Synthesis of Pyrimidine-Annulated Five-Membered Heterocycles: An Overview

(a) Singh, K.; Singh, K.; Wan, B.; Franzblau, S.; Chibale, K.; Balzarini, J. Facile transformation of Biginelli pyrimidin-2(1H)-ones to pyrimidines. In vitro evaluation as inhibitors of Mycobacterium tuberculosis and modulators of cytostatic activity. Eur. J. Med. Chem., 2011, 46(6), 2290-2294.
[http://dx.doi.org/10.1016/j.ejmech.2011.03.010] [PMID: 21450375]
(b) Lauria, A.; Patella, C.; Abbate, I.; Martorana, A.; Almerico, A.M. Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents. Eur. J. Med. Chem., 2012, 55, 375-383.
[http://dx.doi.org/10.1016/j.ejmech.2012.07.046] [PMID: 22892346 ]
(c) Roopan, S.M.; Khan, F.N.; Mandal, B.K. Fe nano particles mediated C-N bond-forming reaction: Regioselective synthesis of 3-[(2-chloroquinolin-3-yl)methyl]pyrimidin-4(3H)ones. Tetrahedron Lett., 2010, 51, 2309-2311.
[http://dx.doi.org/ 10.1016/j.tetlet.2010.02.128]
(d) Bharathi, A.; Roopan, S.M.; Vasavi, C.S.; Gayathri, G.A.; Gayathri, M. In silico molecular docking and in vitro antidiabetic studies of dihydropyrimido[4,5-a]acridin-2-amines. Biomed. Res. Inter., 2014, 971569, 1-9.
(e) Abou El Ella, D.A.; Ghorab, M.M.; Noaman, E.; Heiba, H.I.; Khalil, A.I. Molecular modeling study and synthesis of novel pyrrolo[2,3-d]pyrimidines and pyrrolotriazolopyrimidines of expected antitumor and radioprotective activities. Bioorg. Med. Chem., 2008, 16(5), 2391-2402.
[http://dx.doi.org/10.1016/j.bmc.2007.11.072] [PMID: 18086527]
(f) Gebauer, M.G.; McKinlay, C.; Gready, J.E. Synthesis of quaternised 2-aminopyrimido[4,5-d]pyrimidin-4(3H)-ones and their biological activity with dihydrofolate reductase. Eur. J. Med. Chem., 2003, 38(7-8), 719-728.
[http://dx.doi.org/10.1016/S0223-5234(03)00140-5] [PMID: 12932903]

(a) Nagarajaiah, H.; Mukhopadhyay, A.; Moorthy, J.N. Biginelli reaction: An overview. Tetrahedron Lett., 2016, 57, 5135-5149.
[http://dx.doi.org/ 10.1016/j.tetlet.2016.09.047]
(b) Elattar, K.M.; Rabie, R.; Hammouda, M.M. Recent developments in the chemistry of bicyclic 6-6 systems: Chemistry of pyrido[1,2-c]pyrimidines. Synth. Commun., 2016, 46, 1477-1498.
[http://dx.doi.org/10.1080/00397911.2016.1211702 ]
(c) Jubeen, F.; Iqbal, S.Z.; Shafiq, N.; Khan, M.; Parveen, S.; Iqbal, M.; Nazir, A. Eco-friendly synthesis of pyrimidines and its derivatives: A review on broad spectrum bioactive moiety with huge therapeutic profile. Synth. Commun., 2018, 48, 601-625.
[http://dx.doi.org/ 10.1080/00397911.2017.1408840]
(d) Manvar, A.; Shah, A. Microwave-assisted chemistry of purines and xanthines. An overview. Tetrahedron, 2013, 69, 8105-8127.
[http://dx.doi.org/10.1016/j.tet.2013.06.034]

(a) Melik-Ogandzhanyan, R.G.; Khachatryan, V.E.; Gapoyan, A.S. Furo-, Thieno-, and Pyrrolo-[2,3-d] pyrimidines. Russ. Chem. Rev., 1985, 54, 262.
[http://dx.doi.org/10.1070/RC1985v054n03ABEH003026 ]
(b) Campaigne, E.; Ellis, R.L.; Bradford, M.; Ho, J. Synthesis of some ureidodihydrofurans and related pyrimidones as potential antimalarials. J. Med. Chem., 1969, 12(2), 339-342.
[http://dx.doi.org/10.1021/jm00302a041] [PMID: 5783618 ]
(c) Blume, F.; Arndt, F.; Ress, R. Ger Patent 3712782 1988.
(d) Bhuiyan, M.M.H.; Rahman, K.M.M.; Hossain, M.K.; Rahim, M.A.; Hossain, M.I. Fused pyrimidines. part II: Synthesis and antimicrobial activity of Some furo[3,2-e]imidazo[1,2-c]pyrimidines and furo[2,3-d]pyrimidines. Croat. Chem. Acta, 2005, 78, 633-636.
(e) Gangjee, A.; Zeng, Y.; McGuire, J.J.; Kisliuk, R.L. Synthesis of classical, four-carbon bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates. J. Med. Chem., 2005, 48(16), 5329-5336.
[http://dx.doi.org/10.1021/jm058213s] [PMID: 16078850]
(f) Gangjee, A.; Zeng, Y.; Ihnat, M.; Warnke, L.A.; Green, D.W.; Kisliuk, R.L.; Lin, F.T. Novel 5-substituted, 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors with antiangiogenic and antitumor activity. Bioorg. Med. Chem., 2005, 13(18), 5475-5491.
[http://dx.doi.org/10.1016/j.bmc.2005.04.087] [PMID: 16039863]
(g) Gangjee, A.; Zeng, Y.; McGuire, J.J.; Mehraein, F.; Kisliuk, R.L. Synthesis of classical, three-carbon-bridged 5-substituted furo[2,3-d] pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates. J. Med. Chem., 2004, 47(27), 6893-6901.
[http://dx.doi.org/10.1021/jm040123k] [PMID: 15615538 ]
(h) Dave, C.G.; Shah, R.D. Annellation of triazole and tetrazole systems onto pyrrolo[2,3-d]pyrimidines: Synthesis of tetrazolo[1,5-c]-pyrrolo[3,2-e]-pyrimidines and Triazolo[1,5-c]pyrrolo-[3,2-e]pyrimidines as potential antibacterial agents. Molecules, 2002, 7, 554-565.
[http://dx.doi.org/10.3390/70700554 ]
(i)Janeba, Z.; Balzarini, J.; Andrei, G.; Snoeck, R.; De Clercq, E.; Robins, M.J. Synthesis and biological evaluation of acyclic 3-[(2-hydroxyethoxy)-methyl] analogues of antiviral furo- and pyrrolo[2,3-d]pyrimidine nucleosides. J. Med. Chem., 2005, 48, 4690-4696. (k) Robins, M.J.; Miranda, K.; Rajwanshi, V.K.; Peterson, M.A.; Andrei, G.; Snoeck, R.; De Clercq, E.; Balzarini, J. J. Synthesis and biological evaluation of 6-(alkyn-1-yl)furo[2,3-d]pyrimidin-2(3h)-one base and nucleoside derivatives. J. Med. Chem., 2006, 49, 391-398. l) McGuigan, C.; Balzarini, J. Aryl furanopyrimidines: The most potent and selective anti-VZV agents reported to date. Antiviral Res., 2006, 71, 149-153.

Majumdar, K.C.; Ganai, S.; Nandi, R.K. Regioselective synthesis of pyrimidine-annulated spiro-dihydrofurans by silver-catalyzed 5-endo-digcyclization. N J. Chem., 2011, 35, 1355-1359.
[http://dx.doi.org/10.1039/c1nj20121b]

Majumdar, K.C.; Mukhopadhyay, P.P. Regioselective aryl radical cyclization: Access to pyrimidine-annelated spiro heterocycles through 5-exo ring closure. Synthesis, 2004, 1864-1868.
[http://dx.doi.org/10.1055/s-2004-829133]

(a) Bhattacharya, R.N.; Kundu, P.; Maiti, G. Antimony trichloride catalyzed three-component reaction of urea, aldehydes and cyclic enol ethers: a novel route to 4-arylhexahydrofuro[2,3-d]pyrimidin-2(3H)-ones. Tetrahedron Lett., 2011, 52, 26-28.
[http://dx.doi.org/10.1016/j.tetlet.2010.10.064 ]
(b) Zhu, Y.; Zhao, S.; Zhang, M.; Song, X.; Chang, J. Diastereoselective synthesis of spirobarbiturate-cyclopropanes through organobase-mediated spirocyclopropanation of barbiturate-based olefins with benzyl chlorides. Synthesis, 2019, 51, 899-906.
[http://dx.doi.org/10.1055/s-0037-1609637]

(a) Majumdar, K.C.; Das, U.; Kundu, U.K.; Bandyopadhyay, A. Regioselective synthesis of pyrimidine annelated heterocycles from 6-(cyclohex-2-enyl)-1,3-dimethyl-5-hydroxyuracil. Tetrahedron, 2001, 57, 7003-7007.
[http://dx.doi.org/10.1016/S0040-4020(01)00656-1 ]
(b) Majumdar, K.C.; Samanta, S.K. Synthesis of pyrimidine-annelated heterocycles: Regioselective heterocyclization of 5-(cyclohex-2-enyl)-1,3-dimethyl-6-hydroxyuracil. Monatsh. Chem., 2002, 133, 1187-1192.
[http://dx.doi.org/10.1007/s007060200088]

Hudson, R.H.E.; Moszynski, J.M. A Facile Synthesis of Fluorophores Based on 5-Phenylethynyluracils. Synlett, 2006, 2997-3000.
[http://dx.doi.org/10.1055/s-2006-948176]

(a) Fresneau, N.; Hiebel, M-A.; Agrofoglio, L.A.; Berteina-Raboin, S. One-pot Sonogashira-cyclization protocol to obtain substituted furopyrimidine nucleosides in aqueous conditions. Tetrahedron Lett., 2012, 53, 1760-1763.
[http://dx.doi.org/10.1016/j.tetlet.2012.01.106 ]
(b) Rao, M.S.; Esho, N.; Sergeant, C.; Dembinski, R. 5-Endo-dig electrophilic cyclization of α-alkynyl carbonyl compounds: Synthesis of novel bicyclic 5-iodo- and 5-bromofuranopyrimidine nucleosides. J. Org. Chem., 2003, 68(17), 6788-6790.
[http://dx.doi.org/10.1021/jo0345648] [PMID: 12919049]

Petraityte, G.; Vaitkevicius, V.; Ozer, B.; Masevicius, V. Synthesis of 5-substituted and 5,6-disubstituted furo[2,3-d]pyrimidines from 2-methylthio-4,6-pyrimidindione and bifunctional electrophiles. Tetrahedron Lett., 2019, 60, 1019-1021.
[http://dx.doi.org/10.1016/j.tetlet.2019.03.017]

De Coen, L.M.; Jatczak, M.; Muylaert, K.; Mangelinckx, S.; Stevens, C.V. Straightforward synthesis of functionalized furo[3,4-d]pyrimidine-2,4-diones. Synthesis, 2015, 47, 1227-1237.
[http://dx.doi.org/10.1055/s-0034-1380321]

