The expedient synthesis of 4,2′-difluoro-5′-(7- trifluoromethylimidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile, a GABA α2/3 agonist

Organic Process Research and Development

Volumn 10, Issue 3, 2006, Pages 398-402

  Cameron, Mark ^a   Foster, Bruce S ^a   Lynch, Joseph E ^a   Shi, Yao Jun ^a   Dolling, Ulf H ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33745751315     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op050217j     Document Type: Article

References (28)

1. (a) Mckernan, R. M.; Rosahl, T. W.; Reynolds, D. S.; Sur, C.; Wafford, K. A.; Atack, J. R.; Farrar, S.; Myers, J.; Cook, G.; Ferris, P.; Garret, L.; Bristow, L.; Marshall, G.; Macaulay, A.; Brown, N.; Howell, D. O.; Moore, K. W.; Carling, R. W.; Street, L. J.; Castro, J. L.; Ragan, C. I.; Dawson, G. R.; Whiting, P. J. Nat. Neurosci. 2000, 3, 587.
2. (b) Chambers, M. S.; Goodacre, S. C.; Hallet, D. J.; Jennings, A.; Jones, P.; Lewis, R. T.; Moore, K. W.; Russell, M. G. N.; Street, L. J.; Szekeres, H. J. Imidazol-Pyrimidine Derivatives as Ligands for GABA Receptors. World Patent WO 02/074773 A1, September 26, 2002.
3. Aoyagi, Y.; Inoue, A.; Koizumi, I.; Hashimoto, R.; Tokunaga, K.; Gohma, K.; Komatsu, J.; Seikine, K.; Miyafuji, A.; Kunoh, J.; Homma, R.; Akita, Y.; Ohta, A. Heterocycles 1992, 33, 257-272.
4. Pivsa-Art, S.; Satoh, T.; Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1998, 71, 467-473.
5. Kondo, Y.; Komine, T.; Sakamoto, T. Org. Lett. 2000, 2, 3111-3113.
6. Li, W.; Nelson, D. P.; Jensen, M. S.; Hoerrner, R. S.; Javadi, G. J.; Cai, D.; Larsen,. R. D. Org. Lett. 2003, 5, 4835-4837.
7. Jensen, M. S.; Hoermer, R. S.; Li, W.; Nelson, D. P.; Javadi, G. J.; Dormer, P. G.; Cai, D.; Larsen, R. D. J. Org. Chem. 2005, 70, 6034-6039.
8. Colla, A.; Martins, A. P.; Clar.; G.; Krimmer, S.; Fischer, P. Synthesis 1991, 483-486.
9. By HPLC assay. 5:5a ratio 24:1. 5a readily rejected by swishing 5 in heptane.
10. 3, or dicyclohexylmethylamine.
11. 2.
12. 1H NMR spectrum.
13. Dimroth, O. Annals 1909, 364, 183.
14. Dimroth, O. Annals 1927, 459, 39.
15. Vaughen, K.; LaFrance, R. J.; Tang, Y. J. Heterocycl. Chem. 1991, 28, 1709-1713.
16. Little, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10-11.
17. Beller, M.; Zapf, A. Synlett 1998, 792-793.
18. Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem., Int. Ed. 1998, 37, 481-483.
19. Riermeier, T. H.; Zapf, T. H.; Beller, M. Top Catal. 1997, 4, 301-309.
20. Hermann, W. A.; Brossmer, C.; Reisinger, C.-P.; Reirmeier, T. H.; Ofele, K.; Beller, M. Chem. Eur. J. 1997, 3, 1357-1364.
21. Hermann, W. A.; Brossmer, C.; Ofele, K.; Beller, M.; Fischer, H. J. Mol. Catal. A 1995, 103, 133-146.
22. Hermann, W. A.; Brossmer, C.; Ofele, K.; Resinger, C.-P.; Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int. Ed. Engl. 1995, 34, 1844-1848.
23. Herrmann, W. A.; Elison, M.; Fischer, J.; Köcher, C.; Artus, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2371-2374.
24. Snieckus, V. Chem. Rev, 1990, 90, 879-933.
25. Kalinin, A. V.; Bower, J. F.; Riebel, P.; Snieckus, V. J. Org. Chem, 1999, 64, 2986-2987.
26. Kristensen, J.; Lysén, M.; Vesdø P.; Begtrup, M. Org. Lett, 2001, 3, 1435-1437.
27. Jeffrey, T. J. Chem. Soc., Chem. Commun, 1984, 1287-1289.
28. Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev, 2000, 100, 3009-3006.