Synlett 2012; 23(18): 2609-2614
DOI: 10.1055/s-0032-1317379
letter
© Georg Thieme Verlag Stuttgart · New York

Exploration of the CuAAC Reaction for the Synthesis of Novel 3-(Triazol-1-yl)methyl-imidazo[1,2-a]pyridines

Poonam Khedar
Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India   Fax: +91(1596)244183   Email: anilkumar@bits-pilani.ac.in
,
Kasiviswanadharaju Pericherla
Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India   Fax: +91(1596)244183   Email: anilkumar@bits-pilani.ac.in
,
Anil Kumar*
Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India   Fax: +91(1596)244183   Email: anilkumar@bits-pilani.ac.in
› Author Affiliations
Further Information

Publication History

Received: 25 August 2012

Accepted after revision: 11 September 2012

Publication Date:
18 October 2012 (online)


Abstract

The archetypical CuAAC click chemistry is explored to assemble diverse 3-(triazol-1-yl)methyl-imidazo[1,2-a]pyridines. The approach is simple, general, and environmentally benign to generate a library of novel triazolo-imidazo[1,2-a]pyridine derivatives in good yield (30–90%).

Supporting Information

 
  • References and Notes

  • 1 Kolb HC, Finn MG, Sharpless KB. Angew. Chem. Int. Ed. 2001; 40: 2004
  • 2 Stefani HA, Silva NC. S, Manarin F, Lüdtke DS, Zukerman-Schpector J, Madureira LS, Tiekink ER. T. Tetrahedron Lett. 2012; 53: 1742
  • 3 Kolb HC, Sharpless KB. Drug Discovery Today 2003; 8: 1128
  • 4 van Dijk M, Rijkers DT. S, Liskamp RM. J, van Nostrum CF, Hennink WE. Bioconjugate Chem. 2009; 20: 2001
  • 5 Lutz J.-F, Zarafshani Z. Adv. Drug. Delivery Rev. 2008; 60: 958
  • 6 Best MD. Biochemistry 2009; 48: 6571
  • 7 Al-Tel TH, Al-Qawasmeh RA, Zaarour R. Eur. J. Med. Chem. 2011; 1874
  • 8 Fisher MH, Lusi A. J. Med. Chem. 1972; 15: 982
  • 9 Chezal J.-M, Paeshuyse J, Gaumet V, Canitrot D, Maisonial A, Lartigue C, Gueiffier A, Moreau E, Teulade J.-C, Chavignon O, Neyts J. Eur. J. Med. Chem. 2010; 2044
  • 10 Dahan-Farkas N, Langley C, Rousseau AL, Yadav DB, Davids H, de Koning CB. Eur. J. Med. Chem. 2011; 4573
  • 11 Hamdouchi C, Ezquerra J, Vega JA, Vaquero JJ, Alvarez-Builla J, Heinz BA. Bioorg. Med. Chem. Lett. 1999; 9: 1391
  • 12 Moraski GC, Markley LD, Chang M, Cho S, Franzblau SG, Hwang CH, Boshoff H, Miller MJ. Bioorg. Med. Chem. 2012; 20: 2214
  • 13 Kaminski JJ, Hilbert JM, Pramanik BN, Solomon DM, Conn DJ, Rizvi RK, Elliott AJ, Guzik H, Lovey RG. J. Med. Chem. 1987; 30: 2031
  • 14 Kaminski JJ, Bristol JA, Puchalski C, Lovey RG, Elliott AJ, Guzik H, Solomon DM, Conn DJ, Domalski MS. J. Med. Chem. 1985; 28: 876
  • 15 Kaminski JJ, Doweyko AM. J. Med. Chem. 1997; 40: 427
  • 16 Ismail MA, Brun R, Wenzler T, Tanious FA, Wilson WD, Boykin DW. J. Med. Chem. 2004; 47: 3658
  • 17 Goodacre SC, Street LJ, Hallett DJ, Crawforth JM, Kelly S, Owens AP, Blackaby WP, Lewis RT, Stanley J, Smith AJ, Ferris P, Sohal B, Cook SM, Pike A, Brown N, Wafford KA, Marshall G, Castro JL, Atack JR. J. Med. Chem. 2005; 49: 35
