3634
D. Kaminskyy et al. / European Journal of Medicinal Chemistry 44 (2009) 3627–3636
(Mþ þ 2). Calcd. for C20H15ClF3N3O4: C, 52.93; H, 3.33; N, 9.26;
4.1.1.19. 2-[5-(4-Methoxy-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-
Found: C, 53.00; H, 3.50; N, 9.45%.
N-thiazol-2-yl-acetamide (Ve). Yield 88%, mp 289–290 ꢃC. 1H NMR
[DMSO-d6]
d
: 3.88 (s, 3H), 4.60 (s, 2H), 6.99 (d, J ¼ 5.2 Hz, 1H), 7.08
4.1.1.11. 2-[5-(4-Dimethylamino-benzylidene)-2,4-dioxo-imidazoli-
(d, J ¼ 8.8 Hz, 2H), 7.38 (d, J ¼ 5.2 Hz, 1H), 7.53 (d, J ¼ 8.8 Hz, 2H),
7.88 (s, 1H), 12.30 (s, 1H). EI-MS (m/z): 375 (Mþ). Calcd. for
C16H13N3O4S2: C, 51.19; H, 3.49; N, 11.19; Found: C, 51.00; H, 3.55; N,
11.30%.
din-3-yl]-N-(2-trifluoromethyl-phenyl)-acetamide (Ik). Yield 68%,
mp 297–299 ꢃC. 1H NMR [DMSO-d6]
d: 2,99 (s, 6H), 4.32 (s, 2H),
6.48 (s, 1H), 6.69 (d, J ¼ 8.5 Hz, 2H), 7.39–7.50 (m, 4H), 7.64
(t, J ¼ 7.6 Hz, 1H), 7.70 (d, J ¼ 7.9 Hz, 1H), 9.79 (s, 1H), 10.49 (s, 1H).
EI-MS (m/z): 433 (Mþ þ 1). Calcd. for C21H19F3N4O3: C, 58.33; H,
4.43; N, 12.96; Found: C, 58.50; H, 4.50; N, 13.00%.
4.1.1.20. 2-[2,4-Dioxo-5-(3-phenyl-allylidene)-thiazolidin-3-yl]-N-(2-
trifluoromethyl-phenyl)-acetamid (Vf). Yield 81%, mp 306–308 ꢃC. 1H
NMR [DMSO-d6]
d
: 4.48 (s, 2H), 7.02 (dd, J ¼ 11.3 Hz, J ¼ 15.1 Hz,1H),
4.1.1.12. 2-[5-(4-Methoxy-benzylidene)-2,4-dioxo-imidazolidin-3-yl]
7.23–7.52 (m, 6H), 7.56–7.78 (m, 2H), 10.12 (s, 1H). EI-MS (m/z): 433
(Mþ þ 1). Calcd. for C21H15F3N2O3S: C, 58.33; H, 3.50; N, 6.48; Found:
C, 58.20; H, 3.70; N, 6.30%.
-N-(4-methoxy-phenyl)-acetamide (Il). Yield 81%, mp >230 ꢃC. 1H
NMR [DMSO-d6] d: 3.74 (s, 3H), 3.82 (s, 3H), 4.26 (s, 2H), 6.53 (s,
1H), 6.83 (d, J ¼ 8.8 Hz, 2H), 6.95 (d, J ¼ 8.8 Hz, 2H), 7.47 (d,
J ¼ 8.8 Hz, 2H), 7.60 (d, J ¼ 8.8 Hz, 2H), 10.05 (s, 1H), 10.72 (s, 1H).
LC-MS, (Mþ þ 1) I% – 383.2 (82.15). Calcd. for C20H19N3O5: C, 62.99;
H, 5.02; N, 11.02; Found: C, 63.10; H, 5.10; N, 10.90%.
4.1.1.21. 2-[5-(4-Dimethylamino-benzylidene)-2,4-dioxo-thiazolidin-
3-yl]-N-(2-trifluoromethyl-phenyl)-acetamide (Vg). Yield 79%, mp
296–298 ꢃC. 1H NMR [DMSO-d6]
d: 3.05 (s, 6H), 4.49 (s, 1H), 6.80 (d,
J ¼ 8.9 Hz, 2H), 7.44 (m, 3H), 7.51 (d, J ¼ 8.2 Hz, 1H), 7.64 (d,
J ¼ 8.2 Hz, 1H), 7.72 (d, J ¼ 8.2 Hz, 1H), 7.80 (s, 1H), 9.94 (s, 1H).
EI-MS (m/z): 450 (Mþ þ 1). Calcd. for C21H18F3N3O3S: C, 56.12; H,
4.04; N, 9.35; Found: C, 56.00; H, 3.90; N, 9.50%.
