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CC BY-ND-NC 4.0 · SynOpen 2018; 02(02): 0207-0212
DOI: 10.1055/s-0037-1610157
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A Convenient One-pot Synthesis of 2,3-Disubstituted Thieno[2,3-d]pyrimidin-4(3H)-ones from 2H-Thieno[2,3-d][1,3]oxazine-2,4(1H)-diones, Aromatic Aldehydes and Amines

Feize Liu
a   Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, P. R. of China   Email: xlhou@ms.xjb.ac.cn   Email: guozheng.huang@yahoo.com
b   University of Chinese Academy of Sciences, Yuquan Rd 19 A, Beijing, 100049, P. R. of China
,
Xueling Hou*
a   Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, P. R. of China   Email: xlhou@ms.xjb.ac.cn   Email: guozheng.huang@yahoo.com
,
Li Fei Nie
a   Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, P. R. of China   Email: xlhou@ms.xjb.ac.cn   Email: guozheng.huang@yahoo.com
b   University of Chinese Academy of Sciences, Yuquan Rd 19 A, Beijing, 100049, P. R. of China
,
Khurshed Bozorov
a   Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, P. R. of China   Email: xlhou@ms.xjb.ac.cn   Email: guozheng.huang@yahoo.com
c   Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, Mirzo Ulugbek Str. 77, Tashkent, 100170, Uzbekistan
,
Michael Decker
d   Pharmazeutische und Medizinische Chemie, Institut für Pharmazie und Lebensmittelchemie, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074 Würzburg, Germany
,
Guozheng Huang*
a   Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, P. R. of China   Email: xlhou@ms.xjb.ac.cn   Email: guozheng.huang@yahoo.com
› Author AffiliationsSupport from the Chinese Recruitment Program of Global Experts (G. Huang) and National Foundation for Natural Science of China (K.Bozorov, Grant No. 21550110495) is gratefully acknowledged.

Further Information

Publication History

Received: 28 February 2018

Accepted after revision: 03 May 2018

Publication Date:
13 June 2018 (online)

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Abstract

An efficient, simple protocol has been established for convenient synthesis of novel 2,3-disubstituted thieno[2,3-d]pyrimidin-4(3H)-one derivatives in good to high yields through a one-pot, two-step and three-component reaction from 2H-thieno[2,3-d][1,3]oxazine-2,4(1H)-diones, aromatic aldehydes, and amines.

Key words

thieno[2,3-d]pyrimidin-4(3H)-one - one-pot synthesis - intramolecular cyclization - pyrimidinone - quinazolinone

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610157.
  • Supporting Information
 

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  • 20 Synthesis of 4a–ag; General ProcedureA mixture of 2H-benzo[4,5]thieno[2,3-d][1,3]oxazine-2,4(1H)-dione (0.366 mmol, 1.5 equiv), amine (0.366 mmol, 1.5 equiv) and aldehyde (0.244 mmol, 1.0 equiv) in EtOH was heated to reflux for 10–14 h. After TLC indicated that the aldehyde had been completely consumed, KOH (0.488 mmol, 2.0 equiv) was added and the mixture was heated to reflux for a further 6–10 h. Upon completion of the reaction (verified by TLC), the mixture was concentrated under reduced pressure and purified by silica gel chromatography, eluting with petroleum ether/ethyl acetate (10:1–2:1) to obtain the pure product.3-Benzyl-2-(4-chlorophenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one (4a): Yield: 62%; white solid; m.p. 157–159 °C; 1H NMR (400 MHz, CDCl3): δ = 7.35 (d, J = 8.1 Hz, 2 H), 7.30–7.19 (m, 4 H), 6.94 (t, J = 2.4 Hz, 2 H), 5.23 (s, 2 H), 3.08 (t, J = 5.1 Hz, 2 H), 2.81 (t, J = 5.6 Hz, 2 H), 2.02–1.82 (m, 4 H); 13C NMR (100 MHz, CDCl3): δ = 161.37 (CON), 158.81, 154.72, 136.68, 136.38, 134.74, 133.46, 132.01, 129.74 (2×CH), 128.92 (2×CH), 128.82 (2×CH), 127.65, 126.80 (2×CH),121.52, 48.49 (CH2Ph), 25 .78 (CH2), 25.48 (CH2), 23.09 (CH2), 22.42 (CH2). HRMS: m/z [M+H]+ calcd for C23H20ClN2OS: 407.09849; found: 407.09697.2-(4-Fluorophenyl)-3-(4-hydroxyphenethyl)-3,5,6,8-tetrahydro-4H-pyrano[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-one (4w): Yield: 62%; white solid; m.p.247–249 °C; 1H NMR (400 MHz, DMSO-d 6): δ = 9.23 (s, 1 H), 7.62–7.50 (m, 2 H), 7.42–7.30 (m, 2 H), 6.71–6.55 (m, 4 H), 4.78 (s, 2 H), 4.02–3.88 (m, 4 H), 3.03 (t, J = 4.5 Hz, 2 H), 2.69 (t, J = 7.6 Hz, 2 H); 13C NMR (100 MHz, DMSO-d 6): δ = 163.80 (CF), 161.34, 161.28, 157.59 (NCO), 155.99 (CPhOH), 155.11, 131.40, 130.83, 130.63/ 130.54, 129.27 (2×CH), 128.47, 127.76, 120.17, 115.48/115.27, 115.29 (2×CH), 64.36 (CH2), 63.94 (CH2), 46.99 (CH2N), 32.92 (CH2Ph), 26.02 (CH2); HRMS: m/z [M+H]+ calcd for C23H20FN2O3S: 423.11787; found: 423.11631.
  • 21 CCDC 1813089 contains the supplementary crystallographic data for compound 4w. The data can be obtained free of charge from www.ccdc.cam.ac.uk/getstructures