First direct lithiation of 2-pyridylpiperazine on solid phase

Organic Letters

Volumn 4, Issue 10, 2002, Pages 1759-1761

  Gros, Philippe ^a   Louërat, Frédéric ^a   Fort, Yves ^a  

^a NANCY UNIVERSITÉ   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2 PYRIDYLPIPERAZINE; 2-PYRIDYLPIPERAZINE; CROSS LINKING REAGENT; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; HETEROCYCLIC COMPOUND; LITHIUM; PIPERAZINE DERIVATIVE; PYRIDINE DERIVATIVE;

ARTICLE; CHEMISTRY; SYNTHESIS;

CROSS-LINKING REAGENTS; HETEROCYCLIC COMPOUNDS; INDICATORS AND REAGENTS; LITHIUM; PIPERAZINES; PYRIDINES;

EID: 0037118360     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol025826f     Document Type: Article

References (28)

1. (a) Gallop, M. A.; Barrett, R. W.; Dower, W.; Fodor, S. P. A. Gordon, E. M. J. Med. Chem. 1994, 37, 1233. Gallop, M. A.; Barrett, R. W.; Dower, W.; Fodor, S. P. A. Gordon, E. M. J. Med. Chem. 1994, 37, 1385.
2. (a) Gallop, M. A.; Barrett, R. W.; Dower, W.; Fodor, S. P. A. Gordon, E. M. J. Med. Chem. 1994, 37, 1233. Gallop, M. A.; Barrett, R. W.; Dower, W.; Fodor, S. P. A. Gordon, E. M. J. Med. Chem. 1994, 37, 1385.
3. (b) Thompson, L.; Ellman, J. A. Chem. Rev. 1996, 96, 555-600.
4. (c) Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123.
5. (d) Ellman, J. A. Acc. Chem. Res. 1996, 29, 132. Hemkens, P. H.; Ottenheim, H. C.; Rees, D. Tetrahedron 1996, 52, 4527. Ellman, J. A. Acc. Chem. Res. 1996, 29, 132. Hemkens, P. H.; Ottenheim, H. C.; Rees, D. Tetrahedron 1997, 53, 5643.
6. (d) Ellman, J. A. Acc. Chem. Res. 1996, 29, 132. Hemkens, P. H.; Ottenheim, H. C.; Rees, D. Tetrahedron 1996, 52, 4527. Ellman, J. A. Acc. Chem. Res. 1996, 29, 132. Hemkens, P. H.; Ottenheim, H. C.; Rees, D. Tetrahedron 1997, 53, 5643.
7. (d) Ellman, J. A. Acc. Chem. Res. 1996, 29, 132. Hemkens, P. H.; Ottenheim, H. C.; Rees, D. Tetrahedron 1996, 52, 4527. Ellman, J. A. Acc. Chem. Res. 1996, 29, 132. Hemkens, P. H.; Ottenheim, H. C.; Rees, D. Tetrahedron 1997, 53, 5643.
8. (d) Ellman, J. A. Acc. Chem. Res. 1996, 29, 132. Hemkens, P. H.; Ottenheim, H. C.; Rees, D. Tetrahedron 1996, 52, 4527. Ellman, J. A. Acc. Chem. Res. 1996, 29, 132. Hemkens, P. H.; Ottenheim, H. C.; Rees, D. Tetrahedron 1997, 53, 5643.
9. (e) Krchnack, V.; Holladay, M. W. Chem. Rev. 2002, 102, 61.
10. Zhengong, L.; Ganesan, A. Synlett 1998, 405.
11. (a) Havez, S.; Begtrup, M.; Veso, P. J. Org. Chem. 1998, 63, 7418.
12. (b) Havez, S.; Begtrup, M.; Veso, P.; Anderson, K.; Ruhland, T. Synthesis 2001, 6, 909.
13. (a) Gros, Ph.; Fort, Y.; Caubère, P. J. Chem. Soc., Perkin Trans. 1 1997, 20, 3071.
14. (b) Ph. Gros, Y. Fort, J. Chem. Soc., Perkin Trans. 1 1998, 21, 3515.
15. (c) Ph. Gros, Y. Fort, Synthesis 1999, 5, 754.
16. (d) Gros, Ph.; Ben Younès-Millot, C.; Fort, Y. Tetrahedron Lett. 2000, 41, 303.
17. (e) Choppin, S.; Gros, Ph.; Fort, Y. Org. Lett. 2000, 2, 803.
18. (f) Choppin, S.; Gros, Ph.; Fort, Y. Eur. J. Org. Chem. 2001, 3, 603.
19. (g) Rodriguez, A.; Gros, Ph.; Fort, Y. Tetrahedron: Asymmetry 2001, 12, 2631.
20. (h) Gros, Ph.; Choppin, S.; Mathieu, J.; Fort, Y. J. Org. Chem. 2002, 67, 234.
21. (i) Cuperly, D.; Gros, Ph.; Fort, Y. J. Org. Chem. 2002, 67, 238-241.
22. (a) Thurkauf, A.; Yuan, J.; Chen, X.; He, X.; Wasley, J. W. F.; Hutchinson A.; Woodruff, K.; Meade, R.; Hoffman, D. C.; Donovan, H.; Jones-Hertzog, D. K. J. Med. Chem. 1997, 40, 1.
23. (b) Manetti, D.; Bartolini, A.; Borea, P.; Bellucci, C.; Dei, S.; Ghelardini, C.; Gualtieri, F.; Romanelli, M.; Scapecchi, S.; Teodori, E.; Varani, K. Bioorg. Med. Chem. 1999, 7, 457.
24. (c) Mylari, B. L.; Oates, P. J.; Beebe, D. A.; Brackett, N. S.; Coutcher, J. B.; Dina, M. S.; Zembrowski, W. J. J. Med. Chem. 2001, 44, 2695.
25. This reagent was used to release arylpiperazines, see: Conti, P.; Demont, D.; Cals, J.; Ottenheijm, H.; Leysen, D. Tetrahedron Lett. 1997, 38, 2945.
26. Scherrington, D. C. Chem. Commun. 1998, 2275
27. Under the optimized conditions (8 equiv of BuLi-LiDMAE, rt, 6 h), toluene was metalated in a trace amount (1-2%).
28. General procedure for C-6 functionalization of 2: Resin 2 (0.5 g 0.96 mmol) was first preswelled for 15 min in anhydrous toluene (10 mL). 2-Dimethylaminoethanol (0.8 mL, 8 mmol) was then added under a nitrogen stream. The suspension was cooled at -5°C, and BuLi (10 mL of a 1.6 M solution in hexanes; 16 mmol) was added dropwise. After 15 min, the mixture was allowed to warm at room temperature and stirred for 6 h. The red suspension was then cooled at -5°C, and a solution of appropriate electrophile (9 mmol) in THF (10 mL) was added dropwise. At the end of addition, stirring was continued for 1 h at 0°C and overnight at room temperature. The reaction was then hydrolyzed at 0°C with water (3 mL). The resin was then filtered and washed with water, THF, and ether. After drying, the resin was suspended in dichloromethane (10 mL and treated with methyl chlroformate (0.4 mL, 5.2 mmol) for 3 h at room temperature. The resin was filtered and washed with dichloromethane (20 mL). After evaporation of solvents under reduced pressure, the crude product was purified by column chromatography.