An Efficient Synthesis of Imidazo[1,2-a]pyridines

Piyawat Paengphua; Uthai Wichai; Sirirat Chancharunee

doi:10.14456/nujst.2019.25

Authors

Piyawat Paengphua Department of chemistry, Faculty of science, Chiang Mai University
Uthai Wichai Department of chemistry, Faculty of science, Naraesuan University
Sirirat Chancharunee Department of chemistry, Faculty of science, Chiang Mai University

DOI:

https://doi.org/10.14456/nujst.2019.25

Keywords:

Celite, Cesium Fluoride, One-pot synthesis

Abstract

Imidazo[1,2-a]pyridines are useful building blocks for a number of biologically and pharmaceutically valuable compounds. Its synthetic method started from the reaction of 2-aminopyridines with acetophenones. However, the existing synthetic methods have drawbacks such as relatively high reaction temperatures, long reaction times and the difficult post-treatment. In this article, an improved synthetic method with high yield and simple steps for the synthesis of imidazo[1,2-a]pyridines was reported. It is an improved method that CsF-Celite was used in post-treatment, which enhanced the total yield, and the operations were effectually simplified by the one-pot method. Moreover, CsF-Celite can be recovered for subsequent reactions and reused without any loss of efficiency.

References

Ando, T., & Yamawaki, J. (1979). Potassium Fluoride on celit. A versatile reagent for C-, N-, O-, and S-alkylations. Chemistry Letters, 8(1), 45-46. doi:10.1246/cl.1979.45

Bagdi, A. K., Rahman, M., Santra, S., Majee, A., & Hajra, A. (2013). Copper-catalyzed synthesis of imidazo[1,2-a]pyridines through tandem imine Formation-Oxidative cyclization under ambient air: One-step synthesis of zolimidine on a Gram-Scale. Advanced Synthesis & Catalysis, 355(9), 1741-1747. doi:10.1002/adsc.201300298

Bloch, R., & Orvane, P. (1981). An improved synthesis of 2,2-dialkyl-1,3-indanediones. Synthetic Communications, 11(11), 913-915. doi:10.1080/00397918108065747

Byth, K. F., Geh, C., Forder, C. L., Oakes, S. E., & Thomas, A. P. (2006). The cellular phenotype of AZ703, a novel selective imidazo[1,2-a]pyridine cyclin-dependent kinase inhibitor. Molecular Cancer Therapeutics, 5(3), 655-664. doi:10.1158/1535-7163.mct-05-0205

Cao, H., Liu, X., Liao, J., Huang, J., Qiu, H., Chen, Q., & Chen, Y. (2014). Transition metal-mediated C═O and C═C bond-forming reactions: A regioselective strategy for the synthesis of imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines. The Journal of Organic Chemistry, 79(22), 11209-11214. doi:10.1021/jo501671x

Chancharunee, S., Pinhom, P., Pohmakotr, M., & Perlmutter, P. (2009). One-pot synthesis of 3,4-dihydropyrimidine-2-(1H)-ones using CsF–Celite as catalyst. Synthetic Communications, 39(5), 880-886. doi:10.1080/00397910802439175

Chandra Mohan, D., Reddy Donthiri, R., Nageswara Rao, S., & Adimurthy, S. (2013). Copper(I) iodide-catalysed aerobic oxidative synthesis of imidazo[1,2-a]pyridines from 2-aminopyridines and methyl ketones. Advanced Synthesis & Catalysis, 355(11-12), 2217-2221. doi:10.1002/adsc.201300456

Chioua, M., Soriano, E., Infantes, L., Jimeno, M. L., Marco-Contelles, J., & Samadi, A. (2013). Silver-catalyzed cyclization of N-(prop-2-yn-1-yl)pyridin-2-amines. European Journal of Organic Chemistry, 2013(1), 35-39. doi:10.1002/ejoc.201201258

Clark, J. H. (1980). Fluoride ion as a base in organic synthesis. Chemical Reviews, 80(5), 429-452. doi: 10.1021/cr60327a004

Donohoe, T. J., Kabeshov, M. A., Rathi, A. H., & Smith, I. E. D. (2012). Direct preparation of thiazoles, imidazoles, imidazopyridines and thiazolidines from alkenes. Organic & Biomolecular Chemistry, 10(5), 1093-1101. doi:10.1039/c1ob06587d

Gudmundsson, K. S., Williams, J. D., Drach, J. C., & Townsend, L. B. (2003). Synthesis and antiviral activity of novel erythrofuranosyl imidazo[1,2-a]pyridine C-nucleosides constructed via palladium coupling of iodoimidazo[1,2-a]pyridines and dihydrofuran. Journal of Medicinal Chemistry, 46(8), 1449-1455. doi:10.1021/jm020339r

