3
c The reaction was conducted in DMF.
d ND = no detected by GC-MS.
Szewczak, A. A.; Xu, L.; Yin, H.; Zugay-Murphy, J.; Marshall,
C. G.; Young, J. R. J. Med. Chem. 2011, 54, 7334-7349; (b)
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Maguire, R. J.; Tu, M.; Zeng, D.; Liu, S.; Knafels, J. D.; Litchfield,
J.; Atkinson, K.; Derksen, D. R.; Bourbonais, F.; Gajiwala, K. S.;
Hickey, M.; Johnson, T. O.; Humphries, P. S.; Pfefferkorn, J. A.
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(a) Durán, R.; Zubía, E.; Ortega, M.; Naranjo, S.; Salvá, J.
Tetrahedron 1999, 55, 13225-13232; (b) Doi, I.; Kuse, M.;
Nishikawa, T.; Isobe, M. Bioorg. Med. Chem. 2009, 17, 3399-3404;
(c) Qian, K.; Wang, L.; Cywin, C. L.; Farmer, B. T.; Hickey, E.;
Homon, C.; Jakes, S.; Kashem, M. A.; Lee, G.; Leonard, S.; Li, J.;
Magboo, R.; Mao, W.; Pack, E.; Peng, C.; Prokopowicz, A.;
Welzel, M.; Wolak, J.; Morwick, T. J. Med. Chem. 2009, 52, 1814-
1827; (d) Niculescu-Duvaz, I.; Roman, E.; Whittaker, S. R.;
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416.
e Determined by GC-MS analysis of the crude reaction mixture, failed in
isolated procedure, the protodeborylation product quinoxaline was obtained.
The borylation reaction of 2-tert-butoxy-6-chloro-pyrazine (1a)
could be easily scaled up on the decagram without reducing their
efficiency, and the product was easily purified by
recrystallization (Scheme 1), which indicated the practical
applications of this protocol. This product has been stored on the
benchtop for more than 1 year without decomposition.
7.
Scheme 1. Scale-up reaction
N
N
Pd(OAc)2 (2.0 mol%)
PCy3 (4.0 mol%)
O
B
N
O
Cl
N
O
B2pin2 (1.1 equiv)
AcOK (2.5 equiv)
O
Dioxane, 110 °C, 30 min
8.
9.
Zhang, C. Y.; Tour, J. M. J. Am. Chem. Soc. 1999, 121, 8783–8790
and references cited therein.
1a
2a
18 g
12 g
80%
(a) Peng, H.; Chen, Y.-Q.; Mao, S. L.; Pi, Y. X.; Chen, Y.; Lian, Z.
Y.; Meng, T.; Liu, S. H.; Yu, G. A. Org. Biomol. Chem. 2014, 12,
6944-6952; (b) Conole, D.; Beck, T. M.; Jay-Smith, M.; Tingle, M.
D.; Eason, C. T.; Brimble, M. A.; Rennison, D. Bioorg. Med. Chem.
2014, 22, 2220-2235.
Conclusion
In summary, we have developed a practical, scalable, and
cost-effective method for preparing a range of previously
challenging-to-access pyrazine heterocyclic boronic esters. The
notable advantages of the protocol are its short reaction time,
high yields and easy purification. In most of the cases, the
boronic esters described herein can be isolated as air-stable
materials in chemically pure form. This method is useful for
quick synthesis of various pyrazine boronic esters, which could
be used in pharmaceuticals, natural products, and materials.
10. (a) Deng, J. Z.; Paone, D. V.; Ginnetti, A. T.; Kurihara, H.; Dreher,
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Acknowledgments
We are grateful to the Natural Science Foundation of China
(21172200) and Technology Research and Development Funds
of Zhengzhou (141PRCYY516) for financial support.
References and notes
14. The commercially available pyrazine boronic esters is very
expensive (ca. $500/g), data cited here was come from the CAS
Scifinder® databases.
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3.
4.
the corresponding heterocyclic boronic esters was not obtained.
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