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18 to 19 through aminolysis of the ester by either activating the
ester22 or the amine23 were also unsuccessful. Ultimately, hydro-
lysis of 18 was performed under basic conditions followed by an
EDC-promoted intramolecular amide coupling to provide 19 in
35% (three steps).
In conclusion, a succinct three-step synthesis of a collection
of 3-(tetrazol-5-yl)quinoxalin-2(1H)-ones
6 that employs the
Ugi-Azide MCR followed by cyclization under acidic condition
and immediate oxidation with TEMPO/CAN under aerobic condi-
tions has been reported. The method was expanded to afford
bis-benzodiazepine tetrazole 19 using N-Boc-2-aminobenzyl-
amine 16 in the Ugi-Azide MCR followed by sequential acid-base
treatment and EDC-mediated benzodiazepine formation. Due to
the uniqueness of these chemotypes, the promising pharmaco-
logical properties, and the ease of synthesis, these procedures of-
fer new feasible strategies for file enhancement by the medicinal
chemist.
10. Miyashiro, J.; Woods, K. W.; Park, C. H.; Liu, X.; Shi, Y.; Johnson, E. F.; Bouska, J.
J.; Olson, A. M.; Luo, Y.; Fry, E. H.; Giranda, V. L.; Penning, T. D. Bioorg. Med.
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Kawanishi, N.; Nakatsuru, Y.; Kotani, H.; Iwasawa, Y. Invest. New Drugs 2009,
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Acknowledgments
12. Takano, Y.; Shiga, F.; Asano, J.; Hori, W.; Fukuchi, K.; Anraku, T.; Uno, T. Bioorg.
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The authors thanked the Office of the Director, NIH and the Na-
tional Institute of Mental Health for funding (1RC2MH090878-01),
Kristen Keck for compound purification, Alex Laetsch for com-
pound management and Nicole Schechter for proof-reading.
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References and notes
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