Palladium-Catalyzed Cross-Coupling between 7-Azaindoles and Reformatsky Reagents

Nadja M. Barl; Vladimir Malakhov; Christian Mathes; Philipp Lustenberger; Paul Knochel

doi:10.1055/s-0034-1379459

Synthesis, Table of Contents

Synthesis 2015; 47(05): 692-700
DOI: 10.1055/s-0034-1379459

paper

Palladium-Catalyzed Cross-Coupling between 7-Azaindoles and Reformatsky Reagents

Nadja M. Barl

^aDepartment Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5–13, Haus F, 81377 München, Germany Fax: +49(89)218077680 Email: Paul.Knochel@cup.uni-muenchen.de

,

Vladimir Malakhov

^aDepartment Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5–13, Haus F, 81377 München, Germany Fax: +49(89)218077680 Email: Paul.Knochel@cup.uni-muenchen.de

,

Christian Mathes

^bNovartis Pharma AG, Forum 1, Novartis Campus, 4056 Basel, Switzerland

,

Philipp Lustenberger

^bNovartis Pharma AG, Forum 1, Novartis Campus, 4056 Basel, Switzerland

,

Paul Knochel*

^aDepartment Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5–13, Haus F, 81377 München, Germany Fax: +49(89)218077680 Email: Paul.Knochel@cup.uni-muenchen.de

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Abstract

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Abstract

The preparation of various 2-(7-azaindolyl)carboxylic esters by Pd-catalyzed coupling of Reformatsky reagents with TBDMS-protected 3-bromo-7-azaindoles leading to a wide range of arylated ester derivatives is reported. After removal of the protecting group, the corresponding free 2-(7-azaindolyl)carboxylic esters are obtained in satisfactory yields.

Key words

azaindole - Reformatsky reagents - metalation - palladium - cross-coupling

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References

References

1a Mérour J.-Y, Joseph B. Curr. Org. Chem. 2001; 5: 471
1b Echalier A, Bettayeb K, Ferandin Y, Lozach O, Clément M, Valette A, Liger F, Marquet B, Morris JC, Endicott JA, Joseph B, Meijer L. J. Med. Chem. 2008; 51: 737
1c Power DP, Lozach O, Meijer L, Grayson DH, Connon S. Bioorg. Med. Chem. Lett. 2010; 20: 4940

For reviews, see:

2a Popowycz F, Routier S, Joseph B, Mérour J.-Y. Tetrahedron 2007; 63: 1031
2b Song JJ, Reeves JT, Gallou F, Tan Z, Yee NK, Senanayake CH. Chem. Soc. Rev. 2007; 36: 1120
2c Wang Z, Wang X. Prog. Chem. 2012; 24: 1974
2d Mérour J.-Y, Routier S, Suzenet F, Joseph B. Tetrahedron 2013; 69: 4767

3 Sandham DA, Arnold N, Aschauer H, Bala K, Barker L, Brown L, Brown Z, Budd D, Cox B, Docx C, Dubois G, Duggan N, England K, Everatt B, Furegati M, Hall E, Kalthoff F, King A, Leblanc CJ, Manini J, Meingassner J, Profit R, Schmidt A, Simmons J, Sohal B, Stringer R, Thomas M, Turner KL, Walker C, Watson SJ, Westwick J, Willis J, Williams G, Wilson C. Bioorg. Med. Chem. 2013; 21: 6582
4 Blake J. (Array BioPharma Inc.) Patent PCT Int. Appl. WO 2009089352, 2009
5 Mortimore M (Vertex Pharmaceuticals Inc.) Patent PCT Int. Appl. WO2008079346, 2008
6 Henry JR, Rupert KC, Dodd JH, Turchi IJ, Wadsworth SA, Cavender DE, Fahmy B, Olini GC, Davis JE, Pellegrino-Gensey JL, Schäfer PH, Siekierka JJ. J. Med. Chem. 1998; 41: 4196

7a Metzger A, Bernhardt S, Manolikakes G, Knochel P. Angew. Chem. Int. Ed. 2010; 49: 4665
7b Bernhardt S, Metzger A, Knochel P. Synthesis 2010; 3802
7c Knochel P, Bernhardt S, Metzger A. Patent PCT Int. Appl. WO 2011113925, 2011

8a Mosrin M, Knochel P. Org. Lett. 2009; 11: 1837
8b Mosrin M, Bresser T, Knochel P. Org. Lett. 2009; 11: 3406
8c Unsinn A, Knochel P. Chem. Commun. 2012; 48: 2680
8d Klier L, Bresser T, Nigst TA, Karaghiosoff K, Knochel P. J. Am. Chem. Soc. 2012; 134: 13584

9 Duez S, Bernhardt S, Heppeausen J, Fleming FF, Knochel P. Org. Lett. 2011; 13: 1690

10a Reformatsky S. Ber. Dtsch. Chem. Ges. 1887; 20: 1210
10b For a recent review, see: Orsini F, Sello G. Curr. Org. Synth. 2004; 1: 111

11 Salituro F (Vertex Pharmaceuticals Inc.) Patent PCT Int. Appl. WO 2005095400, 2005
12 Kaila N (Wyeth, LLC) US Pat. Appl. Publ US 20110105509, 2011

13a Niwa T, Yorimitsu H, Oshima K. Angew. Chem. Int. Ed. 2007; 46: 2643
13b Niwa T, Yorimitsu H, Oshima K. Org. Lett. 2007; 9: 2373

14 Milne JE, Buchwald SL. J. Am. Chem. Soc. 2004; 126: 13028
15 Spectral data are in full accordance to those reported in the literature, see: Alvarez M, Fernández D, Joule JA. Synthesis 1999; 615