Efficient N-arylation/dealkylation of electron deficient heteroaryl chlorides and bicyclic tertiary amines under microwave irradiation

Journal of Combinatorial Chemistry

Volumn 11, Issue 3, 2009, Pages 355-363

  Wang, Hong Jun ^a   Wang, Yi ^a   Csakai, Adam J ^a   Earley, William G ^a   Herr, R Jason ^a  

^a ALBANY MOLECULAR RESEARCH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAZABICYCLO[2.2.2]OCTANE; AMINE; CHLORIDE; PIPERAZINE DERIVATIVE; PIPERIDINE DERIVATIVE; QUINUCLIDINE DERIVATIVE;

ARTICLE; CHEMISTRY; ECONOMICS; MICROWAVE RADIATION; MOLECULAR LIBRARY; SYNTHESIS;

AMINES; CHLORIDES; MICROWAVES; PIPERAZINES; PIPERIDINES; QUINUCLIDINES; SMALL MOLECULE LIBRARIES;

EID: 66149138338     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc8001662     Document Type: Article

References (31)

1. Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893.
2. For examples, see:(a) Yoshizawa, T.; Ohmoto, K.; Ogawa, K. PCT Int. Pat. Publ. WO 2005118543, 2005.
3. (b) Fiorino, F.; Perissutti, E.; Severino, B.; Santagada, V.; Cirillo, D.; Terrac-ciano, S.; Massarelli, P.; Bruni, G.; Collavoli, E.; Renner, C.; Caliendo, G. J. Med. Chem. 2005, 48, 5495.
4. (c) Kling, A.; Lange, U. E. W.; Mack, H.; Bakker, M. H. M.; Drescher, K. U.; Hornberger, W.; Hutchins, C. W.; Moeller, A.; Mueller, R.; Schmidt, M.; Unger, L.; Wicke, K.; Schellhaas, K.; Steiner, G. Bioorg. Med. Chem. Lett. 2005, 15, 5567.
5. (d) Waer, M. J. A.; Herdewijn, P. A. M. M.; De Jonghe, S. C. A.; Marchand, A. D. M.; Gao, L.-J. PCT Int. Pat. Publ. WO 2005039587, 2005.
6. (e) Farre, A.; Frigola, J. Drugs Future 1994, 19, 651.
7. (f) Abou-Gharbia, M. A.; Childers, W. E., Jr.; Fletcher, H.; McGaughey, G.; Patel, U.; Webb, M. B.; Yardley, J.; Andree, T.; Boast, C.; Kucharik, R. J., Jr.; Marquis, K.; Morris, H.; Scerni, R.; Moyer, J. A. J. Med. Chem. 1999, 42, 5077.
8. For examples, see:(a) Caldwell, J. J.; Davies, T. G.; Donald, A.; McHardy, T.; Rowlands, M. G.; Aherne, G. W.; Hunter, L. K.; Taylor, K.; Ruddle, R.; Raynaud, F. I.; Verdonk, M.; Workman, P.; Garrett, M. D.; Collins, I. J. Med. Chem. 2008, 51, 2147.
9. (b) Bruton, G.; Johnstone, V.; Orlek, B. S. PCT Int. Pat. Publ. WO 2006029906, 2006.
10. (c) Murphy, M. A.; Schullek, J. R.; Ward, J. S.; Look, G. C.; Jain, R.; Lee, L. PCT Int. Pat. Publ. WO 2005120503, 2005.
11. (d) Bakthavatchalam, R.; Blum, C. A.; Chenard, B. L.; Zheng, X. PCT Int. Pat. Publ. WO 2006065872, 2006.
12. (e) Mealy, N.; Ngo, J.; Castaner, J. Drues Future 1996, 21, 799.
13. (a) Ross, S. D.; Finkelstein, M. J. Am. Chem. Soc. 1963, 85, 2603.
14. See also (b) Matsumoto, K.; Hashimoto, S.; Otani, S. J. Chem. Soc, Chem. Commun. 1991, 306.
15. (c) Yoshida, K.; Taguchi, M. J. Chem. Soc., Perkin Trans. 1 1992, 919.
16. (d) Axelsson, O.; Peters, D. J. Heterocyclic Chem. 1997, 34, 461.
17. (e) Ramakrishna, T. V. V.; Elias, A. J.; Vij, A. Inorg. Chem. 1999, 38, 3022.
18. (f) Khalaf, A. I.; Alvarez, R. G.; Suckling, C. J.; Waigh, R. D. Tetrahedron 2000, 56, 8567.
19. (g) Hamilton, G. L.; Backes, B. J. Tetrahedron Lett. 2006, 47, 2229.
20. (h) Reddy, N. D.; Elias, A. J.; Vij, A. J. Chem. Soc., Dalton Trans. 1999, 1515.
21. Wang, H.-J.; Earley, W. G.; Lewis, R. M.; Srivastava, R. R.; Zych, A. J.; Jenkins, D. M.; Fairfax, D. J. Tetrahedron Lett. 2007, 48, 3043.
22. For recent reviews, see:(a) Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199.
23. (b) Lidström, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron 2001, 57, 9225.
24. (c) Lew, A.; Krutzik, P. O.; Hart, M. E.; Chamberlin, A. R. J. Comb. Chem. 2002, 4, 95.
25. (d) Larhed, M.; Moberg, C.; Hallberg, A. Acc Chem. Res. 2002, 35, 717.
26. (e) Mavandadi, F.; Pilotti, A. Drug Discovery Today 2006, 11, 165.
27. For examples, see:(a) Murray, J. K.; Gellman, S. H. J. Comb. Chem. 2006, 8, 58.
28. (b) Werner, S.; Iyer, P. S.; Fodor, M. D.; Coleman, C. M.; Twining, L. A.; Mitasev, B.; Brummond, K. M. J. Comb. Chem. 2006, 8, 368.
29. (c) Soh, C. H.; Chui, W. K.; Lam, Y. J. Comb. Chem. 2006, 8, 464.
30. (d) Bianchi, I.; Forlani, R.; Minetto, G.; Peretto, I.; Regalia, N.; Taddei, M.; Ravelia, L. F. J. Comb. Chem. 2006, 8, 491.
31. The quaternary ammonium salt was found to be the major component when the reaction was conducted at reflux in THF with conventional heating. Microwave irradiation of the THF reaction mixture normally generated pressures of 8-10 bar at 160 °C (12-15 bar at 180 °C), and because of the unavailability of a high-pressure equipment using conventional heating, these high-pressure experiments were conducted with microwave synthesizers, which provided the required safe environment.