A Convenient Synthesis of 1-Aryl- and 2-Aryl-Substituted Indazolones via Intramolecular C–N Coupling Promoted by KOt-Bu

Abstract

A new method for the synthesis of 1-arylindazolones and 2-arylindazolones from N′-aryl-2-halobenzohydrazides promoted by KOt-Bu was developed. The difference of 2-halogen substituent exerted a significant effect on the distribution of the products. Two distinct reaction pathways are proposed for the generation of 1-arylindazolones and 2-arylindazolones, respectively.

Key words

indazolone - C–N coupling - potassium tert-butoxide - radical reaction - 2-halobenzohydrazide

• References

• 1 For a review, see: Bräse S, Gil C, Knepper K. Bioorg. Med. Chem. 2002; 10: 2415
• 2a Hall IH, Wong OT, Hall ES, Chen LK. Anti-Cancer Drugs 1993; 4: 389
• 2b Das S, Chaudhari SS, Thomas A, Pardeshi SR, Deshmukh VG, Wadekar PD, Khairatkar-Joshi N, Shah DM, Bajpai M. WO 2015087234, 2015
• 3 Magano J, Waldo M, Greene D, Nord E. Org. Process Res. Dev. 2008; 12: 877
• 4a Gibbs AC, Abad MC, Zhang XQ, Tounge BA, Lewandowski FA, Struble GT, Sun WM, Sui ZH, Kuo LC. J. Med. Chem. 2010; 53: 7979
• 4b Zhang XQ, Song FB, Kuo G.-H, Xiang A, Gibbs AC, Abad MC, Sun WM, Kuo LC, Sui ZH. Bioorg. Med. Chem. Lett. 2011; 21: 4762
• 5 Leis J, Carter C. US 20140179637, 2014
• 6 Vega MC, Rolón M, Montero-Torres A, Fonseca-Berzal C, Escario JA, Gómez-Barrio A, Gálvez J, Marrero-Ponce Y, Arán VJ. Eur. J. Med. Chem. 2012; 58: 214
• 7 Schelkun RM, Yuen P.-W. WO 2006056873, 2006
• 8 Bodmer-Narkevitch V, Anthony NJ, Cofre V, Jollya SM, Murphy KL, Ransom RW, Reiss DR, Tang C, Prueksaritanont T, Pettibone DJ, Bock MG, Kuduk SD. Bioorg. Med. Chem. Lett. 2010; 20: 7011
• 9 Selwood DL, Brummell DG, Budworth J, Burtin GE, Campbell RO, Chana SS, Charles IG, Fernandez PA, Glen RC, Goggin MC, Hobbs AJ, Kling MR, Liu Q, Madge DJ, Meillerais S, Powell KL, Reynolds K, Spacey GD, Stables JN, Tatlock MA, Wheeler KA, Wishart G, Woo C.-K. J. Med. Chem. 2001; 44: 78
• 10a Bruneau P, Delvare C. J. Med. Chem. 1991; 34: 1028
• 10b Tachibana S, Fukano A, Sudo K, Tanaka M. J. Chromatogr. B: Biomed. Sci. Appl. 1999; 734: 39
• 10c Dees EC, Whitfield LR, Grove WR, Rummel S, Grochow LB, Donehower RC. Clin. Cancer Res. 2000; 6: 3885
• 10d Zoja C, Corna D, Benedetti G, Morigi M, Donadelli R, Guglielmotti A, Pinza M, Bertani T, Remuzzi G. Kidney Int. 1998; 53: 726
• 11a Runti C, Baiocchi L. Int. J. Tissue React. 1985; 7: 175
• 11b Guglielmotti A, Capezzone de Joannon A, Cazzolla N, Marchetti M, Soldo L, Cavallo G, Pinza M. Pharmacol. Res. 1995; 32: 369
• 11c Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, McDonald DM. Am. J. Pathol. 2004; 165: 35
• 11d Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Morrison MJ, Pallares G, Patel HK, Pritchard S, Wodicka LM, Zarrinkar PP. Nat. Biotechnol. 2008; 26: 127

For synthetic methods for indazolone and its derivatives, see:
• 12a Bird CW, Chng JC. W, Rama NH, Saeed A. Synth. Commun. 1991; 21: 545
• 12b Song JJ, Yee NK. Org. Lett. 2000; 2: 519
• 12c Stadlbauer W In Science of Synthesis . Vol 12. Neier R. Thieme; Stuttgart: 2002: 227
• 12d Viña D, Olmo ED, López-Pérez JL, Feliciano AS. Org. Lett. 2007; 9: 525
• 12e Gaikwad DD, Chapolikar AD, Devkate CG, Warad KD, Tayade AP, Pawar RP, Domb AJ. Eur. J. Med. Chem. 2015; 90: 707
• 13a Tanimori S, Ozaki Y, Iesaki Y, Kirihata M. Synlett 2008; 1973
• 13b Tanimori S, Kobayashi Y, Iesaki Y, Ozaki Y, Kirihata M. Org. Biomol. Chem. 2012; 10: 1381
• 14 Xiong XD, Jiang YW, Ma DW. Org. Lett. 2012; 14: 2552
• 15 Wang WJ, Zhang T, Duan LJ, Zhang XJ, Yan M. Tetrahedron 2015; 71: 9073

For examples of the formation of arynes, see:
• 16a Cano R, Ramón DJ, Yus M. J. Org. Chem. 2011; 76: 654
• 16b Shi L, Wang M, Fan CA, Zhang FM, Tu YQ. Org. Lett. 2003; 5: 3515