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A. E. E. Amr et al.
washed with water, dried, and crystallized to give 8 (62%).
Mp 252ꢄC (DMF); IR (film): ꢁꢀ¼ 3340 (NH), 1609 (C¼N),
1256 (C¼S) cmꢀ1; 1H NMR (DMSO-d6): ꢀ ¼ 1.95 (s, CH3),
7.78, 8.12 (2s, 2 pyr-H), 9.60 (s, NH exchangeable with
D2O) ppm; MS (EI, 70 eV): m=z ¼ 266 [Mþ, 2] and at
251 [100, base peak].
(15 mmol) in 30 cm3 glacial acetic acid was refluxed for
10 h. The reaction mixture was concentrated under reduced
pressure, poured onto water, the formed solid was filtered
off, washed with water, dried and crystallized to yield 12
(80%). Mp 231ꢄC (EtOH); IR (film): ꢁꢀ¼ 3409 (NH), 1605
1
(C¼N) cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 5.65 (s, CH-oxadia-
zole-H), 7.20–8.10 (m, Ar–H), 8.24–8.32 (m, 2 pyr-H, hy-
drazone-H), 11.55, 12.15 (2s, 2NH exchangeable with D2O)
ppm; MS (EI, 70eV): m=z ¼ 413 [Mþ, 2] and at 171 [100,
base peak].
Method B. A mixture of 4 g 11 (10 mmol) and 1.2 g an-
hydrous sodium acetate (15 mmol) in 20 cm3 glacial acetic
acid was refluxed for 3 h. The reaction mixture was con-
centrated under reduced pressure, poured into water. The
obtained solid was filtered off, dried, and crystallized to
give 12 (85%).
5-(5-Chloro-2-methyl[1,2,4]triazolo[1,5-a]pyridin-7-yl)-
[1,3,4]oxadiazole-2-thiol (9, C9H6ClN5OS)
Method A. A solution of 2.6 g 8 (10 mmol) in 20 cm3 absolute
ethanol in the presence of few drops of pipridine was refluxed
for 6 h. The reaction mixture was evaporated under reduced
pressure, the residue was triturated with ether, the formed solid
was filtered off, dried and crystallized to give 9 (68%). Mp
268ꢄC (EtOH=ether); IR (film): ꢁꢀ¼ 3409 (NH), 1610 (C¼N),
1
1257 (C¼S) cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 1.90 (s, CH3),
7.90, 8.30 (2s, 2 pyr-H), 9.75 (s, NH exchangeable with D2O)
ppm; MS (EI, 70 eV): m=z ¼ 266 [Mþ, 2] and at 171 [100,
base peak].
1-[5-{2-Chloro-6-[2-(4-fluorophenyl)vinylamino]pyridin-4-
yl}-2-(4-fluorophenyl)-[1,3,4]oxa-diazol-3-yl]ethanone
(13, C22H16ClF2N5O2)
Method B. A mixture of 2.6 g 8 (10 mmol) and sodium
ethoxide (0.5g sodium metal in 30 cm3 absolute ethanol)
was heated under reflux for 4 h. After cooling, the reaction
mixture was concentrated under reduced pressure, poured onto
water, acidified with 1 N HCl. The product was extracted with
ethyl acetate, dried over sodium sulphate anhydrous, evapo-
rated under reduced pressure, the residue was solidified with
ether, filtered off, dried, and crystallized to give 9 (72%).
Method A. A solution of 2.10 g 11 (5mmol) in 30cm3 acetic
anhydride was heated under reflux for 6 h. The reaction mix-
ture was concentrated under reduced pressure and cooled, the
separated solid was filtered off, washed with petroleum ether,
dried, and crystallized to yield 13 (76%). Mp 195ꢄC (diox-
ane); IR (film): ꢁꢀ¼ 3320 (NH), 1704 (C¼O), 1605 (C¼N)
1
cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 2.10 (s, CH3), 5.62 (s, CH-
oxadiazole-H), 7.75–8.00 (m, Ar–H), 8.18–8.34 (m, 2 pyr-H,
hydrazone-H), 10.95 (s, NH exchangeable with D2O) ppm;
MS (EI, 70 eV): m=z ¼ 455 [Mþ, 65] and at 122 [100, base
peak].
