Use of solid supported nucleophiles and electrophiles for the purification of non-peptide small molecule libraries

Tetrahedron Letters

Volumn 37, Issue 40, 1996, Pages 7193-7196

  Kaldor, Stephen W ^a   Siegel, Miles G ^a   Fritz, James E ^a   Dressman, Bruce A ^a   Hahn, Patric J ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; UREA DERIVATIVE;

ARTICLE; DRUG PURIFICATION; DRUG SYNTHESIS; TECHNIQUE;

LETHRINIDAE;

EID: 0030607141     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01636-X     Document Type: Article

References (24)

1. 1. Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555-600.
2. 2. Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res. 1996, 29, 144-154.
3. 3. DeWitt, S. H.; Czarnik, A. W. Acc. Chem. Res. 1996, 29, 114-122.
4. 4. Früchtel, J. S.; Jung, G. Ang. Chem. Int. Ed. Eng. 1996, 35, 17-42.
5. 5. Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
6. 6. This is distinct from the well precedented use of solid supported reagents and catalysts to effect reactions, where typically one of the reactants or reagents is on solid support: (equation presented) see: Preparative Chemistry Using Supported Reagents; Laszlo, P. ed.; Academic Press, Inc.: San Diego, 1987; Akelah, A.; Sherrington, D. C. Chem. Rev. 1981, 81, 557-587.
7. 6. This is distinct from the well precedented use of solid supported reagents and catalysts to effect reactions, where typically one of the reactants or reagents is on solid support: (equation presented) see: Preparative Chemistry Using Supported Reagents; Laszlo, P. ed.; Academic Press, Inc.: San Diego, 1987; Akelah, A.; Sherrington, D. C. Chem. Rev. 1981, 81, 557-587.
8. 7. Armstrong has applied "resin capture" to covalently link solution phase reaction products to a resin; see Keating, T. A.; Armstrong, R. W. J. Am. Chem. Soc. 1996, 118, 2574-2583, and references cited therein.
9. 8. Fréchet et al. have employed a solid supported amine to remove exo-methylene lactone contaminants from natural oils; see Cheminat, A.; Benezra, C.; Farrall, M. J.; Fréchet, J. M. J. Can. J. Chem. 1981, 59, 1405-1414, and references cited therein.
10. 9. For the use of solid supported piperazine as a scavenger of dibenzofulvene, see Carpino, L. A.; Mansour, E. M. E.; Knapczyk, J. J. Org. Chem. 1983, 48, 666-669, and references cited therein.
11. 10. Seymour, E.; Fréchet, J. M. M. Tetrahedron Lett. 1976, 3669-3672.
12. 1H NMR and high resolution mass spectral data.
13. 12. Rebek, J.; Brown, D.; Zimmerman, S. J. Am. Chem. Soc. 1975, 97, 4407-4408.
14. 13. In some instances we found it difficult to drive reactions to completion to consume the alkylating agent. In these cases, final purification using solid phase extraction provided high purity products.
15. 14. Amberlite IRA 400 borohydride exchange resin, available from Aldrich Chemical Co.
16. 15. Frechet, J. M.; Schuerch, C. J. Am. Chem. Soc. 1971, 93, 492-496.
17. 16. To insure that boron derived from the reducing resin was not contaminating the final products, a representative product was analyzed by atomic emission and found to contain less than 0.08% boron.
18. 17. Leznoff, C. C.; Dixit, D. M. Can. J. Chem. 1977, 55, 3351-3555.
19. 18. Use of polymer-supported isocyanate as scavenger under these conditions results in acetylation of the excess secondary amine; see ref. 12.
20. 19. A few examples of "stubless" SPOS have appeared recently: a) Plunkett, M. J.; Ellman, J. A. J. Org. Chem. 1995, 60, 6006-6007;
21. b) Chenera, B.; Finkelstein, J. A.; Veber, D. F. J. Am. Chem. Soc. 1995, 117, 11999-12000;
22. c) Sucholeiki, I. Tetrahedron Lett. 1994, 35, 7307-7310.
23. 20. Resin cleavage has been exploited as a further diversification reaction: a) Backes, B. J.; Virgilio, A. A.; Ellman, J. A. J. Am. Chem. Soc. 1996, 118, 3055-3056;
24. b) Han, Y.; Walker, S. D.; Young, R. N. Tetrahedron Lett. 1996, 37, 2703-2706.