Highly Regioselective Nitration Reactions Provide a Versatile Method of Functionalizing Benzocycloheptapyridine Tricyclic Ring Systems: Application toward Preparation of Nanomolar Inhibitors of Farnesyl Protein Transferase

Journal of Organic Chemistry

Volumn 63, Issue 3, 1998, Pages 445-451

  George Njoroge, F ^a   Vibulbhan, Bancha ^a   Pinto, Patrick ^a   Chan, Tze Ming ^a   Osterman, Rebecca ^a   Remiszewski, Stacy ^a   Rosario, Jocelyn Del ^a   Doll, Ronald ^a   Girijavallabhan, V ^a   Ganguly, Ashit K ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBAMIC ACID DERIVATIVE; PROTEIN FARNESYLTRANSFERASE INHIBITOR;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; NITRATION; PROTON NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0032488942     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo971100z     Document Type: Article

References (33)

1. Villani, F. J.; Magatti, C. V.; Vashi, D. B.; Wong, J. K.; Popper, T. L. Arzneim-Forsch. Drug Res. 1986, 36, 1311.
2. (a) Piwinski, J. J.; Wong, J. K.; Green, M. J.; Ganguly, A. K.; Billah, M. M.; West, R. E., Jr.; Kreutner, W. J. Med. Chem. 1991, 34, 457.
3. (b) Billah, M. M.; Egan, R. W.; Ganguly, A. K.; Green, M. J.; Kreutner, W.; Piwinski, J. J.; Siegel, M. I.; Villani, F. G.; Wong, J. K. Lipids 1991, 26, 1172.
4. (c) Wong, J. K.; Piwinski, J. J.; Green, M. J.; Ganguly, A. K.; Anthes, J. C.; Billah, M. M. Bioorg. Med. Chem. Lett. 1993, 3, 1073.
5. (a) Njoroge, F. G.; Doll, R. J.; Vibulbhan, B.; Alvarez, C. S.; Bishop, W. R.; Petrin, J.; Kirschmeier, P.; Carruthers, N. I.; Wong, J. K.; Albanese, M. A.; Piwinski, J. J.; Catino, J.; Girijavallabhan, V.; Ganguly, A. K. Bioorg. Med. Chem. 1997, 5, 101.
6. (b) Njoroge, F. G.; Vibulbhan, B.; Alvarez, C. S.; Bishop, W. R.; Petrin, J.; Doll, R. J.; Girijavallabhan, V.; Ganguly, A. K. Bioorg. Med. Chem. Lett. 1996, 6, 2977.
7. (c) Mallams, A. K.; Njoroge, F. G.; Doll, R. J.; Snow, M. E.; Kaminiski, J. J.; Rossman, R. R.; Vibulbhan, B.; Bishop, W. R.; Kirschmeier, P.; Liu, M.; Bryant, M. S.; Alvarez, C. S.; Carr, D.; James L.; King, I.; Li, Z.; Lin, C.-C.; Petrin, J.; Remiszewski S. R.; Taveras, A, G.; Wang, S.; Wong, J. K.; Catino, J.; Girijavallabhan, V.; Ganguly, A. K. Bioorg. Med. Chem. 1997, 5, 93.
8. (d) Bishop, W. R.; Bond, R.; Petrin, J.; Wang, L.; Patton, R.; Doll, R. J.; Njoroge, F. G.; Catino, J.; Schwartz, J.; Windisor, W.; Syto, R.; Carr, D.; James, L.; Kirschmeier, P.; Carr, D. J. Biol. Chem. 1995, 270, 30611.
9. Kreutner, W.; Chapman, R. W.; Gulbenkian, A.; Siegel, M. I.; Allergy (Copenhagen) 1987, 42, 57.
10. (b) Barnett, A.; Iorio, L. L.; Kreutner, W.; Tozzi, S.; Ahn, H. S.: Gulbenkian, A. Agents Actions 1984, 14, 590.
11. (a) Billah, M. M.; Chapman, R.; Egan, R. W.; Gilchrest, H.; Piwinski, J. J.; Sherwood, J.; Siegel, M. I.; West, R. E.; Kreutner, W. Pharmacol. Exp. Ther. 1990, 252, 1090.
