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CC BY-ND-NC 4.0 · SynOpen 2018; 02(02): 0207-0212
DOI: 10.1055/s-0037-1610157
DOI: 10.1055/s-0037-1610157
letter
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
Support 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)
![](https://www.thieme-connect.de/media/10.1055-s-00032269/201802/lookinside/thumbnails/so-2018-d0023-l_10-1055_s-0037-1610157-1.jpg)
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 - quinazolinoneSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610157.
- Supporting Information
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References and Notes
- 1a Asif M. Int. J. Med. Chem. 2014; 395637
- 1b Khan I. Ibrar A. Abbas N. Saeed A. Eur. J. Med. Chem. 2014; 76: 193
- 1c Jafari E. Khajouei MR. Hassanzadeh F. Hakimelahi GH. Khodarahmi GA. Res. Pharm. Sci. 2016; 11: 1
- 1d Khan I. Zaib S. Batool S. Abbas N. Ashraf Z. Iqbal J. Saeed A. Bioorg. Med. Chem. 2016; 24: 2361
- 2a Bozorov K. Ma HR. Zhao JY. Zhao HQ. Chen H. Bobakulov K. Xin XL. Elmuradov B. Shakhidoyatov K. Aisa HA. Eur. J. Med. Chem. 2014; 84: 739
- 2b Bozorov K. Nie LF. Zhao J. Aisa HA. Eur. J. Med. Chem. 2017; 140: 465
- 2c Bozorov K. Zhao J. y. Nie LF. Ma H.-R. Bobakulov K. Hu R. Rustamova N. Huang G. Efferth T. Aisa HA. RSC Advances 2017; 7: 31417
- 3a Dewal MB. Wani AS. Vidaillac C. Oupicky D. Rybak MJ. Firestine SM. Eur. J. Med. Chem. 2012; 51: 145
- 3b Aly AA. Ishak EA. Ramadan M. Germoush MO. El-Emary TI. Al-Muaikel NS. J. Heterocycl. Chem. 2013; 50: 451
- 3c Thiesen L. Kehler J. Clausen RP. Frølund B. Bundgaard C. Wellendorph P. J. Pharmacol. Exp. Ther. 2015; 354: 166
- 3d Actis ML. Ambaye ND. Evison BJ. Shao Y. Vanarotti M. Inoue A. McDonald ET. Kikuchi S. Heath R. Hara K. Hashimoto H. Fujii N. Bioorg. Med. Chem. 2016; 24: 4339
- 3e Wang X. Chen D. Yu S. Zhang Z. Wang Y. Qi X. Fu W. Xie Z. Ye F. Chem. Biol. Drug Des. 2016; 87: 499
- 3f Nie LF. Bozorov K. Niu C. Huang G. Aisa HA. Res. Chem. Intermed. 2017; 43: 6835
- 4a Narasimhan B. Kumari M. Jain N. Dhake A. Sundaravelan C. Bioorg. Med. Chem. Lett. 2006; 16: 4951
- 4b Narender M. Bhandaru JS. Kulandaivelu U. Jojula M. Adidala RR. Umadevi KR. Dusthackeer AV. N. Kaki VR. Akkinepally RR. Bioorg. Med. Chem. Lett. 2016; 26: 836
- 5 Lilienkampf A. Karkola S. Alho-Richmond S. Koskimies P. Johansson N. Huhtinen K. Vihko K. Wähälä K. J. Med. Chem. 2009; 52: 6660
- 6 Nara H. Sato K. Kaieda A. Oki H. Kuno H. Santou T. Kanzaki N. Terauchi J. Uchikawa O. Kori M. Bioorg. Med. Chem. 2016; 24: 6149
- 7 Mavrova AT. Dimov S. Yancheva D. Rangelov M. Wesselinova D. Tsenov JA. Eur. J. Med. Chem. 2016; 123: 69
- 8 Abbas SE. Abdel Gawad NM. George RF. Akar YA. Eur. J. Med. Chem. 2013; 65: 195
- 9 Ameen MA. Karsten S. Liebscher J. Tetrahedron 2010; 66: 2141
- 10 Theoclitou M.-E. Aquila B. Block MH. Brassil PJ. Castriotta L. Code E. Collins MP. Davies AM. Deegan T. Ezhuthachan J. Filla S. Freed E. Hu H. Huszar D. Jayaraman M. Lawson D. Lewis PM. Nadella MV. P. Oza V. Padmanilayam M. Pontz T. Ronco L. Russell D. Whitston D. Zheng X. J. Med. Chem. 2011; 54: 6734
- 11 Maiden TM. Harrity JP. Org. Biomol. Chem. 2016; 14: 8014
- 12 Maleki A. Rabbani M. Shahrokh S. Appl. Organomet. Chem. 2015; 29: 809
- 13 Tajbakhsh M. Ramezanpour S. Balalaie S. Bijanzadeh HR. J. Heterocycl. Chem. 2015; 52: 1559
- 14 Brown CE. Kong T. McNulty J. D’Aiuto L. Williamson K. McClain L. Piazza P. Nimgaonkar VL. Bioorg. Med. Chem. Lett. 2017; 27: 4601
- 15 Huang G. Roos D. Stadtmüller P. Decker M. Tetrahedron Lett. 2014; 55: 3607
- 16a Abbas SY. El-Bayouki KA. M. Basyouni WM. Synth. Commun. 2016; 46: 993
- 16b Zaytsev VP. Revutskaya EL. Nikanorova TV. Nikitina EV. Dorovatovskii PV. Khrustalev VN. Yagafarov NZ. Zubkov FI. Varlamov AV. Synthesis 2017; 49: 3749
- 17a Chen J. Wu D. He F. Liu M. Wu H. Ding J. Su W. Tetrahedron Lett. 2008; 49: 3814
- 17b Tamaddon F. Kazemi Varnamkhasti M. Synlett 2016; 27: 2510
- 18 Ramesh R. Kalisamy P. Malecki JG. Lalitha A. Synlett 2018; 29: 203
- 19 Bardajee RG. Ghaedi A. Hekmat S. Abarashi G. Mahdavi M. Akbarzadeh T. J. Sulfur Chem. 2017; 38: 519
- 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