Journal of the American Chemical Society
Article
a
Scheme 4. Synthesis of Nilotinib Base
a
Reagents and conditions: (a) KOtBu (5.5 equiv), THF, rt, 12 h; 90%. (b) 4 (1.05 equiv), KOtBu (5.5 equiv), THF, rt, 12 h; 85%.
Chem.Eur. J. 2004, 10, 5607. (e) Ma, D.; Cai, Q. Synlett 2004, 128.
(f) Zhang, H.; Cai, Q.; Ma, D. J. Org. Chem. 2005, 70, 5164. (g) Liu,
L.; Frohn, M.; Xi, N.; Dominguez, C.; Hungate, R.; Reider, P. J. J. Org.
Chem. 2005, 70, 10135. (h) Jerphagnon, T.; van Link, G. P. M.; de
Vries, J. G.; van Koten, G. Org. Lett. 2005, 7, 5241. (i) Altman, R. A.;
Buchwald, S. L. Org. Lett. 2006, 8, 2779. (j) Xie, Y.-X.; Pi, S.-F.; Wang,
J.; Yin, D.-L.; Li, J.-H. J. Org. Chem. 2006, 71, 8324. (k) Altman, R. A.;
Koval, E. D.; Buchwald, S. L. J. Org. Chem. 2007, 72, 6190. (l) Zhu, L.;
Cheng, L.; Zhang, Y.; Xie, R.; You, J. J. Org. Chem. 2007, 72, 2737.
(m) Zhu, L.; Guo, P.; Li, G.; Lan, J.; Xie, R.; You, J. J. Org. Chem.
2007, 72, 8535. (n) Lv, X.; Bao, W. J. Org. Chem. 2007, 72, 3863.
(o) Taillefer, M.; Xia, N.; Ouali, A. Angew. Chem., Int. Ed. 2007, 46,
934. (p) Zhu, L.; Li, G.; Luo, L.; Guo, P.; Lan, J.; You, J. J. Org. Chem.
2009, 74, 2200. (q) Liang, L.; Li, Z.; Zhou, X. Org. Lett. 2009, 11,
3294. (r) Chen, H.; Wang, D.; Wang, X.; Huang, W.; Cai, Q.; Ding, K.
Synthesis 2010, 1505. (s) Correction: Chen, H.; Wang, D.; Wang, X.;
Huang, W.; Cai, Q.; Ding, K. Synthesis 2011, 2684.
SNAr or Cu-based systems have not been reported to date.
Thus, the present Pd catalyst system complements existing
SNAr-based and Cu-catalyzed N-arylation methods. Studies of
the Pd-catalyzed arylation of other five-membered nitrogen
heterocycles are currently underway in our laboratory.
ASSOCIATED CONTENT
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S
* Supporting Information
Complete refs 1a and 20d, experimental procedures, product
1
characterization, and copies of H and 13C NMR spectra. This
material is available free of charge via the Internet at http://
AUTHOR INFORMATION
Corresponding Author
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(7) (a) Collman, J. P.; Zhong, M. Org. Lett. 2000, 2, 1233.
(b) Collman, J. P.; Zhong, M.; Zeng, L.; Costanzo, S. J. Org. Chem.
2001, 66, 1528. (c) Collman, J. P.; Zhong, M.; Zhang, C.; Costanzo, S.
J. Org. Chem. 2001, 66, 7892. (d) Yu, X.-Q.; Yamamoto, Y.; Miyaura,
N. Chem.Asian J. 2008, 3, 1517.
ACKNOWLEDGMENTS
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This work was supported by National Institutes of Health
(GM58160). S.U. thanks the Japan Society for the Promotion
of Sciences (JSPS) for a Postdoctral Fellowship for Research
Abroad. We thank Dr. Andrew T. Parsons for helpful
discussions and assistance with the preparation of this
manuscript.
(8) For reviews, see: (a) Bellina, F.; Rossi, R. Adv. Synth. Catal. 2010,
352, 1223. (b) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003,
42, 5400. (c) Monnier, F.; Taillefer, M. Angew. Chem., Int. Ed. 2009,
48, 6954.
(9) Excellent N1 selectivities (N1/N3 = 17/1 and higher) have been
reported only for a few aryl iodide substrates, aryl bromides with bulky
ortho substituents, and 4-arylimidazoles (see refs 6b, 6k, and 6p). N-
Arylations of 4-methylimidazoles with non-ortho-substituted aryl
bromides showed moderate N1 selectivities (N1/N3 = 4.1−5.7/1)
(see refs 4, 6k, 6m, 6r, and 28).
REFERENCES
■
(1) (a) Kantarjian, H.; et al. N. Engl. J. Med. 2006, 354, 2542.
(b) Weisberg, E.; Manley, P.; Mestan, J.; Cowan-Jacob, S.; Ray, A.;
Griffin, J. D. Br. J. Cancer 2006, 94, 1765.
(2) (a) Kimura, T.; Kawano, K.; Doi, E.; Kitazawa, N.; Takaishi, M.;
Ito, K.; Kaneko, T.; Sasaki, T.; Miyagawa, T.; Hagiwara, H.; Yoshida,
Y. US20070117839, 2006. (b) Huang, X.; Aslanian, R.; Zhou, W.; Zhu,
X.; Qin, J.; Greenlee, W.; Zhu, Z.; Zhang, L.; Hyde, L.; Chu, I.; Cohen-
Williams, M.; Palani, A. ACS. Med. Chem. Lett. 2010, 1, 184.
(3) Harada, K.; Aota, M.; Inoue, T.; Matsuda, R.; Mihara, T.; Yamaji,
T.; Ishibashi, K.; Matsuoka, N. Eur. J. Pharmacol. 2006, 553, 171.
(4) Graham, J. P.; Langlade, N.; Northall, J. M.; Roberts, A. J.;
Whitehead, A. J. Org. Process Res. Dev. 2011, 15, 44.
(10) A rare example of Cu-catalyzed N1-selective arylation of 4-
substituted imidazoles was reported using aryllead(IV) reagents as aryl
donors. see: Elliott, G. I.; Konopelski, J. P. Org. Lett. 2000, 2, 3055.
(11) (a) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27.
(b) Torborg, C.; Beller, M. Adv. Synth. Catal. 2009, 351, 3027.
(c) Hartwig, J. F. Nature 2008, 455, 314.
(12) For selected examples, see: (a) Fors, B. P.; Buchwald, S. L. J.
Am. Chem. Soc. 2010, 132, 15914. (b) Fors, B. P.; Watson, D. A.;
Biscoe, M. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008, 130, 13552.
(c) Shen, Q.; Ogata, T.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130,
6586. (d) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N.
M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101. (e) Shen, Q.;
Shekhar, S.; Stambuli, J. P.; Hartwig, J. F. Angew. Chem., Int. Ed. 2005,
44, 1371.
(5) See footnote 1 in ref 6a.
(6) (a) Kiyomori, A.; Marcoux, J.-F.; Buchwald, S. L. Tetrahedron
Lett. 1999, 40, 2657. (b) Klapars, A.; Antilla, J. C.; Huang, X.;
Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7727. (c) Antilla, J. C.;
Baskin, J. M.; Barder, T. E.; Buchwald, S. L. J. Org. Chem. 2004, 69,
5578. (d) Cristau, H.-J.; Cellier, P. P.; Spindler, J.-F.; Taillefer, M.
705
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