Identification and suppression of a dimer impurity in the development of delafloxacin

Organic Process Research and Development

Volumn 13, Issue 1, 2009, Pages 54-59

  Hanselmann, Roger ^a   Johnson, Graham ^a   Reeve, Maxwell M ^a   Huang, Shu Ting ^b  

^a Rib X Pharmaceuticals Incorporated   (United States)

^b ScinoPharm Taiwan Ltd   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 61449171169     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op800238q     Document Type: Article

References (18)

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2. (b) Seybold, U.; Kourbatova, E. V.; Johnson, J. G.; Halvosa, S. J.; Wang, Y. F.; King, M. D.; Ray, S. M.; Blumberg, H. M. Clin. Infect. Dis. 2006, 42, 647.
3. (c) Tenover, F. C.; McDougal, L. K.; Goering, R. V.; Killgore, G.; Projan, S. J.; Patel, J. B.; Dunman, P. M. J. Clin Microbiol. 2006, 44, 108.
4. Klevens, R. M.; Edwards, J. R.; Tenover, F. C.; McDonald, L. C.; Horan, T.; Gaynes, R. Clin. Infect. Dis. 2006, 42, 389.
5. Bush, K. Clin. Microbiol. Infect. 2004, 10 (Suppl. 4), 10.
6. Emmerson, A. M.; Jones, A. M. J. Antimicrob. Chemother. 2003, 51 (Suppl. Sl), 13.
7. Delafloxacin was initially developed by Wakunaga Pharmaceuticals and Abbott Laboratories and was subsequently licensed by Rib-X Pharmaceuticals, Inc.
8. (a) Haight, A. R.; Ariman, S. Z.; Barnes, D. M.; Benz, N. J.; Gueffier, F. X.; Henry, R. F.; Hsu, M. C.; Lee, E. C.; Morin, L.; Pearl, K. B.; Peterson, M. J.; Plata, D. J.; Willcox, D. R. Org. Process Res. Dev. 2006, 4, 751.
9. (b) Barnes, D. M.; Christesen, A. C.; Engstrom, K. M.; Haight, A. R.; Hsu, M. C.; Lee, E. C.; Peterson, M. J.; Plata, D. J.; Raje, P. S.; Stoner, E. J.; Tedrow, J. S.; Wagaw, S. Org. Process Res. Dev. 2006, 4, 803.
10. (a) Yazaki, A.; Niino, Y.; Ohshita, Y.; Hirao, Y.; Amano, H.; Hayashi, N.; Kuramoto, Y. PCT Int. Appl. WO 9711068, 1997. CAN: 126, 305587.
11. (b) Yazaki, A.; Aoki, S. PCT Int. Appl. WO 2001034595 2001. CAN: 134, 366811.
12. The experimental table and results can be found in the Supporting Information.
13. Available from Mettler-Toledo, Inc., 1900 Polaris Parkway, Columbus, OH 43240, U.S.A.
14. In order to determine the amount of 4, the chlorinated samples 2 were saponified to 3.
15. The experimental design and analysis were conducted with JMP, Design of Experiments, Version 7, SAS Institute Inc., Cary, NC, U.S.A., 1989-2007, using a stepwise fit followed by a standard least squares method.
16. Methyl acetate containing less than 500 ppm water was used, prior to adjustment as required by the appropriate experiment in the DoE.
17. A more detailed analysis can be found in the Supporting Information.
18. Saponification and subsequent epoxide formation of 16 prior to condensation with 3 or 17 cannot be ruled out.