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Synthesis 2009(10): 1659-1662  
DOI: 10.1055/s-0028-1088059
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Straightforward and Scalable Synthesis of Orthogonally Protected 3,7-Diazabicyclo[4.1.0]heptane

Heiko Schramma, Maria Pavlovaa, Christoph Hoenkeb, Jens Christoffers*a
a Institut für Reine und Angewandte Chemie, Universität Oldenburg, Carl von Ossietzky-Str. 9-11, 26111 Oldenburg, Germany
Fax: +49(441)7983873; e-Mail: jens.christoffers@uni-oldenburg.de;
b Boehringer Ingelheim Pharma GmbH & Co. KG, Abteilung Chemische Forschung, Birkendorfer Str. 65, 88397 Biberach an der Riß, Germany
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Publikationsverlauf

Received 26 November 2008
Publikationsdatum:
20. April 2009 (online)

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Abstract

Orthogonally N-protected (Boc and Cbz) 3,4-aziridinopiperidine is a versatile building block for the synthesis of 4-substituted 3-aminopiperidines, which are compounds with a high potential for biological activity. A multigram synthesis over five steps, starting with extraordinarily simple materials (pyridine and benzyl chloride), was developed.

Key words

amines - piperidines - aziridines - building blocks - protective groups

    References

  • 1 For a review, see: Horton DA. Bourne GT. Smythe ML. Chem. Rev.  2003,  103:  893 
    CrossrefPubMedSuche in Google Scholar
  • For reviews, see:
  • 2a Källström S. Leino R. Bioorg. Med. Chem.  2008,  16:  601 
    Suche in Google Scholar
  • 2b De Risi C. Fanton G. Pollini GP. Trapella C. Valente F. Zanirato V. Tetrahedron: Asymmetry  2008,  19:  131 
    Suche in Google Scholar
  • 2c Laschat S. Dickner T. Synthesis  2000,  1781 
  • 2d Vilsmaier E. J. Prakt. Chem.  2000,  342:  218 
    Suche in Google Scholar
  • 2e Escolano C. Amat M. Bosch J. Chem. Eur. J.  2006,  12:  8198 
    Suche in Google Scholar
  • For recent examples, see:
  • 3a Eckhardt M. Hauel N. Himmelsbach F. Langkopf E. Nar H. Mark M. Tadayyon M. Thomas L. Guth B. Lotz R. Bioorg. Med. Chem. Lett.  2008,  18:  3158 
    Suche in Google Scholar
  • 3b Eckhardt M. Hauel N. Langkopf E. Himmelsbach F. Tetrahedron Lett.  2008,  49:  1931 
    Suche in Google Scholar
  • 3c Jin J. Wang Y. Shi D. Wang F. Davis RS. Jin Q. Fu W. Foley JJ. Webb EF. Dehaas CJ. Berlanga M. Burman M. Sarau HM. Morrow DM. Rao P. Kallal LA. Moore ML. Rivero RA. Palovich M. Salmon M. Belmonte KE. Busch-Petersen J. J. Med. Chem.  2008,  51:  4866 
    Suche in Google Scholar
  • 3d Diaz JL. Fernandez-Forner D. Bach J. Lavilla R. Synth. Commun.  2008,  38:  2799 
    Suche in Google Scholar
  • 3e Martini E. Ghelardini C. Dei S. Guandalini L. Manetti D. Melchiorre M. Norcini M. Scapecchi S. Teodori E. Romanelli MN. Bioorg. Med. Chem.  2008,  16:  1431 
    Suche in Google Scholar
  • 3f Erickson SD. Banner B. Berthel S. Conde-Knape K. Falcioni F. Hakimi I. Hennessy B. Kester RF. Kim K. Ma C. McComas W. Mennona F. Mischke S. Orzechowski L. Qian Y. Salari H. Tengi J. Thakkar K. Taub R. Tilley JW. Wang H. Bioorg. Med. Chem. Lett.  2008,  18:  1402 
