Solid phase synthesis of urea libraries using a diversifiable thiophenoxy carbonyl linker

Tetrahedron Letters

Volumn 39, Issue 22, 1998, Pages 3631-3634

  Dressman, Bruce A ^a   Singh, Upinder ^b   Kaldor, Stephen W ^a  

^a ELI LILLY AND COMPANY   (United States)

^b GERON CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; CARBONYL DERIVATIVE; ORGANIC COMPOUND; UREA DERIVATIVE;

ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; ORGANIC CHEMISTRY; SYNTHESIS;

EID: 0032575179     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00652-2     Document Type: Article

References (24)

1. 1. Ellman, J. A.; Thompson, L. A. Chem. Rev. 1996, 96, 555-600.
2. 2. A search of the MDDR database using a urea scaffold produced 6700 hits.
3. 3. a) Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Tetrahedron Lett. 1996, 37, 7193-7196.
4. b) Kaldor, S. W.; Fritz, J. E.; Tang, J. McKinney, E. R. Bioorg. Med. Chem. Lett. 1996, 6, 3041-3044.
5. c) Flynn, D. L.; Crich, J. Z.; Devraj, R. V.; Hockerman, S. L.; Parlow, J. J.; South, M. S.; Woodard, S. J. Am. Chem. Soc. 1997, 119, 4874-4886.
6. d) Booth, R. J.; Hodges, J. C. J. Am. Chem. Soc. 1997, 119, 4882-4886.
7. e) Parlow, J. J.; Naing, W.; South, M. S.; Flynn, D. L. Tetrahedron Lett. 1997, 38, 7959-7962.
8. 4. Scialdone, M. A. Tetrahedron Lett. 1996, 37, 8141-8144. Additional references on the use of solid phase chemistries for the synthesis of urea libraries; Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1994, 35, 4055-4058. Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1995, 36, 2583-2586.
9. 4. Scialdone, M. A. Tetrahedron Lett. 1996, 37, 8141-8144. Additional references on the use of solid phase chemistries for the synthesis of urea libraries; Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1994, 35, 4055-4058. Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1995, 36, 2583-2586.
10. 4. Scialdone, M. A. Tetrahedron Lett. 1996, 37, 8141-8144. Additional references on the use of solid phase chemistries for the synthesis of urea libraries; Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1994, 35, 4055-4058. Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1995, 36, 2583-2586.
11. 5. A search of the ACD database produced 318 hits most of which were aryl isocyanates.
12. 6. Dressman, B. A.; Spangle, L. A.; Kaldor, S. W. Tetrahedron Lett. 1996, 37, 937-940.
13. 7. Lorenz, K.; Kunz, H. Angew. Chem. Int. Ed. Engl. 1980, 19, 932-933.
14. 8. a) Flanigan, E.; Marshall, G. R. Tetrahedron Lett. 1970, 27, 2403-2406.
15. b) Marshall, D. L.; Liener, I. E. J. Org. Chem. 1970, 35, 867-868.
16. -1.
17. 10. A slight loss in activity (10-20%) of resin 2 was noted in resin batches which were stored in a dessicator at room temperature for >9 months.
18. 11. Methylisocyanate polystyrene is currently available from Novabiochem.
19. 12. Further mechanistic studies have demonstrated that isocyanate formation is a reversible process in the absence of a nucleophile accounting for the low yield of urea product.
20. 13. Freer, R.; McKillop, A. Synth. Commun. 1996, 26(2), 331-349. More recently, Thavonekham has published similar results: Thavonekham, B. Synthesis 1997, 10, 1189-1194.
21. 13. Freer, R.; McKillop, A. Synth. Commun. 1996, 26(2), 331-349. More recently, Thavonekham has published similar results: Thavonekham, B. Synthesis 1997, 10, 1189-1194.
22. 14. Insufficient washing of resin in between amine additions resulted in contamination of expected urea products with previously formed urea products.
23. 15. All products gave the expected M+1 peak by electrospray MS.
24. 3) δ 1.30-1.50 (m, 2H), 1.85-1.95 (m, 2H), 2.05-2.20 (m, 2H), 2.70-2.85 (m, 2H), 3.52 (s, 2H), 3.53-3.70 (m, 1H), 4.33 (d, J = 5.73 Hz, 2H), 4.57 (brs, 1H), 4.93 (br s, 1H), 7.15-7.45 (m, 10H).