A new and efficient method for the synthesis of pyrazolo[3,4-d] pyrimidines catalyzed by iodine

Document Type : Article


Laboratory of Organic Synthesis and Natural Products, Department of Chemistry, Sharif University of Technology, PO Box 111559516, Tehran, Iran


Fully substituents new pyrazolo[3,4-d]pyrimidines were synthesized. The synthesis starts with cyanomethylphenylketone that reacts with phenyl hydrazine to give the corresponding aminopyrazole. The latter undergoes a cyclocondensation with an N,N'-bis(arylmethylidene)arylmethane yielding the final product. Both synthetic steps are high-yielding (the overall yields between 65-78%). The newly synthesized compounds were characterized by 1H NMR, 13C NMR and elemental analysis


Main Subjects

1. Thansandote, P. and Lautens, M. \Construction of
nitrogen-containing heterocycles by C-H bond functionalization",
Chem. Eur. J., 15(24), pp. 5874-5883
2. Behenna, D.C., Liu, Y., Yurino, T., Kim, J., White,
3310 F. Matloubi Moghaddam et al./Scientia Iranica, Transactions C: Chemistry and ... 25 (2018) 3305{3310
D.E., Virgil, S.C., and Stoltz, B.M. \Enantioselective
construction of quaternary N-heterocycles by
palladium-catalyzed decarboxylative allylic alkylation
of lactams", Nat. Chem., 4(2), pp. 130-133 (2012).
3. Siddiqui, A.B., Trivedi, A.R., Kataria, V.B., and
Shah, V.H. \4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine
containing phenothiazines as antitubercular agents",
Bioorg. Med. Chem. Lett., 24(6), pp. 1493-1495 (2014).
4. Ghorab, M.M., Ragab, F.A., Alqasoumi, S.I., Alafeefy,
A.M., and Aboulmagd, S.A. \Synthesis of some new
pyrazolo[3,4-d]pyrimidine derivatives of expected anticancer
and radioprotective activity", Eur. J. Med.
Chem., 45(1), pp. 171-178 (2010).
5. Chern, J., Shia, K., Hsu, T., Tai, C., Lee, C., Lee, Y.,
Chang, C., Tseng, S., and Shih, S. \Design, synthesis,
and structure-activity relationships of pyrazolo[3,4-
d]pyrimidines: a novel class of potent enterovirus
inhibitors", Bio. Med. Chem. Lett., 14(10), pp. 2519-
2525 (2004).
6. Bakavoli, M., Bagherzadeh, G., Vaseghifar, M., Shiri,
A., Pordel, M., Mashreghi, M., Pordeli, P., and
Araghi, M. \Molecular iodine promoted synthesis of
new pyrazolo[3,4-d]pyrimidine derivatives as potential
antibacterial agents", Eur. J. Med. Chem., 45(10), pp.
1824-1830 (2010).
7. Chauhan, M. and Kumar, R. \Medicinal attributes
of pyrazolo[3,4-d]pyrimidines: A review", Bio. Med.
Chem., 21(18), pp. 5657-5668 (2013).
8. Mahajan, K. and Mahajan, N.P. \ACK1 tyrosine
kinase: targeted inhibition to block cancer cell proliferation",
Cancer Lett., 338(2), pp. 185-192 (2013).
9. Parsons, S.J. and Parsons, J.T. \Src family kinases,
key regulators of signal transduction", Oncogene., 23,
pp. 7906-7909 (2004).
10. Summy, J.M. and Gallick, G.E. \Treatment for advanced
tumors: SRC reclaims center stage", Clin
Cancer Res., 12(5), pp. 1398-1401 (2006).
11. Schenone, S., Manetti, F., and Botta, M. \Synthetic
SRC-kinase domain inhibitors and their structural
requirements", Anticancer Agents Med. Chem., 7(6),
pp. 660-680 (2007).
12. Puligoundla, R.G., Karnakanti, S., Bantu, R.,
Kommu, N., Kondra, S.B., and Nagarapu, L. \A
simple, convenient one-pot synthesis of [1,2,4]triazolo/
benzimidazolo quinazolinone derivatives by using
molecular iodine", Tetrahedron Lett., 54(20), pp. 2480-
2483 (2013).
13. (a) Togo, H. and Iida, S. \Synthetic use of molecular
iodine for organic synthesis", Synlet., 14, pp. 2159-
2175 (2006); (b) Jereb, M., Vrazic, D., and Zupan, M.
\Iodine-catalyzed transformation of molecules containing
oxygen functional groups", Tetrahedron., 67(7),
pp. 1355-1387 (2011).
14. Kavala, V., Lin, C., Kuo, C.W., Fang, H., and
Yao, C.F. \Iodine catalyzed one-pot synthesis of
and tetrahydropyrimidine derivatives via Mannich
type reaction", Tetrahedron, 68(4), pp. 1321-1329
15. Alizadeh, A., Saberi, V., and Mokhtari, J. \A simple
one-pot procedure for the synthesis of 1,2,4-
triazolo[1,5-a]pyridines via pseudo ve-component reactions
catalyzed by molecular iodine", Synlett., 24,
pp. 1825-1829 (2013).
16. Matloubi Moghaddam, F., Khodabakhshi, M.R.,
and Aminaee, M. \Highly ecient synthesis of
pyrimido[4,5-d]pyrimidine-2,4-dione derivatives catalyzed
by iodine", Tetrahedron Lett., 55(34), pp. 4720-
4723 (2014).