Generation of secondary alkyl amines on solid support by borane reduction: Application to the parallel synthesis of PPAR ligands

Synthesis

Volumn , Issue 7, 1997, Pages 778-782

  Brown, Peter J ^a   Hurley, Kevin P ^a   Stuart, L William ^a   Willson, Timothy M ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYL GROUP; AMINE; BORANE DERIVATIVE; FIBRIC ACID DERIVATIVE; LIGAND; PEROXISOME PROLIFERATOR;

ALKYLATION; CHEMICAL STRUCTURE; ORGANIC CHEMISTRY; PROTON NUCLEAR MAGNETIC RESONANCE; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; REVIEW; SOLID PHASE EXTRACTION; SYNTHESIS;

EID: 0030808173     PISSN: 00397881     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1997-1415     Document Type: Review

References (28)

1. (a) Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233.
2. (b) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385.
3. Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555.
4. DeWitt, S. H.; Kiely, J. S.; Stankovic, C. J.; Schroeder, M. C.; Cody, D. M. R.; Pavia, M. R. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6909.
5. Meyers, H. V.; Dilley, G. J.; Durgin, T. L.; Powers, T. S.; Winssinger, N. A.; Zhu, H.; Pavia, M. R. Molecular Diversity 1995, 1, 13.
6. Wang, G. T.; Li, S.; Wideburg, N.; Krafft, G. A.; Kempf, D. J. J. Med. Chem. 1995, 38, 2995.
7. Tempest, P. A.; Brown, S. D.; Armstrong, R. W. Angew. Chem. 1996, 108, 689; Angew. Chem. Int. Ed. Engl. 1996, 35, 640.
8. Tempest, P. A.; Brown, S. D.; Armstrong, R. W. Angew. Chem. 1996, 108, 689; Angew. Chem. Int. Ed. Engl. 1996, 35, 640.
9. Borch, R. F.; Bernstein, M. D.; Durst, H. D. J. Am. Chem. Soc. 1971, 93, 2897.
10. Gordon, D. W.; Steele, J. Bioorg. Med. Chem. Lett. 1995, 5, 47 50.
11. Green, J. J. Org. Chem. 1995, 60, 4287.
12. Salvi, J. P.; Walchshofer, N.; Paris, J. Tetrahedron Lett. 1994, 35, 1181.
13. The Merck Index, 12th ed.; Budavari, S., Ed.; Merck Research Laboratories: Whitehouse Station, NJ; 1996.
14. Kliewer, S. A.; Sundseth, S. S.; Jones, S. A.; Brown, P. J.; Wisely, G. B.; Kobel, C. S.; Devchand, P.; Wahli, W.; Willson, T. M.; Lenhard, J. M.; Lehmann, J. M. Proc. Natl. Acad. Sci., U.S.A., in press.
15. Fibrate is the trivial name for derivatives of 2-phenoxyisobutyric acid.
16. Bargellini, G. Gazz. Chim. Ital. 1906, 36, 337.
17. Mergler, M.; Nyfeler, R.; Gosteli, J.; Grogg, P. Chem. Biol., Proc. Am. Pept. Symp. 10th 1988, 259.
18. Mukaiyama, T. Angew. Chem. 1979, 91, 798; Angew. Chem. Intl. Ed. Engl. 1979, 10, 707.
19. Mukaiyama, T. Angew. Chem. 1979, 91, 798; Angew. Chem. Intl. Ed. Engl. 1979, 10, 707.
20. Khan, N. M.; Arumugam, V.; Balasubramanian. S. Tetrahedron Lett. 1996, 37, 4819.
21. Szardenings, A. K.; Burkoth, T. S.; Look, G. C.; Campbell, D. A. J. Org. Chem. 1996, 61, 6720. These authors report that, even under neutral conditions, reductive alkylation of Gly gave mixtures of secondary and tertiary amines.
22. 3CN. With non-aryl aldehydes the intermediate imine was unstable, and only recovered amine was isolated. Stuart, L. W., unpublished results.
23. A similar coupling/reduction sequence has recently been reported in the synthesis of N-alkylcarbamate oligomers: Paikoff, S. J.; Wilson, I. E.; Cho, C. Y.; Schultz, P. G. Tetrahedron Lett. 1996, 37, 5653.
24. (a) Franzmann, K. W.; O'Connor, K. J.; Hawke, R. L.; Chapman, J. M. PCT Int. Appl. WO 9210468, 1992; Chem. Abstr. 1992, 117, 212163.
25. (b) Hawke, R. L.; Chapman, J. M.; Winegar, D. A.; Salisbury, J. S.; Welch, R. M.; Player, M. A. Brown, A.; Wu, Z.; Seyda, K.; Foshee, M. K.; Sundseth, S. S.; Franzmann, K. W.; Sigel, C. J. Lipid Res., in press.
26. The following carboxylic acids were used: heptanoic acid, phenylacetic acid, 2-phenoxypropionic acid and 3,5-ditrifluoromethylbenzoic acid. The following aryl isocyanates were used: 4-fluorophenyl isocyanate, 2,4-dimethoxyphenyl isocyanate, 4-acetylphenyl isocyanate and 2,3-dichlorophenyl isocyanate.
27. The products 1m-p contained 5 7% of unreduced amide. In solution, benzamides are known to be poorer substrates for borane reduction than alkyl amides: Brown, H. C.; Heim. P. J. Org. Chem. 1973, 38, 912.
28. Mor, G.; Lichtenstein, N. Isr. J. Chem. 1970, 8, 595.