Synlett 2013; 24(7): 837-838
DOI: 10.1055/s-0032-1318492
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of New Propargylated 1-Pyrindane Derivatives as Rasagiline Analogues

Cidália Silva Pereira
a   Centro de Investigação em Química, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal   Fax: +351(220)402009   Email: jrborges@fc.up.pt
,
Sofia Salgado
a   Centro de Investigação em Química, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal   Fax: +351(220)402009   Email: jrborges@fc.up.pt
,
Fabio Rizzo-Aguiar
a   Centro de Investigação em Química, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal   Fax: +351(220)402009   Email: jrborges@fc.up.pt
,
Xerardo Garcia-Mera
b   Departamento de Química Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
,
José E. Rodríguez-Borges*
a   Centro de Investigação em Química, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal   Fax: +351(220)402009   Email: jrborges@fc.up.pt
› Author Affiliations
Further Information

Publication History

Received: 20 December 2012

Accepted after revision: 02 March 2013

Publication Date:
14 March 2013 (online)


Abstract

Rasagiline is a compound with important neuroprotective activity applicable to the treatment of neurodegenerative diseases. This work describes an easy and straightforward methodology to the synthesis of new propargylated rasagiline analogues derived from commercially available 6,7-dihydro-5H-cyclopenta[b]pyridine.

