Introduction: Purine is a privileged nitrogen-containing heterocycle which exists in various bioactive compounds. The biological importance of purines has led to an interest in synthesis of them with pharmaceutical properties such as antiviral [1], antibacterial [2], anticancer [3] and anti-inflammatory activities.[4] They also have agrochemical properties including herbicidal and soil fungicidal activity.[5] On the other hand, pyrazoles are a motif found in a number of small molecules that possess a wide range of agricultural and pharmaceutical activities such as herbicidal, fungicidal, insecticidal and anti-inflammatory properties [6-10]. Also they have applications in polymer chemistry as ligands for transition metal-catalyzed reactions.[11] Methods/Experimentals: The heterocyclization of compound (1) with thiourea (2) in refluxing CH3CN in the presence of Et3N gave compound (3). The latter compound subsequently underwent N-alkylation via reaction with appropriate alkyl halide in KOH/DMF at 80°C to obtain novel pyrazolo[5,1-b]purine derivatives in good yields. Results and Discussion: Our approach is based on using compound (1) as starting material that was obtained via the reaction of 2-(ethylthio)-5-methyl-7-oxo-6,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile with bromine in acetic acid at room temperature [12]. In order to synthesize a novel heterocyclic system, compound (1) was reacted with thiourea (2) as a dinucleophile in the presence of Et3N in CH3CN to give product (3) with either structure (A) or (B). (Scheme 1) The 1H NMR and 13C NMR spectra both revealed the formation of only one product. The IR spectrum did not exactly demonstrate the formation of either structure (A) or (B). Also, the observation of the molecular ion peak at m/z 290 in the mass spectrum together with the elemental analysis confirms the occurrence of heterocyclization through path (A) or (B). Eventually, the N-alkylation of compound (3) with several alkyl halides in KOH/DMF gave the desired new derivatives of products (4a–e) quantitatively. (Scheme 2) An unequivocal establishment of the true structure (A) came from a 2D-NOESY analysis on the newly synthesized derivative (4a). Conclusion: We have reported a protocol for the synthesis of new derivatives of novel heterocyclic system of pyrazolo[5,1-b]purine. These potential pharmacologically active compounds were prepared through the cyclocondensation of compound (1) with thiourea (2) to obtain compound (3) as the novel heterocyclic system. Alkylation of compound (3) with various alkyl halides in KOH/DMF gave the desired alkylated new products (4a–e). References [1] Gazivoda, T.; Plevnik, M.; Plavec, J.; Kraljevic, S.; Kralj, M.; Pavelic, K.; Balzarini, J.; De Clercq, E.; Mintas, M.; Raic-Malic, S. Bioorg. Med. Chem., 2005, 13, 131–139. [2] Hirokawa, Y.; Kinoshita, H.; Tanaka, T.; Nakamura, T.; Fujimoto, K.; Kashimoto, S.; Kojima, T.; Kato, S. Bioorg. Med. Chem. Lett., 2009, 19, 170–174. [3] Montgomery, J.A.; Carroll Jr., T. J. Am. Chem. Soc., 1957, 79, 5238–5242. [4] Wang, Y.; Yang, X.; Zheng, X.; Li, J.; Ye, C.; Song, X. Fitoterapia, 2010, 81, 627–631. [5] Dhivya Vadhana, M.S.; Cinzia, N.; Rosita, G. Cardiovasc. Toxicol., 2010, 10, 199–207. [6] Lahm, G. P.; Cordova, D.; Barry, J. D. Bioorg. Med. Chem., 2009, 17, 4127-4133. [7] Fustero, S.; Roman, R.; Sanz-Cervera, J. F.; Simon-Fuentes, A.; Bueno, J.; Villanova, S. J. Org. Chem., 2008, 73, 8545-8552. [8] Lamberth, C. Heterocycles, 2007, 71, 1467-1502. [9] De Paulis, T.; Hemstapat, K.; Chen, Y.; Zhang, Y.; Saleh, S.; Alagille, D.; Baldwin, R. M.; Tamagnan, G. D.; Conn, P. J. J. Med. Chem., 2006, 49, 3332-3344. [10] Bekhit, A. A.; Abdel-Aziem, T. Bioorg. Med. Chem., 2004, 12, 1935-1945. [11] Halcrow, M. A. Dalton Trans., 2009, 2059-2073. [12] Sheikhi-Mohammareh, S.; Shiri, A.; Bakavoli, M.; Mague, J. J. Heterocycl. Chem., 2016, 53, 1231-123

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