A Trimethylsilylamine-Acyl Fluoride Amide Bond Forming Protocol for Weakly Nucleophilic Amines that is Amenable to the Parallel Synthesis of Di(hetero)arylamides

Abstract

The reaction of a 2-pyridinone-based acid fluoride with the N–TMS derivatives of different weakly nucleophilic heteroaryl/arylamines in acetonitrile containing catalytic fluoride ion provides a clean, efficient and simple means to access a diverse range of polar di(hetero)arylamide structures. This amide bond forming protocol is readily amenable to the parallel synthesis of compound libraries.

Key words

amide coupling - di(hetero)arylamide - acid fluoride - heteroarylamine - N-TMS activation - parallel synthesis

• References

• 1a Cheung PK, Horhant D, Bandy LE, Zamiri M, Rabea SM, Karagiosov SK, Matloobi M, McArthur S, Harrigan PR, Chabot B, Grierson DS. J. Med. Chem. 2016; 59: 1869
• 1b Grierson DS, Cheung PK, Chabot B, Harrigan PR, Cochrane AW. PCT Int. Appl WO 2015164956, 2015
• 2a Montalbetti CA. G. N, Falque V. Tetrahedron 2005; 61: 10827
• 2b El-Faham A, Albericio F. Chem. Rev. 2011; 111: 6557
• 2c Humphrey JM, Chamberlin RA. Chem. Rev. 1997; 97: 2243
• 3 Quelever G, Burlet S, Garino C, Pietrancosta N, Laras Y, Kraus J-L. J. Comb. Chem. 2004; 6: 695
• 4 Dehe D, Munstein I, Reis A, Theil WR. J. Org. Chem. 2011; 76: 1151
• 5a Lippert III JW. ARKIVOC 2005; (xiv): 87
• 5b Carpino LA, Beyermann M, Wenschuh H, Bienert M. Acc. Chem. Res. 1996; 29: 268
• 5c Carpino LA, Sadat-Aalaee D, Chao HG, DeSelms RH. J. Am. Chem. Soc. 1990; 112: 9651
• 6a Rajeswari S, Jones RJ, Cava MP. Tetrahedron Lett. 1987; 28: 5099
• 6b Wenschuh H, Bayermann M, Winter R, Bienert M, Ionescu D, Carpino LA. Tetrahedron Lett. 1996; 37: 5483
• 6c Kim H-O, Gardner B, Kahn M. Tetrahedron Lett. 1995; 36: 6013
• 6d For a related reaction, see: Sakamoto K, Nakahara Y, Ito Y. Tetrahedron Lett. 2002; 43: 1515
• 7 Wallace EM, Lyssikatos J, Blake JF, Seo J, Yang HW, Yeh TC, Perrier M, Jarski H, Marsh V, Poch G, Livingston MG, Otten J, Hingorami G, Woessner R, Lee P, Winkler J, Koch K. J. Med. Chem. 2006; 49: 441
• 8a Carpino LA, El-Faham A. J. Am. Chem. Soc. 1995; 117: 5401
• 8b El-Fahm A, Abdul-Ghani M. Org. Prep. Proced. Int. 2003; 35: 369
• 9a Joullié MM, Lassen KM. ARKIVOC 2010; (viii): 189
• 9b Carpino LA, Ionescu D, El-Faham A, Beyermann M, Henklein P, Hanay CW. H, Bienert M. Org. Lett. 2003; 5: 975
• 10 Mai K, Patil G. J. Org. Chem. 1986; 51: 3545
• 11 Spartan Version 6.1.7 . Wavefunction Inc; Irvine (CA, USA): 2014
• 12 Sircar JC, Capiris T, Bobovski TP, Schwender CF. J. Org. Chem. 1985; 50: 5723
• 13a Bryce MR, Heaton JN, Taylor PC, Anderson M. J. Chem. Soc., Perkin Trans. 1 1994; 1935
• 13b El-Tamany E-SH, Sowellim SZ, Hamed AA, Radwan AS. Res. Chem. Intermed. 2015; 41: 2675
• 13c El-Tammany E-SH, Hamed AA, Sowellim SZ. A, Radwan AS. Natural Sci. 2012; 4: 1013
• 13d Schmidt U, Schwochau M. Monatsh. Chem. 1967; 98: 1492
• 14 Fuchter MJ, Smith CJ, Tsang MW. S, Boyer A, Saubern S, Ryan JH, Holmes AB. Chem. Commun. 2008; 2152
• 15 Kricheldorf HR. Justus Liebigs Ann. Chem. 1971; 745: 81
• 16a Garcia-Alvarez R, Crochet P, Cadierno V. Green Chem. 2013; 15: 46
• 16b Gernignon N, Al-Zoubi RM, Hall DG. J. Org. Chem. 2012; 77: 8386
• 16c Pattabiraman VR, Bode JW. Nature 2011; 480: 471