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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)

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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.

Key words

neuroprotective drugs - pyrindanes - Boekelheide re­arrangement - Swern oxidation - reductive amination

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

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  • 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.