  • 18 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
  • 19 Emmitte KA, Wilson BJ, Baum EW, Emerson HK, Kuntz KW, Nailor KE, Salovich JM, Smith SC, Cheung M, Gerding RM, Stevens KL, Uehling DE, Mook RA. Jr, Moorthy GS, Dickerson SH, Hassell AM, Anthony Leesnitzer M, Shewchuk LM, Groy A, Rowand JL, Anderson K, Atkins CL, Yang J, Sabbatini P, Kumar R. Bioorg. Med. Chem. Lett. 2009; 19: 1004
  • 20 Warshakoon NC, Wu S, Boyer A, Kawamoto R, Sheville J, Renock S, Xu K, Pokross M, Evdokimov AG, Walter R, Mekel M. Bioorg. Med. Chem. Lett. 2006; 16: 5598
  • 21 Zimmermann PJ, Buhr W, Brehm C, Palmer AM, Feth MP, Senn-Bilfinger J, Simon W.-A. Bioorg. Med. Chem. Lett. 2007; 17: 5374
  • 22 Gedda K, Briving C, Svensson K, Maxvall I, Andersson K. Biochem. Pharmacol. 2007; 73: 198
  • 23 Odell LR, Nilsson MT, Gising J, Lagerlund O, Muthas D, Nordqvist A, Karlén A, Larhed M. Bioorg. Med. Chem. Lett. 2009; 19: 4790
  • 24 Roelofs AJ, Hulley PA, Meijer A, Ebetino FH, Russell RG. G, Shipman CM. Int. J. Cancer 2006; 119: 1254
  • 25 Takeuchi M, Sakamoto S, Kawamuki K, Kurihara H, Nakahara H, Isomura Y. Chem. Pharm. Bull. 1998; 46: 1703
  • 26 Hamdouchi C, Zhong B, Mendoza J, Collins E, Jaramillo C, De Diego JE, Robertson D, Spencer CD, Anderson BD, Watkins SA, Zhang F, Brooks HB. Bioorg. Med. Chem. Lett. 2005; 15: 1943
  • 27 Byth KF, Culshaw JD, Green S, Oakes SE, Thomas AP. Bioorg. Med. Chem. Lett. 2004; 14: 2245
  • 28 Wang X.-L, Wan K, Zhou C.-H. Eur. J. Med. Chem. 2010; 4631
  • 29 Jordão AK, Afonso PP, Ferreira VF, de Souza MC. B. V, Almeida MC. B, Beltrame CO, Paiva DP, Wardell SM. S. V, Wardell JL, Tiekink ER. T, Damaso CR, Cunha AC. Eur. J. Med. Chem. 2009; 3777
  • 30 Tripathi RP, Yadav AK, Ajay A, Bisht SS, Chaturvedi V, Sinha SK. Eur. J. Med. Chem. 2010; 142
  • 31 Boechat N, Ferreira VF, Ferreira SB, Ferreira Md. L. G, da Silva Fd. C, Bastos MM, Costa Md. S, Lourenço MC. S, Pinto AC, Krettli AU, Aguiar AC, Teixeira BM, da Silva NV, Martins PR. C, Bezerra FA. F. M, Camilo AL. S, da Silva GP, Costa CC. P. J. Med. Chem. 2011; 54: 5988
  • 32 Wilkinson BL, Bornaghi LF, Houston TA, Innocenti A, Vullo D, Supuran CT, Poulsen S.-A. J. Med. Chem. 2007; 50: 1651
  • 33 Kumar A, Ahmad I, Chhikara BS, Tiwari R, Mandal D, Parang K. Bioorg. Med. Chem. Lett. 2011; 21: 1342
  • 34 Olesen PH, Sørensen AR, Ursø B, Kurtzhals P, Bowler AN, Ehrbar U, Hansen BF. J. Med. Chem. 2003; 46: 3333
  • 35 Röhrig UF, Majjigapu SR, Grosdidier A, Bron S, Stroobant V, Pilotte L, Colau D, Vogel P, Van den Eynde BJ, Zoete V, Michielin O. J. Med. Chem. 2012; 55: 5270
  • 36 Patpi SR, Pulipati L, Yogeeswari P, Sriram D, Jain N, Sridhar B, Murthy RT. A. D, Kalivendi SV, Kantevari S. J. Med. Chem. 2012; 55: 3911
  • 37 Manfredini S, Beatrice VicentiniC, Manfrini M, Bianchi N, Rutigliano C, Mischiati C, Gambari R. Bioorg. Med. Chem. 2000; 8: 2343
