The application of high-throughput synthesis and purification to the preparation of ethanolamines

Tetrahedron Letters

Volumn 38, Issue 35, 1997, Pages 6149-6152

  Shuker, Anthony J ^a   Siegel, Miles G ^a   Matthews, Donald P ^a   Weigel, Leland O ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ETHANOLAMINE DERIVATIVE;

ARTICLE; DRUG PURIFICATION; DRUG SYNTHESIS; ION EXCHANGE CHROMATOGRAPHY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS;

EID: 0030839735     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01421-4     Document Type: Article

References (20)

1. In 1995, thirteen of the top two hundred drugs ranked by prescription volume were ethanolamine-based compounds (source: Pharmacy Times, April 1996).
2. Hieble, J. P.; Bond, R. A. TiPS 1994, 15, 397.
3. Hieble, J. P.; Bondinell, W. E.; R.R. Ruffolo, J. J. Med. Chem. 1995, 38, 3415.
4. Ruffolo, R. R.; Bondinell, W. E.; Hieble, J. P. J. Med. Chem. 1995, 38, 3681.
5. Kick, E. K.; Ellman, J. A. J. Med. Chem. 1995, 38, 1427.
6. Wang, G. T.; Li, S.; Wideburg, N.; Krafft, G. A.; Kempf, D. J. J. Med. Chem. 1995, 38, 2995.
7. Rotella, D. P. J. Am. Chem. Soc. 1996, 118, 12246.
8. Siegel, M. G.; Hahn, P. J.; Dressman, B. A.; Fritz, J. E.; Grunwell, J. R.; Kaldor, S. W. Tetrahedron Lett. 1997, 38, 3357.
9. Cheng, S.; Comer, D. D.; Williams, J. P.; Myers, P. L.; Boger, D. L. J. Am. Chem. Soc. 1996, 118, 2567.
10. Lawrence, R. M.; Biller, S. A.; Fryszman, O. M.; Poss, M. A. Synthesis 1997, 553.
11. Gayo, L. M.; Suto, M. J. Tetrahedron Lett. 1997, 38, 513.
12. 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.
13. Chucholowski, A.; Masquelin, T.; Obrecht, D.; Stadlwieser, J.; Villalgordo, J. M. Chimia 1996, 50, 525.
14. Siegel, M. G.; Shuker, A. J.; .Droste, C. A.; Hahn, P. J.; Jesudason, C. D.; McDonald III, J. H.; Matthews, D. P.; Rito, C. J.; Thorpe, A. J. Mol. Diversity, submitted.
15. Atkins, R. K.; Frazier, J.; Moore, L. L.; Weigel, L. O. Tetrahedron Lett. 1986, 27, 2451.
16. The reaction between epoxide C and amine 5 was used as a model in this case. The corresponding product was also prepared independently for structural validation.
17. Other silylating agents examined included hexamethyldisilazane (HMDS) and trimethylsilylacetamide.
18. Varian SCX columns are sulfonic acid residues covalently linked to silica gel. These prepacked columns are particularly convenient in that they readily fit off the shelf automated solid phase extraction equipment.
19. The preparation of these molecules is exemplified in EP 764640 and EP 7649632.
20. 3) δ 7.43-7.10 (m, 9H), 4.61 (dd, J=6.1 and 10.9 Hz, 1H), 3.1 (br s, 1H), 2.64 (dd, J=6.8 and 13.6 Hz, 2H), 2.19 (dd, J=10.2 and 13.6 Hz, 2H), 1.46 (s, 3H), 1.44 (s, 3H).