3808
Med Chem Res (2013) 22:3802–3811
Anal. Calcd for: C11H7N3OS: C, 57.63; H, 3.08; N, 18.33.
(s, 1H, thiazole-H), 10.45 (s, 1H, NH); MS(m/z): 260
[M??1]. Anal. Calcd for: C11H9N5OS: C, 50.96; H, 3.50;
N, 27.01. Found: C, 50.88; H, 3.52; N, 27.0.
Found: C, 57.60; H, 3.12; N, 18.21.
Synthesis of 5-(2-phenylthiazole-4-yl) [1, 3, 4]
oxadiazole-2-amine (8)
Synthesis of 5-(2-phenylthiazole-4-yl)-1,3,4-oxadiazole-
2(3H)-thione (11)
To sodium bicarbonate (0.96 g, 1.25 mmol) in 5-ml of
water was added to a solution of 3 (0.25 g, 1.11 mmol) in
10 ml of dioxane at room-temperature and stirred for
5 min. To the stirred solution, cyanogens bromide
(0.133 g, 1.25 mmol) was added slowly and it was kept for
stirring for 3 h. The solid product that appeared was filtered
and dried in vacuum. The solid was recrystallized from
ethanol to afford brown-colored product.
Yield = 0.19 g (70 %); m.p. 201–204 °C; IR (cm-1):
3380, 3124 (m, NH2), 3020 (w, Ar–CH), 1615 (m, C = N);
1H NMR (DMSO-d6, d, ppm): 7.37 (bs, 2H, NH2),
7.50–7.96 (m, 5H, Ar–H), 7.97 (s, 1H, thiazole-H); MS(m/
z): 245 [M??1]. Anal. Calcd for: C11H8N4OS: C, 54.09; H,
3.30; N, 22.94. Found: C, 54.0; H, 3.32; N, 22.81.
A mixture of 3 (0.5 g, 2 mmol) and carbon disulfide (3 ml)
in pyridine (10 ml) was refluxed on water bath for 6 h.
After cooling, the solvent was evaporated under reduced
pressure, and the residue was triturated with an ice–water
mixture and neutralized with dilute hydrochloric acid. The
separated solid product was filtered, washed with water,
dried, and crystallized from ethanol afforded 11 as pale
yellow crystals.
Yield = 0.45 g (76 %); m.p. 198–201 °C; IR (cm-1):
3210 (m, NH), 3015 (w, Ar–CH), 1628 (m, C = N),1315
1
(m,C = S); H NMR (DMSO-d6,d, ppm): 7.53-8.01 (m,
5H, Ar–H), 8.50 (s, 1H,thiazole-H), 10.55 (s, 1H, NH);
MS(m/z): 262 [M??1]. Anal. Calcd for: C11H7N3OS2: C,
50.56; H, 2.70; N, 16.08. Found: C, 50.55; H, 2.62; N, 16.0.
Synthesis of 5-(2-phenylthiazole-4-yl)-1, 3, 4-
oxadiazole-2(3H)-one (9)
Synthesis of 4-{2-[5-(2-phenylthiazole-4-yl)-1,3,4-
oxadiazole-2-ylthio]ethyl}-morpholine (12)
A mixture of 3 (0.25 g, 1.11 mmol) and N, N’-carbonyl-
diimidazole (0.27 g, 1.71 mmol) in dioxane (10 ml) was
heated under reflux for 5 h. After cooling, the solvent was
removed under reduced pressure, and the residue was trit-
urated with water. The solid product formed was filtered
off and recrystallized from ethanol to yield colorless
crystals.
A mixture of the oxadiazolinethione 11 (0.2 g, 0.72 mmol),
fused sodium acetate (0.31 g, 3.8 mmol), and 4-(2-chlo-
roethyl) morpholine hydrochloride (0.14 g, 0.7 mmol) in
ethanol (10 ml) was refluxed for 8 h. The solvent was
removed under reduced pressure, and the solid product was
transferred in water, stirred, and filtered to yield 12 as
white crystals.
Yield = 0.2 g (71 %); m.p. 122–125 °C; IR (cm-1):
3015 (w, Ar–CH), 1625 (m, C = N); 1H NMR (DMSO-d6,
d, ppm): 2.45 (t, 4H, J = 4.5 Hz, NCH2) 2.76–2.81 (t, 2H,
J = 6.8 Hz, SCH2CH2N), 3.38-3.42 (t,, 2H, J = 6.8 Hz,
SCH2CH2N), 3.68-3.72 (t, 4H, J = 4.5 Hz, OCH2) 7.37-
7.99 (m, 5H, Ar–H), 8.28 (s, 1H, thiazole-H); MS(m/z):
375 [M??1]. Anal. Calcd for: C17H18N4O2S2: C, 54.53; H,
4.84; N, 14.96. Found: C, 54.55; H, 4.81; N, 14.86 .
Yield = 0.22 g (81 %); m.p. 132–135 °C; IR (cm-1):
3180 (m, NH), 3010 (w, Ar–CH), 1690 (s, C = O), 1622
1
(m, C = N); H NMR (DMSO-d6,d, ppm): 7.34-8.12 (m,
5H, Ar–H), 8.17 (s, 1H, thiazole-H), 9.42 (s, 1H, NH);
MS(m/z): 246 [M??1]. Anal. Calcd for: C11H7N3O2S: C,
53.87; H, 2.88; N, 17.13. Found: C, 53.88; H, 2.82; N,
17.11.
Synthesis of 4-amino-5-(2-phenylthiazole-4-yl)-2,4-
dihydro[1,2,4]triazole-3-one (10)
Synthesis of 4-{2-[5-(2-phenylthiazole-4-yl)-1, 3,
A mixture of the oxadiazolinone 9 (0.3 g, 1.22 mmol) and
hydrazine hydrate (2 ml) in ethanol (5 ml) was heated
under reflux for 3 h. After cooling, the solvent was
removed in vacuum, and the residue obtained was triturated
with water. The solid was filtered and recrystallized from
ethanol, which afforded the title compound 10 as white
crystals.
Yield = 0.21 g (68 %); m.p. 178–181 °C; IR (cm-1):
3253, 3180 (m, NH2), 3156 (m, NH), 3030 (w, Ar–CH),
1690 (s, C = O), 1610 (m, C = N); 1H NMR (DMSO-d6,d,
ppm): 5.20 (bs, 2H, NH2) 7.33-8.10 (m, 5H, Ar–H), 8.45
4-oxadiazole-2-ylthio]ethyl}-dimethyl amine (13)
A mixture of the oxadiazolinethione 11 (0.2 g, 0.7 mmol),
fused sodium acetate (0.31 g, 3.8 mmol), and 2-dimethyl-
aminoethyl chloride hydrochloride (0.11 g, 0.7 mmol) in
ethanol (10 ml) was heated under reflux for 7 h. The sol-
vent was removed under vacuum, and the solid was washed
with water, filtered to yield compound 13 as white crystals.
Yield = 0.2 g (71 %); m.p. 111-114 °C; IR (cm-1):
1
3030 (w, Ar–CH),1632 (m, C = N); H NMR (DMSO-
d6,d, ppm): 2.20 (s, 6H, N(CH3)2, 2.66–2.71 (t, 2H,
123