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An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction

Dao-Lin Wang ,  Dong Wang ,  Liang Yan ,  Guang-Yu Pan ,  Jian-Nan Yang

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引用本文: Dao-Lin Wang,  Dong Wang,  Liang Yan,  Guang-Yu Pan,  Jian-Nan Yang. An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction[J]. Chinese Chemical Letters, 2016, 27(6): 953-956. doi: 10.1016/j.cclet.2016.02.007 shu
Citation:  Dao-Lin Wang,  Dong Wang,  Liang Yan,  Guang-Yu Pan,  Jian-Nan Yang. An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction[J]. Chinese Chemical Letters, 2016, 27(6): 953-956. doi: 10.1016/j.cclet.2016.02.007 shu

An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction

  • College of Chemistry and Chemical Engineering, Liaoning Key Laboratory of Synthesis and Application of Functional Compound, Bohai University, Jinzhou 121003, China

摘要: An efficient method for the synthesis of novel pyrido[3'',2'':4',5']thieno[3',2':2,3]pyrido [4,5:d][1,3]thiazolo[3,2-a]pyrimidine-4-one derivatives (5) has been developed using a Pictet-Spengler reaction between 2-(3-aminothieno[2,3-b]pyridin-2-yl)thiazolo[3,2-a] pyrimidin-5-one (3), which could be obtained from the condensation of 7-(chloromethyl)-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with 3-cyanopyridine-2-thione (2) via Thorpe-Ziegler isomerization, and aromatic aldehydes under NH2SO3H as catalysis in good yields.

English

    1. [1] A. Nefzi, J.M. Ostresh, R.A. Houghten, The current status of heterocyclic combinatorial libraries, Chem. Rev. 97 (1997) 449-472.

    2. [2] E.E. Flefel, M.A. Salama, M. El-Shahat, A novel synthesis of some new pyrimidine and thiazolopyrimidine derivatives for anticancer evaluation, Phosphorus, Sulfur Silicon Relat. Elem. 182 (2007) 1739-1756.

    3. [3] A.A. Abu-Hashem,M.M. Youssef, H.A.R. Hussein, Synthesis, antioxidant, antituomer activities of some new thiazolopyrimidines, pyrrolothiazolo pyrimidines and triazolopyrrolothiazolopyrimidines derivatives, J. Chin. Chem. Soc. 58 (2011) 41-48.

    4. [4] B. Tozkoparan, M. Ertan, P. Kelicen, R. Demirdamar, Synthesis and anti-inflammatory activities of some thiazolo[3,2-a]pyrimidine derivatives, II Farmaco 54 (1999) 588-593.

    5. [5] O. Alam, S.A. Khan, N. Siddiqui, W. Ahsan, Synthesis and pharmacological evaluation of newer thiazolo[3,2-a]pyrimidines for anti-inflammatory and antinociceptive activity, Med. Chem. Res. 19 (2010) 1245-1258.

    6. [6] S.F. Mohamed, E.M. Flefel, A.E. Amra, D.N. Abd El-Shafy, Anti-HSV-1 activity and mechanism of action of some new synthesized substituted pyrimidine, thiopyrimidine and thiazolopyrimidine derivatives, Eur. J. Med. Chem. 45 (2010) 1494-1501.

    7. [7] B. Pan, R. Huang, L. Zheng, et al., Thiazolidione derivatives as novel antibiofilm agents: design, synthesis, biological evaluation, and structure-activity relationships, Eur. J. Med. Chem. 46 (2011) 819-824.

    8. [8] I.V. Kulakov, Intramolecular cyclization of 4-aryl-3,4-dihydropyrimidine-(1H)-2-thiones to give bicyclic thiazolo[3,2-a]pyrimidines, Chem. Heterocycl. Compd. 45 (2009) 1019-1021.

    9. [9] A.E. Abbas, Z. Mahdieh, R.F. Ali, H. Azizollah, An efficient regioselective synthesis of highly functionalized 3-oxo-2,3-dihydro-5H-thiazolo[3,2-a] pyrimidines via an isocyanide-based three-component reaction, Tetrahedron Lett. 53 (2012) 1351-1353.