Gueiffier, A., Mavel, S., Lhassani, M., Elhakmaoui, A., Snoeck, R., Andrei, G., & Chapat, J.-P. (1998). Synthesis of imidazo[1,2-a]pyridines as antiviral agents. Journal of Medicinal Chemistry, 41(25), 5108-5112. doi:10.1021/jm981051y

Hayakawa, M., Kaizawa, H., Kawaguchi, K.-i., Ishikawa, N., Koizumi, T., Ohishi, & T., Workman, P. (2007). Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110α inhibitors. Bioorganic & Medicinal Chemistry, 15(1), 403-412. doi:10.1016/j.bmc.2006. 09.047

Hayat, S., Atta ur, R., Iqbal Choudhary, M., Khan, K. M., Schumann, W., & Bayer, E. (2001). N-Alkylation of anilines, carboxamides and several nitrogen heterocycles using CsF–Celite/alkyl halides/CH3CN combination. Tetrahedron, 57(50), 9951-9957. doi:10.1016/S0040-4020(01) 00989-9

Hieke, M., Rödl, C. B., Wisniewska, J. M., la Buscató, E., Stark, H., Schubert-Zsilavecz, M., & Proschak, E. (2012). SAR-study on a new class of imidazo[1,2-a]pyridine-based inhibitors of 5-lipoxygenase. Bioorganic & Medicinal Chemistry Letters, 22(5), 1969-1975. doi:10.1016/j.bmcl. 2012.01.038

Hodgkiss, R. J., Middleton, R. W., Parrick, J., Rami, H. K., Wardman, P., & Wilson, G. D. (1992). Bioreductive fluorescent markers for hypoxic cells: a study of 2-nitroimidazoles with 1-substituents containing fluorescent, bridgehead-nitrogen, bicyclic systems. Journal of Medicinal Chemistry, 35(10), 1920-1926. doi: 10.1021/jm00088a030

Jenkinson, S., Thomson, M., McCoy, D., Edelstein, M., Danehower, S., Lawrence, W., Gudmundsson, K. (2010). Blockade of X4-tropic HIV-1 cellular entry by GSK812397, a potent noncompetitive CXCR4 receptor antagonist. Antimicrobial Agents and Chemotherapy, 54(2), 817-824. doi:10. 1128/aac.01293-09

Karade, N. N., Kondre, J. M., Gampawar, S. V., & Shinde, S. V. (2009). Synthesis of 2,5-disubstituted 1,3,4-oxadiazine and 1,3,4-thiadiazine from substituted acetophenones and acid hydrazides using [hydroxyl(tosyloxy)iodo]benzene. Synthetic Communications, 39(13), 2279-2287. doi:10.1080/ 00397910802654716

Kielesinski, L., Tasior, M., & Gryko, D. T. (2015). Polycyclic imidazo[1,2-a]pyridine analogs - synthesis via oxidative intramolecular C-H amination and optical properties. Organic Chemistry Frontiers, 2(1), 21-28. doi: 10.1039/c4qo00248b

Lee, J. C., & Choi, Y. (1998). An improved method for preparation of carboxylic esters using CsF-Celite/alkyl halide/CH3CN Combination. Synthetic Communications, 28(11), 2021-2026. doi: 10.1080/00397919808007177

Lhassani, M., Chavignon, O., Chezal, J.-M., Teulade, J.-C., Chapat, J.-P., Snoeck, R., & Gueiffier, A. (1999). Synthesis and antiviral activity of imidazo[1,2-a]pyridines. European Journal of Medicinal Chemistry, 34(3), 271-274. doi:10.1016/S0223-5234(99)80061-0

Mali, R. S., & Kulkarni-Joshi, P. (1999). Synthesis of 6-prenylpyranoflavanones : Total synthesis of (±)-maxima flavanone A. Indian Journal of Chemistry -Section B, 38, 596. Retrieved from http://nopr. niscair.res.in/handle/123456789/16446

Marcinkowska, M., Kołaczkowski, M., Kamiński, K., Bucki, A., Pawłowski, M., Siwek, A., & Bienkowski, P. (2016). Design, synthesis, and biological evaluation of fluorinated imidazo[1,2-a]pyridine derivatives with potential antipsychotic activity. European Journal of Medicinal Chemistry, 124 (Supplement C), 456-467. doi:10.1016/j.ejmech.2016.08.059

Meng, X., Wang, Y., Yu, C., & Zhao, P. (2014). Heterogeneously copper-catalyzed oxidative synthesis of imidazo[1,2-a]pyridines using 2-aminopyridines and ketones under ligand- and additive-free conditions. [10.1039/C4RA03299C]. RSC Advances, 4(52), 27301-27307. doi:10.1039/c4ra 03299c

