Communication
Finally, we validated our novel one-pot synthetic pathway ported by the National Institutes of Health (NIH), USA
towards the preparation of the marketed drug cilostazol, which (1R01GM097082-01) and by the Innovative Medicines Initiative
targets phosphodiesterase and inhibits platelet aggregation; it Joint Undertaking under Grant Agreement No. 115489, resour-
is employed as a direct arterial vasodilator. Notably, this drug is ces of which are composed of financial contributions from the
usually synthesized by multistep procedures, also with the European Union's Seventh Framework Programme (FP7/2007-
[
24]
use of toxic and explosive HN and PCl . Our rapid two-step 2013) and EFPIA companies' in-kind contribution.
3
5
cilostazol synthesis involved the 3CR of 5-chloropentanoic acid
chloride (10), cyclohexylamine (11), and TMSN to form tetraz-
ole intermediate 12, which was followed by coupling with com-
mercially available 6-hydroxy-3,4-dihydro-2(1H)-quinolinone
3
Keywords: Multicomponent reactions · Microwave
chemistry · Azides · Fused-ring systems · Nitrogen heterocycles
(
13, Scheme 2).
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Scheme 2. Two-step synthesis of cilostazol by our MCR methodology.
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chloride (10), cyclohexylamine (11), and TMSN with POCl at
3
3
1
80 °C in a microwave to form tetrazole 12, but we observed
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9 % yield (Scheme 2).
1
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In conclusion, we developed a novel, efficient, safe, and general
microwave-assisted first-in-class MCR-based method to gain ac-
cess to diverse and fused tetrazoles in a single step. Multiple
inter- and intramolecular examples pinpoint the versatility of
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the reaction. The use of TMSN in an almost equimolar ratio
3
makes the process safer than reported protocols. Moreover, the
synthetic utility of this developed methodology was illustrated
in the synthesis of biologically active 1,5-fused tetrazoles, an
amino acid tetrazole, and the marketed drug cilostazol.
[
[
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Acknowledgments
9
81–996.
The authors thank the University of Groningen, The Nether-
lands. The Erasmus Mundus Scholarship “Svaagata” is acknowl-
edged for a fellowship to A. L. C. The work was financially sup-
[
[
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Eur. J. Org. Chem. 2016, 2383–2387
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