 1 H), 7.54 (q, J = 6.4 Hz, 3 H), 7.27 (s, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 2.47 (s, 3 H). 13C NMR (151 MHz, DMSO-d6 ): δ = 161.6, 155.4, 151.5, 145.9, 139.5, 130.4, 130.1, 128.9 (2 × CH), 127.4, 126.7 (2 × CH), 124.4, 116.3, 111.3, 21.6. ESI–HRMS: m/z [M + Na]+ calcd for C16H12N4NaO: 299.0903; found: 299.0906. 7-Chloro-2-phenyl-[1,2,4]triazolo[5,1-b]quinazolin-9(3H)-one (3r): eluent: CH2Cl2–MeOH = 30:1. Isolated yield: 68% (60.4 mg); white solid; mp 281–283 °C. 1H NMR (600 MHz, DMSO-d 6): δ = 8.14–8.19 (m, 3 H), 7.88 (dd, J = 8.8, 2.4 Hz, 1 H), 7.51–7.58 (m, 4 H). 13C NMR (151 MHz, DMSO-d 6): δ = 161.6, 155.0, 151.3, 139.1, 134.5, 131.1, 129.9, 128.3 (2 × CH), 127.9, 127.1, 126.5 (2 × CH), 122.4, 116.6. ESI–HRMS: m/z [M + H]+ calcd for C15H10ClN4O: 297.0538; found: 297.0540. 2-Methyl-[1,2,4]triazolo[5,1-b]quinazolin-9(3H)-one (3w): eluent: CH2Cl2–MeOH = 30:1. Reaction time: 15 h. Isolated yield: 67% (40.3 mg); white solid; mp 312–314 °C. 1H NMR (600 MHz, DMSO-d 6): δ = 8.16 (d, J = 7.7 Hz, 1 H), 7.78 (t, J = 7.4 Hz, 1 H), 7.50 (d, J = 7.9 Hz, 1 H), 7.33 (t, J = 7.5 Hz, 1 H), 2.36 (s, 3 H). 13C NMR (151 MHz, DMSO-d 6): δ = 161.9, 155.2, 151.0, 139.7, 134.8, 127.3, 122.6, 117.2, 113.3, 14.4. ESI–HRMS: m/z [M + H]+ calcd for C10H9N4O: 201.0771; found: 201.0770.