Fully automated polymer-assisted synthesis of 1,5-biaryl pyrazoles

Journal of Combinatorial Chemistry

Volumn 6, Issue 3, 2004, Pages 332-339

  Vickerstaffe, Emma ^a   Warrington, Brian H ^a   Ladlow, Mark ^a   Ley, Steven V ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PYRAZOLE DERIVATIVE; ORGANIC COMPOUND; POLYMER; SOLUTION AND SOLUBILITY;

ARTICLE; AUTOMATION; FILTRATION; MOLECULAR PROBE; POLYMERIZATION; PURIFICATION; ROBOTICS; SYNTHESIS; CATALYSIS; CHEMICAL STRUCTURE; COMBINATORIAL CHEMISTRY; SOLUTION AND SOLUBILITY;

CATALYSIS; COMBINATORIAL CHEMISTRY TECHNIQUES; MOLECULAR STRUCTURE; ORGANIC CHEMICALS; POLYMERS; PYRAZOLES; SOLUTIONS;

EID: 2542589435     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc049977g     Document Type: Article

References (35)

1. (a) Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res. 1996, 29, 144.
2. (b) Li, J.; Murray, C. W.; Waszkowycz, B.; Young, S. C. Drug Discovery Today 1998, 3, 105.
3. (c) Kenny, B. A.; Bushfield, M.; Parry-Smith, D. J.; Fogarty, S.; Treherne J. M. Prog. Drug Res. 1998, 51, 245.
4. (d) Golebiowski, A.; Klopfenstein, S. R.; Portlock, D. E. Curr. Opin. Chem. Biol. 2001, 5, 273.
5. (a) Yoshida, J.; Itami, K. Chem. Rev. 2002, 102, 3693.
6. (b) Ganesan, A. Drug Discovery Today 2002, 7, 47.
7. (c) Dörwald, F. Z. Organic Synthesis on Solid Phase; Wiley-VCH: Weinheim, 2000.
8. (d) Obrecht, D.; Villalgordo, J. M. Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries; Pergamon: Oxford, 1998.
9. (a) Bailey, N.; Cooper, A. W. J.; Deal, M. J.; Dean, A. W.; Gore, A. L.; Hawes, M. C.; Judd, D. B.; Merritt, A. T.; Storer, R.; Travers, S.; Watson, S. P. Chimia 1997, 51, 832.
10. (b) Hughes, I.; Hunter, D. Curr. Opin. Chem. Biol. 2001, 5 (3), 243.
11. (a) Drewry, D. H.; Coe, D. M.; Poon, S. Med. Res. Rev. 1999, 79, 97.
12. (b) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815.
13. (c) Kirschning A.; Monenschein, H.; Wittenberg, R.; Angew. Chem., Int. Ed. Engl. 2001, 40, 650.
14. (d) Flynn, D. L.; Berk, S. C.; Makara, G. M. Curr. Opin. Drug Discovery Dev. 2002, 5, 580.
15. (e) Ley, S. V.; Baxendale, I. R. Nat. Rev. Drug Discovery 2002, 1, 573.
16. Parlow, J. J.; Naing, W.; South, M. S.; Flynn, D. L. Tetrahedron Lett. 1997, 38, 7959.
17. (a) Thompson, L. A. Curr. Opin. Chem. Biol. 2000, 4, 324.
18. (b) Flynn, D. L. Med. Res. Rev. 1999, 19, 408.
19. For example: (a) Carpanone: Baxendale, I. R.; Lee, A.-L.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 2002, 1850; (b) Plicamine: Baxendale, I. R.; Ley, S. V.; Nessi M.; Piutti, C. Tetrahedron 2002, 6285.
20. For example: (a) Carpanone: Baxendale, I. R.; Lee, A.-L.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 2002, 1850; (b) Plicamine: Baxendale, I. R.; Ley, S. V.; Nessi M.; Piutti, C. Tetrahedron 2002, 6285.
21. (a) Caldarelli, M.; Habermann J.; Ley, S. V. Bioorg. Med. Chem. Lett. 1999, 9, 2049;
22. (b) Lee A.; Ellman, J. A. Org. Lett. 2001, 3, 3707.
23. (c) Baxendale I. R.; Ley, S. V. Bioorg. Med. Chem. Lett. 2000, 10, 1983.
24. Vickerstaffe, E.; Warrington, B. H.; Ladlow, M.; Ley, S. V. Org. Biomol. Chem. 2003, 1, 2419.
25. The Zinsser Sophas M6 robotic synthesiser (Zinsser Analytic, www.zinsser-analytic.com) was used in this study.
26. Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.; Carter, J. S.; Collins, P. W.; Docter, S.; Graneto, M. J.; Lee, L. F.; Malecha, J. W.; Miyashiro, J. M.; Rogers, R. S.; Rogier, D. J.; Yu, S. S.; Anderson, G. D.; Burton, E. G.; Cogburn, J. N.; Gregory, S. A.; Koboldt, C. M.; Perkins, W. E.; Seibert, K.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson, P. C. J. Med. Chem. 1997, 40, 1347.
27. (a) Wachter, M.; Ferro, M. U.S. Patent 4826868, 1989.
28. (b) Argentieri, D.; Ritchie, D.; Tolman, E.; Ferro, M.; Wachter, M.; Mezick, J.; Capetola, R. FASEB J. Anti-Inflammatory Agents 1988, 2, A369.
29. (c) Murray, W.; Wachter, M.; Barton, D.; Forero-Kelly, Y. Synthesis 1991, 18.
30. Booth, R. J.; Hodges, J. C. J. Am. Chem. Soc. 1997, 779, 4882.
31. In practice, a higher resin loading allows the use of a smaller quantity per reaction well. This leads to a less viscous suspension and affords better vortex mixing.
32. Gooding, O. W.; Vo. L.; Bhattacharyya, S.; Labadie, J. W. J. Comb. Chem. 2002, 4, 576.
33. This study was performed using a Gilson ReactArray workstation connected to an analytical HPLC (www.reactarray.com).
34. 1 carbonyl centres in these cases.
35. In our experience, when compared to the corresponding manual process, automation of multistep PASP chemistries may lead to some slightly lower isolated yields. This is not a limiting issue, but is largely a consequence of minimizing resin wash volumes and restrictions imposed by the synthesis robot. More importantly, from a high-throughput perspective, compound purities are unaltered for both manual and automated processes.