4.1.1.13. 2-(2,4-Dioxo-imidazolidin-3-yl)-N-(3-trifluoromethyl-phenyl)
-acetamide (IIa). Yield 78%, mp 208–210 ꢃC. IR [cmꢀ1] 3309, 3253
(NH), 1775, 1714, 1678 (CO), 1H NMR [DMSO-d6]
d: 4.00 (s, 2H), 4.19
(s, 2H), 7.41 (d, J ¼ 7.7 Hz, 1H), 7.56 (t, J ¼ 8.0 Hz, 2H), 7.71 (d,
J ¼ 8.4 Hz, 1H), 8.04 (s, 1H), 8.20 (s, 1H), 10.59 (s, 1H). EI-MS (m/z):
301 (Mþ). Calcd. for C12H10F3N3O3: C, 47.85; H, 3.35; N, 13.95; Found:
C, 48.00; H, 3.45; N, 14.05%.
4.1.1.22. N-(4-Chloro-phenyl)-2-{2,4-dioxo-3-[(3-trifluoromethyl-phe-
nylcarbamoyl)-methyl]-thiazolidin-5-ylidene}-acetamide (VIa). Yield
56%, mp 284–286 ꢃC. IR [cmꢀ1] 3339 (NH), 1739, 1687, 1658 (CO),
1601. 1H NMR [DMSO-d6]
d: 4.55 (s, 2H), 7.40 (s, 1H), 7.42 (d,
4.1.1.14. 2-(2,4-Dioxo-imidazolidin-3-yl)-N-(4-sulfamoyl-phenyl)-acet-
J ¼ 8.0 Hz, 1H) 7.44 (d, J ¼ 8.8 Hz, 2H), 7.72 (d, J ¼ 8.8 Hz, 2H), 7.59 (t,
J ¼ 8.0 Hz, 1H), 7.75 (d, J ¼ 8.0 Hz, 1H), 8.05 (s, 1H), 10.75 (s, 1H), 11.05
(s, 1H). Calcd. for C20H13ClF3N3O4S: C, 49.65; H, 2.71; N, 8.68; Found:
C, 49.50; H, 2.80; N, 8.50%.
amide (IIb). Yield 82%, mp 198–200 ꢃC. 1H NMR [DMSO-d6]
d: 4.00 (s,
2H), 4.20 (s, 2H), 7.26 (s, 2H), 7.68 (d, J ¼ 8.5 Hz, 2H), 7.76 (d, J ¼ 8.5 Hz,
2H), 8.19 (s, 1H), 10.58 (s, 1H). EI-MS (m/z): 312 (Mþ). Calcd. for
C11H12N4O5S: C, 42.31; H, 3.87; N, 17.94; Found: C, 42.50; H, 4.00; N,
18.05%.
4.1.1.23. 2-{2,4-Dioxo-3-[(2-trifluoromethyl-phenylcarbamoyl)-meth-
yl]-thiazolidin-5-ylidene}-N-(4-fluoro-phenyl)-acetamide (VIb). Yield
4.1.1.15. 2-[5-(4-Chloro-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-N-
48%, mp 244–246 ꢃC. 1H NMR [DMSO-d6]
d: 4.51(s, 2H), 7.21 (t,
(3-trifluoromethyl-phenyl)-acetamide (Va). Yield 83%, mp 237–
J ¼ 9.0 Hz, 2H), 7.38 (s, 1H), 7.48 (m, 2H), 7.64–7.78 (m, 4H), 10.07 (s,
1H),10.94 (s,1H). Calcd. for C20H13F4N3O4S: C, 51.40; H, 2.80; N, 8.99;
Found: C, 51.50; H, 3.00; N, 9.10%.
238 ꢃC. 1H NMR [DMSO-d6]
d
: 4.53 (s, 1H), 7.34 (d, J ¼ 8.0 Hz, 1H),
7.51 (t, J ¼ 8.0 Hz, 1H), 7.54 (d, J ¼ 8.4 Hz, 2H), 7.64 (d, J ¼ 8.4 Hz,
2H), 7.75 (d, J ¼ 8.0 Hz, 1H), 7.96 (s, 1H), 8.0 (s, 1H), 10.63 (s, 1H). EI-
MS (m/z): 440 (Mþ), 442 (Mþ þ 2). Calcd. for C19H12ClF3N2O3S: C,
51.77; H, 2.74; N, 6.35; Found: C, 52.00; H, 2.80; N, 6.45%.
