Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Synthesis of Ketoconazole Derivatives

  • Ryu, Jae-Chun (Department of Chemistry, Kunsan National University) ;
  • Lee, Kwang-Jae (Department of Chemistry, Kunsan National University) ;
  • Lee, Sang-Hee (Department of Chemistry, Kunsan National University)
  • Published : 2003.04.20
Download PDF
⟨ Previous Next ⟩

Abstract

For the drug master file (DMF) of ketoconazole, four impurities (1-4) contained in ketoconazole were synthesized. During the synthesis of 2, a new synthetic method of 1,4-dihydropyrazine was established. To oxidize the aminoalcohol (2j) to the aminal (2j-1), the standard Swern oxidation condition was modified to mask the nucleophilicity of the amino group temporarily using one equivalent of acetic acid. Derivative 3 was synthesized via regioselective bromination at the 2 position of the 4-aminophenol derivative (3a) using $Br_2$ in the presence of p-TsOH. The etherification of aryl bromide with the phenol derivative (1f) was accomplished by a modification of the general Cu-mediated reaction condition using excess 1f itself as a solvent at elevated temperature (190 ℃).

Keywords

References

  1. The Rules Governing Medicinal Products in the European Union,Quality Guidelines European Drug Master File Procedure forActive Substances; 1998; Vol. 3A.
  2. Bendix, D. Polymer Degradation and Stability 1998, 59, 129. https://doi.org/10.1016/S0141-3910(97)00149-3
  3. Heel, R. C.; Brogden, R. N.; Carmine, A.; Morley, P. A.; Speight, T. M.; Avery, G. S. Drugs 1982, 23, 1. https://doi.org/10.2165/00003495-198223010-00001
  4. Vanden Bossche, H.; Willemsens, G.; Cools, W.; Cornelissen, F.;Lauwers, W.; Van Cutsem, J. M. Antimicrob. Agents Chemother.1980, 17, 922. https://doi.org/10.1128/AAC.17.6.922
  5. Kraemer, F. B.; Pont, A. Am. J. Med. 1986, 80, 616. https://doi.org/10.1016/0002-9343(86)90816-8
  6. Ballard, S. A.; Lodola, A.; Tarbit, M. H. Biochem. Pharmacol.1988, 37, 4643. https://doi.org/10.1016/0006-2952(88)90333-4
  7. Shepherd, F. A.; Hoffert, B.; Evans, W. K.; Emery, G.;Trachtenberg, J. Arch. Intern. Med. 1985, 145, 863. https://doi.org/10.1001/archinte.145.5.863
  8. Camps, P.; Farres, X. Tetrahedron; Asymmetry 1995, 6, 1283. https://doi.org/10.1016/0957-4166(95)00161-H
  9. Heeres, J.; Backx, L. J.; Mostmans, J. H.; Van Cutsem, J. J. Med.Chem. 1979, 22, 1003. https://doi.org/10.1021/jm00194a023
  10. Ishii, Y.; Chatani, N.; Kakiuchi, F.; Murai, S. Tetrahedron Letters1997, 38, 7565. https://doi.org/10.1016/S0040-4039(97)01738-3
  11. Kallinayer, H. J.; Petesch, N. Pharm. Acta Helv. 1991, 66, 178.
  12. Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651. https://doi.org/10.1016/0040-4020(78)80197-5
  13. Keirs, D.; Overton, K. J. Chem. Soc., Chem. Commun. 1987,1660.
  14. Aranyos, A.; Oid, D. W.; Kiyomori, A.; Wolfe, J. P.; Sadighi, J. P.;Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 4369. https://doi.org/10.1021/ja990324r
  15. Marcoux, J. F.; Doye, S.; Buchwald, S. J. Am. Chem. Soc. 1997,119, 10539. https://doi.org/10.1021/ja971901j
  16. Sawyer, J. S.; Schmittling, E. A.; Palkowitz, J. A.; Smith, W. J. J.Org. Chem. 1998, 63, 6338. https://doi.org/10.1021/jo980800g

Cited by

  1. Synthesis, reactions, applications, and biological activity of diethanolamine and its derivatives vol.49, pp.7, 2013, https://doi.org/10.1134/S1070428013070014
  2. Synthesis and antimicrobial activity of chalcones containing benzotriazolylmethyl and imidazolylmethyl substituents vol.50, pp.12, 2014, https://doi.org/10.1134/S1070428014120094
  3. Synthesis of Ketoconazole Derivatives. vol.34, pp.36, 2003, https://doi.org/10.1002/chin.200336131
  4. Alkaline Phosphatase Assay Based on the Chromogenic Interaction of Diethanolamine with 4-Aminophenol vol.90, pp.10, 2018, https://doi.org/10.1021/acs.analchem.8b01371
  5. New diphenylphosphane derivatives of ketoconazole are promising antifungal agents vol.9, pp.1, 2003, https://doi.org/10.1038/s41598-019-52525-7