Synlett, Inhaltsverzeichnis Synlett 2018; 29(01): 89-93DOI: 10.1055/s-0036-1590906 letter © Georg Thieme Verlag Stuttgart · New York A Convenient Method for the Synthesis of Imidazo[1,2-a]pyridines with a New Approach Saeed Balalaie* a Peptide Chemistry Research Center, K.N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran eMail: balalaie@kntu.ac.ir b Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran , Fatemeh Derakhshan-Panah a Peptide Chemistry Research Center, K.N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran eMail: balalaie@kntu.ac.ir c Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran eMail: zolfi@basu.ac.ir eMail: mzolfigol@yahoo.com , Mohammad Ali Zolfigol* c Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran eMail: zolfi@basu.ac.ir eMail: mzolfigol@yahoo.com , Frank Rominger d Organisch-Chemisches Institut der Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany › Institutsangaben Artikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik Dedicated to Prof. Gebhard Haberhauer on the occasion of his birthday Abstract A new approach for the efficient synthesis of imidazo[1,2-a]pyridines is described. The synthesis was carried out via the reaction of functionalized 2-aminopyridine that were formed through a three-component reaction and phenacyl bromide derivatives. Key words Key wordsfunctionalized imidazo[1,2-a]pyridines - 2-aminopyridines - cyclocondensation reaction Volltext Referenzen References and Notes 1a Langtry HD. Benfield P. Drugs 1990; 40: 291 1b Mizushige K. Ueda T. Yukiiri K. Suzuki H. Cardiol. Drug Rev. 2002; 20: 163 1c Kang CB. Sen Y. Del Valle JR. Org. Lett. 2012; 14: 6162 1d Kim YB. Kang CW. Ranatunga S. Yang H. Sebti SM. Del Valle JR. Bioorg. Med. Chem. Lett. 2014; 24: 4650 2a Bottai T. Cartault F. Pouget R. Blayac JP. Petit P. Clin. Neuropharmacol. 1995; 18: 79 2b Herath A. Dahl R. Cosford ND. P. Org. Lett. 2010; 12: 412 3 Biftu T. Feng D. Fisher M. Liang G. Qian X. Scribner A. Dennis R. Lee S. Liberator PA. Brown C. Gurnett A. Leavitt PS. Thompson D. Mathew J. Misura A. Samaras S. Tamas T. Sina JF. McNulty KA. McKnight CG. Schmatz DM. Wyvratt M. Bioorg. Med. Chem. Lett. 2006; 16: 2479 4 Palmer AM. Grobbel B. Jecke C. Brehm C. Zimmermann PJ. Buhr W. Feth MP. Simon WA. Kromer W. J. Med. Chem. 2007; 50: 6240 5a Sumalatha Y. Reddy TR. Reddy PP. Satyanarayana B. Arkivoc 2009; (ii): 315 5b Holm KJ. Goa KL. Drugs 2000; 59: 865 6 Durand A. Thenot JP. Bianchetti G. Morselli PL. Drug Metab. Rev. 1992; 24: 239 7a Nair DK. Mobin SM. Namboothiri IN. N. Org.Lett. 2012; 14: 4580 7b Chernyak N. Gevorgyan V. Angew. Chem. Int. Ed. 2010; 49: 2743 8a Lee H. Kim SJ. Jung KH. Son MK. Yan HH. Hong S. Hong S. Oncol. Rep. 2013; 30: 863 8b Kamal A. Kumar GB. Nayaka VL. Reddya VS. Basha A. Rajender S. Reddy MK. Med. Chem. Commun. 2015; 6: 606 8c Kamal A. Reddy JS. Ramaiah MJ. Dastagiri D. Bharathi EV. Sagar MV. P. Pushpavalli SN. C. V. L. Ray P. Pal-Bhadra M. Med. Chem. Commun. 2010; 1: 355 8d Mohan DC. Donthiri RR. Rao SN. Adimurthy S. Adv. Synth. Catal. 