Synthesis of substituted azaoxindoles for the preparation of aza-tenidap analogs

Journal of Heterocyclic Chemistry

Volumn 33, Issue 2, 1996, Pages 287-293

  Robinson, Ralph P ^a   Donahue, Kathleen M ^a   Son, Paul S ^a   Wagy, Steven D ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AZAOXINDOLE DERIVATIVE; INDOLE DERIVATIVE; NONSTEROID ANTIINFLAMMATORY AGENT; TENIDAP; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS;

EID: 0029999194     PISSN: 0022152X     EISSN: None     Source Type: Journal    
DOI: 10.1002/jhet.5570330213     Document Type: Article

References (21)

1. [a] C. Robinson, Drugs Fut., 15, 898 (1990);
2. [b] Drugs Fut., 18, 875 (1993);
3. [c] A. R. Kraska, F. E. Wilhelm, D. S. Kirby, L. D. Loose, N. Ting, W. R. Shanahan and E. S, Weiner, Arthritis Rheum., 36 (Suppl. 9), S57 (1993);
4. [d] M. R. G. Leeming, Arthritis Rheum., 36 (Suppl. 9), S111 (1993).
5. R. W. Daisley and J. R. Hanbali, Synth. Commun., 11, 743 (1981).
6. A. M. Marfat and M. P. Carta, Tetrahedron Letters, 28, 4027 (1987).
7. R. P. Robinson and K. M. Donahue, J. Org. Chem., 56, 4805 (1991).
8. 5- and 7-Methyl-4-azaoxindole: R. W. Daisley and J. R. Hanbali, Synth. Commun., 5, 53 (1975).
9. G. J. Quallich and P. M. Morrissey, Synthesis, 51 (1993).
10. M. Makosza and J. Winiarski, Acc. Chem. Res., 20, 282 (1987).
11. U. Horn and F. Mutterer, W. D. Weis, Helv. Chim. Acta, 59, 190 (1976).
12. 1H nmr spectrum than the isomeric products 5a and 5b arising from displacement of the chloro substituent para to the nitro group.
13. Prepared from 5-chloro-2-hydroxy-3-nitropyridine by a modification of the literature procedure [T. S. Safonova, L. G. Levkovskaya, Chem. Abstr., 70, 68286y (1969)]. Nitration of 5-chloro-2-hydroxypyridine proved to be cleaner and higher yielding than the literature procedure involving nitration of 2-amino-5-chloropyridine.
14. Prepared by nitration of 5-fluoro-2-hydroxypyridine followed by reaction of the intermediate (5-fluoro-2-hydroxy-3-nitropyridine) with phosphorus oxychloride/phosphorus pentachloride.
15. Obtained by the reaction of phosphorus oxychloride/phosphorus pentachloride with 2-hydroxy-3-nitro-5-trifluoromethylpyridine.
16. Prepared by nitration of 2-hydroxy-6-trifluoromethylpyridine followed by reaction of the intermediate (2-hydroxy-3-nitro-6-trifluoromethylpyridine) with phosphorus oxychloride/phosphorus pentachloride. Separation from the side products, 2-chloro-5-nitro-6-trifluoromethylpyridine and 2-chloro-3,5-dinitro-6-trifluoromethylpyridine was not necessary.
17. M. Makosza, W. Danikiewicz and K. Wojciechowski, Liebigs Ann. Chem., 203 (1988).
18. In contrast, the VNS reaction of 2-chloro-5-nitropyridine with (4-chlorophenoxy)acetonitrile gives two substitution products in very low yield; (6-chloro-3-nitro-2-pyridyl)acetonitrile (7%) and (2-chloro-5-iutro-4-pyridyl)acetonitrile (9%); John E. Macor, unpublished results.
19. S. Nesnow and C. Heidelberger, J. Heterocyclic Chem., 10, 779 (1973). The reported conditions for demethylation of 5-fluoro-2-methoxypyridine (25% HCl/sealed tube/145°) were not used since performing the reaction in refluxing 48% HBr proved to be easier and higher yielding
20. T.-Y. Shen, R. L. Clark, A. A. Pessolano, B. E. Witzel and T. J. Lanza, British Patent 1,421,619; Chem. Abstr., 80, 95916s (1974). The starting material, 2-chloro-5-trifluoromethylpyridine was obtained from Ishihara Corporation.
21. F. E. Torba, U. S. Patent 3,609,158; Chem. Abstr., 76, 3699q (1972). The starting material, 2-chloro-6-trifluoromethylpyridine, was obtained from Ishihara Corporation.