(a) Chun, B.K.; Song, G.Y.; Chu, C.K. Stereocontrolled syntheses of carbocyclic C-nucleosides and related compounds. J. Org. Chem., 2001, 66(14), 4852-4858.
[http://dx.doi.org/10.1021/jo010224f] [PMID: 11442416]
(b) Prashad, M.; Har, D.; Chen, L.; Kim, H-Y.; Repic, O.; Blacklock, T.J. An efficient and large-scale enantioselective synthesis of PNP405: A purine nucleoside phosphorylase inhibitor. J. Org. Chem., 2002, 67(19), 6612-6617.
[http://dx.doi.org/10.1021/jo020256i] [PMID: 12227788 ]
(c) Kamath, V.P.; Juarez-Brambila, J.J.; Morris, C.B.; Winslow, C.D.; Morris, P.E. Development of a practical synthesis of a purine nucleoside phosphorylase inhibitor: BCX-4208. Org. Process Res. Dev., 2009, 13, 928-932.
[http://dx.doi.org/ 10.1021/op9001142]
(d) Semeraro, T.; Mugnaini, C.; Corelli, F. Preparation of a set of 4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-4-ones as potential Hsp90 ligands. Tetrahedron Lett., 2008, 49, 5965-5967.
[http://dx.doi.org/ 10.1016/j.tetlet.2008.07.158]
(e) Oguro, Y.; Miyamoto, N.; Takagi, T.; Okada, K.; Awazu, Y.; Miki, H.; Hori, A.; Kamiyama, K.; Imamura, S. N-phenyl-N'-[4-(5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as novel inhibitors of VEGFR and FGFR kinases. Bioorg. Med. Chem., 2010, 18(20), 7150-7163.
[http://dx.doi.org/10.1016/j.bmc.2010.08.042] [PMID: 20833551 ]
(f) Gomtsyan, A.; Didomenico, S.; Lee, C.H.; Stewart, A.O.; Bhagwat, S.S.; Kowaluk, E.A.; Jarvis, M.F. Synthesis and biological evaluation of pteridine and pyrazolopyrimidine based adenosine kinase inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(16), 4165-4168.
[http://dx.doi.org/10.1016/j.bmcl.2004.06.029] [PMID: 15261263]
(g) Ishikawa, T.; Seto, M.; Banno, H.; Kawakita, Y.; Oorui, M.; Taniguchi, T.; Ohta, Y.; Tamura, T.; Nakayama, A.; Miki, H.; Kamiguchi, H.; Tanaka, T.; Habuka, N.; Sogabe, S.; Yano, J.; Aertgeerts, K.; Kamiyama, K. Design and synthesis of novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors bearing a pyrrolo[3,2-d]pyrimidine scaffold. J. Med. Chem., 2011, 54(23), 8030-8050.
[http://dx.doi.org/10.1021/jm2008634] [PMID: 22003817 ]
(h) Xie, R.; Hu, Y.; Wan, H.; Hu, Y.; Chen, S.; Zhang, S.; Zhang, Y. An efficient synthesis of 4,6-substituted pyrrolo[3,2-d]pyrimidines by silver-catalyzed cyclization of acetylene amine. Tetrahedron Lett., 2016, 57, 2418-2421.
[http://dx.doi.org/10.1016/j.tetlet.2016.04.077]

Ponra, S.; Gohain, M.; Donka, R.; van Tonder, J.H. Al(OTf) 3-catalyzed one-pot synthesis of pyrrolo[3,2-d]pyrimidinedione derivatives. Tetrahedron Lett., 2018, 59, 2909-2912.
[http://dx.doi.org/10.1016/j.tetlet.2018.06.039]

(a) Majumdar, K.C.; Biswas, A.; Mukhopadhyay, P.P. Regioselective synthesis of pyrrolo[2,3-d]pyrimidine derivatives by amine oxide rearrangement. Synthesis, 2005, 1164-1168.
[http://dx.doi.org/ 10.1055/s-2005-861811]
(b) Majumdar, K.C.; Das, U.; Jana, N.K. Studies on pyrimidine-annelated heterocycles: Synthesis of pyrrolo[3,2-d]pyrimidines by amine oxide rearrangement. J. Org. Chem., 1998, 63, 3550-3553.
[http://dx.doi.org/10.1021/jo9718861]

Sekhar, N.M.; Acharyulu, P.V.R.; Anjaneyulu, Y. A short and efficient synthetic protocol for the synthesis of 5-substituted-4,6-dioxo-pyrrolo[2,3-d]pyrimidines. Tetrahedron Lett., 2011, 52, 4140-4144.
[http://dx.doi.org/10.1016/j.tetlet.2011.05.141]

El-Ablak, F.Z.; Abu-Elenein, N.S.; Sofan, M.A. Synthesis of new pyrrolo heterocycles (I): Novel Synthesis of Pyrano[2,3-c] pyrrole, Isoindoline, Pyrrolo[3,4-b]pyridine, and Pyrrolo[3,4-d]pyrimidine Derivatives. J. Heterocycl. Chem., 2016, 53, 1999-2006.
[http://dx.doi.org/10.1002/jhet.2520]

(a) Jiang, X.; Sun, D.; Jiang, Y.; Ma, D. Efficient synthesis of pyrrolo[2,3-d]pyrimidines via a Cu(I)/6-methylpicolinic acid catalyzed coupling reaction. Tetrahedron Lett., 2015, 56, 3259-3261.
[http://dx.doi.org/10.1016/j.tetlet.2014.12.098 ]
(b) Mayasundari, A.; Fujii, N. Efficient formation of 4,6-disubstituted pyrrolo[2,3-d]pyrimidines: A novel route to TWS119, a glycogen synthase kinase-3β inhibitor. Tetrahedron Lett., 2010, 51, 3597-3598.
[http://dx.doi.org/10.1016/j.tetlet.2010.05.032 ]
(c) Prieur, V.; Rubio-Martinez, J.; Font-Bardia, M.; Guillaumet, G.; Pujol, M.D. Microwave-assisted synthesis of substituted pyrrolo[2,3-d] pyrimidines. Eur. J. Org. Chem., 2014, 1514-1524.
[http://dx.doi.org/10.1002/ejoc.201301496]

Paul, S.; Das, A.R. A new application of polymer supported, homogeneous and reusable catalyst PEG-SO₃H in the synthesis of coumarin and uracil fused pyrrole derivatives. Catal. Sci. Technol., 2012, 2, 1130-1135.
[http://dx.doi.org/10.1039/c2cy20117h]

Pink, J.H.; Culshaw, J. A Concise synthesis of fused tricyclic pyrrolo[3,2-d]pyrimidine. Synlett, 2016, 27, 2368-2371.
[http://dx.doi.org/10.1055/s-0035-1561482]

(a) Shen, M.; Zhou, S.; Li, Y.; Li, D.; Hou, T. Theoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2 inhibitors: Insight into structure-based inhibitor design. Mol. Biosyst., 2013, 9(10), 2435-2446.
[http://dx.doi.org/10.1039/c3mb70168a] [PMID: 23881296]
(b) Ghorab, M.M.; Ragab, F.A.; Heiba, H.I.; Youssef, H.A.; El-Gazzar, M.G. Synthesis of novel pyrrole and pyrrolo[2,3-d]pyrimidine derivatives bearing sulfonamide moiety for evaluation as anticancer and radiosensitizing agents. Bioorg. Med. Chem. Lett., 2010, 20(21), 6316-6320.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.005] [PMID: 20850308 ]
(c) Clark, M.P.; George, K.M.; Bookland, R.G.; Chen, J.; Laughlin, S.K.; Thakur, K.D.; Lee, W.; Davis, J.R.; Cabrera, E.J.; Brugel, T.A.; VanRens, J.C.; Laufersweiler, M.J.; Maier, J.A.; Sabat, M.P.; Golebiowski, A.; Easwaran, V.; Webster, M.E.; De, B.; Zhang, G. Development of new pyrrolopyrimidine-based inhibitors of Janus kinase 3 (JAK3). Bioorg. Med. Chem. Lett., 2007, 17(5), 1250-1253.
[http://dx.doi.org/10.1016/j.bmcl.2006.12.018] [PMID: 17189692]
(d) Gangjee, A.; Zhao, Y.; Raghavan, S.; Ihnat, M.A.; Disch, B.C. Design, synthesis and evaluation of 2-amino-4-m-bromoanilino-6-arylmethyl-7H-pyrrolo[2,3-d]pyrimidines as tyrosine kinase inhibitors and antiangiogenic agents. Bioorg. Med. Chem., 2010, 18(14), 5261-5273.
[http://dx.doi.org/10.1016/j.bmc.2010.05.049] [PMID: 20558072 ]
(e) Wang, L.; Cherian, C.; Kugel Desmoulin, S.; Mitchell-Ryan, S.; Hou, Z.; Matherly, L.H.; Gangjee, A. Synthesis and biological activity of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl regioisomers as inhibitors of de novo purine biosynthesis with selectivity for cellular uptake by high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier. J. Med. Chem., 2012, 55(4), 1758-1770.
[http://dx.doi.org/10.1021/jm201688n] [PMID: 22243528 ]
(f) Ding, S.; Wu, T.Y.H.; Brinker, A.; Peters, E.C.; Hur, W.; Gray, N.S.; Schultz, P.G. Synthetic small molecules that control stem cell fate. Proc. Natl. Acad. Sci. USA, 2003, 100(13), 7632-7637.
[http://dx.doi.org/10.1073/pnas.0732087100] [PMID: 12794184 ]
(g) Wang, Y.; Mitchell-Ryan, S.; Raghavan, S.; George, C.; Orr, S.; Hou, Z.; Matherly, L.H.; Gangjee, A. Novel 5-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-amino-imidazole-4-carboxamide ribonucleotide formyltransferase and as potential antitumor agents. J. Med. Chem., 2015, 58(3), 1479-1493.
[http://dx.doi.org/10.1021/jm501787c] [PMID: 25602637]

Saikia, L.; Roudragouda, P.; Thakur, A.J. A one pot, two-step synthesis of 5-arylpyrrolo[2,3-d]pyrimidines and screening of their preliminary antibacterial properties. Bioorg. Med. Chem. Lett., 2016, 26(3), 992-998.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.047] [PMID: 26739778]

Taylor, E.C.; Liu, B. A new and efficient synthesis of pyrrolo[2,3-d]pyrimidine anticancer agents: Alimta (LY231514, MTA), homo-Alimta, TNP-351, and some aryl 5-substituted pyrrolo[2,3-d]pyrimidines. J. Org. Chem., 2003, 68(26), 9938-9947.
[http://dx.doi.org/10.1021/jo030248h] [PMID: 14682686]

Li, C.; Zhang, F. l-Proline-catalyzed cyclization of 6-aminopyrimidine-4(3h)-ones with nitroolefins: Synthesis of polysubstituted 5-arylpyrrolo[2,3-d]pyrimidin-4-ones. Synlett, 2017, 28, 1315-1320.
[http://dx.doi.org/10.1055/s-0036-1588757]

Mieczkowski, A.; Tomczyk, E.; Makowska, M.A.; Nasulewicz-Goldeman, A.; Gajda, R.; Woźniak, K.; Wietrzyk, J. Synthesis and investigation of the antitumor properties of novel, bicyclic furopyrimidine, pyrrolopyrimidine and pyrimidopyridazine nucleoside analogues. Synthesis, 2016, 48, 566-572.
[http://dx.doi.org/10.1055/s-0035-1561277]

Shekarrao, K.; Kaishap, P.P.; Gogoi, S.; Gogoi, S.; Boruah, R.C. A facile synthesis of steroidal D-ring fused pyrazolo[1,5-a]pyrimidines. Tetrahedron Lett., 2014, 55, 5251-5255.
[http://dx.doi.org/10.1016/j.tetlet.2014.07.119]

Majumdar, K.C.; Ghosh, T.; Shyam, P.K. Facile regioselective synthesis of functionalized heterocycle-tethered spiro compounds via an intramolecular electrophilic ipso-iodocyclization process. Synlett, 2011, 2657-2662.
[http://dx.doi.org/10.1055/s-0031-1289526]

(a) Li, X.; Xia, C.; Wang, T.; Liu, L.; Zhao, Q.; Yang, D.; Hu, F.; Zhang, M.; Huang, K.; Geng, Y.; Zheng, Y.; Guan, Y.; Wu, H.; Chen, X.; Pan, G.; Chen, J.; Du, J.; Wang, J. Pyrimidoindole derivative UM171 enhances derivation of hematopoietic progenitor cells from human pluripotent stem cells. Stem Cell Res. (Amst.), 2017, 21, 32-39.
[http://dx.doi.org/10.1016/j.scr.2017.03.014] [PMID: 28368243]
(b) Fares, I.; Chagraoui, J.; Gareau, Y.; Gingras, S.; Ruel, R.; Mayotte, N.; Csaszar, E.; Knapp, D.J.H.F.; Miller, P.; Ngom, M.; Imren, S.; Roy, D-C.; Watts, K.L.; Kiem, H-P.; Herrington, R.; Iscove, N.N.; Humphries, R.K.; Eaves, C.J.; Cohen, S.; Marinier, A.; Zandstra, P.W.; Sauvageau, G. Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal. Science, 2014, 345(6203), 1509-1512.
[http://dx.doi.org/10.1126/science.1256337] [PMID: 25237102]