Mohammed Khan, K., Hayat, S., Zia, U., Atta ur, R., Iqbal Choudhary, M., Maharvi, G. M., & Bayer, E. (2003). An alternative method for the synthesis of γ-lactones by using cesium fluoride-celite/acetonitrile combination. Synthetic Communications, 33(19), 3435-3453. doi:10.1081/scc-120024003

Monir, K., Bagdi, A. K., Ghosh, M., & Hajra, A. (2014). Unprecedented Catalytic Activity of Fe(NO3)3·9H2O: Regioselective synthesis of 2-nitroimidazopyridines via oxidative amination. Organic Letters, 16(17), 4630-4633. doi:10.1021/ol502218u

Mukaiyama, T., Pai, F.-C., Onaka, M., & Narasaka, K. (1980). A useful method for selective acylation of alcohols using 2,2′-bipyridyl-6-yl carboxylate and cesium fluoride. Chemistry Letters, 9(5), 563-566. doi:10.1246/cl.1980.563

Oaksmith, J. M., & Ganem, B. (2009). Synthesis of a COMC–estradiol conjugate for targeted, tissue-selective cancer chemotherapy. Tetrahedron Letters, 50(26), 3497-3498. doi:10.1016/j.tetlet. 2009.03.083

Paengphua, P., & Chancharunee, S. (2018). Facile synthesis of imidazo[1,2-a]pyridines promoted by room-temperature ionic liquids under ultrasound irradiation. Monatshefte für Chemie - Chemical Monthly, 149(10), 1835-1840. doi:10.1007/s00706-018-2238-3

Patil, S. V., Gaikwad, N. D., & Bobade, V. D. A simple and efficient synthesis of imidazolo[1,2-a]pyridines using MgO in aqueous medium. Arabian Journal of Chemistry. doi:10.1016/j.arabjc.2012.04.017

Polshettiwar, V., & Kaushik, M. P. (2005). Microwave enhanced chemistry of CsF–Celite: an efficient catalyst for the synthesis of esters, ethers and their thio-analogues. Catalysis Communications, 6(3), 191-194. doi:10.1016/j.catcom.2004.12.007

Saldabol, N. O., & Giller, S. A. (1976). Synthesis of imidazo[1,2- a] pyridines directly from methyl or methylene ketones. iodination of imidazo[1,2-a] pyridines. Chemistry of Heterocyclic Compounds, 12(10), 1155-1162. doi:10.1007/bf00945605

Starrett, J. E., Montzka, T. A., Crosswell, A. R., & Cavanagh, R. L. (1989). Synthesis and biological activity of 3-substituted imidazo[1,2-a]pyridines as antiulcer agents. Journal of Medicinal Chemistry, 32(9), 2204-2210. doi:10.1021/jm00129a028

Stasyuk, A. J., Banasiewicz, M., Cyrański, M. K., & Gryko, D. T. (2012). Imidazo[1,2-a]pyridines susceptible to excited state intramolecular proton transfer: One-pot synthesis via an ortoleva–king reaction. The Journal of Organic Chemistry, 77(13), 5552-5558. doi:10.1021/jo300643w

Wang, H., Wang, Y., Liang, D., Liu, L., Zhang, J., & Zhu, Q. (2011). Copper-catalyzed intramolecular dehydrogenative aminooxygenation: Direct access to formyl-substituted aromatic N-heterocycles. Angewandte Chemie International Edition, 50(25), 5678-5681. doi:10.1002/anie.201100362

Yousefi, B. H., Manook, A., von Reutern, B., Schwaiger, M., Drzezga, A., Wester, H.-J., & Henriksen, G. (2012). Development of an improved radioiodinated 2-phenylimidazo[1,2-a]pyridine for non-invasive imaging of amyloid plaques. MedChemComm, 3(7), 775-779. doi:10.1039/c2md20115a

Zeng, J., Tan, Y. J., Leow, M. L., & Liu, X.-W. (2012). Copper(II)/Iron(III) Co-catalyzed Intermolecular Diamination of Alkynes: Facile Synthesis of Imidazopyridines. Organic Letters, 14(17), 4386-4389. doi:10.1021/ol301858j

Zhuang, Z.-P., Kung, M.-P., Wilson, A., Lee, C.-W., Plössl, K., Hou, C., & Kung, H. F. (2003). Structure−Activity Relationship of Imidazo[1,2-a]pyridines as Ligands for Detecting β-Amyloid Plaques in the Brain. Journal of Medicinal Chemistry, 46(2), 237-243. doi:10.1021/jm020351j