Sequential mono-N-arylation of piperazine nitrogens. Part 1: A simplified method and its application to the preparation of a key N,N'-biaryl piperazine antifungal intermediate

Tetrahedron Letters

Volumn 40, Issue 31, 1999, Pages 5655-5659

  Hepperle, Michael ^a   Eckert, Jeffrey ^a   Gala, Dinesh ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; N (4 HYDROXYPHENYL) N' (4 AMINOPHENYL)PIPERAZINE; NITROGEN; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; PARTIAL DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0033618356     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01103-X     Document Type: Article

References (28)

1. Xia, Y.; Mirzai, B.; Chackamannil, S.; Czarniecki, M.; Wang, S.; Clemmons, A.; Ahn, H.-S.; Boykow, G. C. Bioorg. Med. Chem. Lett. 1996, 6, 919.
2. Perez, M.; Fourrier, C.; Sigogneau, I.; Pauwels, P. J.; Palmier, C.; John, G. W.; Valentin, J.-P.; Halazy, S. J. Med. Chem. 1995, 38, 3602.
3. (a) van Maarseveen, J. H.; den Hartog, J. A. J.; Tipker, K.; Reinders, J.-H.; Brakkee, J.; Schon, U.; Kehrbach, W.; Kruse, C. G. Bioorg. Med. Chem. Lett. 1998, 8, 1531;
4. (b) Morreale, A.; Galvez-Ruano, E.; Iriepa-Canalda, I.; Boyd, D. B. J. Med. Chem. 1998, 41, 2029;
5. (c) Orjales, A.; Mosquera, R.; Labeaga, L.; Rodes, R. J. Med. Chem. 1997, 40, 586. Compound 18 represents 7 of Ref. 3c. A small amount of bis arylation was seen for 18. The crude reaction was high yielding, unoptimized isolation procedure caused lower isolated yields of 18.
6. (a) Heeres, J.; Backx, L. J. J.; VanCutsem, J. J. Med. Chem. 1984, 27, 894;
7. (b) Saksena, A. K.; Girijvallabhan, V. M.; Wang, H.; Liu, Y.-T.; Pike, R. E.; Ganguly, A. K. Tetrahedron Lett. 1996, 37, 5657;
8. (c) Tanoury, G. J.; Senanayake, C. H.; Hett, R.; Kuhn, A. M.; Kessler, D. W.; Wald, S. A. Tetrahedron Lett. 1998, 39, 6845.
9. Jaisinghani, H. G.; Khadilkar, B. M. Tetrahedron Lett. 1997, 38, 6875.
10. Reitz, A. B.; McDonnell, M. E.; Baxter, E. W.; Codd, E. E.; Wu, W.-N. Bioorg. Med. Chem. Lett. 1997, 7, 1927.
11. Mishani, E.; Dence, C. S.; McCarthy, T. J.; Welch, M. J. Tetrahedron Lett. 1996, 37, 319.
12. (a) Pollard, C. B.; Wicker, T. J. J. Am. Chem. Soc. 1954, 76, 1853;
13. (b) Pollard, C. B.; MacDowell, L. G. J. Am. Chem. Soc. 1934, 56, 2199.
14. (a) JP-09255671 (Konica Chem KK); 1997;
15. (b) Budai, Z.; Galambos, T.; Mezei, T.; Reiter, J. Humg. Pat. 91-1601: CA: 119 (15): 160318p;
16. (c) Schroeder, W.; Ruider, G. Eur. Pat. 91-103485; CA 115 (21): 232295w.
17. (a) Bartulin, J.; Zuniga, C.; Retamal, J. Bol. Soc. Chil. Quim. 1982, 27, 144 [CA 97:55773]. In some cases the use of alkyl/arylamine in place of ammonia results in moderate yields of differentially N,N' substituted piperazines;
18. (b) Perez, M.; Potier, P.; Halazy, S. Tetrahedron Lett. 1996, 37, 8487.
19. Bent, R. L.; Dessloch, J. C.; Dunnebier, F. C.; Fassett, D. W.; Glass, D. B.; James, T. H.; Julian, D. B.; Ruby, W. R.; Snell, J. M.; Sterner, J. H.; Thirtle, J. R.; Vittum, P. W.; Weissberger, A. J. Am. Chem. Soc. 1951, 73, 3100.
20. Stewart, H. W.; Turner, R. J.; Denton, J. J.; Kushner, S.; Brancone, W. L.; McEwen, W. L.; Hewitt, R. I.; Subbarow, Y. J. Org. Chem. 1948, 13, 134.
21. Neuville, L.; Zhu, J. Tetrahedron Lett. 1997, 38, 4091.
22. (a) Goldman, L.; Williams, J. H. J. Org. Chem. 1953, 18, 815;
23. (b) Swain, A. P.; Naegele, S. K. J. Am. Chem. Soc. 1954, 76, 5091.
24. Baltzly, R.; Buck, J. S.; Lorz, E.; Schon, W. J. Am. Chem. Soc. 1944, 66, 2631.
25. 2) electron withdrawing groups on the aryl group (e.g. 15 and 16); (iii) improving the hydrogen bonding capacity as shown in the following article in this issue (Eckert, J.; Chan, T.-M.; Gala, D. Tetrahedron Lett. 1999, 40, 5661); or (iv) by enhancing the electrophilicity of the reacting species, as in the case of formation of 30 (via metal catalysis).
26. Cohen, T.; Dietz Jr., A. G.; Miser, J. R. J. Org. Chem. 1977, 42, 2053.
27. Similar arylations of nitrogen containing compounds were recently reported (see Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M. P. Tetrahedron Lett. 1998, 39, 2933); however, this is the first example of a piperazine derivative. Also, the use of DMSO as solvent was contraindicated in the reference, but for our example, it was the best solvent used.
28. Andrews, D. R.; Gala, D.; Gosteli, J.; Gunter, F.; Mergelsberg, I.; Sudhakar, A. US Patent 5625064: Process for the Preparation of Triazolones, April 29, 1997.