Synthesis of the quinolone ABT-492: Crystallizations for optimal processing

Organic Process Research and Development

Volumn 10, Issue 4, 2006, Pages 751-756

  Haight, Anthony R ^a   Ariman, Sema Z ^a   Barnes, David M ^a   Benz, Nancy J ^a   Gueffier, Francoix X ^a   Henry, Rodger F ^a   Hsu, Margaret C ^a   Lee, Elaine C ^a   Morin, Larry ^a   Pearl, Kurt B ^a   Peterson, Matthew J ^a   Plata, Daniel J ^a   Willcox, David R ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33746887838     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op060054e     Document Type: Article

References (25)

1. (a) Baskin, R. J.; Bowker, M. J.; Slater, B. J. Org. Process Res. Dev. 2000, 4, 427.
2. Myerson, A. S., Ed. Handbook of Industrial Crystallization; Butterworth-Heinemann: Woburn, MA, 1992.
3. (b) Desikan, S.; Anderson, S. R.; Meenan, P. A.; Toma, P. H. Curr. Opin. Drug Discovery Dev. 2000, 3, 723.
4. Mueller, M.; Schneeberger, R.; Wieckhusen, D.; Cooper, M. Org. Process Res. Dev. 2004, 3, 376.
5. (a) Harnett, S. J.; Fraise, A. P.; Andrews, J. M.; Jevons, G.; Brenwald, N. P.; Wise, R. Journal of Antimicrobial Chemotherapy 2004, 53, 783-792.
6. (b) Da Silva, A. D.; de Almeida, M. V.; de Souza, M. V. N.; Couri, M. R. C. Current Medicinal Chemistry 2003, 10, 21-39.
7. Barnes, D. M.; Christensen, A.; Engstrom, K. M.; Haight, A. R.; Hsu, M. C.; Lee, E. C.; Peterson, M.; Plata, D. J.; Raje, P.; Stoner, E. J.; Tedrow, J. S.; Wagaw, S. H. Org. Process Res. Dev. 2006, submitted.
8. Berge, S. M.; Bighley, L. D.; Monkhouse, D. C. J. Pharm. Sci. 1977, 66, 1.
9. If the excess TEOF was not hydrolyzed, N-formylation impurities of 3 and 4 were observed in the reaction mixture.
10. Particle size was measured by microscopy, as laser diffraction techniques proved unsuccessful in differentiating particles.
11. Kawashima, Y.; Okumura, M.; Takenaka, H. Science 1982, 216 (4550), 1127.
12. 90 of the chord length from 95 μm to 70 μm over 3 h.
13. Agitation was increased by increasing the rpm of the agitator blade in a vessel. Scaling up based on the power density (W/L) appeared to give comparable agglomerates on several scales.
14. Addition rates between 1 and 3 h were reproducibly obtained on scale with hold times of 2-5 hours
15. Impellers such as the A-310 used here are designed to improve axial flow and mixing with reduced power input.
16. Bates, R. Mixing Theory and Practice; Academic: New York; Vol. 1, Chapter 3, p 111.
17. This proved critical for the following NCS chlorination step which appeared to be catalyzed by Li and conversely inhibited by fluoride.
18. The solution concentration of 7b is the critical in the rate of interconversion between Forms II and III. Solution concentrations <20 mg/mL can require days for complete conversion.
19. EtOAc was added to decrease the viscosity of the mixture to improve the crystal growth.
20. For ease of operation, the seeds were added in a slurry. Lab experiments with dry seeding also was successful.
21. Slow addition was critical to avoid formation of Form II which does not convert in an acceptable time frame to Form III after the quench.
22. Solubilities: pH 8.5 = 4 mg/mL; 9.0 = 16 mg/mL; 9.5 = 55 mg/mL; 10.0 = 194 mg/mL
23. A retreating bar agitator was used with a tip speed of 9.6 m/min.
24. Docherty, R.; Clydesdale, G.; Roberts, K. J.; Bennema, P. J. Phys. D: Appl. Phys. 1991, 24, 89.
25. Even in the presence of seeds, the desupersaturation rate requires approximately 48 h at ∼38 °C to reach equilibrium in water versus <2 h in 20% aqueous 2-propanol.