  • 38 Spiteri C, Moses JE. Angew. Chem. Int. Ed. 2010; 49: 31
  • 39 General Procedure for the Preparation of 3-(Triazol-1-yl)methyl-imidazo[1,2-a]pyridines (6) To a 25 mL round-bottom flask was added 3-(azidomethyl)-2-pheny-lH-imidazo[1,2-a]pyridine (1.0 mmol), phenylacetylene (1.2 mmol), CuI (0.05 mmol), and PEG-400–H2O (1:1 v/v) (10 mL). The resulting mixture was stirred at r.t. for 5–7 h. After completion of the reaction H2O (20 mL) was added to the reaction mixture and extracted with EtOAc (3 × 10 mL). The combined organic layer was dried over anhyd Na2SO4 and evaporated the volatiles. The crude was purified by column over silica gel to give 6.
  • 40 Spectroscopic Data of Selected Compounds 6 Compound 6b: 1H NMR (500 MHz, CDCl3): δ = 8.16 (d, J = 6.8 Hz, 1 H), 7.72 (d, J = 9.1 Hz, 1 H), 7.69 (dd, J = 3.3, 1.1 Hz, 1 H), 7.68–7.66 (m, 5 H), 7.50 (s, 1 H), 7.35–7.31 (m, 1 H), 6.92 (d, J = 1.7 Hz, 1 H), 6.90 (t, J = 3.2 Hz, 2 H), 6.02 (s, 2 H), 3.82 (s, 3 H). 13C NMR (126 MHz, CDCl3): δ = 159.8, 148.6, 132.3, 132.1, 131.2, 130.0, 128.6, 127.0, 126.5, 123.8, 123.2, 122.6, 117.8, 117.8, 114.2, 113.8, 105.4, 55.3, 43.9. ESI-MS: m/z = 460 [M + H]+. Compound 6d: 1H NMR (500 MHz, DMSO-d 6): δ = 8.73 (s, 1 H), 8.69 (s, 2 H), 8.37 (s, 1 H), 8.27 (d, J = 7.3 Hz, 1 H), 7.83 (d, J = 6.9 Hz, 4 H), 7.47–7.39 (m, 3 H), 7.31 (t, J = 6.9 Hz, 1 H), 7.09 (d, J = 5.4 Hz, 1 H), 6.26 (s, 2 H). 13C NMR (126 MHz, DMSO-d 6): δ = 148.6, 147.0, 134.6, 130.9, 129.3, 128.5, 126.9, 125.7, 124.5, 123.2, 123.1, 122.0, 122.0, 117.7, 113.8, 43.5. ESI-MS: m/z = 397 [M + H]+. Compound 6j: 1H NMR (500 MHz, CDCl3): δ = 8.12 (d, J = 6.7 Hz, 1 H), 7.70 (d, J = 9.0 Hz, 1 H), 7.65 (d, J = 8.3 Hz, 2 H), 7.46 (d, J = 8.2 Hz, 2 H), 7.31 (dd, J = 8.4, 7.4 Hz, 1 H), 7.26–7.25 (m, 1 H), 7.24 (s, 1 H), 7.19 (t, J = 5.5 Hz, 3 H), 7.05 (s, 1 H), 6.89 (t, J = 6.8 Hz, 1 H), 5.91 (s, 2 H), 4.02 (s, 2 H). 13C NMR (126 MHz, CDCl3): δ = 148.5, 145.1, 138.6, 134.8, 131.6, 130.6, 129.8, 129.4, 129.2, 128.6, 128.6, 126.6, 126.3, 123.9, 120.6, 117.8, 113.6, 43.8, 32.2. ESI-MS: m/z = 400 [M + H]+. Compound 6k: 1H NMR (500 MHz, CDCl3): δ = 8.12 (d, J = 6.8 Hz, 1 H), 7.70 (t, J = 8.9 Hz, 3 H), 7.49 (d, J = 8.4 Hz, 2 H), 7.33–7.29 (m, 1 H), 7.10 (s, 1 H), 6.89 (t, J = 6.7 Hz, 1 H), 5.95 (s, 2 H), 2.63 (t, J = 7.6 Hz, 2 H), 1.64–1.62 (m, 2 H), 0.91 (t, J = 7.4 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ = 149.3, 143.0, 134.8, 131.8, 129.7, 129.3, 126.2, 125.9, 125.4, 123.8, 119.8, 117.8, 113.6, 43.7, 27.7, 22.6, 13.7. ESI-MS: m/z = 352 [M + H]+. Compound 6o: 1H NMR (500 MHz, CDCl3): δ = 8.13 (d, J = 6.7 Hz, 1 H), 7.73 (dd, J = 7.9, 5.4 Hz, 5 H), 7.55 (s, 1 H), 7.34–7.29 (m, 1 H), 7.07 (dd, J = 9.4, 8.2 Hz, 4 H), 6.89 (t, J = 6.7 Hz, 1 H), 6.04 (s, 2 H), 3.88 (s, 3 H). 13C NMR (126 MHz, CDCl3): δ = 160.2, 147.8, 145.6, 130.9, 129.8, 128.8, 127.5, 127.5, 126.3, 125.3, 123.7, 118.5, 117.5, 115.9, 115.8, 114.6, 113.6, 55.4, 44.1. ESI-MS: m/z = 400 [M + H]+.