2013; 355: 2217 8e Al-Tel TH. Al-Qawasmeh RA. Eur. J. Med. Chem. 2010; 45: 5848 9a Kim O. Jeong Y. Lee H. Hong S. Hong S. J. Med. Chem. 2011; 54: 2455 9b Cai L. Cuevas J. Temme S. Herman MM. Dagostin C. Widdowson DA. Innis RB. Pike VW. J. Med. Chem. 2007; 50: 4746 9c Starr JT. Sciotti RJ. Hanna DL. Huband MD. Mullins LM. Cai H. Gage JW. Lockard M. Rauckhorst MR. Owen RM. Lall MS. Tomilo M. Chen H. McCurdy SP. Barbachyn MR. Bioorg. Med. Chem. Lett. 2009; 19: 5302 9d Al-Tel TH. Al-Qawasmeh RA. Zaarour R. Eur. J. Med. Chem. 2011; 46: 1874 10 Shono H. Ohkawa T. Tomoda H. Mutai T. Araki KC. ACS Appl. Mater. Interfaces 2011; 3: 654 11a Wang Y. Frett B. Li H. Org. Lett. 2014; 16: 3016 11b Stasyuk V. Banasiewicz V. Cyraneski V. Gryko V. J. Org. Chem. 2012; 77: 5552 12 Yadav JS. Reddy BV. S. Rao YG. Srinivas M. Narsaiah AV. Tetrahedron Lett. 2007; 48: 7717 13 Ueno V. Togo H. Synthesis 2004; 2673 14a Nair DK. Mobin SM. Namboothiri IN. N. Org. Lett. 2012; 14: 4580 14b Santra S. Bagdi AK. Majee A. Hajra A. Adv. Synth. Catal. 2013; 355: 1065 15a Yan H. Wang Y. Pan C. Zhang H. Yang S. Ren X. Li J. Huang G. Eur. J. Org. Chem. 2014; 2754 15b Ramesha AB. Raghavendra GM. Nandeesh KN. Rangappa KS. Mantelingu K. Tetrahedron Lett. 2013; 54: 95 16 Liu P. Deng C.-L. Lei X. Lin G.-Q. Eur. J. Org. Chem. 2011; 7308 17 Wang H. Wang Y. Liang D. Liu L. Zhang J. Zhu Q. Angew. Chem. Int. Ed. 2011; 50: 5678 18 Wang H. Wang Y. Peng C. Zhang J. Zhu Q. J. Am. Chem. Soc. 2010; 132: 13217 19a Donohoe TJ. Kabeshov MA. Rathi AH. Smith IE. D. Org. Biomol. Chem. 2012; 10: 1093 19b Gao Y. Yin M. Wu W. Huang H. Jiang H. Adv. Synth. Catal. 2013; 355: 2263 20 Bagdi AK. Santra S. Monir K. Hajra A. Chem. Commun. 2015; 51: 1555 21a Haas G. Stanton JL. von Sprecher A. Wenk P. J. Heterocycl. Chem. 1981; 18: 607 21b Gašparová R. Lácová M. Molecules 2005; 10: 937 21c Plaskon AS. Ryabukhin SV. Volochnyuk DM. Gavrilenko KS. Shivanyuk AN. Tolmachev AA. J. Org. Chem. 2008; 73: 6010 21d Sanchez LM. Sathicq ÁG. Jios JL. Baronetti GT. Thomas HJ. Romanelli GP. Tetrahedron Lett. 2011; 52: 4412 21e Balalaie S. Bijanzadeh HR. Mehrparvar S. Rominger S. Synlett 2016; 27: 782 21f Bijanzadeh HR. Mehrparvar S. Balalaie S. J. Iran. Chem. Soc. 2015; 12: 1859 21g Mehrparvar S. Balalaie S. Rabbanizadeh M. Rominger F. Ghabraie E. Org. Biomol. Chem. 2014; 12: 5757 21h Mehrparvar S. Balalaie S. Rabbanizadeh M. Ghabraie E. Rominger F. Mol. Diversity 2014; 18: 535 22a Ghabraie E. Balalaie S. Mehrparvar S. Rominger F. J. Org. Chem. 2014; 79: 7926 22b Maghari S. Ramezanpour S. Balalaie S. Darvish F. Rominger F. Bijanzadeh HR. J. Org. Chem. 2013; 78: 6450 22c Bararjanian M. Balalaie S. Rominger F. Movassagh B. Bijanzadeh HR. Mol. Diversity 2011; 15: 583 23a Khadem S. Marles RJ. Molecoules 2011; 17: 191 23b Gasper A. Matos MJ. Garido J. Uriarte E. Borges F. Chem. Rev. 2014; 114: 4960 24 Balalaie, S.; Esmaeilabadi, H.; Mehrparvar, S.; Rominger, F.; Hamdan, F.; Bijanzadeh, H. R.; submitted for publication. 25 Procedure for the Synthesis of 2-Amino-5-(2-Hydroxybenzoyl)nicotinonitrile (4a) A mixture of 3-formylchromone (1 mmol, 174 mg), malononitrile (1.2 mmol, 79 mg), and diammonium hydrogen phosphate (20% mol, 27 mg) was stirred in water (6 mL) at r.t. for 30 min. The mixture was then added to diammonium hydrogen phosphate (1 mmol, 27 mg), and the reaction mixture was stirred at 50 °C for 3 h. The obtained precipitate was filtered and washed with aq EtOH. Procedure for the Synthesis of 6-(2-Hydroxybenzoyl)-2-phenylimidazo[1, 2-a]pyridine-8-carbonitrile (6a) A mixture of 2-amino-5-(2-hydroxybenzoyl)nicotinonitrile (1 mmol, 239 mg) and phenacyl bromide (1 mmol, 199 mg) was stirred in DMF (2 mL) for 4 h under reflux. After completion of the reaction, the mixture was allowed to cool, water was added, and the reaction mixture was extracted with CH2Cl2. The organic phase was dried using Na2SO4. Further purification was carried out using column chromatography (eluent; n-hexane–CH2Cl2 = 1:1). 