The Reaction of N-Trimethylsilyl-Substituted Heteroarylamines with Esters and Thioesters: An Efficient Protocol To Access Diheteroarylamides

Abstract

The S-benzyl thioester and methyl ester derivatives of a representative 4-pyridinone-based carboxylic acid were sufficiently activated to react efficiently in amide coupling reactions with the amide anion generated in situ from the N-trimethylsilyl derivative of different weakly nucleophilic heteroarylamines. In acetonitrile as solvent, the precipitated diheteroarylamide products were isolated in pure form by vacuum filtration. This simple amide bond forming protocol can be readily adapted to the parallel synthesis of compound libraries.

Key words

amide coupling - diheteroarylamides - N-trimethylsilyl activation - thioesters - esters - parallel synthesis

• References

• 1 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
• 2 Shkreta L, Blanchette M, Toutant J, Wilhelm E, Bell B, Story BA, Balachandran A, Cochrane A, Cheung PK, Harrigan PR, Grierson DS, Chabot B. Nucleic Acids Res. 2017; 45: 4051
• 3a Rivalle C, Wendling F, Tambourin P, Hloste JM, Bisagni E, Cherman JC. J. Med. Chem. 1983; 26: 181
• 3b Miller CM, McCarthy FO. RSC Adv. 2012; 2: 8883
• 3c Stiborová M, Poljaková J, Martinková E, Bořek-Dohalská L, Eckschlager T, Kizek R, Frei E. Interdiscip. Toxicol. 2011; 4: 98
• 3d Martinez R, Chacon-Garcia L. Curr. Med. Chem. 2005; 12: 127
• 4a Montalbetti CA. G. N, Falque V. Tetrahedron 2005; 61: 10827
• 4b El-Faham A, Albericio F. Chem. Rev. 2011; 111: 6557
• 4c Humphrey JM, Chamberlin RA. Chem. Rev. 1997; 97: 2243
• 5a Quelever G, Burlet S, Garino C, Pietrancosta N, Laras Y, Kraus J.-L. J. Comb. Chem. 2004; 6: 695
• 5b Due-Hansen ME, Pandey SK, Christiansen E, Andersen R, Hansena SV. F, Ulven T. Org. Biomol. Chem. 2016; 14: 430
• 6 Zamiri M, Grierson DS. Synthesis 2017; 49: 571
• 7 Dehe D, Munstein I, Reis A, Theil WR. J. Org. Chem. 2011; 76: 1151
• 8a Yang W, Drueckhammer DG. M. J. Am. Chem. Soc. 2001; 123: 11004
• 8b Castro EA. Chem. Rev. 1999; 99: 3505
• 9a Carpino LA, El-Faham A. J. Am. Chem. Soc. 1995; 117: 5401
• 9b El-Fahm A, Abdul-Ghani M. Org. Prep. Proced. Int. 2003; 35: 369
• 9c El-Fahm A, Khatab SN, Abdul-Ghani M. ARKIVOC 2006; (xii): 57
• 10 Kricheldorf HR. Justus Liebigs Ann. Chem. 1971; 745: 81
• 11 Spartan Version 6.1.7 . Wavefunction, Inc; Irvine (CA, USA): 2014
• 12 Mai K, Patil G. J. Org. Chem. 1986; 51: 3545
• 13a Geiger W, Boshagen H, Medenwald H. Chem. Ber. 1969; 102: 1961
• 13b Boshagen H, Geiger W. Chem. Ber. 1976; 109: 659
• 14a Wu Y.-Y, Chen Y, Gou G.-Z, Mu W.-H, Lv X.-J, Du M.-L, Fu W.-F. Org. Lett. 2012; 14: 5226
• 14b Chen X, Wen Z, Xian M, Ramachandran N, Tang X, Schlegel B, Mutus B, Wang PG. J. Org. Chem. 2001; 66: 6064
• 14c Singh B. Tetrahedron Lett. 1971; 321
• 15a Yang K.-W, Cannon JG, Rose JG. Tetrahedron Lett. 1970; 1791
• 15b Ruggeri RB, Heathcock CL. J. Org. Chem. 1987; 52: 5745
• 15c Ooi T, Tayama E, Yamada M, Maruoka K. Synlett 1999; 729
• 16a Tanwar B, Kumar A, Yogeeswari P, Sriram D, Chakraborti AK. Bioorg. Med. Chem. Lett. 2016; 26: 5960
• 16b Kim BR, Lee H.-G, Kang S.-B, Sung GH, Kim J.-J, Park JK, Lee S.-G, Yoon Y.-J. Synthesis 2012; 44: 42
• 17a Kadam S, Kim SS. Green Chem. 2010; 12: 94
• 17b Talami S, Stirling JM. Can. J. Chem. 1999; 77: 1105
• 18a Ross WJ. C. J. Chem. Soc. C 1966; 1816
• 18b Lang R, Wahl A, Skurk T, Yagar EF, Schmiech L, Eggers R, Hauner H, Hofmann T. Anal. Chem. 2010; 82: 1486
• 19a Yi X, Chen J, Xu X, Ma Y. Synth. Commun. 2017; 47: 872
• 19b Ma YM, Hider RC. Tetrahedron Lett. 2010; 51: 5230
• 20a Hasegawa J.-Y, Hamada M, Miyamoto T, Nishide K, Kajimoto T, Uenishi J.-I, Node M. Carbohydr. Res. 2005; 340: 2360
• 20b Node M, Kumar K, Nishide K, Ohsugi S.-I, Miyamoto T. Tetrahedron Lett. 2001; 42: 9207
• 20c Chae J. Arch. Pharmacal Res. 2008; 31: 305
• 20d Matoba M, Kajimoto T, Node M. Synlett 2007; 1930