    10. [10] E.A. Abd El-Galil, S.S. Maigali, M.M. Abdulla, Synthesis, and analgesic and antiparkinsonian activities of thiopyrimidine, pyrane, pyrazoline, and thiazolopyrimidine derivatives from 2-chloro-6-ethoxy-4-acetylpyridine, Monatsh. Chem. 139 (2008) 1409-1415.

    11. [11] V.P. Litvinov, V.V. Dotsenko, S.G. Krivokolysko, The chemistry of thienopyridine, Adv. Heterocycl. Chem. 93 (2007) 117-178.

    12. [12] (a) C.G. Dave, P.R. Shah, A.B. Shah, K.C. Dave, et al., Synthesis and biological activity of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines, J. Indian Chem. Soc. 66 (1989) 48-50;

    13. [13]

      (b) V.L. Ivanov, V.A. Artemov, L.A. Rodinovskaya, et al., New approaches to the synthesis of functionally substituted pyrido[3'2':4,5]thieno[3,2-b] pyridines and the structure of the product obtained, Chem. Heterocycl. Compd. 32 (1996) 105-111;

    14. [14]

      (c) J.M. Quintela, C. Peinador, C. Veiga, et al., Synthesis and antiallergic activity of pyridothienopyrimidines, Bioorg. Med. Chem. Lett. 6 (1998) 1911-1925;

    15. [15]

      (d) L.A. Rodinovskaya, A.M. Shestopalov, A.V. Gromova, et al., One-pot synthesis of diverse 4-di(tri)fluoromethyl-3-cyanopyridine-2(1H)-thiones and their utilities in the cascade synthesis of annulated heterocycles, J. Comb. Chem. 10 (2008) 313-322;

    16. [16]

      (e) A.K. Elansary, A.A. Moneer, H.H. Kadry, et al., Synthesis and anticancer activity of some novel fused pyridine ring system, Arch. Pharm. Res. 35 (2012) 1909-1917.

    17. [13] A. Pictet, T.T. Spengler, Über die bildung von isochinolin-derivaten durch einwirkung von methylal auf phenyl-thylamin, phenyl-alanin und tyrosin, Ber. Dtsch. Chem. Ges. 44 (1911) 2030-2036.

    18. [14] (a) S.W. Youn, The Pictet-Spengler reaction: efficient carboncarbon bond forming reaction in heterocyclic synthesis, Org. Prep. Proced. Int. 38 (2006) 505-591;

    19. [19]

      (b) B. Kundu, P.K. Agarwal, S.K. Sharma, et al., Pictet-Spengler reaction revisited: engineering of tetherd biheterocycles into annulated polyheterocycles, Curr. Org. Synth. 9 (2012) 357-376.

    20. [15] (a) D.L. Wang, Q.T. Cui, S.S. Feng, et al., A new synrhesis approch to azuleno[2,1-b]pyridine-4(1H)-ones, Heterocyles 85 (2012) 697-704;

    21. [21]

      (b) D.L. Wang, Z. Dong, Q.T. Cui, et al., Synthesis of some pyrazole-fused pyrido[3,2-a]azulenes, Heterocyles 87 (2013) 2343-2350;

    22. [22]

      (c) D.L. Wang, Z. Dong, Z. Liu, et al., Efficient one-pot synthesis of 1,4-dihydropyridino[3,2-c]coumarins, Chin. J. Org. Chem. 34 (2014) 783-787;

    23. [23]

      (d) D.L. Wang, J.Y. Wu, D. Wu, et al., An efficient synthesis of 1-oxo-1, 2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles, Chin. Chem. Lett. 25 (2014) 1555-1558;

    24. [24]

      (e) D.L. Wang, D. Wu, W. Zhao, et al., An efficient synthesis of benzo[b]benzofurano[2,3-e][1,6]naphthyridine-8-ones, Chin. Chem. Lett. 26 (2015) 251-254.

    25. [16] S. Djekou, A. Gellisa, H. El-Kashef, P. Vanelle, Anefficient synthesis of new thiazolopyrimidinones under microwave irradiation, J. Heterocycl. Chem. 43 (2006) 1225-1229.

