A Versatile Synthesis of 7-Azaindoles

Abstract

1,3-Disubstituted 7-azaindoles were synthesized from 2,6-dichloropyridine using DoM and intramolecular aromatic ­substitution after epoxide opening by an amine. Even the sterically demanding adamantylamine may be incorporated leading to derivatives which are not accessible by alkylation of the parent compound.

azaindoles - pyridines - metalations - nucleophilic aromatic substitutions - ring closure

References

For recent publications see:

<A NAME="RG08305ST-1A">1a</A> Ujjainwalla F. Walsh TF. Tetrahedron Lett.  2001,  42:  6441 

<A NAME="RG08305ST-1B">1b</A> Routier S. Ayerbe N. Mérour J.-Y. Coudert G. Bailly C. Pierré A. Pfeiffer B. Caignard D.-H. Renard P. Tetrahedron  2002,  58:  6621 

<A NAME="RG08305ST-1C">1c</A> Sanderson PEJ. Stanton MG. Dorsey BD. Lyle TA. McDonough C. Sanders WM. Savage KL. Naylor-Olsen AM. Krueger JA. Lewis SD. Lucas BJ. Lynch JJ. Yan Y. Bioorg. Med. Chem. Lett.  2003,  13:  795 

<A NAME="RG08305ST-1D">1d</A> Kuo G.-H. Prouty C. DeAngelis A. Shen L. O’Neill DJ. Shah C. Connolly PJ. Murray WV. Conway BR. Cheung P. Westover L. Xu JZ. Look RA. Demarest KT. Emanuel S. Middleton SA. Jolliffe L. Beavers MP. Chen X. J. Med. Chem.  2003,  46:  4021 

<A NAME="RG08305ST-1E">1e</A> Wang T. Zhang Z. Wallace OB. Deshpande M. Fang H. Yang Z. Zadjura LM. Tweedie DL. Huang S. Zhao F. Ranadive S. Robinson BS. Gong Y.-F. Riccardi K. Spicer TP. Deminie C. Rose R. Wang H.-GH. Blair WS. Shi P.-Y. Lin P.-f. Colonno RJ. Meanwell NA. J. Med. Chem.  2003,  46:  4236 

<A NAME="RG08305ST-1F">1f</A> Hugon B. Pfeiffer B. Renard P. Prudhomme M. Tetrahedron Lett.  2003,  44:  4607 

<A NAME="RG08305ST-1G">1g</A> Larraya C. Guillard J. Renard P. Audinot V. Boutin JA. Delagrange P. Bennejean C. Viaud-Massuard M.-C. Eur. J. Med. Chem.  2004,  515 

<A NAME="RG08305ST-1H">1h</A> Zhang H.-C. Ye H. Conway BR. Derian CK. Addo MF. Kuo G.-H. Hecker LR. Croll DR. Li J. Westover L. Xu JZ. Look R. Demarest KT. Andrade-Gordon P. Damiano BP. Maryanoff BE. Bioorg. Med. Chem. Lett.  2004,  14:  3245 

<A NAME="RG08305ST-1I">1i</A> Oh S.-J. Choe Y.-S. Chi D.-Y. Ryu EK. Saji H. Choe YS. Chi DY. Kim SE. Lee J. Kim B.-T. Bioorg. Med. Chem.  2004,  12:  5505 

<A NAME="RG08305ST-1J">1j</A> Wang S. Wan NC. Harrison J. Miller W. Chuckowree I. Sohal S. Hancox TC. Baker S. Folkes A. Wilson F. Thompson D. Cocks S. Farmer H. Boyce A. Freathy C. Broadbridge J. Scott J. Depledge P. Faint R. Mistry P. Charlton P. J. Med. Chem.  2004,  47:  1339 

<A NAME="RG08305ST-1K">1k</A> Hilmy KMH. Arch. Pharm.  2004,  337:  15 

<A NAME="RG08305ST-2A">2a</A> Desarbre E. Coudret S. Meheust C. Mérour J.-Y. Tetrahedron  1997,  53:  3637 

<A NAME="RG08305ST-2B">2b</A> Park SS. Choi J.-K. Yum EK. Tetrahedron Lett.  1998,  39:  627 

<A NAME="RG08305ST-2C">2c</A> Ujjainwalla F. Warner D. Tetrahedron Lett.  1998,  39:  5355 

<A NAME="RG08305ST-2D">2d</A> Alvarez M. Fernández D. Joule JA. Synthesis  1999,  615 

<A NAME="RG08305ST-2E">2e</A> Chi SM. Choi J.-K. Yum EK. Chi DY. Tetrahedron Lett.  2000,  41:  919 