(a) Biswas, S.; Batra, S. One-step synthesis of 2-amino-5h-pyrimido[5,4-b]indoles, substituted 2-(1,3,5-triazin-2-yl)-1h-indoles, and 1,3,5-triazines from aldehydes. Eur. J. Org. Chem., 2012, 3492-3499.
[http://dx.doi.org/10.1002/ejoc.201200276 ]
(b) Ren, Y-w.; Wang, X.; Wang, W.; Li, B.; Shi, Z-j.; Zhang, W. Photochemical and thermal cyclizations of 4-(2-azidophenyl)-3,4-dihydropyri-midin-2-ones for the synthesis of 4-methylenepyrimidino[5,4-b]indol-2-ones. Tetrahedron Lett., 2011, 52, 192-195.
[http://dx.doi.org/10.1016/j.tetlet.2010.10.176]

Gupta, S.; Sharma, S.K.; Mandadapu, A.K.; Gauniyal, H.M.; Kundu, B. Three-component tandem reaction involving acid chlorides, terminal alkynes, and ethyl 2-amino-1H-indole-3-carboxylates: Synthesis of highly diversified pyrimido[1,2-a]indoles via sequential Sonogashira and [3+3] cyclocondensation reactions. Tetrahedron Lett., 2011, 52, 4288-4291.
[http://dx.doi.org/10.1016/j.tetlet.2011.06.021]

Kopchuk, D.S.; Chepchugov, N.V.; Khasanov, A.F.; Kovalev, I.S.; Santra, S.; Nosova, E.V.; Zyryanov, G.V.; Majee, A.; Rusinov, V.L.; Chupakhin, O.N. A one-pot approach to 10-(1H-1,2,3-triazol-1-yl)pyrimido[1,2-a]indoles via aryne-mediated transformations of 3-(pyrimidin-2-yl)-1,2,4-triazines. Tetrahedron Lett., 2016, 57, 3862-3865.
[http://dx.doi.org/10.1016/j.tetlet.2016.07.052]

Chen, X.; Hu, X.; Bai, S.; Deng, Y.; Jiang, H.; Zeng, W. Rh(III)-Catalyzed [4 + 2] Annulation of indoles with diazo compounds: Access to pyrimido[1,6-a] indole-1(2H)-ones. Org. Lett., 2016, 18(2), 192-195.
[http://dx.doi.org/10.1021/acs.orglett.5b03231] [PMID: 26710082]

Xu, G.; Zheng, L.; Dang, Q.; Bai, X. Total Synthesis of 4-Azaeudistomin Y1 and analogues by inverse-electron¬demand diels-alder reactions of 3-aminoindoles with 1,3,5-triazines. Synthesis, 2013, 45, 743-752.
[http://dx.doi.org/10.1055/s-0032-1316857]

Kapti, T.; Dengiz, C.; Balci, M. The chemistry of ethyl 3-(2-ethoxy-2-oxoethyl)-1h-indole-2-carboxylate: synthesis of pyrimido[4,5-b] indoles and diethyl 4-hydroxyquinoline-2,3-dicarboxylate via intramolecular cyclizations. Synthesis, 2016, 48, 1898-1904.

Majumdar, K.C.; Das, T.K.; Jana, M. Regioselective synthesis of pyrimidine-annulated spiro heterocycles by radical cyclization synth. Commun., 2005, 35, 1961-1969.

Mulakayala, N.; Reddy, U.; Chaitany, M.; Hussain, M.M.; Kumar, C.S.; Golla, N. Novel and efficient synthesis of 7-trifluoromethyl-substituted pyrazolo[1,5-a] pyrimidines with potent antitumor agents. J. Kore. Chem. Soc., 2011, 55, 719-722.
[http://dx.doi.org/10.5012/jkcs.2011.55.4.719]

Farag, M.A.; Dawood, K.M.; Elmenoufy, H.A. A convenient route to pyridones, pyrazolo[2, 3-a] pyrimidines and pyrazolo[5,1-c]triazines incorporating antipyrine moiety. Heteroatom Chem., 2004, 15, 508-514.
[http://dx.doi.org/10.1002/hc.20046]

Kiselyov, A.S.; Smith, L.I.I. Novel one pot synthesis of polysubstituted pyrazolo[1,5-a]- and imidazo[1, 2-a] pyrimidines. Tetrahedron Lett., 2006, 47, 2611-2614.
[http://dx.doi.org/10.1016/j.tetlet.2006.02.031]

(a) Quiroga, J.; Portilla, J.; Abonıa, R.; Insuasty, B.; Nogueras, M.; Cobo, J. Regioselective synthesis of novel polyfunctionally substituted pyrazolo[1,5-a]pyrimidines under solvent-free conditions. Tetrahedron Lett., 2007, 48, 6352-6355.
[http://dx.doi.org/10.1016/j.tetlet.2007.07.041 ]
(b) Quiroga, J.; Portilla, J.; Abonıa, R.; Insuasty, B.; Nogueras, M.; Cobo, J. Regioselective synthesis of novel substituted pyrazolo[1,5-a] pyrimidines under solvent-free conditions. Tetrahedron Lett., 2008, 49, 6254-6256.
[http://dx.doi.org/10.1016/j.tetlet.2008.08.044]

Al-Qalaf, F.; Abdelkhalik, M.M.; Al-Enezi, A.; Al-Ajmi, J.R. Studies with functionally substituted enamines: Synthesis of 2-aroyl-3-dimethylamino-2-propenenitrile and their reactivity toward nitrogen nucleophiles. Heterocycles, 2008, 75, 145-156.
[http://dx.doi.org/10.3987/COM-07-11196]

Lombar, K.; Groselj, U.; Dahmann, G.; Stanovnik, B.; Svete, J. Synthesis of 6-Alkyl-7-oxo-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-3-carboxamides. Synthesis, 2015, 47, 497-506.

Mirnik, J.; Groselji, U.; Novak, A.; Dahmann, G.; Golobic, A.; Kasunic, M.; Stanovnik, B.; Svete, J. A novel synthesis of tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones. Synthesis, 2013, 45, 3404-3412.
[http://dx.doi.org/10.1055/s-0033-1339977]

(a) Stepaniuk, O.O.; Matvienko, V.O.; Kondratov, I.S.; Shishkin, O.V.; Volochnyuk, D.M.; Mykhailiuk, P.K.; Tolmachev, A.A. Regioselective reactions of ethyl (4,5-dihydrofuran-3-yl)-2-oxoacetate and ethyl 2-(3,4-dihydro-2h-pyran-6-yl)-2-oxoacetate with 1-unsubstituted aminoazoles. Synthesis, 2012, 44, 895-902.
[http://dx.doi.org/10.1055/s-0031-1289733 ]
(b) Stepaniuk, O.O.; Matviienko, V.O.; Kondratov, I.S.; Vitruk, I.V.; Tolmachev, A.O. Synthesis of new pyrazolo[1,5-a]pyrimidines by reaction of β,γ-unsaturated γ-alkoxy-α-keto esters with n-unsubstituted 5-aminopyra-zoles. Synthesis, 2013, 45, 925-930.
[http://dx.doi.org/10.1055/s-0032-1318329]

Abed, H.B.; Mammoliti, O.; Lommen, G.V.; Herdewijn, P. Simple approach to the synthesis of 3-fluoro pyrazolo[1,5-a]pyrimidine analogues. Tetrahedron Lett., 2013, 54, 2612-2614.
[http://dx.doi.org/10.1016/j.tetlet.2013.03.015]

(a) Jismy, B.; Guillaumet, G.; Allouchi, H.; Akssira, M.; Abarbri, M. Concise and efficient access to 5,7-disubstituted pyrazolo[1,5-a]pyrimidines by Pd-catalyzed sequential arylation, alkynylation and SNAr reaction. Eur. J. Org. Chem., 2017, 6168-6178.
[http://dx.doi.org/10.1002/ejoc.201701024 ]
(b) Jismy, B.; Allouchi, H.; Guillaumet, G.; Akssira, M.; Abarbri, M. An Efficient synthesis of new 7-trifluoromethyl-2,5-disubstituted pyrazolo[1,5-a]pyrimidines. Synthesis, 2018, 50, 1675-1686.
[http://dx.doi.org/10.1055/s-0036-1591752]

Ghelani, S.M.; Naliapara, Y.T. Design, Multicomponent synthesis and characterization of diversely substituted pyrazolo[1,5-a] pyrimidine derivatives. J. Heterocycl. Chem., 2016, 53, 1843-1851.
[http://dx.doi.org/10.1002/jhet.2496]

Belaroussi, R.; El Bouakher, A.; Marchivie, M.; Massip, S.; Jarry, C.; El Hakmaoui, A.; Guillaumet, G.; Routier, S.; Akssira, M. Convenient synthesis of new n-3-substituted pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyrimidine-2,4(1h, 3h)-dione derivatives. Synthesis, 2013, 45, 2557-2566.
[http://dx.doi.org/10.1055/s-0033-1338514]

Bajwa, J.J.; Sykes, P.J. New steroidal heterocycles: The synthesis and structure of androsteno[2,3-g]-, androstano[3,2-f]-, and androsteno[16,17-g]-pyrazolo[1,5-a]pyrimidines. J. Chem. Soc., Perkin Trans. 1, 1980, 481-486.
[http://dx.doi.org/10.1039/p19800000481]

(a) Daniels, R.; Kim, K.; Lebois, E.; Muchalski, H.; Hughes, M.; Lindsley, C. Microwave-assisted protocols for the expedited synthesis of pyrazolo[1,5-a] and [3,4-d] pyrimidines. Tetrahedron Lett., 2008, 49, 305-310.
[http://dx.doi.org/ 10.1016/j.tetlet.2007.11.054]
(b) Quiroga, J.; Mejia, D.; Insuasty, B.; Abonia, R.; Nogueras, M.; Sanchez, A.; Cobo, J. Synthesis of 6-(2-hydroxybenzoyl)pyrazolo[1,5a]pyrimidines by reaction of -5-amino-1h-pyrazoles and 3-formylchromone. J. Heterocycl. Chem., 2002, 39, 51-54.
[http://dx.doi.org/10.1002/jhet.5570390106]

Saikia, P.; Kaishap, P.P.; Prakash, R.; Shekarrao, K.; Gogoi, S.; Boruah, R.C. A facile one-pot synthesis of 7-substituted pyrazolo[1,5-a] pyrimidines by base induced three-component reaction. Tetrahedron Lett., 2014, 55, 3896-3900.
[http://dx.doi.org/10.1016/j.tetlet.2014.05.021]

Kaishap, P.P.; Baruah, S.; Shekarrao, K.; Gogoi, S.; Boruah, R.C. A facile method for the synthesis of steroidal and nonsteroidal 5-methyl pyrazolo[1,5-a] pyrimidines. Tetrahedron Lett., 2014, 55, 3117-3121.
[http://dx.doi.org/10.1016/j.tetlet.2014.04.011]

(a) Ivachtchenko, A.V.; Dmitriev, D.E.; Golovina, E.S.; Kadieva, M.G.; Koryakova, A.G.; Kysil, V.M.; Mitkin, O.D.; Okun, I.M.; Tkachenko, S.E.; Vorobiev, A.A. (3-Phenylsulfonylcycloalkano[e and d]pyrazolo[1,5-a]pyrimidin-2-yl)amines: Potent and selective antagonists of the serotonin 5-HT6 receptor. J. Med. Chem., 2010, 53(14), 5186-5196.
[http://dx.doi.org/10.1021/jm100350r] [PMID: 20560595 ]
(b) Petrov, A.A.; Kasatochkin, A.N.; Emelina, E.E. Study of regioselectivity of reactions between 3(5)-aminopyrazoles and 2-acetylcycloalkanones. Russ. J. Org. Chem., 2012, 48, 1111-1120.
[http://dx.doi.org/10.1134/S1070428012080131]