    26. [17] Physical and spectral (IR, NMR, Anal.) data: 5a: Mp > 300 ℃. IR (KBr, cm-1): v 1680 (C=O). 1H NMR (400 MHz, DMSO-d6): δ 7.49-7.53 (m, 3H), 7.63-7.64 (m, 1H), 7.68-7.71 (m, 3H), 8.07 (d, J = 4.8 Hz, 1H), 8.77 (d, J = 7.6 Hz, 1H), 8.87 (d, J = 3.6 Hz, 1H). 13C NMR (100 MHz, DMSO-d6): δ 107.6, 115.5, 123.1, 123.2, 123.3, 127.8, 128.6, 128.9, 129.6, 131.5, 132.8,135.8, 141.9, 144.4, 153.5, 155.3, 162.2, 170.3. Anal. Calcd. for C20H10N4OS2: C 62.16, H 2.61, N 14.50. Found: C 62.24, H 2.72, N 14.59. 5b: Mp > 300 ℃. IR (KBr, cm-1): n 1686 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 2.39 (s, 3H),7.29-7.31 (m, 2H), 7.41-7.49 (m, 3H), 7.64-7.66 (m, 1H), 8.02 (d, J = 4.8 Hz, 1H), 8.71 (d, J = 6.8 Hz, 1H), 8.81 (d, J = 4.0 Hz, 1H). 13C NMR (400 MHz, CF3CO2D): δ 19.5, 107.5, 123.1, 126.4, 127.9, 128.6, 129.6, 131.2, 135.3, 141.8, 141.9. 144.3, 145.1, 145.2, 153.4, 155.4, 155.5, 162.6, 170.2. Anal. Calcd. for C21H12N4OS2: C 62.98, H 3.02, N 13.99. Found: C 63.07, H 3.11, N 14.06. 5c: Mp > 300 ℃. IR (KBr, cm-1): v 1682 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 3.61 (s, 3H), 7.03-7.13 (m, 2H), 7.24-7.35 (m, 2H), 7.56-7.65 (m, 1H), 8.11-8.21 (m, 2H), 9.09-9.18 (m, 1H), 9.55-9.63 (m, 1H). 13C NMR (CF3CO2D): δ 54.8, 108.9, 111.3, 111.4, 118.7, 121.1, 122.9, 123.0, 123.2, 128.5, 131.4. 134.7, 136.1, 141.8, 144.3, 153.1, 153.4, 155.0, 158.8, 159.9, 170.1. Anal. Calcd for C21H12N4O2S2: C 60.56, H 2.90, N 13.45. Found: C 60.67, H 2.96, N 13.54. 5d: Mp > 300 ℃. IR (KBr, cm-1): v 1682 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 3.61 (s, 3H), 7.03-7.13 (m, 2H), 7.24-7.35 (m, 2H), 7.56-7.65 (m, 1H), 8.11-8.21 (m, 2H), 9.09-9.18 (m, 1H), 9.55-9.63 (m, 1H). 13C NMR (100 MHz, CF3CO2D): δ 54.8, 108.9, 111.3, 111.4, 118.7, 121.1, 122.9, 123.0, 123.2, 128.5, 131.4. 134.7, 136.1, 141.8, 144.3, 153.1, 153.4, 155.0, 158.8, 159.9, 170.1. Anal. Calcd. for C21H12N4O2S2: C 60.56, H 2.90, N 13.45. Found: C 60.67, H 2.96, N 13.54. 5e: Mp > 300 ℃. IR (KBr, cm-1): v 1689 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 4.00 (s, 3H), 7.25 (d, J = 7.2 Hz, 1H), 7.33 (s, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 4.8 Hz, 1H), 7.61-7.65 (m, 1H), 8.28-8.30 (m, 2H), 9.26 (d, J = 4.4 Hz, 1H), 9.72 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CF3CO2D): δ 55.3, 108.0, 113.5, 115.4, 117.4, 121.2, 123.4, 123.5, 128.8, 131.0, 131.2. 131.9, 136.0, 142.4, 144.7, 153.7, 153.8, 155.5, 159.0, 161.4, 170.7. Anal. Calcd. for C21H12N4O2S2: C 60.56, H 2.90, N 13.45. Found: C 60.64, H 2.98, N 13.56. 