Thermal Amination of 2,6-Dihalopyridines
by Sterically Demanding Amines

Andreas Faust; Oliver Wolff; Siegfried R. Waldvogel

doi:10.1055/s-0028-1083268

PAPER

Thermal Amination of 2,6-Dihalopyridines by Sterically Demanding Amines

Andreas Faust^a, Oliver Wolff^b, Siegfried R. Waldvogel*^b
^a Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Münster, Domagkstr. 5, 48149 Münster, Germany
^b Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
Fax: +49(228)739608; e-Mail: waldvogel@uni-bonn.de;

Abstract

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Abstract

When transition-metal-catalyzed transformations fail, the amination reaction of activated bromo- and chloropyridines can be achieved thermally. The auxiliary base 2,2,6,6-tetramethylpiperidine turned out to be the key for the conversion of highly sterically demanding and acid labile amines.

Key words

aminations - nucleophilic aromatic substitutions - steric hindrance - pyridines - tetramethylpiperidine

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References

<A NAME="RC05808SS-1A">1a</A> Klebl B, Baumann M, Hoppe E, Brehmer D, Daub H, Keri G, Varga Z, Marosfalvi J, and Oerfi L. inventors; WO 2006,021,458.

<A NAME="RC05808SS-1B">1b</A> Chung JYL. Cvetovich RJ. Curr. Opin. Drug Discovery Dev. 2006, 9: 792

<A NAME="RC05808SS-2A">2a</A> Babu PA. Narasu ML. Srinivas K. ARKIVOC 2007, (ii): 247

<A NAME="RC05808SS-2B">2b</A> De Clercq E. Naesens L. J. Clin. Virol. 2006, 37: S82

<A NAME="RC05808SS-2C">2c</A> Gassel M. Breitenlechner C. Herrero S. Engh R. Bossemeyer D. Handbook of Experimental Pharmacology Vol. 167: Pinna LA. Cohen PTW. Springer; Heidelberg: 2005. p.85

<A NAME="RC05808SS-3">3</A> Dalton King H. Denhart DJ. Deskus JA. Ditta JL. Epperson JR. Higgins MA. Kung JE. Marcin LR. Sloan CP. Mattson GK. Molski TF. Krause RG. Bertekap RL. Lodge NJ. Mattson RJ. Macor JE. Bioorg. Med. Chem. Lett. 2007, 17: 5647

<A NAME="RC05808SS-4">4</A> Scholz U. Schlummer B. In Science of Synthesis Vol. 31: Ramsden C. Georg Thieme Verlag; Stuttgart: 2007. p.1565

<A NAME="RC05808SS-5A">5a</A> Muci AR. Buchwald SL. Top. Curr. Chem. 2002, 219: 131

<A NAME="RC05808SS-5B">5b</A> Jiang L. Buchwald SL. In Metal-Catalyzed Cross-Coupling Reactions 2nd ed.: de Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004.

<A NAME="RC05808SS-6">6</A> Klapars A. Huang X. Buchwald SL. J. Am. Chem. Soc. 2002, 124: 7421

<A NAME="RC05808SS-7A">7a</A> Kaila N. Green N. Li H. Hu Y. Janz K. Gavrin LK. Thomason J. Tam S. Powell D. Cuozzo J. Hall JP. Telliez J. Hsu S. Nickerson-Nutter C. Wang Q. Lin L. Bioorg. Med. Chem. 2007, 15: 6425

<A NAME="RC05808SS-7B">7b</A> Stoit AR. den Hartog AP. Mons H. van Schaik S. Barkhuijsen N. Stroomer C. Coolen HKAC. Reinders JH. Adolfs TJP. van der Neut M. Keizer H. Kruse CG. Bioorg. Med. Chem. Lett. 2008, 18: 188

<A NAME="RC05808SS-7C">7c</A> Matsumoto K. Minatogawa H. Toda M. Munakata M. Heterocycles 1990, 31: 1217

<A NAME="RC05808SS-7D">7d</A> Laufer SA. Hauser DRJ. Liedtke AJ. Synthesis 2008, 253

<A NAME="RC05808SS-8A">8a</A> Modern Supramolecular Chemistry Diederich F. Stang PJ. Tykwinski RR. Wiley-VCH; Weinheim: 2008.

<A NAME="RC05808SS-8B">8b</A> Steed JW. Atwood JL. Supramolecular Chemistry Wiley; Chichester: 2000.

<A NAME="RC05808SS-9A">9a</A> Siering C. Kerschbaumer H. Nieger M. Waldvogel SR. Org. Lett. 2006, 8: 1471

<A NAME="RC05808SS-9B">9b</A> Schopohl MC. Siering C. Kataeva O. Waldvogel SR. Angew. Chem. Int. Ed. 2003, 42: 2620

<A NAME="RC05808SS-9C">9c</A> Waldvogel SR. Fröhlich R. Schalley CA. Angew. Chem. Int. Ed. 2000, 39: 2472

<A NAME="RC05808SS-10A">10a</A> Schade W. Bohling C. Hohmann K. Bauer C. Orghici R. Waldvogel SR. Scheel D. Photonik Int. 2007, 1: 32

<A NAME="RC05808SS-10B">10b</A> Orghici R. Willer U. Gierszewska M. Waldvogel SR. Schade W. Appl. Phys. B 2008, 90: 355

<A NAME="RC05808SS-11">11</A> Bomkamp M. Siering C. Landrock K. Stephan H. Fröhlich R. Waldvogel SR. Chem. Eur. J. 2007, 13: 3724

<A NAME="RC05808SS-12">12</A> Katritzki AR. Pozharskii AF. Handbook of Heterocyclic Chemistry Pergamon; London: 2003. p.178

<A NAME="RC05808SS-13">13</A> Schopohl MC. Mirk D. Faust A. Fröhlich R. Kataeva O. Waldvogel SR. Eur. J. Org. Chem. 2005, 2987

<A NAME="RC05808SS-14">14</A> Faust A. Ph.D. Thesis University Münster; Germany: 2003.

Compounds 4 and 5 were identified by GC/MS and ^¹H NMR spectroscopy.

<A NAME="RC05808SS-16">16</A> Kampmann D. Stuhlmüller G. Simon R. Cottet F. Leroux F. Schlosser M. Synthesis 2005, 1028

<A NAME="RC05808SS-17">17</A> Bacqué E. El Qacemi M. Zard SZ. Org. Lett. 2004, 6: 3671

<A NAME="RC05808SS-18">18</A> Maurin JK. Lasek W. Gorska A. Switaj T. Jakubowska AB. Kazimierczuk Z. Chem. Biodiversity 2004, 1: 1498

<A NAME="RC05808SS-19">19</A> Kazimierczuk Z, Lasek W, and Sikorska A. inventors; WO 2001,074,778.