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Synthesis of 2,6-Disubstituted Imidazo[2,1-b][1,3,4]thiadiazoles
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compounds containing the rare imidazo[2,1-b][1,3,4]thiadi-
azole central skeleton.
Experimental Section
General Procedure A for the Synthesis of 2-Bromo-(6-substituted)-
imidazo[2,1-b][1,3,4]thiadiazoles E: A mixture of 2-amino-5-bromo-
1,3,4-thiadiazole (1, 1.0 equiv.) and α-bromo ketone C (1.1 equiv.)
in ethanol was heated at reflux for 18 h. The mixture was then
cooled to room temperature and slightly concentrated under vac-
uum. If a salt precipitated (procedure A1), it was filtered and then
suspended in water, and the solution was neutralized with a satu-
rated solution of sodium carbonate under vigorous stirring. Finally,
the precipitate was washed with ethanol and the product fully char-
acterized without any further purification. If homogeneity occurred
after cooling the reaction (procedure A2), the solution was concen-
trated in vacuo, then diluted with dichloromethane, and washed
with a saturated solution of sodium carbonate. The organic layers
were dried with magnesium sulfate, filtered, and then concentrated
before purification by silica gel flash chromatography.
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General Procedure B for the Synthesis of 2,6-Disubstituted Imid-
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azo[2,1-b][1,3,4]thiadiazoles D Under Suzuki–Miyaura Cross-Cou-
pling Conditions: Bromide derivative
E (1.0 equiv.), K2CO3
(2.0 equiv.), the boronic acid (1.1 equiv.), Xantphos (0.2 equiv.),
Pd(OAc)2 (0.1 equiv.), and degassed 1,4-dioxane were subsequently
added into a 2–5-mL microwave vial. The resulting mixture was
subjected to microwave irradiation at 150 °C for 30 min. Once the
heating cycle was completed, the solvent was evaporated under re-
duced pressure, and the residue was diluted in CH2Cl2. The organic
layers were washed with water, dried with anhydrous MgSO4, fil-
tered, and concentrated under vacuum. The crude residue was then
washed successively with acetone, methanol, and diethyl ether. Af-
ter drying under vacuum, the obtained product was pure enough
to be fully characterized.
Supporting Information (see footnote on the first page of this arti-
1
cle): Characterization data and copies of H NMR and 13C NMR
spectra for all new compounds.
Acknowledgments
The authors thank the Ligue Contre le Cancer du Grand Ouest
(Comités des Deux Sèvres, du Finistère, de l’Ile et Vilaine, du Loir-
et-Cher, du Loire Atlantique, du Loiret, de la Vienne), la Région
Centre, the Cancéropôle Grand Ouest (strand “valorisation des
produits de la mer”) and the Ministère de l’Enseignement Supéri-
eur et de la Recherche (MESR) for their financial support.
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Chemical Indexing Equivalent to 153:600790 (FR).
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101 pp.
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Received: February 28, 2012
Published Online:
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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