Supporting Information

 
  • References and Notes

    • 1a Aluf Y, Vaya J, Khatib S, Loboda Y, Finberg JP. M. Neuropharmacology 2013; 65: 48
    • 1b Van der Schyf CJ, Geldenhuys WJ. Int. Rev. Neurobiol. 2011; 100: 107
    • 1c Weireb O, Amit T, Bar-Am O, Youdim MB. H. Int. Rev. Neurobiol. 2011; 100: 191
    • 2a Chahine LM, Stern MB. Int. Rev. Neurobiol. 2011; 100: 151
    • 2b Weinreb O, Amit T, Riederer P, Youdim MB. H, Mandel SA. Int. Rev. Neurobiol. 2011; 100: 127
    • 2c Bar-Am O, Weinreb O, Amit T, Youdim MB. H. J. Neurochem. 2010; 112: 1131
    • 2d Youdim MB. H, Fridkin M, Zheng H. Mech. Ageing Dev. 2005; 126: 317
    • 2e Youdim MB. H, Amit T, Bar-Am O, Weinstock M, Yogev-Falach M. Ann. N.Y. Acad. Sci. 2003; 993: 378
    • 2f Youdim MB. H, Weinstock M. Mech. Ageing Dev. 2002; 123: 1081
    • 2g Zheng H, Gal S, Weiner LM, Bar-Am O, Warshawsky A, Fridkin M, Youdim MB. H. J. Neurochem. 2005; 95: 68
    • 2h Zhu W, Xie W, Pan T, Jankovic J, Li J, Youdim MB. H, Le W. J. Neurochem. 2008; 105: 1970
    • 2i Am OB, Amit T, Youdim MB. H. Neurosci. Lett. 2004; 355: 169
    • 2j Barac YD, Bar-Am O, Liani E, Amit T, Frolou L, Ovcharenko E, Angel I, Youdim MB. H, Binah O. PLoS One 2012; 7: e47890
    • 2k Meier-Davis SR, Dines K, Arjmand FM, Hamlin R, Huang B, Wen J, Christianson C, Shudo J, Nagata T. Cutan. Ocul. Toxicol. 2012; 31: 312
  • 3 Cymerman Craig J, Purushothaman KK. J. Org. Chem. 1970; 35: 1721
    • 4a Youssif S. ARKIVOC 2001; (i): 242
    • 4b Robison MM. J. Am. Chem. Soc. 1958; 80: 6254
    • 4c Lyle MP. A, Narine AA, Wilson PD. J. Org. Chem. 2004; 69: 5060
    • 4d Lyle MP. A, Draper ND, Wilson PD. Org. Biomol. Chem. 2006; 4: 877
    • 4e Andreotti D, Miserazzi E, Nalin A, Pozzan A, Profeta R, Spada S. Tetrahedron Lett. 2010; 51: 6526
    • 4f Li J. Name Reactions in Heterocyclic Chemistry. Li J.-J, Corey EJ. John Wiley and Sons; Hoboken: 2005
  • 5 Omura K, Swern D. Tetrahedron 1978; 34: 1651
  • 6 Abdel-Magid AF, Carson KG, Harris BD, Maryanoff CA, Shah RD. J. Org. Chem. 1996; 61: 3849
  • 7 Selected 1H NMR and HRMS Data Compound 1: 1H NMR (400 MHz, CDCl3): δ = 2.09–2.16 (1 H, m), 2.32–2.39 (1 H, m), 2.42 (1 H, t, J = 2.4 Hz, OCH2CCH), 2.77 (1 H, ddd, J 1 = 4.6 Hz, J 2 = 8.7 Hz, J 3 = 13.3 Hz), 3.00–3.08 (1 H, m), 4.38 (1 H, dd, J 1 = 2.4 Hz, J 2 = 15.6 Hz, OCHHCCH), 4.46 (1 H, dd, J 1 = 2.4 Hz, J 2 = 15.7 Hz, OCHHCCH) 4.98 (1 H, dd, J 1 = 3.7 Hz, J 2 = 7.0 Hz), 7.10 (1 H, dd, J 1 = 4.9 Hz, J 2 = 7.6 Hz, Harom), 7.51 (1 H, dd, J 1 = 0.6 Hz, J 2 = 7.6 Hz, Harom), 8.39 (1 H, d, J = 4.9 Hz, Harom). ESI-HRMS: m/z calcd for [C11H11NO + H]+: 174.0913 [M + H+]; found: 174.0917. Compound 2: 1H NMR (400 MHz, CDCl3): δ = 1.87–2.03 (m + br s, 1 H + NHCHHCCH), 2.26 (1 H, t, J = 2.4 Hz, NHCHHCCH), 2.45–2.53 (1 H, m), 2.84–2.92 (1 H, m), 2.91 (1 H, ddd, J 1 = 3.8 Hz, J 2 = 8.8 Hz, J 3 = 12.7 Hz), 3.58 (1 H, dd, J 1 = 2.3 Hz, J 2 = 17.0 Hz, NHCHHCCH), 3.72 (1 H, dd, J 1 = 2.4 Hz, J 2 = 17.0 Hz, NHCHHCCH), 4.42 (1 H, t, J = 7.0 Hz), 7.12 (1 H, dd, J 1 = 5.0 Hz, J 2 = 6.9 Hz, Harom), 7.55 (1 H, d, J = 7.6 Hz, Harom), 8.42 (1 H, d, J = 4.9 Hz, Harom). ESI-HRMS: m/z calcd for [C11H12N2 + H]+: 173.1073 [M + H+]; found: 173.1072. Compound 3: 1H NMR (400 MHz, CDCl3): δ = 2.22 (2 H, t, J = 2.4 Hz, 2 × NHCHHCCH), 2.23–2.40 (2 H, m), 2.77–2.85 (1 H, m), 3.01 (1 H, ddd, J 1 = 5.1 Hz, J 2 = 8.6 Hz, J 3 = 13.7 Hz), 3.70 (2 H, dd, J 1 = 2.4 Hz, J 2 = 16.9 Hz, 2 × NHCHHCCH), 3.83 (2 H, dd, J 1 = 2.4 Hz, J 2 = 16.9 Hz, 2 × NHCHHCCH), 4.44 (1 H, t, J = 6.7 Hz), 7.11 (1 H, dd, J 1 = 4.9 Hz, J 2 = 7.6 Hz, Harom), 7.52 (1 H, dd, J 1 = 1.3 Hz, J 2 = 7.6 Hz, Harom), 8.45 (1 H, d, J = 4.2 Hz, Harom). ESI-HRMS: m/z calcd for [C14H14N2 + H]+: 211.1230 [M + H+]; found: 211.1224.