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Synthesis 2012; 44(16): 2537-2546
DOI: 10.1055/s-0031-1290953
DOI: 10.1055/s-0031-1290953
special topic
Automated Multistep Continuous Flow Synthesis of 2-(1H-Indol-3-yl)thiazole Derivatives
Weitere Informationen
Publikationsverlauf
Received: 01. März 2012
Accepted: 15. März 2012
Publikationsdatum:
25. Mai 2012 (online)
Abstract
The multistep continuous flow assembly of 2-(1H-indol-3-yl)thiazoles using a Syrris AFRICA® synthesis station is reported. Sequential Hantzsch thiazole synthesis, deketalization, and Fischer indole synthesis provides rapid and efficient access to highly functionalized, pharmacologically significant 2-(1H-indol-3-yl)thiazoles. These complex drug-like small molecules are generated in reaction times of less than 15 minutes and in high yields (38–82% over three chemical steps without isolation of intermediates).
Key words
heterocycles - indoles - condensation - tandem reactions - microreactor - microfluidic synthesisSupporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis. Included are NMR spectra for final compounds and the structures of α-bromoketones 5a–l and hydrazines 10a–k.
- Supporting Information
-
References
- 1a Chighine A, Sechi G, Bradley M. Drug Discovery Today 2007; 12: 459
- 1b Huryn DM, Cosford ND. P. Annu. Rep. Med. Chem. 2007; 42: 401
- 2a Baxendale IR, Hayward JJ, Lanners S, Ley SV, Smith CD. Microreactors in Organic Synthesis and Catalysis . Wirth T. Wiley-VCH; Weinheim: 2008
- 2b Ehrfeld W, Hessel V, Lowe H. Microreactors: New Technology for Modern Chemistry. Wiley-VCH; Weinheim: 2000
-
3a Glasnov TN, Kappe CO. J. Heterocycl. Chem. 2011; 48: 11
-
3b Webb D, Jamison TF. Chem. Sci. 2010; 1: 675
- 3c Geyer K, Gustafsson T, Seeberger PH. Synlett 2009; 2382
- 3d Mak XY, Laurino P, Seeberger PH. Beilstein J. Org. Chem. 2009; 5: No. 19
- 3e Weiler A, Junkers M. Pharm. Technol. 2009; S6: S10-S11
- 3f Baxendale IR, Hayward JJ, Ley SV. Comb. Chem. High Throughput Screening 2007; 10: 802
- 3g Watts P. Curr. Opin. Drug Discovery Dev. 2004; 7: 807
- 4 Kang L, Chung BG, Langer R, Khademhosseini A. Drug Discovery Today 2008; 13: 1
- 5 Grant D, Dahl R, Cosford ND. P. J. Org. Chem. 2008; 73: 7219
- 6 Herath A, Dahl R, Cosford ND. P. Org. Lett. 2010; 12: 412
- 7 Herath A, Cosford ND. P. Org. Lett. 2010; 12: 5182
- 8 Pagano N, Herath A, Cosford ND. P. J. Flow Chem. 2011; 1: 28
- 9 Razzaq T, Kappe CO. Chem.–Asian J. 2010; 5: 1274
- 10 Daugan A, Grondin P, Ruault C, Le Monnier de Gouville A.-C, Coste H, Linget J.-M, Kirilovsky J, Hyafil F, Labaudinière R. J. Med. Chem. 2003; 46: 4533
- 11a Moody CJ, Roffey JR. A, Stephens MA, Stratford I. J. Anti-Cancer Drugs 1997; 8: 489
- 11b Mezencev R, Updegrove T, Kutschy P, Repovská M, McDonald JF. J. Nat. Med. 2011; 65: 488
- 12a Moody CJ, Roffey JR. A, Swann E, Lockyer S, Houlbrook S, Stratford I. J. Anti-Cancer Drugs 1999; 10: 577
- 12b Moody CJ, Swann E. J. Med. Chem. 1995; 38: 1039
- 13 Wahab B, Ellames G, Passey S, Watts P. Tetrahedron 2010; 66: 3861
- 14 O’Brien AG, Levesque F, Seeberger PH. Chem. Commun. 2011; 47: 2688
- 15a Zamir LO, Nguyen C. J. Labelled Compd. Radiopharm. 1988; 25: 1189
-
15b Paquette LA, Efremov I. J. Am. Chem. Soc. 2001; 123: 4492
- 16a Vazquez E, Davies IW, Payack JF. J. Org. Chem. 2002; 67: 7551
- 16b For boronic acid reactions, see: Pagano N, Maksimoska J, Bregman H, Williams DS, Webster RD, Xue F, Meggers E. Org. Biomol. Chem. 2007; 5: 1218
- 16c See also: de Koning CB, Michael JP, Rousseau AL. J. Chem. Soc., Perkin Trans. 1 2000; 1705
- 17 Tietze L.-F, Meier H, Voβ E. Synthesis 1988; 274
- 18 Klaver WJ, Hiemstra H, Speckamp WN. J. Am. Chem. Soc. 1989; 111: 2588
For recent selected reviews, see:
For boronic acid synthesis, see: