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Green Chemistry
Page 4 of 6
COMMUNICATION
Journal Name
worth noting that the latter has been operated at kilogram 7. G. C. Moraski, L. D. Markley, P. A. Hipskind, H. Boshoff, S.
scale with optimised work-up to improve E-factor and PMI
through reduction of solvent use. The effective mass yield
Cho, S. G. Franzblau and M. J.DMOIi:ll1e0r.1,0A39C/SC6MGCed01ic6i0n1aDl
Chemistry Letters, 2011, , 466-470.
2
(EMY)53 shows higher efficiency for the new route, even 8. E. J. Barreiro, in Privileged Scaffolds in Medicinal Chemistry
compared to the optimised current process, although this
metric requires definition of benign substances which can be
: Design, Synthesis, Evaluation, ed. S. Bräse, 2015, ch.
1, pp. 1-15.
contentious. Importantly the space-time-yield (STY) in the 9. S. Boggs, V. I. Elitzin, K. Gudmundsson, M. T. Martin and M.
alkylation step is 7-14 times higher, and the STY in the
J. Sharp, Organic Process Research & Development,
2009, 13, 781-785.
cyclisation step is 185-363 times higher, than the comparative
i
processes. In addition, the solvents in our process, i.e. PrOH, 10. R. Bellingham, A. M. Buswell, B. M. Choudary, A. H.
EtOAc and water, are all ‘recommended’ solvents, while the
main solvents in the current processes, 1,2-dimethoxyethane,
is considered ‘hazardous’.52 Finally, the much faster reactions
Gordon, S. O. Moore, M. Peterson, M. Sasse, A.
Shamji and M. W. J. Urquhart, Organic Process
Research & Development, 2010, 14, 1254-1263.
reported here mean that a telescoped process can potentially 11. S. Feng, D. Hong, B. Wang, X. Zheng, K. Miao, L. Wang, H.
be carried out with acceptable solvents, heating and cooling.
In conclusion, we report a novel and green route to
Yun, L. Gao, S. Zhao and H. C. Shen, ACS Medicinal
Chemistry Letters, 2015, , 359-362.
6
imidazo[1,2-a]pyridines which involves no metal catalyst and is 12. H. Kishino, M. Moriya, S. Sakuraba, T. Sakamoto, H.
extremely fast when performed in water. This route benefits
from highly competitive green metrics and 1-2 magnitude
higher STY compared to current synthetic processes.
Investigation to expand the substrate scope and to understand
Takahashi, T. Suzuki, R. Moriya, M. Ito, H. Iwaasa, N.
Takenaga, A. Ishihara, A. Kanatani, N. Sato and T.
Fukami, Bioorganic & Medicinal Chemistry Letters,
2009, 19, 4589-4593.
the effect of water in this reaction is in progress and will be 13. M. Shiozaki, K. Maeda, T. Miura, M. Kotoku, T. Yamasaki, I.
disseminated in the near future.
Matsuda, K. Aoki, K. Yasue, H. Imai, M. Ubukata, A.
Suma, M. Yokota, T. Hotta, M. Tanaka, Y. Hase, J.
Haas, A. M. Fryer, E. R. Laird, N. M. Littmann, S. W.
Andrews, J. A. Josey, T. Mimura, Y. Shinozaki, H.
Yoshiuchi and T. Inaba, Journal of Medicinal
Chemistry, 2011, 54, 2839-2863.
Acknowledgements: BAK thanks AstraZeneca for an industrial
CASE studentship. MRC thanks the University of Leeds and
AstraZeneca for a studentship. MHTK thanks the EPSRC,
AstraZeneca and YProTech for an Industrial CASE studentship.
14. J. Koubachi, S. El Kazzouli, M. Bousmina and G. Guillaumet,
European Journal of Organic Chemistry, 2014, 2014
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,
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‡ Footnotes relating to the main text should appear here. These
might include comments relevant to but not central to the
matter under discussion, limited experimental and spectral data,
and crystallographic data.
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