12. (b) Billah, M. M.; Chapman, R.; Watnick, A. S.; Egan, R. W.; Siegel, M. I.; Kreutner, W. New Drugs Asthma Therapy 1991, 313.
13. (a) Finar, I. L.; Miller, D. B. J. Chem. Soc. 1961, 2769.
14. (b) Drewry, D. T.; Scrowston, R. M. J. Chem. Soc. 1969, C, 2750.
15. (c) Newman, M. S.; Dhawan, B.; Tuncay, A. J. Org. Chem. 1976, 41, 3924.
16. (a) Wisansky, W. A.; Ansbacher, S. Organic Syntheses; Wiley: New York, 1955; Collect. Vol. III, p 138.
17. (b) Basu, B.; Mukherjee, D. Tetrahedron Lett. 1984, 25, 4445.
18. (c) Chatterjee, A.; Banerjee, D. J. Chem Soc. 1971, 1859.
19. Hall D. M. J. Chem. Soc. 1951, 1375.
20. Ranu, B. C.; Sarkar, D. C.; Charkraborty, R. Synth. Commun. 1992, 22, 1095.
21. Schumacher, D. P.; Murphy, B. L.; Clark, J. E.; Tahbaz, P.; Mann, T. A. J. Org. Chem. 1989, 54, 242.
22. Villani, F. J.; Daniels, P. J. L.; Ellis, C. A.; Mann, T. A.; Wang, K.-C. J. Heterocycl. Chem. 1971, 8, 73.
23. Pendergast W.; Johnson, J. V.; Dickerson, S. H.; Dev. I. K.; Duch, D. S.; Ferone, R.; Hall, W. R.; Humpreys, J.; Kelly, J. M.; Wilson, D. C. J. Med. Chem. 1993, 36, 2279.
24. Buncel, E.; Mennon, B. C. J. Am. Chem. Soc. 1980, 102, 3499.
25. Olah, G. A.; Ramaiah, P.; Sandford, G.; Orlinkov, A.; Prakash, G. K. S. Synthesis 1994, 468.
26. Gokhale, U. B.; Joshi, A. A. Indian. J. Chem. 1993, 325 1073.
27. Masci, B. J. Org. Chem. 1985, 50, 0, 4081.
28. 4 and conducting the reaction at very high temperatures (330°C): Ege, S. Organic Chemistry; Health: Lexington, 1984, 1827. Kirpalt, A.; Reiter, E. Ber. Dtsch. Chem. Ges. 1925, 58, 699. More recently, Bakke and co-workers have successfully nitrated pyridine to give 3-nitropyridine in moderate yields: Bakke, J. M.; Rane, E. Synthesis 1997, 281.
29. 4 and conducting the reaction at very high temperatures (330°C): Ege, S. Organic Chemistry; Health: Lexington, 1984, 1827. Kirpalt, A.; Reiter, E. Ber. Dtsch. Chem. Ges. 1925, 58, 699. More recently, Bakke and co-workers have successfully nitrated pyridine to give 3-nitropyridine in moderate yields: Bakke, J. M.; Rane, E. Synthesis 1997, 281.
30. 4 and conducting the reaction at very high temperatures (330°C): Ege, S. Organic Chemistry; Health: Lexington, 1984, 1827. Kirpalt, A.; Reiter, E. Ber. Dtsch. Chem. Ges. 1925, 58, 699. More recently, Bakke and co-workers have successfully nitrated pyridine to give 3-nitropyridine in moderate yields: Bakke, J. M.; Rane, E. Synthesis 1997, 281.
31. In the course of this nitration we observed formation of 4-[3-nitro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-6]pyridin-11-ylidene]-1- nitropiperidine.
32. Evans, P. A.; Longmire, J. M. Tetrahedron Lett. 1994, 35, 8345.
33. Njoroge, F. G.; Vibulbhan, B.; Rane, D. F.; Bishop, W. R.; Petrin, J.; Patton, R.; Bryant, M. S.; Chen, K.-J.; Nomeir, A. A.; Lin, C, C-.; Liu, M.; King, I.; Chen, J.; Lee, S.; Yaremko, B.; Dell, J.; Lipari, P.; Malkowski, M.; Li, Z.; Catino, J.; Doll, R. J.; Girijavallabhan, V.; and Ganguly, A. K. J. Med. Chem. 1997, 40, 4290.