(a) Ryabukhin, S.V.; Plaskon, A.S.; Volochnyuk, D.M.; Pipko, S.E.; Tolmachev, A.A. Chlorotrimethylsilane mediated synthesis of 5-(2-hydroxybenzoyl)pyrimidines from 3-formylchromones. Heterocycles, 2008, 75, 583-597.
[http://dx.doi.org/ 10.3987/COM-07-11240]
(b) Zimmerman, J.R.; Myers, B.J.; Bouhall, S.; McCarthy, A.; Johntony, O.; Manpadi, M. A two-step, single pot procedure for the synthesis of substituted dihydropyrazolo-pyrimidines. Tetrahedron Lett., 2014, 55, 936-940.
[http://dx.doi.org/10.1016/j.tetlet.2013.12.057]

(a) Ryabukhin, S.V.; Granat, D.S.; Plaskon, A.S.; Shivanyuk, A.N.; Tolmachev, A.A.; Volovenko, Y.M. High throughput synthesis of extended pyrazolo[3,4-d]dihydropyrimidines. ACS Comb. Sci., 2012, 14(8), 465-470.
[http://dx.doi.org/10.1021/co300063x] [PMID: 22775440]
(b) Ryabukhina, S.V.; Granat, D.S.; Plaskon, A.S.; Shivanyuk, A.; Lukin, O. Synthesis of pyrazolo[3,4-d]-4,5-dihydropyrimidin-6-ones. Tetrahedron Lett., 2014, 55, 1846-1847.
[http://dx.doi.org/10.1016/j.tetlet.2014.01.131]

Boyd, S.; Campbell, L.; Liao, W.; Meng, Q.; Peng, Z.; Wang, X.; Waring, M.J. A one step synthesis of 1-alkylpyrazolo[5,4-d]pyrimidines. Tetrahedron Lett., 2008, 49, 7395-7397.
[http://dx.doi.org/10.1016/j.tetlet.2008.10.065]

Adams, N.D.; Schmidt, S.J.; Knight, S.D.; Dhanak, D. A novel synthesis of substituted 4H-pyrazolo[3,4-d]pyrimidin-4-ones. Tetrahedron Lett., 2007, 48, 3983-3986.
[http://dx.doi.org/10.1016/j.tetlet.2007.04.043]

Sambaiaha, M.; Mallesham, P.; Kumar, K.S.; Bobde, Y.; Hota, P.K.; Yennam, S.; Ghosh, B.; Behera, M. Tandem schiff-base formation/hetero-cyclization: An approach to the synthesis of fused pyrazolo–pyrimidine/isoxazolo-pyrimidine hybrids. Synlett, 2019, 30, 586-592.
[http://dx.doi.org/10.1055/s-0037-1612081]

Bagleya, M.C.; Baashen, M.; Paddock, V.L.; Kipling, D.; Davis, T. Regiocontrolled synthesis of 3- and 5-aminopyrazoles, pyrazolo[3,4-d]pyrimidines, pyrazolo[3,4-b]pyridines and pyrazolo[3,4-b]quinolinones as MAPK inhibitors. Tetrahedron, 2013, 69, 8429-8438.
[http://dx.doi.org/10.1016/j.tet.2013.07.055]

Morrill, C.; Babu, S.; Almstead, N.G.; Moon, Y-C. Synthesis of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines from 4,6-dichloropyrimidine-5-carboxaldehyde: Insights into selectivity and reactivity. Synthesis, 2013, 45, 1791-1806.
[http://dx.doi.org/10.1055/s-0033-1338862]

Liu, J.; Zhang, X-w.; Wang, Y.; Chen, Y.; Zhang, M-r.; Cai, Z-q.; Zhou, Y-p.; Xu, L-f. A new efficient synthesis of 4-alkoxy-1,6-diaryl-1H-pyrazolo[3,4-d]pyrimidine derivatives. Synth. Commun., 2015, 45, 1009-1017.
[http://dx.doi.org/10.1080/00397911.2014.996296]

(a) Maia, L.; de Mendonça, A. Does caffeine intake protect from Alzheimer’s disease? Eur. J. Neurol., 2002, 9(4), 377-382.
[http://dx.doi.org/10.1046/j.1468-1331.2002.00421.x] [PMID: 12099922 ]
(b) Cui, P.; Macdonald, T.L.; Chen, M.; Nadler, J.L. Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes. Bioorg. Med. Chem. Lett., 2006, 16(13), 3401-3405.
[http://dx.doi.org/10.1016/j.bmcl.2006.04.036] [PMID: 16650991 ]
(c) Stine, R.J.; Marcus, R.H.; Parvin, C.A. Aminophylline loading in asthmatic patients: A protocol trial. Ann. Emerg. Med., 1989, 18(6), 640-646.
[http://dx.doi.org/10.1016/S0196-0644(89)80518-9] [PMID: 2658694]
(d) Song, B.; Xiao, T.; Qi, X.; Li, L-N.; Qin, K.; Nian, S.; Hu, G-X.; Yu, Y.; Liang, G.; Ye, F. Design and synthesis of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(4), 1739-1742.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.094] [PMID: 22257893]
(e) Roy, A.C.; Lunn, F.A.; Bearne, S.L. Inhibition of CTP synthase from Escherichia coli by xanthines and uric acids. Bioorg. Med. Chem. Lett., 2010, 20(1), 141-144.
[http://dx.doi.org/10.1016/j.bmcl.2009.11.017] [PMID: 20004571 ]
(f) Szentmiklósi, A.J.; Cseppentō, A.; Gesztelyi, R.; Zsuga, J.; Körtvély, A.; Harmati, G.; Nánási, P.P. Xanthine derivatives in the heart: blessed or cursed? Curr. Med. Chem., 2011, 18(24), 3695-3706.
[http://dx.doi.org/10.2174/092986711796642391] [PMID: 21774759 ]
(g) Nehlig, A.; Daval, J-L.; Debry, G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res. Brain Res. Rev., 1992, 17(2), 139-170.
[http://dx.doi.org/10.1016/0165-0173(92)90012-B] [PMID: 1356551]
(h) Schultze-Werninghaus, G.; Meier-Sydow, J. The clinical and pharmacological history of theophylline: first report on the bronchospasmolytic action in man by S. R. Hirsch in Frankfurt (Main) 1922. Clin. Allergy, 1982, 12(2), 211-215.
[http://dx.doi.org/10.1111/j.1365-2222.1982.tb01641.x] [PMID: 7042115]
(i)Watanabe, Y.; Murata, T.; Shimizu, K.; Morita, H.; Inui, M.; Tagawa, T. Phosphodiesterase 4 regulates the migration of B16-F10 melanoma cells. Exp. Ther. Med., 2012, 4(2), 205-210.
[http://dx.doi.org/10.3892/etm.2012.587] [PMID: 22970026 ]
(j)Tesarik, J.; Mendoza, C.; Carreras, A. Effects of phosphodiesterase inhibitors caffeine and pentoxifylline on spontaneous and stimulus-induced acrosome reactions in human sperm. Fertil. Steril., 1992, 58(6), 1185-1190.
[http://dx.doi.org/10.1016/S0015-0282(16)55567-8] [PMID: 1333994]

Burbiel, J.C.; Hockemeyer, J.; Müller, C.E. Synthesis of xanthine derivatives by microwave-assisted ring closure reaction. ARKIVOC, 2006, 2, 77-82.

Zajac, M.A.; Zakrzewski, A.G.; Kowal, M.G.; Narayan, S. A novel method of caffeine synthesis from uracil. Synth. Commun., 2003, 33, 3291-3297.
[http://dx.doi.org/10.1081/SCC-120023986]

(a) Zablocki, J.; Kalla, R.; Perry, T.; Palle, V.; Varkhedkar, V.; Xiao, D.; Piscopio, A.; Maa, T.; Gimbel, A.; Hao, J.; Chu, N.; Leung, K.; Zeng, D. The discovery of a selective, high affinity A(2B) adenosine receptor antagonist for the potential treatment of asthma. Bioorg. Med. Chem. Lett., 2005, 15(3), 609-612.
[http://dx.doi.org/10.1016/j.bmcl.2004.11.044] [PMID: 15664822 ]
(b) Nieto, M.I.; Balo, M.C.; Brea, J.; Caamaño, O.; Cadavid, M.I.; Fernández, F.; Mera, X.G.; López, C.; Rodríguez-Borges, J.E. Synthesis of novel 1-alkyl-8-substituted-3-(3-methoxypropyl) xanthines as putative A(2B) receptor antagonists. Bioorg. Med. Chem., 2009, 17(9), 3426-3432.
[http://dx.doi.org/10.1016/j.bmc.2009.03.029] [PMID: 19346133]

Bandyopadhyay, P.; Agrawal, S.K.; Sathe, M.; Sharma, P. Kaushik; M. P. A facile and rapid one-step synthesis of 8-substituted xanthine derivatives via tandem ring closure at room temperature. Tetrahedron, 2012, 68, 3822-3827.
[http://dx.doi.org/10.1016/j.tet.2012.03.050]

Bandyopadhyay, P.; Sathe, M.; Sharma, P. Kaushik; M. P. Exploration of polystyrene-supported 2-isobutoxy-1-isobutoxycarbonyl-1,2-dihydroquino-line (PS-IIDQ) as new coupling agent for the synthesis of 8-substituted xanthine derivatives. Tetrahedron Lett., 2012, 53, 4631-4635.
[http://dx.doi.org/10.1016/j.tetlet.2012.04.135]

Dong, M.; Sitkovsky, M.; Kallmerten, A.E. Jones; G. B. Synthesis of 8-substituted xanthines via 5,6-diaminouracils: An efficient route to A2A adenosine receptor antagonists. Tetrahedron Lett., 2008, 49, 4633-4635.
[http://dx.doi.org/10.1016/j.tetlet.2008.05.071]

Beer, D.; Bhalay, G.; Dunstan, A.; Glen, A.; Haberthuer, S.; Moser, H. A solid-phase approach towards the synthesis of PDE5 inhibitors. Bioorg. Med. Chem. Lett., 2002, 12(15), 1973-1976.
[http://dx.doi.org/10.1016/S0960-894X(02)00296-2] [PMID: 12113821]

Shimizu, M.; Hayama, N.; Kimachi, T.; Inamoto, K. Copper-catalyzed intramolecular C–H amination: A new entry to substituted xanthine derivatives. Synthesis, 2017, 49, 4183-4190.
[http://dx.doi.org/10.1055/s-0036-1588821]

(a) Areias, F.M.; Proenca, M.F. A base-catalyzed cascade route to phenolic 6-cyanopurines via o-alkylformamidoximes. Synlett, 2014, 25, 2595-2598.
[http://dx.doi.org/ 10.1055/s-0034-1379237]
(b) Liu, B.; Gong, Y.; Lu, S.; Li, D.; Fan, H. Synthesis of fused purine heterocycles via a one-pot cascade reaction of a trisubstituted pyrimidine. Synlett, 2018, 29, 1796-1800.
[http://dx.doi.org/10.1055/s-0036-1591585]

Senhoraes, N.; Costa, A.L.; Silva, D.I.; Proenc¸, M.F.; Dias, A.M. N1- and C6-substituted adenines: A regioselective and efficient synthesis. Tetrahedron, 2013, 69, 10014-10021.
[http://dx.doi.org/10.1016/j.tet.2013.09.063]

Maji, P.K.; Mahalanobish, A. copper accelerated one-pot sequential tandem synthesis of tetra hedropurinoisoquinoline derivatives. Heterocycles, 2017, 94, 1847-1855.
[http://dx.doi.org/10.3987/COM-17-13694]

