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Synlett 2020; 31(13): 1308-1312
DOI: 10.1055/s-0040-1707853
DOI: 10.1055/s-0040-1707853
letter
Synthesis of 5- and 6-Azaindoles by Sequential Site-Selective Palladium-Catalyzed C–C and C–N Coupling Reactions
This work has been supported by the RoHan Project funded by the German Academic Exchange Service (DAAD, No. 57315854) and the Federal Ministry for Economic Cooperation and Development (BMZ) inside the framework ‘SDG Bilateral Graduate school programme.’Weitere Informationen
Publikationsverlauf
Received: 15. April 2020
Accepted after revision: 12. Mai 2020
Publikationsdatum:
03. Juni 2020 (online)
![](https://www.thieme-connect.de/media/synlett/202013/lookinside/thumbnails/st-2020-d0214-l_10-1055_s-0040-1707853-1.jpg)
Abstract
Two-step sequential procedures for the Pd-catalyzed synthesis of 5- and 6-azaindoles are reported. The reactions proceed in very good yields. 6-Azaindoles are formed through site-selective Pd-catalyzed Sonogashira reaction of 3,4-dibromopyridine with alkynes, followed by a Pd-catalyzed tandem C–N coupling and cyclization with amines. On the other hand, 5-azaindoles are obtained by a site-selective Pd-catalyzed C–N coupling reaction of 3,4-dibromopyridine with amines, followed by C–C coupling and cyclization with alkynes.
Key words
fused heterocycles - C–N coupling - azaindoles - palladium catalysis - Sonogashira reaction - Buchwald–Hartwig reactionSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707853.
- Supporting Information
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References and Notes
- 1a Prudhomme M. Eur. J. Med. Chem. 2003; 38: 123
- 1b Walker SR, Carter EJ, Huff BC, Morris JC. Chem. Rev. 2009; 109: 3080
- 1c Blaazer AR, Lange JH. M, van der Neut MA. W, Mulder A, den Boon FS, Werkman TR, Kruse CG, Wadman WJ. Eur. J. Med. Chem. 2011; 46: 5086
- 1d 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, Everett 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
- 1e Lee H.-Y, Pan S.-L, Su M.-C, Liu Y.-M, Kuo C.-C, Chang Y.-T, Wu J.-S, Nien C.-Y, Mehndiratta S, Chang C.-Y, Wu S.-Y, Lai M.-J, Chang J.-Y, Liou J.-P. J. Med. Chem. 2013; 56: 8008
- 1f Mérour J.-Y, Buron F, Plé K, Bonnet P, Routier S. Molecules 2014; 19: 19935
- 2a Popowycz F, Routier S, Joseph B, Mérour J.-Y. Tetrahedron 2007; 63: 1031
- 2b Mérour J.-Y, Routier S, Suzenet F, Joseph B. Tetrahedron 2013; 69: 4767
- 3a Giblin GM. P, Billinton A, Briggs M, Brown AJ, Chessell IP, Clayton NM, Eatherton AJ, Goldsmith P, Haslam C, Johnson MR, Mitchell WL, Naylor A, Perboni A, Slingsby BP, Wilson AW. J. Med. Chem. 2009; 52: 5785
- 3b Khoje DA, Charnock C, Wan B, Franzblay S, Gundersen L.-L. Bioorg. Med. Chem. 2011; 19: 3483
- 4 Ganser C, Lauermann E, Maderer A, Stauder T, Kramb J.-P, Plutizki S, Kindler T, Moehler M, Dannhardt G. J. Med. Chem. 2012; 55: 9531
- 5 Meanwell NA, Krystal MR, Nowicka-Sans B, Langley DR, Conlon DA, Eastgate MD, Grasela DM, Timmins P, Wang T, Kadow JF. J. Med. Chem. 2018; 61: 62
- 6a Zhao S.-B, Wang S. Chem. Soc. Rev. 2010; 39: 3142
