Pd-catalyzed aminations of aryl triazolones: Effective synthesis of hydroxyitraconazole enantiomers

Tetrahedron Letters

Volumn 39, Issue 38, 1998, Pages 6845-6848

  Tanoury, Gerald J ^a   Senanayake, Chris H ^a   Hett, Robert ^a   Kuhn, Amy M ^a   Kessler, Donald W ^a   Wald, Stephen A ^a  

^a SUNOVION PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; HYDROXYITRACONAZOLE; ITRACONAZOLE;

ALKYLATION; AMINATION; ANTIFUNGAL ACTIVITY; ARTICLE; CHEMICAL REACTION; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER;

EID: 0032541736     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01493-2     Document Type: Article

References (21)

1. 1. Neuvonen, P.J.; Jalava, K.-M. Clin. Pharmacol. Ther. 1996, 60, 54.
2. 2. (a) Vanden Bossche, H.; Marichal, P.; LeJeune, L.; Coene, M-C.; Gorrens, J.; Cools, W. Antimicrob. Agents Chemotherapy 1993, 37, 2101.
3. (b) Vanden Bossche, H.; Heeres, J.; Backx, L.; Marichal, P.; Willemsens, G. in Cutaneous Antifungal Agents; J. Rippons, W. and Fromtling, R. A., Eds.; Marcel Dekker, Inc.: New York, 1993; pp 171-197.
4. (c) Vanden Bossche, H.; Marichal, P.; Gorrens, J.; Bellens, D.; Coene, M.-C.; Lauwers, W.; Le Jeune, L.; Moereels, H.; Janssen, P. A. J. in Mycoses in AIDS Patients; Vanden Bossche, H., Mackenzie, D. W. R., Causenbergh, G., Van Cutsem, J., Drouhet, E., and Dupont, B., Eds.; Plenum Press: New York, 1990; pp 223-243.
5. (d) Banden Bossche, H.; Marichal, P.; Gorrens, J.; Coene, M.-C.; Willemsens, G.; Bellens, D.; Roels, I.; Moereels, H.; Janssen, P. A. J. Mycoses, 1989, 32 (Suppl. 1), 35.
6. (e) Vanden Bossche, H.; Marichal, P.; Gorrens, J.; Geerts, H.; Janssen, P. A. J. An. N.Y. Acad. Sci. 1988, 544, 191.
7. 3. Tanoury, G. J.; Senanayake, C. H.; Hett, R.; Hong, Y.; Wald, S. A. Tetrahedron Letters 1997, 38, 7839.
8. 4. (a) Wolfe, J. P.; Wagaw, S.; Buchwald, L. S. J Am. Chem. Soc. 1996, 118, 7215.
9. (b) Wagaw, S.; Buchwald, L. S. J. Org. Chem. 1996, 61, 7241.
10. (c) Wolfe, J. P.; Buchwald, L. S. J. Org. Chem. 1996, 61, 1135.
11. 5. (a) Paul, F.; Patt, J.; Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969.
12. (b) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 4708.
13. (c) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118, 7217.
14. 6. (a) Gao, Y.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 7538.
15. (b) Klotz, W.; Schmidt, R. R. Synthesis 1996, 6, 687.
16. 7. The enantiomeric purity of 7 and its enantiomer were determined by chiral HPLC analysis of the dibenzyl ester of the 2,3-butanediol precursor. The analysis gave the following results: (R,R)-2,3-butane diol dibenzyl ester-99.89% (R,R), 0.11% (S,S) and (S,S)-2,3-butanediol dibenzyl ester-99.16%(S,S), 0.23% (R,R), 0.61% meso. HPLC conditions: Chiralpak AD, 10 μm, 4.6 mm × 25 cm, hexane/2-propanol (97:3), 1.0 mL/min, 220 nm
17. 2 resulted in 60% conversion after 16 hr at room temperature.
18. 9. The enantiomeric purity of 11 and its enantiomer were determined by chiral HPLC analysis. The analysis gave the following results: (2′S,3′R)-11-99.89% (2′S,3′R), 0.11% (2′R,3′S) and (2′R,3′S)-11-99.16%(2′R,3′S), 0.23% (2′S,3′R), 0.61% (2′R*,3′R*). HPLC conditions: Chiralpak AD, 10 μm, 4.6 mm × 25 cm, hexane/ethanol (95:5), 1.0 mL/min, 220 nm
19. 10. Compound S-3a can be prepared analogously to (2′S,3′R)-9 by the alkylation of 6 with 2R-tosyloxybutane without racemization.
20. 11. Attempts to couple the desilylated analog of (2′S,3′R)-11 resulted in partial product formation (<10%) and catalyst deactivation, even in the presence of 2.8 equivalents of NaOtBu.
21. 3): δ 152.6, 152.0, 151.3, 150.7, 145.9, 144.9, 136.0, 134.3, 134.0, 133.1, 131.4, 129.6, 127.2, 125.3, 123.7 (2C), 118.4 (2C), 116.6 (2C), 115.2 (2C), 107.6, 74.7, 69.8, 67.6, 67.4, 57.3, 53.5, 50.5 (2C), 49.1 (2C), 19.4, 12.4.