Synthesis of thieno[2,3-d]pyrimidine analogues from a thiophene moiety
Abstract
Four novel thieno[2,3-d]pyrimidine analogues, 6a-b and 7a-b were synthesized by using 6-Bromo-2-chloro-thieno[2,3-d]pyrimidine (3), which was synthesized from commercially available thiophene derivative, 2-aminothiophene-3-carboxylate (1). Initially, pyrimidine framework was performed by strong heating of 1 in formamide and then by using Vilsmeier reagent, conversion of 4-oxo group of 2 into chlorine was achieved. By regioselectivity approach at position 6 of 3 with n-BuLi and CBr4 at low temperature gives 4a-b. Introduction of Suzuki coupling reactions on 4a-b with 4-fluorophenylboronic acid afforded the desired compounds 5a-b respectively. Finally, by using different reagents under mild and vigorous conditions, the position 4 of 5a-b, 6a-b and 7a-b were synthesized.
Keywords:
Thieno[2,3-d]pyrimidine, 6-Bromo-2-chloro-thieno[2,3-d]pyrimidine, Vilsmeier reagent and Suzuki coupling.
References
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Bousquet E, Romeo G, Guerrera F, Caruso A, Amico-Roxas M. 1985. Synthesis and Antimicrobial Activity of Tricyclic Thienopyrimidines and 1, 3, 4-Triazole Fused Thienopyrimidines. Farmaco Ed Sci, 40, 869-874.
Cannito A, Perrissin M, Luu Duc C, Huguet F, Gaultier C, Narcisse G. 1990. Synthesis and pharmacological activities of some 3-substituted thienopyrimidin-4-one-2-thiones. Eur J Med Chem, 25, 635-639.
Devani MB, Shishoo JC, Pathak US, Shah GF, Padjya AC. 1976. Synthesis and Bioevaluation of Thieno[2,3-d]pyrimidinone Derivatives as Potential Tumor Cell Growth Inhibitors. J Pharm Sci, 65 (5), 660-664.
Gillespie E, Dungan KW, Gomol AW, Seidehamel RJ. 1985. Selected immunologic properties of tiprinast, a non-steroidal antiallergy agent. Int J Immunopharmacol, 7 (5), 655-660.
Gomoll AW and Temple DL. 1987. Mechanism of acute vasodepressor responses elicited by tiprinast and disodium cromoglycate following intravenous injection in anesthetized dog. Drug Dev Res, 10 (1), 57-62.
Hala M Aly, Nashwa M Saleh. 2011. Design and Synthesis of Some New Thiophene ,Thienopyrimidine and Thieno thiadiazine derivatives of antipyrine as potential antimicrobial agents. Eur J Med Chem, 46 (9), 4566-4572.
Ives JL and Heym J. 1989. Anti depressant agents-Radical Ideas about Monoamine Oxidase. J Ann Rep Med Chem, 24, 21-29.
Kent S. Gates and Richard B. Silverman. 1990. 5-(Aminomethyl)-3-aryl-2-oxazolidinones. A novel class of mechanism-based inactivators of monoamine oxidase B. J Am Chem Soc, 112 (25), 9364-9372.
El-Kashef HS, Geies AA, Kamal El-Dean AM, Abdel-Hafez AA. 1993. Synthesis of thieno[2,3‐c]pyridines and related heterocyclic systems. J Chem Tech Biotechn,, 57, 15-19.
Kharizomenova IA, Grinev AN, Samsonova NV, Panisheva EK, Kaplina NV, Nikolaeva IS, Pushkina TV, Pershin GN. 1981. Functional derivatives of thiophen XX. Synthesis and antiviral activity of 3-aminothieno[2,3-d]pyrimidines. Pharm Chem J, 15(9), 645-648.
Oganisyan AS, Noravyan AS, Dzhagatspanyan IA, Nazaryan IM, Akopyan AG. 2007. Derivatives of condensed thienopyrimidines: Synthesis and anticonvulsant and tranquilizer activity of hydrochlorides of pyrano [4′,3′:4,5]thieno[3,2-]imidazo[1,2a]pyrimidines. Pharm Chem J, 41, 588.
Perrissian M, Farve M, Cuong LD, Huguet F, Gaultier C, Narcisse G. 1988. Synthesis and pharmacological activities of some substituted thienopyrimidine-4-ones. Eur J Med Chem, 23 (5), 453-456.
Shwarsinh I, Rathod S, Pillai AS. 2000. Synthesis and analgesic activity of 2-arylamino-3-aryl-5-methyl-6-(substituted) thieno[2,3-d]pyrimidin-4(3H)-ones. Indian J Heterocycl Chem, 10, 93-96.
Russell RK, Press JB, Rampulla RA, McNally JJ, Falotico R, Keiser JA, Brigcht DA, Tobia A. 1988. Thiophene systems: Thienopyrimidinedione derivatives as potential antihypertensive agents. J Med Chem, 31, 1786-1793.
Russo F, Santagati A, Santagati M, Caruso A, Leone MG, Felice A, Amico-Roxas M. 1989. Studies on annelated thiazolopyrimidines IV. Synthesis and pharmacological properties of thiazolothienopyrimidine derivatives. Eur J Med Chem, 24 (1), 91-95.
Santagati A, Modica M, Santagati M, Caruso A, Cutuli V. 1994. Synthesis of 2,3-dihydro-3-amino-6-phenyl-2-thioxothieno [2,3-d]pyrimidin-4(1H)-one and of potential antiinflammatory agents 2-aryl-7-phenyl-3H,9H-pyrimido[2,1-b]thieno-[2',3':4,5]]1,3,4] thiadiazin-9-ones. Pharmazie, 49 (1), 64-65.
Shishoo JC, Shirsath VS, Rathod IS, Yande VD. 2000. Design, synthesis and antihistaminic (H1) activity of some condensed 3-aminopyrimidin-4(3H)-ones. Eur J Med Chem, 35 (3), 351-358.
Stewart AO, Bhatia PA, McCarty MC, Meena MV, Staeger MA, Arendsen Dl et al., 2001. Discovery of inhibitors of cell adhesion molecule expression in human endothelial cells. 1. Selective inhibition of ICAM-1 and E-selectin expression. J Med Chem, 15, 44 (6), 988-1002.
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Teja B, R., M, S., Kumar G , A., & K, P. (2018). Synthesis of thieno[2,3-d]pyrimidine analogues from a thiophene moiety. Journal of Integral Sciences, 1(3), 6-11. Retrieved from https://jisciences.com/index.php/journal/article/view/16
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