Evaluation of kilogram-scale Sonagashira, Suzuki, and Heck coupling routes to oncology candidate CP-724,714

Organic Process Research and Development

Volumn 9, Issue 4, 2005, Pages 440-450

  Ripin, David H Brown ^a   Bourassa, Dennis E ^a   Brandt, Thomas ^a   Castaldi, Michael J ^a   Frost, Heather N ^a   Hawkins, Joel ^a   Johnson, Phillip J ^a   Massett, Stephen S ^a   Neumann, Karin ^a   Phillips, James ^a   Raggon, Jeffery W ^a   Rose, Peter R ^a   Rutherford, Jennifer L ^a   Sitter, Barbara ^a   Stewart III, A Morgan ^a   Vetelino, Michael G ^a   Wei, Lulin ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 23044509202     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op050039u     Document Type: Article

References (50)

1. Prepared in 75% by published methods from iodoanthranillic acid (5): (a) Edincott, M. M.; Alden, B. W.; Sherrell, M. L. J. Am. Chem. Soc. 1946, 68, 1303.
2. (b) Hudson, A. T.; Vile, S.; Barraclough, P.; Franzmann, K. W.; McKeown, S. C.; Page, M. J. World Patent WO9609294, 1996.
3. Prepared from propargylamine and BOC anhydride in methylene chloride at 0°C. The material is a low-melting solid (MP = ∼25-30°C) and was handled as a melt. Spectral data was consistent with that reported in the literature (ref 6).
4. Cheng, S.; Tarby, C. M.; Comer, D. D.; Williams, J. P.; Caporale, L. H.; Myers, P. L.; Boger, D. L. Bioorg. Med. Chem. 1996, 4, 727.
5. 2, methanol, water).
6. The LLNA (local lymph node assay) is an indicator as to whether a compound is a sensitizer.
7. Reviews: (a) Heck, R. F. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon: New York, 1991; Vol. 4, Chapter 4.3.
8. (b) Bräse, S.; deMeijere, A. In Metal-catalyzed Cross-coupling Reactions; Deiderich, F., Stang, P. J., Eds.; Wiley: New York, 1998; Chapter 3.
9. (c) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2.
10. (d) deMeijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379.
11. Heck reactions of aryl chlorides: (a) For an overview: Riermeier, T. H.; Zapf, A.; Beller, M. Top. Catal. 1997, 4, 301.
12. (b) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10.
13. (c) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem., Int. Ed. 1998, 37, 481.
14. (d) Beller, M.; Zapf, A. Synlett 1998, 792.
15. (e) Ben-David, Y.; Portnoy, M.; Gozin, M.; Milstein, D. Organometallics 1992, 11, 1995.
16. (f) Portnoy, M.; Ben-David, Y.; Milstein, D. Organometallics 1993, 12, 4734.
17. (g) Portnoy, M.; Ben-David, Y.; Rousso, I.; Milstein, D. Organometallics 1994, 13, 3465.
18. (h) Herrmann, W. A.; Brossmer, C.; Öfele, K.; Reisinger, C.-P.; Priermeier, T.; Beller, M.; Fischer H. Angew. Chem., Int. Ed. Engl. 1995, 34, 1844.
19. (i) Herrmann, W. A.; Elison, M.; Fischer J.; Köcher, C.; Artus, G. R. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 2371.
20. (j) Herrmann, W. A.; Brossmer, C.; Reisinger, C.-P.; Riermeier, T. H.; Öfele, K.; Beller, M. Chem. Eur. J. 1997, 3, 1357.
21. (a) Suzuki, A. In Metal-catalyzed Cross-coupling Reactions; Deiderich, F., Stang, P. J., Eds.; Wiley: New York, 1998; Chapter 3.
22. (b) Miyamura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
23. Suzuki reactions of aryl chlorides: (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37, 3387.
24. (b) Wolfe, J. P.; Buchwald, S. L. Angew. Chem., Int. Ed. 1999, 38, 2413.
25. (c) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020.
26. Decomposition with a release of > 1000 J/g occurs ∼228°C.
27. If less than 2 equiv of hydroborating agent are employed in the acetylene hydroboration, a number of impurities are formed in the Suzuki coupling at higher levels (vide supra).
28. Colberg, J. C.; Rane, A.; Vaquer, J.; Soderquist, J. A. J. Am. Chem. Soc. 1993, 115, 6065.
29. Anon. Aldrichimica Acta 1989, 22, 80.
30. (a) Evans, D. A.; Starr, J. T. Angew. Chem., Int. Ed. 2002, 41, 1787.
31. b) Arase, A.; Hoshi, M.; Mijin, A.; Nishi, K. Synth. Commun. 1995, 25, 1957.
32. As precedented by the instability of the dimesylate salt.
33. Concern about the presence of residual borane in the solids, possibly rendering them pyrrophoric, led to this decision.
34. Due to the solubility of 9-BBN.
35. Boiling Liquid Escaping Vapor Explosion.
36. Reisch, M. Chem. Eng. News 2002, 80, 7.
37. Sergeyev, S.; Hesse, M. Synth. Lett. 2002, 8, 1313.
38. All materials going into the final drug substance crystallization are filtered in solution or neat through a 1 μm filter prior to crystallization per an internal operating procedure.
39. Olofsson, K.; Sahlin, H.; Larhed, M.; Hallberg, A. J. Org. Chem. 2001, 66, 544.
40. Kawamoto, A. M.; Wills, M. J. Chem. Soc., Perkin Trans. 1 2001, 16, 1916.
41. Connell, R. D.; Rein, T.; Akermark, B.; Helquist, P. J. Org. Chem. 1988, 53, 3845.
42. Allan, R. D.; Johnston, G. A. R.; Kazlauskas, R.; Tran, H. W. J. Chem. Soc., Perkin Trans. 1 1983, 2983.
43. Johnson, T. R.; Silverman, R. B. Bioorg. Med. Chem. 1999, 7, 1625-1636.
44. Ripin, D. H. B.; Vetelino, M. Synlett 2003, 2353.
45. The solids melt into a solid wax if they are not entirely dried of residual solvent at a low temperature.
46. This rate acceleration was also observed on the salt-free isolated solids when TBABr was added. The TBABr is likely accelerating the Heck reaction via the Jeffery affect. Jeffery, T. Tetrahedron 1996, 52, 10113.
47. A majority of the optimization for the Heck reaction described in this section was conducted on an Anachem SK233 Workstation (www.reactarray.com). In this workstation, up to 10 reactions can be run at once with individual stirring and temperature control. Samples are taken via the liquid handler from the reactions at defined intervals and are quenched and diluted. Online HPLC analyses are then conducted to monitor quantities of starting materials, products, and byproducts. For another study using the Anachem SK233 Workstation, see: Armitage, M. A.; Smith, G. E.; Veal, K. T. Org. Process Res. Dev. 1999, 3, 189.
48. MOMCl is the product of methoxyacetyl chloride decomposition. Stadlwieser, J. Synthesis 1985, 5, 490. In addition to the hazards associated with MOMCl present in the reagent, one drum of methoxyacetyl chloride actually swelled on storage, presumably due to CO buildup during decomposition.
49. Ostwald, W. Lehrbuch Algemeinen Chem. 1896, 2, 444.
50. Toluene denatured ethanol.