Organic Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
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S
Experimental details, characterization data, and NMR
AUTHOR INFORMATION
Corresponding Authors
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(10) Two 4-isocyanopyridines (2-Br and 2-Cl) were also synthesized,
since they have similar electronic properties. Because these
compounds showed rapid degradation, we did not include them in
our screening.
Notes
(11) Thompson, M. J.; Chen, B. J. Org. Chem. 2009, 74, 7084.
(12) (a) Dawson, P. E.; Muir, T. W.; Clarklewis, I.; Kent, S. B. H.
Science 1994, 266, 776−779. (b) Ramakers, B. E. I.; van Hest, J. C. M.;
The authors declare the following competing financial
interest(s): VU Amsterdam has filed a patent application on
2-isocyanopyridines and their use in multicomponent reactions
as well as transformation of the resulting products from which
the authors may receive royalty payments.
Lowik, D. W. P. M. Chem. Soc. Rev. 2014, 43, 2743.
̈
(13) Carfentanil was previously synthesized in a similar fashion using
cyclohexenyl isocyanide, but the methanolysis required harsher
conditions and afforded carfentanil in lower yield and purity compared
to our procedure: Malaquin, S.; Jida, M.; Gesquiere, J.-C.; Deprez-
Poulain, R.; Deprez, B.; Laconde, G. Tetrahedron Lett. 2010, 51, 2983.
(14) van Daele, P. G. H.; de Bruyn, M. F. L.; Boey, J. M.; Sanczuk, S.;
Agten, J. T. M.; Janssen, P. A. J. Arzneim.-Forsch. 1976, 26, 1521.
ACKNOWLEDGMENTS
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We thank Elwin Janssen for technical assistance, Sanne
Bouwman for HRMS measurements, and Dr. Andreas W.
Ehlers for NMR maintenance (all VU Amsterdam). The
research leading to these results has received funding from the
Innovative Medicines Initiative Joint Undertaking project
CHEM21 under Grant Agreement No. 115360, resources of
which are composed of financial contribution from the
European Union’s Seventh Framework Programme (FP7/
2007-2013) and EFPIA companies’ in kind contribution.
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