OXADIAZOLES FROM DIACYL HYDRAZINES
3025
of our protocol easily to install an oxadiazole ring in the center of a molecule will
increase the popularity of this moiety in medicinal chemistry. Further research is
necessary to identify a truly general set of conditions for this cyclization. It is also
to be hoped the N-methylimidazole may serve as a cheap and effective alternative
to 2,6-di-t-butyl-4-methylpyridine in other processes involving triflic anhydride,
such as the preparation of triflates from lactams. Preliminary results from our
laboratories suggest that this is indeed the case.
ACKNOWLEDGMENT
Thanks go to Mike Kinns for spectroscopic studies elucidating the structure of
compound 5.
REFERENCES
1. Warren, R.; Liu, G. ZD4054: A specific endothelin A receptor antagonist with promising
activity in metastatic castration-resistant prostate cancer. Exper. Op. Invest. Drugs 2008,
17, 1237.
2. Summa, V.; Petrocchi, A.; Bonelli, F.; Crescenzi, B.; Donghi, M.; Ferrara, M.; Fiore, F.;
Gardelli, C.; Gonzalez Paz, O.; Hazuda, D. J.; Jones, P.; Kinzel, O.; Laufer, R.;
Monteagudo, E.; Muraglia, E.; Nizi, E.; Orvieto, F.; Pace, P.; Pescatore, G.; Scarpelli,
R.; Stillmock, K.; Witmer, M. V.; Rowley, M. Discovery of raltegravir, a potent, selective,
orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection.
J. Med. Chem. 2008, 51, 5843.
3. For example, sulfuric acid, as exemplified in Libman, D. D.; Slack, R. Congeners of
pyridine-4-carboxyhyrazide, part 1: Derivatives of 4-cyanopyridine and 2-cyanothiazole.
J. Chem. Soc. 1956, 2253, and PPA, as exemplified in Komaraiah, A.; Sailu, B.; Reddy,
P. S. N. Synthesis of some novel 1,3,4-oxadiazol-2-yl-4(3H)-quinazolinones. Synth.
Commun. 2008, 38, 114.
4. Rigo, B.; Couturier, D. Studies on pyrrolidinones: A convenient synthesis of 2-methyl-5-
(5-oxo-1-benzyl-2-pyrrolidinyl)-1,3,4-oxadiazole. J. Heterocycl. Chem. 1986, 23, 253
(methane sulfonic acid in combination with P2O5); Rigo, B.; Cauliez, P.; Fasseur, D.;
Couturier, D. Acid-catalysed cyclization of bis silyl diacylhydrazines: A new 1,3,4-oxadia-
zole synthesis. Synth. Commun. 1988, 18, 1247 (triflic acid with Me2SiCl2).
5. Exemplified in Alker, D.; Campbell, S. F.; Cross, P. E.; Burges, R. A.; Carter, A. J.;
Gardiner, D. G. Long-acting dihydropyridine calcium antagonists, 3: Synthesis and
structure–activity relationships for a series of 2-[(heterocycllmethoxy)methyl] derivatives.
J. Med. Chem. 1989, 32, 2381.
6. Verkoyen, C.; Rademacher, P. Synthesis of b-thiolactams and reduction with Raney
nickel. Chem. Ber. 1985, 118, 653.
7. Sitzmann, M. E. 1,3,4-Oxadiazoles with SF5-containing substituents. J. Fluorine Chem.
1995, 70, 31.
8. For leading references, consult Yang, Y.-H.; Shi, M. Halogen effects in Robinson–
Gabriel-type reaction of cyclopropanecarboxylic acid N0-substituted hyrazides with
PPh3=CX4. Tetrahedron Lett. 2005, 46, 6285.
´
9. James, C. A.; Poirier, B.; Grise, C.; Martel, A.; Ruediger, E. H. General synthesis of tetra-
substituted alkenyl-1,3,4-oxadiazoles. Tetrahedron Lett. 2006, 47, 511.
10. Hobbs, C. J.; Lynch, R.; Mellor, S. L.; Radford, F.; Gilbert, J. C.; Stokes, S.; Glen, A.;
Fuimana, A.; Earnshaw, C. G.; Knutsen, L. J. S.; Dean, K. E. S. Acyclic sulfonamides.
WO Patent 2006=030211, 2006.