Synthesis, Table of Contents Synthesis 2023; 55(16): 2543-2546DOI: 10.1055/a-2044-9772 paper Special Issue Honoring Prof. Guoqiang Lin’s Contributions to Organic Chemistry Hectogram-Scale Synthesis of Indobufen from Diludine-Triggered Metal-Free Cascade Authors Author Affiliations Yueting Hua a Shenyang Pharmaceutical University, Shenyang 110016, P. R. of China Bingxin Liu a Shenyang Pharmaceutical University, Shenyang 110016, P. R. of China Jiaxuan Cai a Shenyang Pharmaceutical University, Shenyang 110016, P. R. of China Tao Wang b Shanghai High Standard Pharm & Med Co., Ltd, Shanghai 200120, P. R. of China Maosheng Cheng∗ a Shenyang Pharmaceutical University, Shenyang 110016, P. R. of China Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract In this study, indobufen was successfully synthesized from diludine-triggered metal-free cascade in good yield. This process includes esterification, reduction, reductive amination/condensation cascade, hydrolysis, and recrystallization. Additionally, the post-treatment procedure was greatly simplified, and indobufen can be obtained by simple recrystallization that complies with the pharmacopoeia standards. Moreover, this work will be used as a basis for further research into the efficient production of indobufen on an industrial scale. Key words Key wordsindobufen - anticoagulant - diludine - isoindolinone - hectogram-scale Full Text References References 1 Current address: Minhang, Shanghai, China. 2a Valencia E, Freyer AJ, Shamma M, Fajardo V. Tetrahedron Lett. 1984; 25: 599 2b Desai SJ, Chaturvedi R, Mulchandani NB. J. Nat. Prod. 1990; 53: 496 2c Speck K, Magauer T. J. Org. Chem. 2013; 9: 2048 3a Xu X, Guzman FS, Gloer JB. J. Org. Chem. 1992; 57: 6700 3b Egbertson MS, Hartman GD, Gould RJ, Bednar B, Bednar RA, Cook JJ, Gaul SL, Holahan MA, Libby LA, Lynch JJ. Jr, Lynch RJ, Sitko GR, Stranieri MT, Vassallo LM. Bioorg. Med. Chem. Lett. 1996; 6: 2519 3c Boger DL, Lee JK, Goldberg J, Jin Q. J. Org. Chem. 2000; 65: 1467 3d Wehlan H, Jezek E, Lebrasseur N, Pavé G, Roulland E, White AJ. P, Burrows JN, Barrett AG. M. J. Org. Chem. 2006; 71: 8151 3e Lee S, Shinji C, Ogura K, Shimizu M, Maeda S, Sato M, Yoshida M, Hashimoto Y, Miyachi H. Bioorg. Med. Chem. Lett. 2007; 17: 4895 3f Lee JH, Byeon SR, Kim Y, Lim SJ, Oh SJ, Moon DH, Yoo KH, Chung BY, Kim DJ. Bioorg. Med. Chem. Lett. 2008; 18: 5701 4a Norman MH, Minick DJ, Rigdon GC. J. Med. Chem. 1996; 39: 149 4b Lawrence NJ, Liddle J, Bushell S, Jackson DA. J. Org. Chem. 2002; 67: 457 4c Park JS, Moon SC, Baik KU, Cho JY, Yoo ES, Byun YS, Park MH. Arch. Pharm. Res. 2002; 125: 137 4d Libbers T, Angehrn P, Gminder H, Herzig S. Bioorg. Med. Chem. Lett. 2007; 17: 4708 4e Uno M, Ban HS, Nakamura H. Bioorg. Med. Chem. Lett. 2009; 19: 3166 4f Ghosh U, Bhattacharyya R, Keche A. Tetrahedron 2010; 66: 2148 5 Grigg R, Dorrity MJ. R, Malone JF, Mongkolaussavaratana T, Norbert WD. J. A, Sridharan V. Tetrahedron Lett. 1990; 31: 3075 6a Enders D, Braig V, Raabe G. Can. J. Chem. 2001; 79: 1528 6b Adachi S, Onozuka M, Yoshida Y, Ide M, Saikawa Y, Nakata M. Org. Lett. 2014; 16: 358 7a Comins DL, Schilling S, Zhang Y. Org. Lett. 2005; 7: 95 7b Pérard J, Prangé T, Tomas A, Royer J. Tetrahedron 2002; 58: 5103 8 McAlonan H, Murphy JP, Nieuwenhuyzen M, Reynolds K, Sarma PK. S, Stevenson PJ, Thompson N. J. Chem. Soc., Perkin Trans. 1 2002; 69 9 Zhao J, Wang Y, Qin L. Guangdong Chem. Ind. 2018; 45: 12 10 Tian Y, Wei J, Wang M, Li G, Xu F. Tetrahedron Lett. 2018; 59: 1866 11 Achmatowicz O, Malinowska I, Szechner B. Tetrahedron 1997; 53: 7917 12 Nakae T, Kato M, Fujita T, Kawabata K, Ohno H. US Patent 5795890, 1998 13 Deng H, Zhou Q, Wu J. Angew. Chem. Int. Ed. 2018; 57: 12661 Supplementary Material Supplementary Material Supporting Information (PDF)