(a) DeWald, H.A.; Beeson, N.W.; Hershenson, F.M.; Wise, L.D.; Downs, D.A.; Heffner, T.G.; Coughenour, L.L.; Pugsley, T.A. Synthesis and potential antipsychotic activity of 1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidines. J. Med. Chem., 1988, 31(2), 454-461.
[http://dx.doi.org/10.1021/jm00397a032] [PMID: 2892936]
(b) Hirota, T.; Sasaki, K.; Tashima, Y.; Nakayama, T. Polycyclic N-hetero compounds. XXXIV. Syntheses and evaluation of antidepressive activity of benzofuro-[2,3-e]imidazo[1,2-c]pyrimidines and their precursors. J. Heterocycl. Chem., 1991, 28, 263-267.
[http://dx.doi.org/ 10.1002/jhet.5570280210]
(c) Camp, D.; Li, Y.; McCluskey, A.; Moni, R.W.; Quinn, R.J. Diimidazo[1,2-c:4′,5′-e]pyrimidines: N6-N1 conformationally restricted adenosines. Bioorg. Med. Chem. Lett., 1998, 8(6), 695-698.
[http://dx.doi.org/10.1016/S0960-894X(98)00101-2] [PMID: 9871585]
(d) Peet, N.P.; Lentz, N.L.; Sunder, S.; Dudley, M.W.; Ogden, A.M.L. Conformationally restrained, chiral (phenylisopropyl)amino-substituted pyrazolo[3,4-d]pyrimidines and purines with selectivity for adenosine A1 and A2 receptors. J. Med. Chem., 1992, 35(17), 3263-3269.
[http://dx.doi.org/10.1021/jm00095a024] [PMID: 1507211]
(e) Chhabria, M.T.; Jani, M.H. Design, synthesis and antimycobacterial activity of some novel imidazo[1,2-c]pyrimidines. Eur. J. Med. Chem., 2009, 44(10), 3837-3844.
[http://dx.doi.org/10.1016/j.ejmech.2009.04.002] [PMID: 19423196]

Juskenas, R.; Masevicius, V.; Tumkevicius, S. Reactivity of the pyrimidine nitrogen atom toward an acetal moiety: Formation of 3-ethoxy-2,3-dihydroimidazo[1,2-c]pyrimidines by intramolecular cyclization of n-(2,2-diethoxyethyl)pyrimidine-4-amines. Synthesis, 2013, 45, 2438-2446.
[http://dx.doi.org/10.1055/s-0033-1339350]

Lebed, P.S.; Kos, P.O.; Tolmachev, A.; Vovk, M.V.; Boyko, A.N.; Chekotylo, A. A facile synthesis of functionalized 1,2,6,7-tetrahydroimidazo[1,5-c]pyrimidine-3,5-diones. Synth. Commun., 2013, 43, 2343-2348.
[http://dx.doi.org/10.1080/00397911.2012.707738]

Law, R.P.; Ukuser, S.; Tape, D.T.; Talbot, E.P.A. Regioselective synthesis of 3-aminoimidazo[1,2-a] pyrimidines with triflic anhydride. Synthesis, 2017, 49, 3775-3794.
[http://dx.doi.org/10.1055/s-0036-1588425]

(a) Reddy, M.V.; Byeon, K.R.; Park, S.H.; Kim, D.W. Polyethylene glycol methacrylate-grafted dicationic imidazolium-based ionic liquid: Heterogeneous catalyst for the synthesis of aryl-benzo[4,5]imidazo[1,2-a]pyrimidine amines under solvent-free conditions. Tetraheron, 2017, 73, 5289-5296.
[http://dx.doi.org/ 10.1016/j.tet.2017.07.025]
(b) Liu, J.; Lei, M.; Hu, L. Thiamine hydrochloride (VB1): an efficient promoter for the one-pot synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine and [1,2,4]triazolo[1,5-a]pyrimidine derivatives in water medium. Green Chem., 2012, 14, 840-846.
[http://dx.doi.org/ 10.1039/c2gc16499j]
(c) Hemmati, B.; Javanshir, S.; Dolatkhah, Z. Hybrid magnetic Irish moss/Fe₃O₄ as a nano-biocatalyst for synthesis of imidazopyrimidine derivatives. RSC Advances, 2016, 6, 50431-50436.
[http://dx.doi.org/10.1039/C6RA08504K ]
(d) Kalita, S.J.; Deka, D.C.; Mecadon, H. Organocatalytic domino Knöevenagel-Michael reaction in water for the regioselective synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines and pyrido[2,3-d]pyrimidin-2-amines. RSC Advances, 2016, 6, 91320-91324.
[http://dx.doi.org/10.1039/C6RA21376F]

Jadhav, A.M.; Kim, Y.I.; Lim, K.T.; Jeong, Y.T. Application of p-TSA in the one pot synthesis of N-methyl-3-nitro-aryl-benzo[4,5]imidazo[1,2-a]pyrimidin-2-amine. Tetrahedron Lett., 2018, 59, 554-557.
[http://dx.doi.org/10.1016/j.tetlet.2018.01.008]

Al-Tel, T.H.; Al Qawasmeh, R.A.; Voelter, W. Rapid assembly of polyfunctional structures using a one-pot five- and six-component sequential groebke–blackburn/ugi/passerini Process. Eur. J. Org. Chem., 2010, 29, 5586-5593.
[http://dx.doi.org/10.1002/ejoc.201000808]

(a) Rawat, M.; Rawat, D.S. Copper oxide nanoparticle catalysed synthesis of imidazo[1,2-a]pyrimidine derivatives, their optical properties and selective fluorescent sensor towards zinc ion. Tetrahedron Lett., 2018, 59, 2341-2346.
[http://dx.doi.org/10.1016/j.tetlet.2018.05.005]
(b) Ho, S.L.; Dao, P.D.Q.; Cho, C.S. Microwave-assisted synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines from β-bromo-α,β-unsaturated aldehydes and 2-aminobenzi-midazoles. Synlett, 2017, 28, 1811-1815.
[http://dx.doi.org/10.1055/s-0036-1588834]

(a) Büyükafşar, K.; Yazar, A.; Düşmez, D.; Oztürk, H.; Polat, G.; Levent, A. Effect of trapidil, an antiplatelet and vasodilator agent on gentamicin-induced nephrotoxicity in rats. Pharmacol. Res., 2001, 44(4), 321-328.
[http://dx.doi.org/10.1006/phrs.2001.0864] [PMID: 11592868 ]
(b) Liu, M.; Sun, Q.; Wang, Q.; Wang, X.; Lin, P.; Yang, M.; Yan, Y. Effect of trapidil in myocardial ischemia-reperfusion injury in rabbit. Indian J. Pharmacol., 2014, 46(2), 207-210.
[http://dx.doi.org/10.4103/0253-7613.129320] [PMID: 24741195]
(c) Gomha, S.M.; Mohamed, A.M.G.; Zaki, Y.H.; Ewies, M.M.; Elroby, S.A. Structural elucidation and antimicrobial evaluation of novel [1,2,4]Triazolo[4,3-a]pyrimidines and Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinones. J. Heterocycl. Chem., 2018, 55, 1147-1156.
[http://dx.doi.org/ 10.1002/jhet.3146]
(d) Edrees, M.M.; Farghaly, T.A. Synthesis and antitumor activity of benzo [6 ″, 7 ″] cyclohepta [1 ″, 2 ″: 4′, 5′] pyrido [2′, 3′-d][1, 2, 4] triazolo [4, 3-a] pyrimidin-5-ones. Arab. J. Chem., 2017, 10, S1613.
[http://dx.doi.org/ 10.1016/j.arabjc.2013.06.002]
(e) Kumar Biswas, B.; Malpani, Y.R.; Ha, N.; Kwon, D.H.; Soo Shin, J.; Kim, H.S.; Kim, C.; Bong Han, S.; Lee, C.K.; Jung, Y.S. Enterovirus inhibitory activity of C-8-tert-butyl substituted 4-aryl-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-ones. Bioorg. Med. Chem. Lett., 2017, 27(15), 3582-3585.
[http://dx.doi.org/10.1016/j.bmcl.2017.05.030] [PMID: 28587824]
(f) Pan, F.J.; Wang, S.B.; Liu, D.C.; Gong, G.H.; Quan, Z.S. Synthesis of 4-phenylthieno[2,3-e][1,2,4]triazolo[4,3-a]pyrimidine-5(4h)-one derivatives and evaluation of their anti-inflammatory activity. Lett. Drug Des. Discov., 2016, 13, 141-148.
[http://dx.doi.org/10.2174/1570180812666150630184439]

(a) Li, C.; Li, Z.; Wang, Q. A convenient route for the synthesis of novel 2-substituted [1,2,4]triazolo[1,5-c]pyrimidine derivatives. Synlett, 2010, 14, 2179-2183.
(b) Tang, C.; Wang, C.; Li, Z.; Wang, Q. Synthesis of 8-Bromo-7-chloro[1,2,4]triazolo[4,3-c]pyrimidines, their ring rearrangement to [1,5-c] analogues, and further diversification. Synthesis, 2014, 46, 2734-2746.
[http://dx.doi.org/10.1055/s-0034-1378453]

Karami, B.; Farahi, M.; Banaki, Z. A Novel One-pot method for highly regioselective synthesis of triazoloapyrimidinedicarboxylates using silica sodium carbonate. Synlett, 2015, 26, 1804-1807.
[http://dx.doi.org/10.1055/s-0034-1380677]

Singh, M.; Fatma, S.; Ankit, P.; Singh, S.B.; Singh, J. Boric acid in aqueous micellar medium: An effective and recyclable catalytic system for the synthesis of aryl-7,8-dihydro[1,2,4]triazolo[4,3-a]pyrimidine-6-carbonitriles. Tetrahedron Lett., 2014, 55, 525-527.
[http://dx.doi.org/10.1016/j.tetlet.2013.11.090]

He, X.; Kassab, S.E.; Heinzl, G.; Xue, F. Base-catalyzed one-step synthesis of 5,7-disubstituted-1,2,4-triazolo[1,5-a] pyrimidines. Tetrahedron Lett., 2015, 56, 1034-1037.
[http://dx.doi.org/10.1016/j.tetlet.2014.12.135]

Kolosov, M.A.; Shvets, E.H.; Manuenkov, D.A.; Vlasenko, S.A.; Omel’chenko, I.N.; Shishkina, S.V.; Orlov, V.D. A synthesis of 6-functionalized 4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidines. Tetrahedron Lett., 2017, 58, 1207-1210.
[http://dx.doi.org/10.1016/j.tetlet.2017.02.035]

Vilapara, K.; Butani, H.; Gami, S.; Khunt, H.; Naliapara, Y. One-pot sequential approach for the construction of highly functionalized triazolo[4,3-c]pyrimidine library. Synth. Commun., 2015, 45, 2355-2363.
[http://dx.doi.org/10.1080/00397911.2015.1083579]

Mohamed, M.M.; Khalil, A.K.; Abbass, E.M.; El-Naggar, A.M. Design, synthesis of new pyrimidine derivatives as anticancer and antimicrobial agents. Synth. Commun., 2017, 47, 1441-1457.
[http://dx.doi.org/10.1080/00397911.2017.1332223]

