Efficient Preparation of Imidazo[1,5-a]pyridine-1-carboxylic Acids

Abstract

We report a novel and efficient approach to the synthesis of imidazo[1,5-a]pyridine-1-carboxylic acids. By using the reaction of 2-(aminomethyl)pyridine with acyl chlorides followed by one-pot treatment with trifluoroacetic anhydride, 2,2,2-trifluoro-1-imidazo[1,5-a]pyridin-1-ylethanones were obtained, which were then converted into imidazo[1,5-a]pyridine-1-carboxylic acids in high preparative yields through haloform cleavage.

Key words

amides - cyclization - heterocycles - bicyclic compounds - acylation­

• References

• 1 Gueiffier A, Lhassani M, Elhakmaoui A, Snoeck R, Andrei G, Chavignon O, Teulade J.-C, Kerbal A, Essassi EM, Debouzy J.-C, Witvrouw M, Blache Y, Balzarini J, De Clercq E, Chapet J.-P. J. Med. Chem. 1996; 39: 2856
• 2 Kaminski JJ, Bristol JA, Lovey RG, Puchalsky C, Lovey RG, Elliot AJ, Guzik H, Solomon DM, Conn DJ, Domalski MS. J. Med. Chem. 1985; 28: 876
• 3 Lober S, Hubner H, Gmeiner P. Bioorg. Med. Chem. Lett. 1999; 9: 97
• 4 Trotter BW, Nanda KK, Burgey CS, Potteiger CM, Deng JZ, Green AI, Hartnett JC, Kett NR, Wu Z, Henze DA, Penna KD, Desai R, Leitl MD, Lemaire W, White RB, Yeh S, Urban MO, Kane SA, Hartman GD, Bilodeau MT. Bioorg. Med. Chem. Lett. 2011; 21: 2354
• 5 Ford NF, Browne LJ, Campell T, Gemenden C, Goldstein R, Gude C, Waley JW. F. J. Med. Chem. 1985; 28: 164
• 6a Browne LJ, Gude C, Rodriguez H, Steele RE, Bhatnager A. J. Med. Chem. 1991; 2: 725
• 6b Pettit GR, Collins JC, Knight JC, Herald DL, Nieman RA, Williams MD, Pettit RK. J. Nat. Prod. 2003; 66: 544
• 6c Mohamed M, Goncalves TP, Whitby RJ, Sneddon HF, Harrowven DC. Chem. Eur. J. 2011; 17: 13698
• 6d Knueppel D, Martin SF. Angew. Chem. Int. Ed. 2009; 48: 2569
• 6e Markey MD, Kelly TR. J. Org. Chem. 2008; 73: 7441
• 7a Kamal A, Ramakrishna G, Raju P, Subba Rhao AV, Viswanath A, Lakshma Nayak V, Ramakrishna S. Eur. J. Med. Chem. 2011; 46: 2427
• 7b Kamal A, Ramakrishna G, Ramaiah MJ, Viswanath A, Rao AV. S, Bagul C, Mukhopadyay D, Pushpavalli SN. C. V. L, Pal-Bhadra M. Med. Chem. Commun. 2013; 4: 697
• 7c Kamal A, Rao AV. S, Nayak VL, Reddy NV. S, Swapna K, Ramakrishna G, Alvala M. Org. Biomol. Chem. 2014; 12: 9864
• 7d Nirogi R, Mohammed AR, Shinde AK, Bogaraju N, Gagginapalli SR, Ravella SR, Kota L, Bhyrapuneni G, Muddana NR, Benade V, Palacharla RC, Jayarajan P, Subramanian R, Goyal VK. Eur. J. Med. Chem. 2015; 103: 289
• 8a Markey MD, Kelly TR. J. Org. Chem. 2008; 73: 7441
• 8b Wallach O. Justus Liebigs Ann. Chem. 1877; 184: 1
• 8c Bower JD, Ramage CR. J. Chem. Soc. 1955; 2834
• 9 Kim D, Wang L, Hale JJ, Lynch CL, Budhu RJ, MacCoss M, Mills SG, Malkowitz L, Gould SL, DeMartino JA, Springer MS, Hazuda D, Miller M, Kessler J, Hrin RC, Carver G, Carella A, Henry K, Lineberger J, Schleif WA, Emini EA. Bioorg. Med. Chem. Lett. 2005; 15: 2129
• 10 Kovtun YuP, Prostova YA. Chem. Heterocycl. Comp. 2000; 36: 557
• 11 Fos E, Bosca F, Mauleon D, Carganico G. J. Heterocycl. Chem. 1993; 30: 473
• 12 Ashauer U, Wolff C, Haller R. Arch. Pharm. 1986; 1: 43
• 13 Crawforth JM, Paoletti M. Tetrahedron Lett. 2009; 50: 4916
• 14 Pelletier G, Charette AB. Org. Lett. 2013; 9: 2290
• 15 Schreber SL. Tetrahedron Lett. 1980; 1027
• 16 Meyers AI, Marra JM. Tetrahedron Lett. 1985; 48: 5863
• 17 Khodakovskiy PV, Volochnyuk DM, Panov DM, Pervak II, Zarudnitskii EV, Shishkin OV, Yurchenko AA, Shivanyuk A, Tolmachev AA. Synthesis 2008; 948
• 18a Arvapalli VS, Chen G, Kosarev S, Tan ME, Xie D, Yet L. Tetrahedron Lett. 2010; 51: 284
• 18b Hickey DM. B, Moody CJ, Rees CW, Williams DJ. J. Chem. Soc., Chem. Commun. 1982; 4
• 19 Bermudez J, Fake CS, Joiner GF, Joiner KA, King FD, Miner WD, Sanger GJ. J. Med. Chem. 1990; 33: 1924