4.1.1.24. N-(4-Chloro-phenyl)-2-{2,4-dioxo-3-[(2-trifluoromethyl-phe-
nylcarbamoyl)-methyl]-thiazolidin-5-ylidene}-acetamide (VIc). Yield
52%, mp 260–262 ꢃC. IR [cmꢀ1] 3366 (NH), 1714, 1685, 1658 (CO),
4.1.1.16. 2-[5-(4-Chloro-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-N-
1599. 1H NMR [DMSO-d6]
d: 4.51(s, 2H), 7.35 (s, 1H), 7.38 (d,
(2-trifluoromethyl-phenyl)-acetamide
(Vb). Yield
79%,
mp
J ¼ 8.0 Hz, 2H), 7.46 (t, J ¼ 8.0 Hz, 1H), 7.50 (d, J ¼ 8.0 Hz, 1H), 7.66 (t,
J ¼ 8.0 Hz,1H) 7.69 (d, J ¼ 8.0 Hz, 2H), 7.72 (d, J ¼ 8.0 Hz,1H),10.00 (s,
1H), 10.95 (s, 1H). Calcd. for C20H13ClF3N3O4S: C, 49.65; H, 2.71; N,
8.68; Found: C, 49.50; H, 2.95; N, 8.50%.
256–258 ꢃC. 1H NMR [DMSO-d6]
d
: 4.52 (s, 2H), 7.42–7.50 (m, 2H),
7.51–7.55 (m, 8H), 7.99 (s, 1H), 10.12 (s, 1H). EI-MS (m/z): 440 (Mþ),
442 (Mþ þ 2). Calcd. for C19H12ClF3N2O3S: C, 51.77; H, 2.74; N,
6.35; Found: C, 51.90; H, 2.85; N, 6.20%.
4.1.1.25. N-(4-Chloro-phenyl)-2-{3-[(4-chloro-phenylcarbamoyl)-me-
thyl]-2,4-dioxo-thiazolidin-5-ylidene}-acetamide (VId). Yield 46%,
mp 290–292 ꢃC. IR [cmꢀ1] 3344 (NH), 1741, 1685, 1658 (CO),1599. 1H
4.1.1.17. 2-[5-(4-Chloro-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-N-
(4-chloro-phenyl)-acetamide (Vc). Yield 88%, mp >260 ꢃC. IR
[cmꢀ1] 3257 (NH), 1748, 1688, 1669 (CO), 1605 (Ar-CH]). 1H NMR
NMR [DMSO-d6]
d
: 4.47(s, 2H), 7.27 (d, J ¼ 8.0 Hz, 2H), 7.31(d,
[DMSO-d6]
d
: 4.96 (s, 2H), 7.28 (d, J ¼ 8.8 Hz, 2H), 7.54 (d,
J ¼ 8.0 Hz, 2H), 7.40 (s, 1H), 7.57 (d, J ¼ 8.0 Hz, 2H), 7.69 (d, J ¼ 8.0 Hz,
2H), 10.40 (s, 1H), 10.88 (s, 1H). Calcd. for C19H13Cl2N3O4S: C, 50.68;
H, 2.91; N, 9.33; Found: C, 50.50; H, 3.00; N, 9.10%.
J ¼ 8.8 Hz, 2H), 7.58 (d, J ¼ 8.8 Hz, 2H), 7.63 (d, J ¼ 8.8 Hz, 2H), 7.95
(s, 1H), 10.41 (s, 1H). EI-MS (m/z): 408 (Mþ þ 1). Calcd. for
C18H12Cl2N2O3S: C, 53.08; H, 2.97; N, 6.88; Found: C, 52.90; H,
3.05; N, 7.00%.
4.1.2. General procedure for synthesis of compounds III and IV
A mixture of 5 mmol of appropriate acid and 1.2 g of thionyl
chloride in 3 ml of dioxane was heated under reflux for 0.5 h,
cooled, and treated with 10 ml of hexane. The precipitate was
separated by filtration and used without further purification. To
a solution of 10 mmol of the corresponding amine and 1 ml of
triethylamine in 10 ml of anhydrous dioxane was added the solu-
tion of 10 mmol of respective acid chloride in 10 ml of the same
solvent. The mixture was heated for 10 min at 100 ꢃC, cooled, and
4.1.1.18. N-(4-Chloro-phenyl)-2-[2,4-dioxo-5-(3-phenyl-allylidene)-ꢀth1-
iazolidin-3-yl]-acetamide (Vd). Yield 62%, mp 275–276 ꢃC. IR [cm
3319 (NH), 1741, 1680 (CO), 1583 (Ar-CH]). H NMR [DMSO-d6]
]
:
1
d
4.42(s, 2H), 7.04 (dd, J ¼ 11.3 Hz, J ¼ 15.2 Hz, 1H,), 7.30–7.47 (m, 6H),
7.49–7.61 (m, 2H), 7.62–7.76 (m, 3H), 10.52 (s, 1H). EI-MS (m/z): 398
(Mþ) 400 (Mþ þ 2). Calcd. for C20H15ClN2O3S: C, 60.23; H, 3.79; N,
7.02; Found: C, 60.30; H, 3.90; N, 7.20%.