Practical amination of nitropyridones by silylation

Organic Process Research and Development

Volumn 12, Issue 6, 2008, Pages 1261-1264

  Singer, Robert A ^a   Doré, Michaël ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 58149133909     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op800201u     Document Type: Article

References (24)

1. Crey-Desiolles, C.; Kotera, M. Bioorg. Med. Chem. 2006, 14, 1935-1941.
2. Provencal, D. P.; Gesenberg, K. D.; Wang, H.; Escobar, C.; Wong, H.; Brown, M. A.; Staab, A. J.; Pendri, Y. R. Org. Process Res. Dev. 2004, 8, 903-908.
3. Material Safety Data Sheets on 2-chloro-3-nitropyridine and 4-chloro3-nitropyridine indicate that these materials are severe irritants and that the 2-chloro isomer is a skin sensitizer.
4. (a) Mugnaini, C.; Petricci, E.; Botta, M.; Corelli, F.; Mastromarino, P.; Giorgi, G. Eur. J. Med. Chem. 2007, 42, 256-262.
5. (b) Cain, G. A.; Beck, J. P. Heterocycles 2001, 55, 439-446.
6. (c) Zhao, H.; Serby, M. D.; Xin, Z.; Szczepankiewicz, B. G.; Liu, M.; Kosogof, C.; Liu, B.; Nelson, L. T. J.; Johnson, E. F.; Wang, S.; Pederson, T.; Gum, R. J.; Clampit, J. E.; Haasch, D. L.; Abad-Zapatero, C.; Fry, E. H.; Rondinone, C.; Trevillyan, J. M.; Sham, H. L.; Liu, G. J. Med. Chem. 2006, 49, 4455-4458.
7. Phosphonium salts have often been formed with reagents such as BOP, see: (a) Rang, F.-A.; Kodah, J.; Guan, Q.; Li, X.; Murray, W. V. J. Org. Chem. 2005, 70, 1957-1960.
8. (b) Wan, Z.-K.; Binnum, E.; Wilson, D. P.; Lee, J. Org. Lett. 2005, 7, 5877-5880.
9. (c) Wan, Z.-K.; Wacharasindhu, S.; Binnum, E.; Mansour, T. Org. Lett. 2006, 8, 2425-2428.
10. (a) Bamford, M. J.; Alberti, M. J.; Bailey, N.; Davies, S.; Dean, D. K.; Gaiba, A.; Garland, S.; Hailing, J. D.; Jung, D. K.; Panchal, T. A.; Parr, C. A.; Steadman, J. G.; Takle, A. K.; Townsend, J. T.; Wilson, D. M.; Witherington, J. Bioorg. Med. Chem. Lett. 2005, 15, 3402-3406.
11. (b) Lanza, T. J.; Durette, P. L.; Rollins, T.; Siciliano, S.; Cianciarulo, D. N.; Kobayashi, S. V.; Caldwell, C. G.; Springer, M. S.; Hagmann, W. K. J. Med. Chem. 1992, 35, 252-258.
12. The price of 4-methoxy-3-nitropyridine is about $5/g to $20/g in cost (depending on the choice of supplier) while the corresponding hydroxypyridine is about $l/g to $4/g. In addition we had issues with the quality of 4-methoxy-3-nitropyridine; one supplier provided samples contaminated with up to 50% of N-methyl-3-nitro-4-pyridone.
13. 3 can be hazardous for both laboratory use and the environment, see: (a) Kapias, T.; Griffiths, R. F. J. Hazard. Mater. 2001, 81, 223-249.
14. Due to the high affinity of silicon to oxygen, silylation always occurs on oxygen rather than nitrogen, see: (a) Vorbruggen, H.; Krolikiewicz, K. Liebigs Ann. Chem. 1976, 745-761.
15. (b) Vorbruggen, H.; Krolikiewicz, K.; Niedballa, U. Liebigs Ann. Chem. 1975, 988-1002.
16. (c) Cook, M. J.; Katritzky, A. R.; Linda, P. Adv. Heterocycl. Chem. 1974, 17, 255-356.
17. HMDS has been used in the past to activate hydroxy pyridines toward substitution by amines, see: (a) Vorbruggen, H.; Krolikiewicz, K. Chem. Ber. 1984, 117, 1523-1541.
18. (b) Vorbruggen, H. Angew. Chem., Int. Ed. Engl. 1972, 11, 305-306.
19. Polar solvents generally are favored for aromatic substitution reactions which most likely progress through a charged intermediate such as a Meisenheimer salt, see: (a) Meisenheimer, J. Liebigs Ann. Chem. 1902, 323, 205-246.
20. (b) Illuminati, G.; Stegel, F. Adv. Heterocycl. Chem. 1983, 34, 305-444.
21. (c) Brewis, D. M.; Chapman, N. B.; Paine, J. S.; Shorter, J.; Wright, D. J. J. Chem. Soc., Perkin Trans. 2 1974, 15, 1787-801.
22. The decomposition of DMF to dimethylamine and CO is well-known, see: (a) Neumeyer, J. L.; Cannon, J. G. J. Org. Chem. 1961, 26, 4681-4682.
23. Silylation of nitro groups to facilitate nucleophilic aromatic substitution has been observed, see: Makosza, M.; Surowiec, M. Tetrahedron 2003, 59, 6261-6266.
24. We had tested compound 5a as a potential mutagen and found that it was negative in the Sprial Ames test as well as in the in Vitro Micronucleus test.