    Suche in Google Scholar
  • 3g Acker BA. Jacobsen EJ. Rogers BN. Wishka DG. Reitz SC. Piotrowski DW. Myers JK. Wolfe ML. Groppi VE. Thornburgh BA. Tinholt PM. Walters RR. Olson BA. Fitzgerald L. Staton BA. Raub TJ. Krause M. Li KS. Hoffmann WE. Hajos M. Hurst RS. Walker DP. Bioorg. Med. Chem. Lett.  2008,  18:  3611 
    Suche in Google Scholar
  • 3h Duan JJ.-W. Chen L. Lu Z. Xue C.-B. Liu R.-Q. Covington MB. Qian M. Wasserman ZR. Vaddi K. Christ DD. Trzaskos JM. Newton RC. Decicco CP. Bioorg. Med. Chem. Lett.  2008,  18:  241 
    Suche in Google Scholar
  • 3i Zhou Y. Chow C. Murphy DE. Sun Z. Bertolini T. Froelich JM. Webber SE. Hermann T. Wall D. Bioorg. Med. Chem. Lett.  2008,  18:  3369 
    Suche in Google Scholar
  • 3j Levy DE. Wang D.-X. Lu Q. Chen Z. Perumattam J. Xu Y.-j. Higaki J. Dong H. Liclican A. Laney M. Mavunkel B. Dugar S. Bioorg. Med. Chem. Lett.  2008,  18:  2395 
    Suche in Google Scholar
  • 3k Isaacs RCA. Solinsky MG. Cutrona KJ. Newton CL. Naylor-Olsen AM. McMasters DR. Krueger JA. Lewis SD. Lucas BJ. Kuo LC. Yan Y. Lynche JJ. Lyle EA. Bioorg. Med. Chem. Lett.  2008,  18:  2062 
    Suche in Google Scholar
  • 3l Mishra M. Kolhatkar R. Zhen J. Parrington I. Reith MEA. Dutta AK. Bioorg. Med. Chem.  2008,  16:  2769 
    Suche in Google Scholar
  • 4a Hu XE. Kim NK. Ledoussal B. Colson A.-O. Tetrahedron Lett.  2002,  43:  4289 
    Suche in Google Scholar
  • 4b Hu XE. Tetrahedron Lett.  2002,  43:  5315 
    Suche in Google Scholar
  • 4c Majchrzak MW. Kotelko A. Lambert JB. Org. Magn. Reson.  1983,  21:  539 
    Suche in Google Scholar
  • For recent examples, see:
  • 5a Rosiak A. Hoenke C. Christoffers J. Eur. J. Org. Chem.  2007,  4376 
  • 5b Rosiak A. Müller RM. Christoffers J. Monatsh. Chem.  2007,  138:  13 
    Suche in Google Scholar
  • 5c Rosiak A. Frey W. Christoffers J. Eur. J. Org. Chem.  2006,  4044 
  • 6 For a review, see: Tanner D. Angew. Chem. Int. Ed.  1994,  33:  599 ; Angew. Chem. 1994, 106, 625
    CrossrefSuche in Google Scholar
  • 7 Takemura S. Miki Y. Uono M. Yoshimura K. Kuroda M. Suzuki A. Chem. Pharm. Bull.  1981,  29:  3026 
    CrossrefSuche in Google Scholar
  • 8 Imanishi T. Shin H. Hanaoka M. Momose T. Imanishi I. Chem. Pharm. Bull.  1982,  30:  3617 
    CrossrefSuche in Google Scholar
  • 9 Oediger H. Joop N. Liebigs Ann. Chem.  1972,  764:  21 
    Suche in Google Scholar
  • 10 Wang D. Nugent WA. J. Org. Chem.  2007,  72:  7307 
    CrossrefSuche in Google Scholar
  • 11 Christoffers J. Schulze Y. Pickardt J. Tetrahedron  2001,  57:  1765 
    CrossrefSuche in Google Scholar
  • 12a Baldwin JJ, Claremon DA, Tice C, Cacatian S, Dillard LW, Ishchenko AV, Yuan J, Xu Z, McGeehan G, Simpson RD, Singh SB, Zhao W, and Flaherty PT. inventors; WO 2007/070201  A1.  ; Chem. Abstr. 2007, 147, 95545
  • 12b Baldwin JJ, Claremon DA, Tice C, Cacatian S, Dillard LaW, Ishchenko AV, Yuan J, Xu Z, McGeehan G, Zhao W, Simpson RD, Singh SB, Flaherty PT, and Wery J.-P. inventors; WO 2006/042150  A1.  ; Chem. Abstr. 2006, 144, 432692