6-(2-Hydroxybenzoyl)-2-phenylimidazo[1,2-a]pyridine-8-carbonitrile (6a) Colorless powder, 176 mg, 52%, mp 198–200 °C. IR (KBr): νmax = 3411, 2237, 1626, 1604 cm–1. 1HNMR (300 MHz, DMSO-d 6): δ = 6.99 (t, 1 H, J = 8.1 Hz, H-Ar), 7.01–7.04(d, 1 H, J = 7.5 Hz, H-Ar), 7.35–7.51 (m, 5 H, H-Ar), 7.97 (d, 2 H, J = 7.5 Hz, H-Ar), 8.20 (br s, 1 H, H-2-pyridyl), 8.67 (s, 1 H, H-imidazole), 9.22 (d, 1 H, J = 1.56 Hz, H-4-pyridyl), 10.36 (s, 1 H, OH). 13CNMR (75 MHz, DMSO-d 6): δ = 99.6, 112.3, 115.2, 117.0, 119.5, 122.9, 124.2, 126.0, 129.0, 129.0, 130.5, 132.1, 132.3, 133.7, 136.1, 142.6, 146.9, 156.4, 192.0. ESI-HRMS: m/z calcd for C21H13N3O2 [M + H]+: 340.1083; found: 340.1083. 2-(4-Bromophenyl)-6-(5-fluoro-2-hydroxybenzoyl)imidazo[1,2-a]pyridine-8-carbonitrile (6g) Yellow powder, 235 mg, 54%, mp 259–261 °C. IR: (KBr): νmax = 3402, 2225, 1674, 1593 cm–1.1HNMR (300 MHz, DMSO-d 6): δ = 6.99–7.03(m, 1 H, H-Ar), 7.26–7.37 (m, 2 H, H-Ar), 7.65 (d, 2 H, J = 8.34 Hz, H-Ar), 7.90 (d, 2 H, J = 8.35 Hz, H-Ar), 8.24 (s, 1 H, H-2-pyridyl), 8.68 (s, 1 H, H-imidazole), 9.24 (s, 1 H, H-4-pyridyl), 10.27 (s, 1 H, OH). 13CNMR (75 MHz, DMSO-d 6): δ = 99.8, 112.7, 115.0, 115.8, 116.1, 118.2, 118.3 ( 3J C–F = 7.2 Hz), 120.0, 120.3 ( 2J C–F = 24 Hz), 122.0, 122.6, 124.9, 125.0, 127.9, 131.5, 131.9, 132.2, 136.5, 142.7, 145.8, 152.4, 153.6, 156.7 ( 1J C–F = 234.75 Hz), 190.5. ESI-HRMS: m/z calcd for C21H11BrFN3O2 [M + H]+: 436.0094; found: 436.0094. Yellow crystal (polyhedron), dimensions 0.160 × 0.130 × 0.130 mm3, crystal system monoclinic, space group P21/c, Z = 4, a = 8.5182(4) Å, b = 8.5756(4) Å, c = 24.0705(12) Å, α =90°, β = 94.4088(8)°, γ = 90°, V = 1753.12(15) Å3, ρ = 1.653 g cm–3, T = 200(2) K, θ max = 28.313°, radiation Mo Kα, λ = 0.71073 Å, 0.5° Ω scans with CCD area detector, covering the asymmetric unit in reciprocal space with a mean redundancy of 3.92 and a completeness of 99.8% to a resolution of 0.75 Å, 17588 reflections measured, 4356 unique (R(int) = 0.0291), 3370 observed (I > 2σ(I)), intensities were corrected for Lorentz and polarization effects, an empirical scaling and absorption correction was applied using SADABS26a based on the Laue symmetry of the reciprocal space, μ = 2.38 mm–1, Tmin = 0.90, Tmax = 0.97, structure refined against F 2 with a full-matrix least-squares algorithm using the SHELXL-2016/6 (Sheldrick, 2016) software, 257 parameters refined, hydrogen atoms were treated using appropriate riding models, except H32 of the hydroxy group, which was refined isotropically, goodness of fit 1.04 for observed reflections, final residual values R1(F) = 0.034, wR(F 2) = 0.082 for observed reflections, residual electron density –0.68 to 0.72 eÅ–3. CCDC 1557527 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.26b 26a Sheldrick GM. SADABS. Bruker Analytical X-ray-Division; Madison, WI: 2014 26b Sheldrick GM. Acta Crystallogr., Sect. C: Struct. Chem. 2015; 71: 3 Zusatzmaterial Zusatzmaterial Supporting Information