(a) Emelina, E.E.; Petrov, A.A. α-aminoazoles in the Synthesis of heterocycles: V. Synthesis of azolo[1,5-a]pyrimidines from 2-ethoxyvinyl trifluoromethyl ketones and 2,2-diethoxyvinyl trifluoromethyl ketone. Russ. J. Org. Chem., 2009, 45, 417-420.
[http://dx.doi.org/10.1134/S1070428009030117 ]
(b) Andrade, V.P.; Mittersteiner, M.; Bonacorso, H.G.; Frizzo, C.P.; Martins, M.A.P.; Zanatta, N. Regioselective Synthesis of 5-(Trifluoromethyl)[1, 2,4]triazolo[1,5-a]pyrimidi-nes from β-Enamino Diketones. Synthesis, 2019, 51, 2311-2317.
[http://dx.doi.org/ 10.1055/s-0037-1611765]
(c) Frizzo, C.P.; Scapin, E.; Marzari, M.R.B.; München, T.S.; Zanatta, N.; Bonacorso, H.G.; Buriol, L.; Martins, M.A.P. Ultrasound irradiation promotes the synthesis of new 1,2,4-triazolo[1,5-a]pyrimidine. Ultrason. Sonochem., 2014, 21(3), 958-962.
[http://dx.doi.org/10.1016/j.ultsonch.2013.12.007] [PMID: 24394386 ]
(d) Chernyshev, V.M.; Astakhov, A.V.; Starikova, Z.A. Reaction of 1-substituted 3,5-diamino-1,2,4-triazoles with β-keto esters: Synthesis and new rearrangement of mesoionic 3-amino-2H-[1,2,4]triazolo-[4,3-a]pyrimidin-5-ones. Tetrahedron, 2010, 66, 3301-3313.
[http://dx.doi.org/10.1016/j.tet.2010.03.009]

Souza, L.A.; Santos, J.M.; Mittersteiner, M.; Andrade, V.P.; Lobo, M.M.; Santos, F.B.; Bortoluzzi, A.J.; Bonacorso, H.G.; Martins, M.A.P.; Zanatta, N. Synthetic versatility of β-alkoxyvinyl trichloromethyl ketones for obtaining [1,2,4]triazolo[1,5-a]pyrimidines. Synthesis, 2018, 50, 3686-3695.
[http://dx.doi.org/10.1055/s-0037-1610191]

Alnajjar, A.; Abdelkhalik, M.M.; Raslan, M.A.; Ibraheem, S.M.; Sadek, K.U. Synthesis of new [1,2,4]triazolo[1,5-a]pyrimidine derivatives: Reactivity of 3-amino[1,2,4]triazole towards enaminonitriles and enaminones. J. Heterocycl. Chem., 2018, 55, 1804-1808.
[http://dx.doi.org/10.1002/jhet.3222]

(a) El Ashry, E.S.H.; Rashed, N. 1,2,3-Triazolo[x, y-z]pyrimidines. Adv. Heterocycl. Chem., 1998, 71, 57-114.
[http://dx.doi.org/10.1016/S0065-2725(08)60831-4 ]
(b) Fischer, G. Recent progress in 1,2,4-triazolo[1,5-a]pyrimidine chemistry. Adv. Heterocycl. Chem., 2008, 95, 143-219.
[http://dx.doi.org/10.1016/S0065-2725(07)95003-5 ]
(c) Ohnishi, H.; Yamaguchi, K.; Shimada, S.; Suzuki, Y.; Kumagai, A. A new approach to the treatment of atherosclerosis and trapidil as an antagonist to platelet-derived growth factor. Life Sci., 1981, 28(14), 1641-1646.
[http://dx.doi.org/10.1016/0024-3205(81)90320-9] [PMID: 6264257 ]
(d) Novinson, T.; Springer, R.H. OíBrien, D.E.; Scholten, M.B.; Miller, J.P.; Robins, R.K. 2-(Alkylthio)-1,2,4-triazolo[1,5-a]pyrimidines as adenosine 3′,5′-monophosphate phosphodiesterase inhibitors with potential as new cardiovascular agents. J. Med. Chem., 1982, 25, 420-426.
[http://dx.doi.org/10.1021/jm00346a017] [PMID: 6279846]
(e) Gujjar, R.; Marwaha, A.; El Mazouni, F.; White, J.; White, K.L.; Creason, S.; Shackleford, D.M.; Baldwin, J.; Charman, W.N.; Buckner, F.S.; Charman, S.; Rathod, P.K.; Phillips, M.A. Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice. J. Med. Chem., 2009, 52(7), 1864-1872.
[http://dx.doi.org/10.1021/jm801343r] [PMID: 19296651]
(f) Chen, Q.; Zhu, X.L.; Jiang, L.L.; Liu, Z.M.; Yang, G.F. Synthesis, antifungal activity and CoMFA analysis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives. Eur. J. Med. Chem., 2008, 43(3), 595-603.
[http://dx.doi.org/10.1016/j.ejmech.2007.04.021] [PMID: 17618711 ]
(g) Yu, W.; Goddard, C.; Clearfield, E.; Mills, C.; Xiao, T.; Guo, H.; Morrey, J.D.; Motter, N.E.; Zhao, K.; Block, T.M.; Cuconati, A.; Xu, X. Design, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion. J. Med. Chem., 2011, 54(16), 5660-5670.
[http://dx.doi.org/10.1021/jm200696v] [PMID: 21786803 ]
(h) El-Gendy, M.M.A.; Shaaban, M.; Shaaban, K.A.; El-Bondkly, A.M.; Laatsch, H. Essramycin: A first triazolopyrimidine antibiotic isolated from nature. J. Antibiot. (Tokyo), 2008, 61(3), 149-157.
[http://dx.doi.org/10.1038/ja.2008.124] [PMID: 18503193 ]
(i)Allen, J.G.; Bourbeau, M.P.; Wohlhieter, G.E.; Bartberger, M.D.; Michelsen, K.; Hungate, R.; Gadwood, R.C.; Gaston, R.D.; Evans, B.; Mann, L.W.; Matison, M.E.; Schneider, S.; Huang, X.; Yu, D.; Andrews, P.S.; Reichelt, A.; Long, A.M.; Yakowec, P.; Yang, E.Y.; Lee, T.A.; Oliner, J.D. Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein interaction. J. Med. Chem., 2009, 52(22), 7044-7053.
[http://dx.doi.org/10.1021/jm900681h] [PMID: 19856920 ]
(j)Tang, W.; Shi, D.Q. Synthesis and herbicidal activity of O,O-dialkyl N-[2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yloxy)benzoxyl]-1-amino-1-substitutedbe-nzyl phosphonates. J. Heterocycl. Chem., 2010, 47, 162-166.
(k)Chen, Q.; Liu, Z.M.; Chen, C.N.; Jiang, L.L.; Yang, G.F. Synthesis and fungicidal activities of new 1,2,4-triazolo[1,5-a]pyrimidines. Chem. Biodivers., 2009, 6(8), 1254-1265.
[http://dx.doi.org/10.1002/cbdv.200800168] [PMID: 19697344 ]
(l)El-Koussi, N.A.; Omar, F.A.; Abdel-Aziz, S.A.; Radwan, M.F. Synthesis and antibacterial screening of some 2, 5, 7-triaryl-1, 2, 4-triazolo. Pyrimidines. Bull. Pharm. Sci., 2004, 27, 141-154.
(m)Lakomska, I.; Wojtczak, A.; Sitkowski, J.; Kozerski, L.; Szlyk, E. Platinum(IV) complexes with purine analogs. Studies of molecular structure and antiproliferative activity in vitro. Polyhedron, 2008, 27, 2765-2770.
[http://dx.doi.org/10.1016/j.poly.2008.05.032 ]
(n)Lakomska, I. Molecular structure and antitumor activity of platinum(II) complexes containing purine analogs. Inorg. Chim. Acta, 2009, 362, 669-681. http://
[http://dx.doi.org/10.1016/j.ica.2008.02.030]

Li, T-J.; Yao, C-S.; Yu, C-X.; Wang, X-S.; Tu, S-J. Ionic liquid–mediated one-pot synthesis of 5-(trifluoromethyl)-4,7-dihydrotetrazolo[1,5-a] pyrimidine derivatives. Synth. Commun., 2012, 42, 2728-2738.
[http://dx.doi.org/10.1080/00397911.2011.566460]

Kolosov, M.A.; Shvets, E.H.; Manuenkov, D.A.; Kulyk, O.G.; Mazepa, A.V.; Orlov, V.D. A synthesis of 6-functionalized 7-unsubstituted- and 7-methyl[1,2,4]azolo[1,5-a]pyrimidine derivatives. Synth. Commun., 2019, 49, 611-615.
[http://dx.doi.org/10.1080/00397911.2019.1566476]

Wendt, M.D.; Kunzer, A.; Henry, R.F.; Cross, J.; Pagano, T.G. Regiochemistry of addition of aminoheterocycles to α-cyanocinnamonitriles: Formation of aza-bridged bi- and tricycles. Tetrahedron Lett., 2007, 48, 6360-6363.
[http://dx.doi.org/10.1016/j.tetlet.2007.07.039]

(a) Kjær, S.; Linch, M.; Purkiss, A.; Kostelecky, B.; Knowles, P.P.; Rosse, C.; Riou, P.; Soudy, C.; Kaye, S.; Patel, B.; Soriano, E.; Murray-Rust, J.; Barton, C.; Dillon, C.; Roffey, J.; Parker, P.J.; McDonald, N.Q. Adenosine-binding motif mimicry and cellular effects of a thieno[2,3-d]pyrimidine-based chemical inhibitor of atypical protein kinase C isoenzymes. Biochem. J., 2013, 451(2), 329-342.
[http://dx.doi.org/10.1042/BJ20121871] [PMID: 23418854]
(b) Horiuchi, T.; Takeda, Y.; Haginoya, N.; Miyazaki, M.; Nagata, M.; Kitagawa, M.; Akahane, K.; Uoto, K. Discovery of novel Thieno[2,3-d]pyrimidin-4-yl hydrazone-based cyclin-dependent kinase 4 inhibitors: synthesis, biological evaluation and structure-activity relationships. Chem. Pharm. Bull. (Tokyo), 2011, 59(8), 991-1002.
[http://dx.doi.org/10.1248/cpb.59.991] [PMID: 21804244]
(c) Horiuchi, T.; Nagata, M.; Kitagawa, M.; Akahane, K.; Uoto, K. Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of cyclin D1-CDK4: Synthesis, biological evaluation and structure-activity relationships. Part 2. Bioorg. Med. Chem., 2009, 17(23), 7850-7860.
[http://dx.doi.org/10.1016/j.bmc.2009.10.039] [PMID: 19889545 ]
(d) McClellan, W.J.; Dai, Y.; Abad-Zapatero, C.; Albert, D.H.; Bouska, J.J.; Glaser, K.B.; Magoc, T.J.; Marcotte, P.A.; Osterling, D.J.; Stewart, K.D.; Davidsen, S.K.; Michaelides, M.R. Discovery of potent and selective thienopyrimidine inhibitors of Aurora kinases. Bioorg. Med. Chem. Lett., 2011, 21(18), 5620-5624.
[http://dx.doi.org/10.1016/j.bmcl.2011.06.041] [PMID: 21778056 ]
(e) Gangjee, A.; Li, W.; Kisliuk, R.L.; Cody, V.; Pace, J.; Piraino, J.; Makin, J. Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymi-dylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents. J. Med. Chem., 2009, 52(15), 4892-4902.
[http://dx.doi.org/10.1021/jm900490a] [PMID: 19719239 ]
(f) Gangjee, A.; Qiu, Y.; Li, W.; Kisliuk, R.L. Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d] pyrimidine antifolates. J. Med. Chem., 2008, 51(18), 5789-5797.
[http://dx.doi.org/10.1021/jm8006933] [PMID: 18800768]
(g) Gangjee, A.; Qiu, Y.; Kisliuk, R.L. Synthesis of classical and nonclassical 2-amino-4-oxo-6-benzylthieno-[2,3-d]pyrimidines as potential thymidylate synthase inhibitors. J. Heterocycl. Chem., 2004, 41, 941-946.
[http://dx.doi.org/10.1002/jhet.5570410613]

(a) Majumdar, K.C.; Maji, P.K.; Pal, A.K. Synthesis of pyrimidine-annulated heterocycles: Facile sulfoxide rearrangement of 1, 3-dimethyl-5-(aryloxybut-2-ynylthio) pyrimidine-2, 4-dione. Lett. Org. Chem., 2007, 4, 134-136.
[http://dx.doi.org/10.2174/157017807780414127 ]
(b) Majumdar, K.C.; Pal, N.; Chattopadhyay, S.K. An efficient route to thieno[2,3-d]pyrimidine derivatives by tandem [2, 3] and Sigmatropic Rearrangement. Lett. Org. Chem., 2006, 3, 709-711. [3, 3].
[http://dx.doi.org/10.2174/157017806778700033]