<A NAME="RG08305ST-2F">2f</A> Allegretti M. Arcadi A. Marinelli F. Nicolini L. Synlett  2001,  609 

<A NAME="RG08305ST-2G">2g</A> Konradin C. Dohle W. Rodriguez AL. Schmid B. Knochel P. Tetrahedron  2003,  59:  1571 

<A NAME="RG08305ST-2H">2h</A> Thibault C. L’Heureux A. Bhide RV. Ruel R. Org. Lett.  2003,  5:  5023 

<A NAME="RG08305ST-2I">2i</A> Hong CS. Seo JY. Yum EK. Sung N.-D. Heterocycles  2004,  63:  631 

<A NAME="RG08305ST-2J">2j</A> L’Heureux A. Thibault C. Ruel R. Tetrahedron Lett.  2004,  45:  2317 

<A NAME="RG08305ST-2K">2k</A> Cottineau B. O’Shea DF. Tetrahedron Lett.  2005,  46:  1935 

<A NAME="RG08305ST-2L">2l</A> Debenham SD. Chan A. Liu K. Price K. Wood HB. Tetrahedron Lett.  2005,  46:  2283 

<A NAME="RG08305ST-3">3</A> For a review see: Mérour J.-Y. Joseph B. Curr. Org. Chem.  2001,  5:  471 

<A NAME="RG08305ST-4">4</A> Tambute A. C. R. Seances Acad. Sci., Ser. C  1974,  278:  1239 

<A NAME="RG08305ST-5A">5a</A> Fleming I. Woolias M. J. Chem. Soc., Perkin Trans. 1  1979,  827 

<A NAME="RG08305ST-5B">5b</A> Fleming I. Woolias M. J. Chem. Soc., Perkin Trans. 1  1979,  829 

<A NAME="RG08305ST-6A">6a</A> Radinov R. Chanev C. Haimova M. J. Org. Chem.  1991,  56:  4793 

For reviews of the DoM technique see:

<A NAME="RG08305ST-6B">6b</A> Snieckus V. Chem. Rev.  1990,  90:  879 

<A NAME="RG08305ST-6C">6c</A> Clayden J. Organolithiums: Selectivity for Synthesis   Pergamon; Oxford: 2002. 

<A NAME="RG08305ST-7">7</A> For a recent report on the deprotonation with lithium magnesates see: Awad H. Mongin F. Trécourt F. Quéguiner G. Marsais F. Tetrahedron Lett.  2004,  45:  7873 

<A NAME="RG08305ST-8">8</A> Mongin F. Quéguiner G. Tetrahedron  2001,  57:  4059 

<A NAME="RG08305ST-9A">9a</A> Güngör T. Marsais F. Quéguiner G. J. Organomet. Chem.  1981,  215:  139 

<A NAME="RG08305ST-9B">9b</A> Mallet M. Branger G. Marsais F. Quéguiner G. J. Organomet. Chem.  1990,  382:  319 

<A NAME="RG08305ST-9C">9c</A> See also: Mallet M. J. Organomet. Chem.  1991,  406:  49 

<A NAME="RG08305ST-10A">10a</A> Mongin F. Tognini A. Cottet F. Schlosser M. Tetrahedron Lett.  1998,  39:  1749 

<A NAME="RG08305ST-10B">10b</A> Schlosser M. Rausis T. Eur. J. Org. Chem.  2004,  1018 

<A NAME="RG08305ST-11">11</A> Rodrigues I. Bonnet-Delpon D. Bégué J.-P. J. Org. Chem.  2001,  66:  2098 

<A NAME="RG08305ST-12A">12a</A> Tietze LF. Beifuss U. Angew. Chem., Int. Ed. Engl.  1993,  32:  131 ; Angew. Chem. 1993, 105, 137

<A NAME="RG08305ST-12B">12b</A> Tietze LF. Chem. Rev.  1996,  96:  115 

<A NAME="RG08305ST-12C">12c</A> Tietze LF. Haunert F. In Stimulating Concepts in Chemistry   Vögtle F. Stoddart JF. Shibasaki M. Wiley-VCH; Weinheim: 2000.  p.39 

<A NAME="RG08305ST-13">13</A> D’Andrea SV. Bonner D. Bronson JJ. Clark J. Denbleyker K. Fung-Tomc J. Hoeft SE. Hudyma TW. Matiskella JD. Miller RF. Misco PF. Pucci M. Sterzycki R. Tsai Y. Ueda Y. Wichtowski JA. Singh J. Kissick TP. North JT. Pullockaran A. Humora M. Boyhan B. Vu T. Fritz A. Heikes J. Fox R. Godfrey JD. Perrone R. Kaplan M. Kronenthal D. Mueller RH. Tetrahedron  2000,  56:  5687