- 6b Song JJ, Reeves JT, Gallou F, Tan Z, Yee NK, Senanayake CH. Chem. Soc. Rev. 2007; 36: 1120
- 7 Twine SM, Murphy L, Phillips RS, Callis P, Cash MT, Szabo AG. J. Phys. Chem. B 2003; 107: 637
- 8 Jeanty M, Blu J, Suzenet F, Guillaumet G. Org. Lett. 2009; 11: 5142
- 9 Zhang Z, Yang Z, Meanwell NA, Kadow JF, Wang T. J. Org. Chem. 2002; 67: 2345
- 10 Robinson MM, Robison BL. J. Am. Chem. Soc. 1955; 77: 457
- 11 Ryan RP, Hamby RA, Wu Y.-H. J. Org. Chem. 1975; 40: 724
- 12 Buchan R, Fraser M, Shand C. J. Org. Chem. 1977; 42: 2448
- 13 Fresneda PM, Molina P, Delgado S, Bleda JA. Tetrahedron Lett. 2000; 41: 4777
- 14 Larock RC, Yum EK. J. Am. Chem. Soc. 1991; 113: 6689
- 15a Jensen T, Pedersen H, Bang-Andersen B, Madsen R, Jørgensen M. Angew. Chem. Int. Ed. 2008; 47: 888
- 15b Pires MJ. D, Poeira DL, Purificação SI, Marques MM. B. Org. Lett. 2016; 18: 3250
- 16a Whelligan DK, Thomson DW, Taylor D, Hoelder S. J. Org. Chem. 2010; 75: 11
- 16b Fang Y.-Q, Yuen J, Lautens M. J. Org. Chem. 2007; 72: 5152
- 17 Willis MC, Brace GN, Holmes IP. Angew. Chem. Int. Ed. 2005; 44: 403
- 18 Cacchi S, Fabrizi G, Parisi LM. J. Comb. Chem. 2005; 7: 510
- 19 Li X, Yin W, Sarma PV. V. S, Zhou H, Ma J, Cook JM. Tetrahedron Lett. 2004; 45: 8569
- 20 Purificação SI, Pires MJ. D, Rippel R, Santos AS, Marques MM. B. Org. Lett. 2017; 19: 5118
- 21 Venkateshwarlu R, Singh SN, Siddaiah V, Ramamohan H, Dandela R, Pal M. Tetrahedron Lett. 2019; 60: 151326
- 22 Pham NN, Dang TT, Ngo TN, Ehlers P, Langer P. Org. Biomol. Chem. 2015; 13: 6047
- 23 Ngo TN, Ehlers P, Dang TT, Villinger A, Langer P. Org. Biomol. Chem. 2015; 13: 3321
- 24 1,2-Diphenyl-1H-pyrrolo[2,3-c]pyridine (5a); Typical Procedure 3-Bromo-2-(phenylethynyl)pyridine (77.4 mg; 0.3 mmol; 1 equiv), aniline (30.69 mg, 0.33 mmol, 1.1 equiv), Pd(OAc)2 (6.7 mg, 0.03 mmol, 0.1 equiv), Xantphos (17.6 mg, 0.03 mmol, 0.1 equiv), and Cs2CO3 (293.22 mg, 0.9 mmol, 3 equiv) were added to a dried pressure tube equipped with a septum. Dried and degassed DMF (4 mL) was then added under argon. The tube was backfilled with argon three times, and the septum was replaced by a Teflon cap. The mixture was stirred at 120 °C for 24 h, then cooled to r.t. and filtered through a pad of Celite. The filtrate was dried under reduced pressure, and residue was purified by flash chromatography (silica gel, EtOAc) to give a white solid; yield: 54.33 mg (67%). 1H NMR (300 MHz, CDCl3): δ = 8.62 (s, 1 H), 8.29 (d, J = 5.5 Hz, 1 H), 7.54 (dd, J = 5.5, 1.1 Hz, 1 H), 7.46–7.33 (m, 3 H), 7.26 (s, 6 H), 7.24–7.22 (m, 2 H), 6.76 (d, J = 0.8). 13C NMR (75 MHz, CDCl3): δ = 143.99, 139.82, 133.92, 132.92, 131.37, 129.46, 129.16, 128.29, 128.21, 127.85, 127.70, 114.61, 102.63. GC/MS (EI, 70 eV): m/z (%) = 270 (100), 135 (25), 77 (27), 51 (25).
- 25a Wagaw S, Rennels RA, Buchwald SL. J. Am. Chem. Soc. 1997; 119: 8451
- 25b Louie J, Driver MS, Hamann BC, Hartwig JF. J. Org. Chem. 1997; 62: 1268
- 25c Green RA, Hartwig JF. Org. Lett. 2014; 16: 4388
- 26 Elangovan A, Wang Y.-H, Ho T.-I. Org. Lett. 2003; 5: 1841