Synthesis of 1-(pyrrolidin-2-ylmethyl)-1H-azoles and their piperidine-derived homologues

• Authors: Sergey Zhersh , Oleksandr Karpenko , Vasyl Ripenko , Andrey Tolmachev , Oleksandr Grygorenko
• Languages of publication: EN

Abstracts

EN

A convenient preparation of 1-(pyrrolidin-2-yl)-1H-pyrazoles, -imidazoles, and -1H-1,2,4-triazoles, 1-(piperidin-2-yl)-1H-pyrazoles and -1H-1,2,4-triazoles, and 1-(piperidin-3-yl)-1H-1,2,4-triazoles by alkylation of azoles (viz. pyrazoles, imidazoles, and triazoles) with N-Cbz-prolinol mesylate or its analogues and subsequent deprotection is reported. The two-step method allows for synthesis of the title compounds in 16–65% yields. The utility of the procedure has been demonstrated by multigram preparation of a 15-member building block mini-library for the lead-oriented synthesis of compound libraries. These building blocks perfectly fit the definition of low-molecular-weight hydrophilic three-dimensional templates, which leave much room for the lead-oriented synthesis of the compound libraries. [...]

Keywords

EN

Azoles; Saturated nitrogen heterocycles; Molecular rigidity; Lead-oriented synthesis; Alkylation

• Publisher: De Gruyter Open
• Journal: Open Chemistry
• Year: 2014
• Volume: 12
• Issue: 1
• Pages: 67-73

Dates

published

1 - 1 - 2014

online

27 - 10 - 2013

Contributors

author

Sergey Zhersh

author

Oleksandr Karpenko

• Enamine Ltd., Kyiv, 01103, Ukraine

author

Vasyl Ripenko

• Enamine Ltd., Kyiv, 01103, Ukraine

author

Andrey Tolmachev

author

Oleksandr Grygorenko

• Department of Chemistry, Taras Shevchenko National University of Kyiv, Kyiv, 01601, Ukraine

References

• [1] M.P. Gleeson, J. Med. Chem. 51, 817 (2008) http://dx.doi.org/10.1021/jm701122q[Crossref]
• [2] T.I. Oprea, A.M. Davis, S.J. Teague, P.D. Leeson, J. Chem. Inf. Comp. Sci. 41, 1308 (2001) http://dx.doi.org/10.1021/ci010366a[Crossref]
• [3] P.D. Leeson, B. Springthorpe, Nat. Rev. Drug Discovery 6, 881 (2007) http://dx.doi.org/10.1038/nrd2445[Crossref]
• [4] A. Polinsky, In: C. G. Wermuth (Ed.), Practice of Medicinal Chemistry, 3rd edition (Academic Press/Elsevier, Amsterdam, 2008) 244
• [5] A. Nadin, C. Hattotuwagama, I. Churcher, Angew. Chem. Int. Ed. 51, 1114 (2012) http://dx.doi.org/10.1002/anie.201105840[Crossref]
• [6] N.V. Shevchuk, K. Liubchak, K.G. Nazarenko, A.A. Yurchenko, D.M. Volochnyuk, O.O. Grygorenko, A.A. Tolmachev, Synthesis 44, 2041 (2012) http://dx.doi.org/10.1055/s-0031-1291126[Crossref]
• [7] A.V. Borisov, V.V. Voloshchuk, M.A. Nechayev, O.O. Grygorenko, Synthesis 45, 2413 (2013) http://dx.doi.org/10.1055/s-0033-1339325[Crossref]
• [8] A.G. Yaremenko, D.M. Volochnyuk, V.V. Shelyakin, O.O. Grygorenko, Tetrahedron 69, 6799 (2013) http://dx.doi.org/10.1016/j.tet.2013.06.029[Crossref]
• [9] R. Kombarov, A. Altieri, D. Genis, M. Kirpichenok, V. Kochubey, N. Rakitina, Z. Titarenko, Mol. Diversity 14, 193 (2010) http://dx.doi.org/10.1007/s11030-009-9157-5[Crossref]
• [10] C.A. Brooks, C.H.-T. Chen, Y.S. Cho, L. Jiang, G. Liu, M. Shultz, PCT International Patent WO 2012/025164, 2012.03.01
• [11] J.J. Cui, L.A. Funk, L. Jia, P.-P. Kung, J.J. Meng, M.D. Nambu, M.A. Pairish, H. Shen, M.B. Tran-Dube, PCT International Patent WO 2006/021881, 2006.03.02
• [12] C. Kallus, H. Kallus, H. Heitsch, A. Lindenschmidt, S. Grueneberg, H. Szillat, PCT International Patent WO 2005/105781, 2005.11.10
• [13] S. Chandrasekhar, T.P. Kumar, K. Haribabu, C.R. Reddy, C.R. Kumar, Tetrahedron: Asymmetry 22, 697 (2011) http://dx.doi.org/10.1016/j.tetasy.2011.04.010[Crossref]
• [14] D. Dang, P. Wu, C. He, Z. Xie, C. Duan, J. Am. Chem. Soc. 132, 14321 (2010) http://dx.doi.org/10.1021/ja101208s[Crossref]
• [15] L. Zhang, J.-P. Cheng, S. Luo, X. Mi, S. Liu, Y. Qiao, H. Xu, Org. Biomol. Chem. 6, 567 (2008) http://dx.doi.org/10.1039/b713843a[Crossref]
• [16] Y. Abe, T. Hirakawa, S. Nakajima, N. Okano, S. Hayase, M. Kawatsura, T. Itoh, Y. Hirose, Adv. Synth. Cat. 350, 1954 (2008) http://dx.doi.org/10.1002/adsc.200800382[Crossref]
• [17] S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J.-P. Cheng, Tetrahedron 63, 1923 (2007) http://dx.doi.org/10.1016/j.tet.2006.12.079[Crossref]
• [18] S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J.-P. Cheng, Angew. Chem. Int. Ed. 45, 3093 (2006) http://dx.doi.org/10.1002/anie.200600048[Crossref]
• [19] D. Xu, S. Luo, H. Yue, L. Wang, Y. Liu, Z. Xu, Synlett 2569 (2006) [Crossref]
• [20] S. Zhersh, V.V. Buryanov, O.V. Karpenko, O.O. Grygorenko, A.A. Tolmachev, Synthesis 3669 (2011)
• [21] Instant JChem 6. 0.2 (ChemAxon, Budapest, Hungary, 2013) (www.chemaxon.com)

Identifiers

DOI

10.2478/s11532-013-0344-y