5f: Mp > 300 ℃. IR (KBr, cm-1): v 1685 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 4.02 (s, 3H), 7.22 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 4.8 Hz, 1H), 7.66 (d, J = 8.4 Hz, 2H), 8.26-8.29 (m, 2H), 9.23 (d, J = 5.6 Hz, 1H), 9.74 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CF3CO2D): δ 55.2, 107.7, 115.0, 115.8, 122.5, 123.5, 123.6, 129.0, 131.0, 131.4. 136.1, 142.3, 144.6, 157.8, 153.9, 155.9, 162.2, 163.4, 170.4. Anal. Calcd. for C21H12N4O2S2: C 60.56, H 2.90, N 13.45. Found: C 60.64, H 2.97, N 13.54. 5g: Mp > 300 ℃. IR (KBr, cm-1): v 1679 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 3.96 (s, 3H), 4.07 (s, 3H), 7.23 (d, J = 8.4 Hz, 1H), 7.29 (s, 1H), 7.34-7.36 (m, 1H), 7.54 (d, J = 4.8 Hz, 1H), 8.29-8.34 (m, 2H), 9.26 (d, J = 5.6 Hz, 1H), 9.76 (d, J = 8.4 Hz, 1H). 13C NMR (100 MHz, CF3CO2D): δ 55.4, 55.8, 108.0, 111.7, 112.6, 115.9, 122.8, 123.3, 123.5, 123.6, 129.0, 131.7. 136.2, 142.4, 144.7, 148.8, 153.0, 153.9, 154.0, 155.7, 161.7, 170.6. Anal. Calcd. for C22H14N4O3S2: C 59.18, H 3.16, N 12.55. Found: C 59.26, H 3.25, N 12.74. 5h: Mp > 300 ℃. IR (KBr, cm-1): v 1682 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 7.51-7.62 (m, 5H), 8.24-8.29 (m, 2H), 9.24 (d, J = 4.8 Hz, 1H), 9.70 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CF3CO2D): δ 107.9, 115.7, 123.4, 123.5, 123.9, 128.8, 129.5, 129.6, 131.8. 136.1, 140.5, 142.2, 144.7, 153.6, 153.7, 155.7, 161.2, 170.0. Anal. Calcd. for C20H9ClN4OS2: C 57.07, H 2.16, N 13.31. Found: C 57.14, H 2.25, N 13.38. 5i: Mp > 300 ℃. IR (KBr, cm-1): v 1688 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 7.29-7.31 (m, 2H), 7.48-7.49 (m, 1H), 7.64-7.65 (m, 2H), 8.23-8.29 (m, 2H), 9.22-9.28 (m, 1H), 9.68-9.70 (m, 1H). 13C NMR (100 MHz, CF3CO2D): δ 108.2, 116.6 (J = 20.9 Hz), 116.9, 123.7, 123.8, 125.9, 129.1, 131.2, 131.7. 132.0 (J = 8.3 Hz), 136.3, 142.4, 144.9, 154.0, 155.6, 164.9 (J = 243.6 Hz), 167.5, 170.8. Anal. Calcd. for C20H9FN4OS2: C 59.39, H 2.24, N 13.85. Found: C 59.47, H 2.35, N 13.95. 5j: Mp > 300 ℃. IR (KBr, cm-1): v 1683 (C=O). 1H NMR (400 MHz, CF3CO2D): d 7.45-7.51 (m, 1H), 7.79-86 (m, 2H), 8.10-8.12 (m, 2H), 8.21-8.23 (m, 2H), 9.18-9.25 (m, 1H), 9.62-9.69 (m, 1H). 13C NMR (100 MHz,CF3CO2D): δ 107.9, 123.1, 123.3, 123.8, 128.6, 129.5, 129.6, 132.0, 136.2. 136.4, 142.0, 144.6, 149.5, 153.4, 153.5, 154.6, 158.8, 170.5. Anal. Calcd. for C20H9N5O3S2: C 55.68, H 2.10, N 16.23. Found: C 55.75, H 2.17, N 16.30. 5k: Mp > 300 ℃. IR (KBr, cm-1): v 1689 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 6.67-6.89 (m, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.93 (d, J = 1.6 Hz, 1H), 8.10-8.12 (m, 1H), 8.32 (d, J = 4.8 Hz, 1H), 8.66 (d, J = 4.0 Hz, 1H), 9.14 (d, J = 4.2 Hz, 1H), 9.82-9.83 (m, 1H). 