2-[6-Chloro-4-(5-mercapto[1,3,4]oxadiazol-2-yl)pyridin-2-
ylamino)isoindole-1,3-dione (10, C15H8ClN5O3S)
A mixture of 2.4 g 5 (10 mmol) and 1.48 g of phthalic anhy-
dride (10 mmol) in 50cm3 glacial acetic acid was heated under
reflux for 6 h. The reaction mixture was concentrated under
reduced pressure, the obtained solid was filtered off and crys-
tallized to yield 10 (72%). Mp >300ꢄC (dioxane); IR (film):
Method B. A solution of 4 g 12 (10 mmol) in 15cm3 acetic
anhydride was refluxed for 2 h. The separated solid was fil-
tered off, dried, and crystallized to give 13 (70%).
1
ꢁꢀ¼ 3331 (NH), 1600 (C¼N), 1258 (C¼S) cmꢀ1; H NMR
N-{6-Chloro-4-[5-(4-fluorophenyl)[1,3,4]oxadiazol-2-yl]-
pyridin-2-yl}-N0-(4-fluorobenzylidine)-hydrazine
(DMSO-d6): ꢀ ¼ 7.95–8.42 (m, 2 pyr-H, 4H–Ar–H), 8.65, 9.62
(2s, 2NH exchangeable with D2O) ppm; MS (EI, 70 eV):
m=z ¼ 373 [Mþ, 10] and at 313 [100, base peak].
(14, C20H12ClF2N5O)
To a suspension solution of 4.13g 11 (10 mmol), 1.2 g anhy-
drous sodium acetate (15 mmol) in 20 cm3 glacial acetic acid,
1.6 g bromine (10 mmol) in 10cm3 glacial acetic acid was
added. The reaction mixture was refluxed for 1 h, after cool-
ing, it was poured onto water, the formed solid was filtered off,
washed with water, dried, and crystallized to afford 14 (85%).
Mp 266ꢄC (EtOH); IR (film): ꢁꢀ¼ 3328 (NH), 1605 (C¼N)
2-Chloro-6-[N0-(4-fluorobenzylidene)hydrazino]isonicotinic
acid (4-fluorobenylidine)hydrazide (11, C20H14ClF2N5O)
A mixture of 2.10 g 4 (10 mmol) and 2.4 g of p-flourobenzal-
dehyde (20 mmol) in 50 cm3 absolute ethanol was refluxed
for 3 h. After, cooling, the separated solid was filtered off,
dried, and crystallized to give 11 (98%). Mp 279ꢄC (dioxane);
IR (film): ꢁꢀ¼ 3260–3230 (NH), 1665 (C¼O), 1602 (C¼N)
cmꢀ1; 1H NMR (DMSO-d6): ꢀ ¼ 7.65–8.05 (m, Ar–H), 8.25–
8.42 (m, 2 pyr-H, 2H hydrazone-H), 11.60, 12.20 (2s, 2 NH
exchangeable with D2O) ppm; MS (EI, 70eV): m=z ¼ 413
[Mþ, 40] and at 171 [100, base peak].
1
cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 7.82–8.5 (m, Ar–H), 8.22–
8.30 (m, 2 pyr-H, hydrazone-H), 11.24 (s, NH exchangeable
with D2O) ppm; MS (EI, 70eV): m=z ¼ 411 [Mþ, 100, base
peak].
2-Chloro-N-[3-chloro-2-(4-fluorophenyl)-4-oxoazetidin-1-yl]-
6-[3-chloro-2-(4-fluorophenyl)-4-oxoazetidin-1-ylamino]-
isonicotinamide (15, C24H16Cl3F2N5O3)
To a solution of 4.1 g 11 (10 mmol) in 20 cm3 dioxane
containing few drops of TEA as a catalyst, 2.24 cm3 chlor-
oacetyl chloride (20 mmol) was added drop-wise with
stirring at room temperature. The solution was heated
2-Chloro-N-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-6-
(1,3-dioxo-1H,3H-benzo[de]iso-quinolin-2-ylamino)iso-
nicotinamide (12, C20H14ClF2N5O)
Method A. A mixture of 2.1g 4 (10 mmol), 2.4 g p-fluoro-
benzaldehyde (20 mmol) and 1.2 g anhydrous sodium acetate