The discovery and development of a safe, practical synthesis of ABT-869

Organic Process Research and Development

Volumn 13, Issue 6, 2009, Pages 1419-1425

  Kruger, Albert W ^a   Rozema, Michael J ^a   Chu Kung, Alexander ^a   Gandarilla, Jorge ^a   Haight, Anthony R ^a   Kotecki, Brian J ^a   Richter, Steven M ^a   Schwartz, Albert M ^a   Wang, Zhe ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 72449186083     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op900208y     Document Type: Article

References (27)

1. Ferrara, N.; Kerbel, R. S. Nature 2005, 438, 967-974.
2. Carmeliet, P.; Jain, R. K Nature 2000, 407, 249-257.
3. Dai, Y.; Hartandi, K.; Ji, Z.; Ahmed, A. A.; Albert, D. H.; Bauch, J. L.; Bouska, J. J.; Bousquet, P. F.; Cunha, G. A.; Glaser, K. B.; Harris, C. M.; Hickman, D.; Guo, J.; Li, J.; Marcotte, P. A.; Marsh, K. C.; Moskey, M. D.; Martin, R. L.; Olson, A. M.; Osterling, D. J.; Pease, L. J.; Soni, N. B.; Stewart, K. D.; Stoll, V. S.; Tapang, P.; Reuter, D. R.; Davidsen, S. K.; Michaelides, M. R. J. Med. Chem. 2007, 50, 1584-1597.
4. The first-generation route is similar to the route that emerged from Medicinal Chemistry.
5. 3 the rate of glass erosion was 0.0 cm/year, but small amounts of etching still occurred by visual inspection.
6. Metal oxides can catalyze the exothermic decomposition of hydrazine derivatives, see: Speight, J. G., Ed. Lange's Handbook of Chemistry; McGraw-Hill: New York, 2005.
7. For a general discussion on the safe use of hydrazine, see: Kuethe, J. T.; Childers, K. G.; Peng, Z.; Journet, M.; Humphrey, G. R.; Vickery, T.; Bachert, D.; Lam, T. T. Org. Process Res. Dev. 2009, 13, 576-580.
8. Hansen, K. B.; Balsells, J.; Dreher, S.; Hsiao, Y.; Kubryk, M.; Palucki, M.; Rivera, N.; Steinhuebel, D.; Armstrong, J. D.; Askin, D.; Grabowski, E. J. J. Org. Process Res. Dev. 2005, 9, 634-639.
9. Beck, G.; Degener, E.; Heitzer, H. Liebigs Ann. Chem. 1968, 716, 47-60.
10. Lukin, K.; Hsu, M. C.; Fernando, D.; Leanna, M. R. J. Org. Chem. 2006, 71, 8166-8172.
11. Intermediate A was prepared in ref 8 and found to cyclize to 10 in 75 °C (1 h, THF solvent).
12. Reaction calorimetry to determine ATR was done on a Mettler Toledo RC1 instrument.
13. Adiabatic calorimetry to screen for thermal stability was done on an TIAX ARC or a VSP2 system from Fauske. See http://www.fauske. com for more information.
14. Differential scanning calorimetry (DSC) was done on a Mettler DSC.
15. For a general Suzuki review, see: Bellina, F; Carpita, A.; Rossi, R. Synthesis 2004, 2419-2440.
16. For an aryl-chloride Suzuki review, see: Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176-4211.
17. For a survey of aryl-chloride Suzuki couplings in pharmaceutically relevant settings, see: Guram, A. S.; Wang, X.; Bunel, E. E.; Faul, M. M; Larsen, R. D.; Martinelli, M. J. J. Org. Chem. 2007, 72, 5104-5112.
18. Colacot, T. J.; Shea, H. A. Org. Lett. 2004, 6, 3731-3734.
19. 2 in Suzuki reactions, see: Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719-2724.
20. Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020-4028.
21. For a leading reference on the use of 16, see: Billingsley, K.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 3358-3366.
22. Billingsley, K. L; Anderson, K. W.; Buchwald, S. L. Angew. Chem., Int. Ed. 2006, 45, 3484-3488.
23. 2/12 catalyst system is similar to that used by Itoh, but precomplexation was not required in that case
24. 2 and phosphines lead to phosphine oxide formation. See: Amatore, C.; Jutand, A.; M'Barki, M. A. Organometallics 1992, 11, 3009-3013.
25. Ozawa, F.; Kubo, A.; Hayashi, T. Chem. Lett. 1992, 2177-2180.
26. There was significant scatter in the data at the 2 h time point. The 24 h conversion data is more important for definition of the critical oxygen concentration.
27. See the Supporting Information for a discussion of the apparatus and the method of estimating the required sparge time to reach the necessary dissolved oxygen level from the headspace measurement.