Synthesis of nitrogen and sulfur analogues of the seco-CI alkylating agent

Abstract

Two complementary syntheses of amino seco-CI (CI = 1a,2,3,5-tetrahydro-1H-cycloprop[1,2-c]indol-5-one) alkylating agents starting from isomeric chloronitrobenzoic acids are reported. Further reactions of these compounds, including diazotisation to phenol and thiophenol derivatives, and alkylation and acylation reactions relevant to the preparation of pro-drug forms are also described.

References

1. D. L. Boger and D. S. Johnson, Angew. Chem., Int. Ed. Engl., 1996, 35, 1438 and references cited therein.
2. For recent examples: (a) Y. Fukuda, Y. Oomori, Y. Kusama and S. Terashima, Bioorg. Med. Chem. Lett., 1997, 7, 749; (b) P. G. Baraldi, B. Cacciari, M. J. Pineda de las Infantas, R. Romagnoli, G. Spalluto, P. Cozzi and N. Mongelli, Anti-Cancer Drug Des., 1997, 12, 67.
3. Y. Wang, R. Gupta, L. Huang and J. W. Lown, J. Med. Chem., 1993, 36, 4172.
4. For recent examples: (a) S. Nagamura, A. Asai, N. Amishiro, E. Kobayashi, K. Gomi and H. Saito, J. Med. Chem., 1997, 40, 972; (b) D. L. Boger, B. Bollinger and D. S. Johnson, Bioorg. Med. Chem. Lett., 1996, 6, 2207; (c) Y. Wang, R. Gupta, L. Huang, W. Luo and J. W. Lown, Anti-Cancer Drug Des., 1996, 11, 15.
5. D. L. Boger and P. Mésini, J. Am. Chem. Soc., 1995, 117, 11 647.
6. R. H. White, P. G. Parsons, A. S. Prakash and D. J. Young, Bioorg. Med. Chem. Lett., 1995, 5, 1869.
7. (a) D. L. Boger, T. Ishizaki, H. Zarrinmayeh, S. A. Munk, P. A. Kitos and O. Suntornwat, J. Am. Chem. Soc., 1990, 112, 8961; (b) D. L. Boger, S. A. Munk, H. Zarrinmayeh, T. Ishizaki, J. Haught and M. Bina, Tetrahedron, 1991, 47, 2661.
8. (a) S. Nagamura, A. Asai, Y. Kanda, E. Kobayashi, K. Gomi and H. Saito, Chem. Pharm. Bull., 1996, 44, 1723; (b) S. Nagamura, Y. Kanda, E. Kobayashi, K. Gomi and H. Saito, Chem. Pharm. Bull., 1995, 43, 1530.
9. L. F. Tietze, R. Hannemann, W. Buhr, M. Lögers, P. Menningen, M. Lieb, D. Starck, T. Grote, A. Döring and I. Schuberth, Angew. Chem., Int. Ed. Engl., 1996, 35, 2674.
10. S. Nagamura, E. Kobayashi, K. Gomi and H. Saito, Bioorg. Med. Chem., 1996, 4, 1379.
11. (a) M. Tercel, W. A. Denny and W. R. Wilson, Bioorg. Med. Chem. Lett., 1996, 6, 2735; (b) M. Tercel, W. A. Denny and W. R. Wilson, Bioorg. Med. Chem. Lett., 1996, 6, 2741.
12. M. A. Warpehoski, I. Gebhard, R. C. Kelly, W. C. Krueger, L. H. Li, J. P. McGovren, M. D. Prairie, N. Wicnienski and W. Wierenga, J. Med. Chem., 1988, 31, 590.
13. Previously reported in 30% yield: S. Basterfield and L. A. Hamilton, Trans. Roy. Soc. Can., 1933, 27, 125.
14. K. Ninomiya, T. Shioiri and S. Yamada, Tetrahedron, 1974, 30, 2151.
15. T. Cohen, A. G. Dietz, Jr. and J. R. Miser, J. Org. Chem., 1977, 42, 2053.
16. N. Satyamurthy, J. R. Barrio, G. T. Bida and M. E. Phelps, Tetrahedron Lett., 1990, 31, 4409.
17. C. F. H. Allen and D. D. Mackay, Org. Synth., 1943, Coll. Vol. II 580.
18. I. W. J. Still and V. A. Sayeed, Synth. Commun., 1983, 13, 1181.
19. L. J. Fielding, Q. N. Porter and G. Winter, Aust. J. Chem., 1980, 33, 2615.
20. Y. Fukuda, Y. Itoh, K. Nakatani and S. Terashima, Tetrahedron, 1994, 50, 2793.