Kobayashi, K.; Suzuki, T.; Kozuki, T.; Matsumoto, N.; Hiyoshi, H.; Umezu, K. Synthesis of 5,6-disubstituted thieno[2,3-d]pyrimidines from 4-chloro-pyrimidines. Heterocycles, 2012, 85, 1405-1416.
[http://dx.doi.org/10.3987/COM-12-12463]

Balti, M.; Hachicha, M.; Efrit, M.L.E. An efficient synthetic route towards novel 3N-sunstituted thieno[2,3-d]pyrimidin-4(3H)-Ones. Heterocycles, 2015, 91, 1455-1464.
[http://dx.doi.org/10.3987/COM-15-13236]

Wilding, B.; Faschauner, S.; Klempier, N. A practical synthesis of 5-functionalized thieno[2,3-d]pyrimidines. Tetrahedron Lett., 2015, 56, 4486-4489.
[http://dx.doi.org/10.1016/j.tetlet.2015.05.104]

Yang, J.; Shi, D.; Hao, P.; Yang, D.; Zhang, Q.; Li, J. An innovative synthesis of tertiary hydroxyl thieno[2,3-d]pyrimidinone skeleton: Natural-like product from the tandem reaction of o-aminothienonitrile and carbonyl compound. Tetrahedron Lett., 2016, 57, 2455-2461.
[http://dx.doi.org/10.1016/j.tetlet.2016.04.088]

Moustafa, A.H.; Ahmed, W.W.; Khodairy, A. Syntheses of some new n-linked pyrimidine-2-amines with pyrazinopyrimidines, thienopyrimidines, and benzazoles via reactions of various nucleophiles with cyanamides. J. Heterocycl. Chem., 2017, 54, 3490-3497.
[http://dx.doi.org/10.1002/jhet.2972]

Lemaire, L.; Leleu-Chavain, N.; Tourteau, A.; Abdul-Sada, A.; Spencer, J.; Millet, R. A rapid route for the preparation of pyrimido[5,4-d]- and pyrido[3,2-d]oxazoles. Tetrahedron Lett., 2015, 56, 2448-2450.
[http://dx.doi.org/10.1016/j.tetlet.2015.03.082]

Mieczkowski, A.; Bazlekowa, M.; Bagiński, M.; Wójcik, J.; Winczura, A.; Miazga, A.; Ghahe, S.S.; Gajda, R.; Woźniak, K.; Tudek, B. A mild and efficient approach to the 6H-oxazolo[3,2-f]pyrimidine-5,7-dione scaffold via unexpected rearrangement of 2,3-dihydropyrimido[6,1-b][1,5,3]dioxazepine-7,9(5H,8H)-diones: Synthesis, crystallographic studies, and cytotoxic activity screening. Tetrahedron Lett., 2016, 57, 743-746.
[http://dx.doi.org/10.1016/j.tetlet.2016.01.006]

(a) Mondal, B.; Hazra, S.; Naktode, K.; Panda, T.K.; Roy, B.PhI. (OAc)2 and BF₃–OEt₂ mediated heterocyclization: Metal-free synthesis of pyrimidine-annulated oxazolines. Tetrahedron Lett., 2014, 55, 5625-5628.
[http://dx.doi.org/ 10.1016/j.tetlet.2014.08.051]
(b) Roy, B.; Hazra, S.; Mondal, B.; Majumdar, K.C. Cu(OTf)2-catalyzed dehydrogenative C-H activation under atmospheric oxygen: An expedient approach to pyrrolo[3,2-d] pyrimidine derivatives. Eur. J. Org. Chem., 2013, 4570-4577.
[http://dx.doi.org/10.1002/ejoc.201300275]

Shirsale, A.; Patil, Y.; Rawal, G.K.; Pabba, J.; Berthon, G.; Sonawane, R.P.; Sikervar, V. A Convenient and concise metal-free approach to functionalized bicyclic pyrimidinones from oxazine-2,6-diones. Synthesis, 2018, 1, 2087-2093.
[http://dx.doi.org/10.1055/s-0037-1609364]

(a) Jiang, K-M.; Jin, Y. Lin J. 1,3-Dipolar cycloaddition of uracil derivatives with nitrile oxides: Synthesis of [1,2,4]oxadiazolo[4,5-c]pyrimidine-5,7(6H)-dione derivatives. Tetrahedron, 2017, 73, 6662-6668.
[http://dx.doi.org/10.1016/j.tet.2017.10.024 ]
(b) Liu, X.; Song, X.; Liu, Y.; Xie, M.; Yu, W.; Yan, S.; Lin, J.; Jin, Y. Novel 5H-[1,2,4]oxadiazolo[4,5-a]pyri-midin-5-one derivatives as antibacterial and anticancer agents: Synthesis and biological evaluation. Tetrahedron Lett., 2018, 59, 3767-3772.
[http://dx.doi.org/10.1016/j.tetlet.2018.09.011]

(a) Pan, B.; Huang, R.; Zheng, L.; Chen, C.; Han, S.; Qu, D.; Zhu, M.; Wei, P. Thiazolidione derivatives as novel antibiofilm agents: Design, synthesis, biological evaluation, and structure-activity relationships. Eur. J. Med. Chem., 20011, 46(3), 819-824.
[http://dx.doi.org/10.1016/j.ejmech.2010.12.014] [PMID: 21255878]
(b) Zhi, H.; Chen, L-M.; Zhang, L-L.; Liu, S-J.; Wan, D.C.C.; Lin, H-Q.; Hu, C. Design, synthesis, and biological evaluation of 5H-thiazolo[3,2-a]pyrimidine derivatives as a new type of acetylcholinesterase inhibitors. ARKIVOC, 2008, 13, 266-277.
(c) Quan, Z-J.; Zhang, Z.; Wang, J-K.; Wang, X-C.; Liu, Y-J.; Ji, P-Y. Efficient synthesis of 5H-thiazolo[3,2-a]pyrimidines from reactions of 3,4-dihydropyrimidine-thiones with α-bromoacetone in aqueous media. Heteroatom Chem., 2008, 2, 149-153.
[http://dx.doi.org/10.1002/hc.20386]

Singh, S.; Schober, A.; Gebinoga, M.; Groß, G.A. Convenient method for synthesis of thiazolo[3,2-a]pyrimidine derivatives in a one-pot procedure. Tetrahedron Lett., 2011, 52, 3814-3817.
[http://dx.doi.org/10.1016/j.tetlet.2011.05.067]

Zhao, B.; Jiang, L-L.; Liu, Z.; Deng, Q-G.; Wang, L-Y.; Song, B.; Gao, Y. A microwave assisted synthesis of highly substituted 7-methyl-5H-thiazolo[3,2-a] pyrimidine-6-carboxylate derivatives via one-pot reaction of aminothiazole, aldehyde and ethyl acetoacetate. Heterocycles, 2013, 87(10), 2093-2102.
[http://dx.doi.org/10.3987/COM-13-12797]

Yadav, L.D.S.; Dubey, S.; Yadav, B.S. Solvent-free one-pot reactions for annulating a pyrimidine ring on thiazoles under microwave irradiation. Tetrahedron, 2003, 59, 5411-5415.
[http://dx.doi.org/10.1016/S0040-4020(03)00854-8]

(a) Xiao, D.; Han, L.; Sun, Q.; Chen, Q.; Gong, N.; Lv, Y.; Suzenet, F.; Guillaumet, G.; Cheng, T.; Li, R. Copper-mediated synthesis of N-fused heterocycles via Csp-S coupling reaction and 5-endo-dig cyclization sequence. RSC Advances, 2012, 2, 5054-5057.
[http://dx.doi.org/10.1039/c2ra20254a ]
(b) Shelke, A.V.; Bhong, B.Y.; Karade, N.N. New synthesis of 3,5-disubstituted-5H-thiazolo[3,2-a]pyrimidine via ring annulation of 3,4-dihydropyrimidin-2(1H)-thione using alkynyl(aryl)iodonium salts. Tetrahedron Lett., 2013, 54, 600-603.
[http://dx.doi.org/10.1016/j.tetlet.2012.11.098]

(a) Studzinska, R.; Wroblewski, M.; Draminski, M. Synthesis of new thiazolo[3,2-a]pyrimidin-5-one derivatives in reaction of 3-allyl-2-thiouracils cyclization. Heterocycles, 2008, 75, 1953-1961.
[http://dx.doi.org/ 10.3987/COM-08-11365]
(b) Studzinska, R.; Wroblewski, M.; Karczmarska-Wodzka, A.; Kołodziejska, R. A facile synthesis of the novel thiazolo[3,2-a]pyrimidine derivatives. Tetrahedron Lett., 2014, 55, 1384-1386.
[http://dx.doi.org/10.1016/j.tetlet.2014.01.033]

Lashmanova, E.A.; Rybakov, V.B.; Shiryaev, A.K. Synthesis of adamantylated pyrimidines using the Biginelli reaction. Synthesis, 2016, 48, 3965-3970.
[http://dx.doi.org/10.1055/s-0035-1562459]

(a) Behalo, M.S. Synthesis of Some Novel Thiazolo[3,2-a]pyrimidine and Pyrimido[2,1-b][1,3]thiazine derivatives and their antimicrobial evaluation. J. Heterocycl. Chem., 2018, 55, 1391-1397.
[http://dx.doi.org/10.1002/jhet.3174 ]
(b) Elmaaty, T.A.; El-Taweel, F.; Abdeldayem, S.; Elfarh, A.A. Synthesis of some new thiazolo[3,2-a]pyrimidine derivatives and their applications as disperse dyes. J. Heterocycl. Chem., 2019, 56, 922-929.
[http://dx.doi.org/10.1002/jhet.3470]

(a) Silpa, L.; Petrignet, J.; Abarbri, M. Direct access to fluorinated thiadiazolo[3,2-a]pyrimidin-7-one systems. Synlett, 2014, 25, 1827-1830.
[http://dx.doi.org/10.1055/s-0034-1378332 ]
(b) Dong, H.; Zhao, Y. Highly regioselective synthesis of 7-oxo-7h-[1,3,4]thiadiazolo[3,2-a]pyrimidine-5-carboxylate derivatives under mild conditions. Tetrahedron Lett., 2019, 60, 1399-1403.
[http://dx.doi.org/10.1016/j.tetlet.2019.04.005]

Zhao, B.; Xu, Y.; Deng, Q-G.; Liu, Z.; Wang, L-Y.; Gao, Y. One-pot, three component synthesis of novel 5H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-6-carboxylate derivatives by microwave irradiation. Tetrahedron Lett., 2014, 55, 4521-4524.
[http://dx.doi.org/10.1016/j.tetlet.2014.06.073]

Kasaboina, S.; Bollu, R.; Gomedhika, P.M.; Ramineni, V.; Nagarapu, L.; Dumala, N.; Grover, P.; Nanubolu, J.B. A green protocol for one pot synthesis of benzosuberone tethered thiadiazolopyrimidine-6-carboxylates using PEG-400 as potent anti-proliferative agents. Tetrahedron Lett., 2018, 59, 3015-3019.
[http://dx.doi.org/10.1016/j.tetlet.2018.06.068]

Yavari, I.; Hojati, M.; Azad, L.; Halvagar, M.R. A Synthesis of spirocyclic oxazinoisoquinolines and oxazinoquinolines bearing thiazolopyrimidine moieties. Synlett, 2018, 29, 1024-1027.
[http://dx.doi.org/10.1055/s-0037-1609302]

Hamama, W.S.; Ibrahim, M.E.; Zoorob, H.H. Synthesis and in vitro antitumor activity of new isoxazolo[5,4-d]pyrimidine systems. J. Heterocycl. Chem., 2016, 53, 2007-2012.
[http://dx.doi.org/10.1002/jhet.2521]

