Optically active antifungal azoles. IX. An alternative synthetic route for 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol- 1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)1,2,4- triazolone and its analogs

Chemical and Pharmaceutical Bulletin

Volumn 47, Issue 3, 1999, Pages 360-368

  Kitazaki, Tomoyuki ^a   Tasaka, Akihiro ^a   Hosono, Hiroshi ^a   Matsushita, Yoshihiro ^a   Itoh, Katsumi ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

Antifungal azole; Chiral synthesis; Imidazolidinone; Imidazolone; TAK 187; Triazolone

Indexed keywords

1 [2 (2 FLUOROPHENYL) 2 HYDROXY 1 METHYL 3 (1H 1,2,4 TRIAZOL 1 YL)PROPYL] 3 [4 (2,2,3,3 TETRAFLUOROPROPOXY)PHENYL] 2 IMIDAZOLIDINONE; 1 [2 (2,4 DIFLUOROPHENYL) 2 HYDROXY 1 METHYL 3 (1H 1,2,4 TRIAZOL 1 YL)PROPYL] 3 [4 (2,2,3,3 TETRAFLUOROPROPOXY)PHENYL] 2(1H,3H) IMIDAZOLONE; 2 [2 (2,4 DIFLUOROPHENYL) 2 HYDROXY 1 METHYL 3 (1H 1,2,4 TRIAZOL 1 YL)PROPYL] 4 [4 (2,2,3,3 TETRAFLUOROPROPOXY)PHENYL] 1,2,4 TRIAZOL 3(2H) ONE; 2 [2 (2,4 DIFLUOROPHENYL) 2 HYDROXY 1 METHYL 3 (1H 1,2,4 TRIAZOL 1 YL)PROPYL] 4 [4 (2,2,3,3 TETRAFLUOROPROPOXY)PHENYL] 3(2H,4H) 1,2,4 TRIAZOLONE; 2 [2 (2,4 DIFLUOROPHENYL) 2 OXO 1 METHYLETHYL] 4 [4 (2,2,3,3 TETRAFLUOROPROPOXY)PHENYL] 3(2H,4H) 1,2,4 TRIAZOLONE; ANTIFUNGAL AGENT; ESTER; LACTIC ACID; PYRROLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; OPTICAL ROTATION;

EID: 0032919081     PISSN: 00092363     EISSN: None     Source Type: Journal    
DOI: 10.1248/cpb.47.360     Document Type: Article

References (27)

1. Part VIII: Kitazaki T., Tasaka A., Tamura N., Matsushita Y., Hosono H., Hayashi R., Okonogi K., Itoh K., Chem. Pharm. Bull., submitted.
2. Kitazaki T., Tamura N., Tasaka A., Matsushita Y., Hayashi R., Okonogi K., Itoh K., Chem. Pharm. Bull., 44, 314-327 (1996).
3. a) Tasaka A., Kitazaki T., Tsuchimori N., Matsushita Y., Hayashi R., Okonogi K., Itoh K., Chem. Pharm. Bull., 45, 321-326 (1997);
4. b) Itoh K., Okonogi K., Tasaka A , Hayashi R., Tamura N., Tsuchimori N., Kitazaki T., Matsushita Y., Obita J., Abstr. of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, F74, p. 112 (1996);
5. c) Okonogi K., Itoh K., Tasaka A., Kitazaki T., Hayashi R., Obita J., Kitamoto N., Tsuchimori N., Abstr. of the 17th Symposium on Medicinal Chemistry, Tsukuba, 1-P-35, p.124 (1997).
6. We attempted to isolate triflate 5 by evaporation of the eluate obtained from silica gel column chromatography. Considerable decomposition was observed and, therefore, the concentrated eluate containing the triflate was used immediately in the subsequent nucleophilic displacement reaction.
7. a) Wulfman D. S., Linstrumelle G., Cooper C. F., "Synthetic Application of Diazoalkanes, Diazocyclopentadienes and Diazoazacyclopentadienes. The Chemistry of Diazonium and Diazo Groups," ed. by Patai S., John Wiley & Sons Inc., New York, 1978, p.821-976;
8. b) Corey E. J., Chaykovsky M., J. Am. Chem. Soc., 87, 1353-1364 (1965);
9. c) Tamao K., Ishida N., Tetrahedron Lett., 25, 4245-4248 (1984);
10. d) Konosu T., Tajima Y., Takeda N., Miyaoka T., Kasahara M., Yasuda H., Oida S., Chem. Pharm. Bull., 38, 2476-2486 (1990);
11. e) Konosu T., Miyaoka T., Tajima Y., Oida S., ibid., 39, 2241-2246 (1991);
12. f) Konosu T., Miyaoka T., Tajima Y., Oida S., ibid., 40, 562-564 (1992);
13. g) Mooto D. R., Fraser-Reid B., J. Chem. Soc., Perkin Trans. 1, 1990, 739-746;
14. h) Cainelli G., Ronchi A. U., Bertini F., Grasselli P., Zubiani G., Tetrahedron, 27, 6109-6114 (1971);
15. i) Ohta H., Kimura Y., Sugano Y., Sugai T., ibid., 45, 5469-5476 (1989);
16. j) Park J., Pedersen S. F., ibid., 48, 2069-2080 (1992);
17. k) Clerici A., Porta O., J. Org. Chem., 54, 3872-3878 (1989);
18. l) Imamoto T., Takeyama T., Yokoyama M., Tetrahedron Lett., 25, 3225-3226 (1984);
19. m) Schroder M., Chem. Rev., 80, 187-213 (1980).
20. 2 : MeOH=5 : 5 : 1): Kitazaki T., Asano T., Kato K., Kishimoto S., Itoh K., Chem. Pharm. Bull., 42, 2636-2640 (1994).
21. Tasaka A., Tamura N., Matsushita Y., Teranishi K., Hayashi R., Okonogi K., Itoh K., Chem. Pharm. Bull., 41, 1035-1042 (1993).
22. We attempted the synthesis of the oxirane 6 from 8 by Corey's method. 5b) However, the reaction proceeded without stereoselectivity to give 6 as a diastereomeric mixture with low optical purity.
23. 5d-f)
24. 2) 11) The TLC analysis of the reaction mixture at the initial stage indicated the formation of the oxirane 6, which diminished with increasing reaction time to produce TAK-187.
25. The formation of the O-substituted by-product was detected by HPLC analysis of the reaction mixture. This by-product was unstable and decomposed during the work-up using aqueous solutions.
26. Tasaka A., Tsuchimori N., Kitazaki T., Hiroe K., Hayashi R., Okonogi K., Itoh K., Chem. Pharm. Bull., 43, 441-449 (1995).
27. Radddatz P., Minck K.-O., Rippmann F., Schmitges C.-J., J. Med. Chem., 37, 486-497 (1994).