13C NMR (100 MHz, CF3CO2D): δ 104.9, 115.1, 118.3, 122.8, 123.3, 128.5, 129.3, 129.4, 135.1, 141.9, 142.2. 143.9, 146.6, 150.4, 153.6, 153.7, 154.3, 169.4. Anal. Calcd. for C18H8N4O2S2: C 57.44, H 2.14, N 14.88. Found: C 57.52, H 2.23, N 14.95. 5l: Mp > 300 ℃. IR (KBr, cm-1): v 1680 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 7.25-7.26 (d, J = 4.8 Hz, 1H), 7.46 (d, J = 4.8 Hz, 1H), 7.67 (d, J = 3.6 Hz, 1H), 7.88 (d, J = 4.8 Hz, 1H), 8.22-8.24 (m, 1H), 9.17 (d, J = 4.0 Hz, 1H), 9.17 (d, J = 4.6 Hz, 1H), 9.89 (d, J = 8.4 Hz, 1H). 13C NMR (100 MHz, CF3CO2D): δ 107.6, 118.2, 123.1, 123.2, 127.9, 128.2, 128.4, 131.8, 133.8, 133.9. 135.7, 141.9, 144.2, 153.3, 153.4, 154.9, 155.4, 170.0. Anal. Calcd. for C18H14N4OS3: C 55.08, H 2.05, N 14.28. Found: C 55.15, H 2.13, N 14.35. 5m: Mp > 300 ℃. IR (KBr, cm-1): v 1678 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 1.11 (t, J = 6.4 Hz, 3H), 1.84-1.86 (m, 2H), 3.71 (t, J = 6.8 Hz, 2H), 7.43 (d, J = 4.4 Hz, 1H), 8.21-8.24 (m, 1H), 8.30 (d, J = 4.4 Hz, 1H), 9.13 (d, J = 4.4 Hz, 1H), 9.66 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CF3CO2D): d 12.3, 22.9, 36.1, 107.7, 115.1, 123.1, 123.2, 128.5, 130.7 135.4, 141.7, 144.1, 153.3. 153.5, 154.7, 167.6, 169.9. Anal. Calcd. for C17H12N4OS2: C 57.93, H 3.43, N 15.90. Found: C 58.02, H 3.59, N 15.98. 5n: Mp. 269-271 ℃. IR (KBr, cm-1): v 1675 (C=O). 1H NMR (400 MHz, CF3CO2D): δ 0.91 (t, J = 6.4 Hz, 3H), 1.54-1.56 (m, 2H), 1.76-1.78 (m, 2H), 3.74 (t, J = 6.8 Hz, 2H), 7.42 (d, J = 4.8 Hz, 1H), 8.21-8.23 (m, 1H), 8.30 (d, J = 4.4 Hz, 1H), 9.12 (d, J = 3.2 Hz, 1H), 9.64 (d, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CF3CO2D): δ 11.5, 22.3, 31.4, 34.3, 107.7, 115.0, 123.0, 123.2, 128.5, 130.6 135.4, 141.3, 144.0, 153.2. 153.6, 154.7, 167.8, 169.9. Anal. Calcd. for C18H14N4OS2: C 58.99, H 3.85, N 15.29. Found: C 59.06, H 3.94, N 15.36.

    27. [18] (a) A.M. Shestopalov, A.E. Fedorov, P.A. Belyakov, Study of the orientation of the Thorpe-Ziegler reaction, Chem. Heterocycl. Comp. 36 (2000) 609-610;

    28. [28]

      (b) V. Gefenas,Ž. Stankevičūte, A. Malinauskas, Novel method for the synthesis of furo[2,3-d]pyrimidines by cyclization of 4-(phenacyloxy)pyrimidine-5-carbonitriles, Chem. Heterocycl. Comp. 46 (2010) 372-374;

    29. [29]

      (c) H.F. Zhang, Z.Q. Ye, G. Zhao, Enantioselective synthesis of functionalized fluorinated dihydropyrano[2,3-c]pyrazoles catalyzed by a simple bifunctional diaminocyclohexane-thiourea, Chin. Chem. Lett. 25 (2014) 535-540.

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