Gumuş, M.K.; Gorobets, N.Y.; Sedash, Y.V.; Shishkina, S.V.; Desenko, S.M. Rapid formation of chemical complexity via a modified Biginelli reaction leading to dihydrofuran-2(3H)-one spiro-derivatives of triazolo[1,5-a]pyrimidine. Tetrahedron Lett., 2017, 58, 3446-3448.
[http://dx.doi.org/10.1016/j.tetlet.2017.07.071]

Loidreau, Y.; Levacher, V.; Besson, T. Suzuki cross-coupling of 5-bromothieno[2,3-b]pyridines for the convenient synthesis of 8-arylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-amines. Tetrahedron Lett., 2013, 54, 1160-1163.
[http://dx.doi.org/10.1016/j.tetlet.2012.12.077]

Gnanasekaran, K.K.; Muddala, N.P.; Bunce, R.A. Pyrazoloquinazolinones and pyrazolopyridopyrimidinones by a sequential N-acylation–SNAr reaction. Tetrahedron Lett., 2015, 56, 1367-1369.
[http://dx.doi.org/10.1016/j.tetlet.2015.01.146]

Pyatakov, D.A.; Astakhov, A.V.; Sokolov, A.N.; Fakhrutdinov, A.N.; Fitch, A.N.; Rybakov, V.B.; Chernyshev, V.V.; Chernyshev, V.M. Alkoxy base-mediated selective synthesis and new rearrangements of 1,2,4-triazolodi-pyrimidinones. Tetrahedron Lett., 2017, 58, 748-754.
[http://dx.doi.org/10.1016/j.tetlet.2017.01.030]

Krishnammagari, S.K.; Cho, B.G.; Kim, J.T.; Jeongm, Y.T. An efficient and solvent-free one-pot multi-component synthesis of novel highly substituted pyrido[2′,3′:3,4] pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives catalyzed by tetramethylguanidine. Synth. Commun., 2018, 48, 2663-2674.
[http://dx.doi.org/10.1080/00397911.2018.1514053]

Marquise, N.; Nguyen, T.T.; Chevallier, F.; Picot, L.; Thiéry, V.; Lozach, O.; Bach, S.; Ruchaud, S.; Mongin, F. Azine and diazine functionalization using 2,2,6,6-tetramethylpiperidino-based lithium-metal combinations: Application to the synthesis of 5,9-disubstituted pyrido[3′,2′:4,5]pyrrolo[1,2-c]pyri-midines. Synlett, 2015, 26, 2811-2816.
[http://dx.doi.org/10.1055/s-0035-1560496]

Soleimany, M.; Lari, J.; Vahedi, H.; Imanpour, M. New facile route to synthesize furo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine and Furo[3,2-e][1,2,4]tri-azolo[1,5-c]pyrimidine derivatives. Synth. Commun., 2014, 44, 1-9.
[http://dx.doi.org/10.1080/00397911.2014.943344]

Dolzhenko, A.V.; Pastorin, G.; Chui, W.K. A new synthesis of 2,8-disubstituted pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines. Tetrahedron Lett., 2009, 50, 5617-5621.
[http://dx.doi.org/10.1016/j.tetlet.2009.07.113]

Ravi, K.N.; Poornachandra, Y.; Krishna, S.D.; Jitender, D.G.; Ganesh, K.C.; Narsaiah, B. Synthesis of novel ethyl 2,4-disubstituted 8-(trifluoromethyl) pyrido [2′, 3′:3,4]pyrazolo[1,5-a]pyrimidine-9-carboxylate derivatives as promising anticancer agents. Bioorg. Med. Chem. Lett., 2016, 26, 5203-5206.
[http://dx.doi.org/10.1016/j.bmcl.2016.09.062] [PMID: 27720296]

Rote, R.V.; Shelar, D.P.; Patil, S.R.; Jachak, M.N. A convenient synthesis of new pyrazolo[4,3-d]pyrimidines and their fused heterocycles. J. Heterocycl. Chem., 2014, 51, 815-823.
[http://dx.doi.org/10.1002/jhet.2006]

(a) Gorbunov, E.B.; Rusinov, G.L.; Ulomskii, E.N.; Isenov, M.L.; Charushin, V.N. Synthesis of 2H-azolo[1,5-a] [1,2,3]triazolo[4,5-e]pyrimidines. Chem. Heterocycl. Compd., 2015, 51, 491-495.
[http://dx.doi.org/ 10.1007/s10593-015-1725-2]
(b) Gorbunov, E.B.; Rusinov, G.L.; Ulomsky, E.N.; Rusinov, V.L.; Charushin, V.N.; Chupakhin, O.N. C–H functionalization of triazolo[a]-annulated 8-azapurines. Tetrahedron Lett., 2016, 57, 2303-2305.
[http://dx.doi.org/10.1016/j.tetlet.2016.04.052]

Liu, B.; Li, X-F.; Liu, H-C.; Yu, X-Y. Unexpected nitrilimine cycloaddition of thiazolo[3,2-a] pyrimidine derivatives. Tetrahedron Lett., 2013, 54, 6952-6954.
[http://dx.doi.org/10.1016/j.tetlet.2013.10.062]

Agrebi, A.; Allouche, F.; Chabchoub, F.; El-Kaim, L.; Alves, S.; Baleizão, C.; Farinha, J.P. Sc(OTf)₃ promoted multicomponent synthesis of fluorescent imidazo[1,2-c]pyrazolo[3,4-d]pyrimidine. Tetrahedron Lett., 2013, 54, 4781-4784.
[http://dx.doi.org/10.1016/j.tetlet.2013.06.136]

Akbarzadeh, M.; Bakavoli, M.; Eshghi, H.; Shiri, A. Synthesis of Oxazolo[5,4-d][1,2,4]triazolo[4,3-a]pyrimidines as a new class of heterocyclic compounds. J. Heterocycl. Chem., 2016, 53, 832-839.
[http://dx.doi.org/10.1002/jhet.2346]

Ustalar, A.; Yilmaz, M. Microwave assisted synthesis of 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones using Mn(OAc)3. Tetrahedron Lett., 2017, 58, 516-519.
[http://dx.doi.org/10.1016/j.tetlet.2016.12.067]

Qiu, F.; Shi, D.; Yang, J.; Zhang, Q.; Li, J. Synthesis of thieno[2,3-b]thiophene fused pyrimidine derivatives via sequential conversion of 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarbonitrile with carbonyl compounds. Tetrahedron Lett., 2016, 57, 1210-1214.
[http://dx.doi.org/10.1016/j.tetlet.2016.01.040]

Gharpure, S.J.; Niranjana, P.; Porwal, S.K. Cascade radical cyclization to vinylogous carbonates/carbamates for the synthesis of oxa- and aza-angular triquinanes: Diastereoselectivity depends on the ring size of radical precursor. Synthesis, 2018, 50, 2954-2967.
[http://dx.doi.org/10.1055/s-0036-1589541]

Ramesh, E.; Raghunathan, R. An expedient microwave-assisted, solvent-free, solid-supported synthesis of pyrrolo[2,3-d]pyrimidine-pyrano[5,6-c]coumarin/[6,5-c]chromone derivatives by intramolecular hetero Diels–Alder reaction. Tetrahedron Lett., 2008, 49, 1812-1817.
[http://dx.doi.org/10.1016/j.tetlet.2008.01.059]

Dabiri, M.; Azimi, S.C.; Khavasi, H.R.; Bazgir, A. A novel reaction of 6-amino-uracils and isatins. Tetrahedron, 2008, 64, 7307-7311.
[http://dx.doi.org/10.1016/j.tet.2008.05.063]

Sun, T.; Li, H.; Wu, Z.; Li, C.; Ren, X.; Zhang, F. Three-component strategy for synthesis of dihydropyrido[2,3-d]pyrimidine and spirooxindole derivatives. J. Heterocycl. Chem., 2018, 55, 2270-2276.
[http://dx.doi.org/10.1002/jhet.3278]

Abdel-Aziem, A.; El-Gendy, M.S.; Abdelhamid, A.O. Synthesis and antimicrobial activities of pyrido[2,3-d] pyrimidine, pyridotriazolopyrimidine, triazolopyrimidine, and pyrido[2,3-d:6,5d’]dipyrimidine derivatives. Eur. J. Chem., 2012, 3, 455-460.
[http://dx.doi.org/10.5155/eurjchem.3.4.455-460.683]

Aarhus, T.; Fritze, U.F.; Hennum, M.; Gundersen, L-L. Sodium borohydride mediated reduction of N-Boc protected purines and applications in the synthesis of 7-alkyladenines and tetrahydro[1, 4]diazepino-[1,2,3-gh]purines. Tetrahedron Lett., 2014, 55, 5748-5750.
[http://dx.doi.org/10.1016/j.tetlet.2014.08.102]

Acosta, P.; Insuasty, B.; Abonia, R.; Quiroga, J. Annelation of pyrrolo[1,2-a]pyrimidine and pyrido[1,2-a]pyrimidine systems to a pyrazolopyridine framework by a cascade of two cyclization reactions. Tetrahedron Lett., 2015, 56, 2917.
[http://dx.doi.org/10.1016/j.tetlet.2015.04.068]

Reddy, M.V.; Kim, J.S.; Lim, K.T.; Jeong, Y.T. Polyethylene glycol (PEG-400): an efficient green reaction medium for the synthesis of benzo[4,5]imidazo[1,2-a]-pyrimido[4,5-d]pyrimidin-4(1H)-ones under catalyst-free conditions. Tetrahedron Lett., 2014, 55, 6459-6462.
[http://dx.doi.org/10.1016/j.tetlet.2014.09.135]

(a) Kumar, A.S.; Nagarajan, R. Copper- or palladium-catalyzed amidation and cyclization route for the synthesis of pyrimido[4,5-b]carbazoles. Synthesis, 2013, 45, 2893-2903.
[http://dx.doi.org/10.1055/s-0033-1339490 ]
(b) Grošelj, U.; Podlogar, A.; Novak, A.; Dahmann, G.; Golobič, A.; Stanovnik, B.; Svete, J. Synthesis of tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H, 3H)-diones. Synthesis, 2013, 45, 639-650.
[http://dx.doi.org/10.1055/s-0032-1318107]

Metwally, N.H.; Abdallah, M.A.; Almabrook, S.A. Pyrazolo[1,5-a] pyrimidine derivative as precursor for some novel pyrazolo[1,5-a]pyrimidines and tetraheterocyclic compounds. J. Heterocycl. Chem., 2017, 54, 347-354.
[http://dx.doi.org/10.1002/jhet.2590]

Campos, J.F.; Queiroz, M-J.R.P.; Berteina-Raboin, S. Synthesis of new annulated pyrazinothienotriazolopyrimidinones and triazolylthienopyrazines. Synthesis, 2018, 50, 1159-1165.
[http://dx.doi.org/10.1055/s-0036-1589136]

Darehkordi, A.; Fazli-Zafarani, S.M.; Kamali, M. Direct synthesis of trichloro-thiazolo[3,2-a]pyrimidine and thiazolo[2,3-b]quinazoline derivatives. J. Heterocycl. Chem., 2017, 54, 2287-2296.
[http://dx.doi.org/10.1002/jhet.2816]

Sirakanyan, S.N.; Geronikaki, A.; Spinelli, D.; Hovakimyan, A.A.; Noravyan, A.S. Synthesis and structure of condensed triazolo- and tetrazolopyrimidines. Tetrahedron, 2013, 69, 10637-10643.
[http://dx.doi.org/10.1016/j.tet.2013.10.015]

Sirakanyan, S.N.; Spinelli, D.; Geronikaki, A.; Kartsev, V.G.; Hakobyan, E.K.; Hovakimyan, A.A. Synthesis and structure of a new heterocyclic system: pyrido[3′,2′:4,5]furo[3,2-d][1,2,4]triazolo[4,3-a]pyrimidin-7(8)-one. Tetrahedron Lett., 2016, 57, 5338-5340.
[http://dx.doi.org/10.1016/j.tetlet.2016.10.058]

Gomha, S.M.; Riyadh, S.M. Multicomponent synthesis of novel penta-heterocyclic ring systems incorporating a benzopyranopyridine scaffold. Synthesis, 2014, 46, 258-262.