S.-O. Zaraei, R.M. Sbenati, N.N. Alach et al.
European Journal of Medicinal Chemistry 224 (2021) 113674
(m, 2H), 7.16 (s, 1H), 7.08 (dd, 1H, J ¼ 2.0, 8.0 Hz), 6.96 (d, 1H,
2H), 7.25e7.17 (m, 3H), 6.90e6.89 (m, 1H), 6.83 (d, 1H, J ¼ 3.5 Hz),
J ¼ 4.5 Hz), 5.32 (s, 2H); 13C NMR (CDCl3, 125 MHz)
d
194.2, 158.7,
5.16 (s, 2H); 13C NMR (CDCl3, 125 MHz)
d 194.3, 158.2, 148.9, 142.7,
158.5, 156.4, 156.0, 152.9, 150.5, 136.1, 134.5, 134.1, 130.3, 129.0 (2C),
128.2 (2C), 122.7, 122.6, 120.5, 117.0, 116.4, 115.0, 112.9, 70.9; LC/MS
m/z: 413.38 (Mþ þ 1); CHN analysis: calculated C:66.97%, H:3.91%,
N:13.58%; found: C:67.03%, H:3.86%, N:13.45%.
135.6, 134.7, 133.9, 130.3, 129.7, 129.5, 129.4, 128.9, 128.7, 128.3,
123.2, 121.0, 117.6, 115.2, 113.1, 112.9, 70.8; LC/MS m/z: 411.36
(Mþ þ 1); CHN analysis: calculated C:73.15%, H:4.42%, N:6.82%;
found: C:73.04%, H:4.37%, N:6.91%.
4.4.22. 6-(3-(Benzyloxy)phenyl)-5-phenylimidazo[2,1-b]thiazole
(IIIa)
4.4.27. 6-(3-(Benzyloxy)phenyl)-5-(3-(methylsulfonyl)phenyl)
imidazo[2,1-b]thiazole (IVa)
Purified by normal phase column chromatography, eluent hex-
Purified by normal phase column chromatography, eluent hex-
ane:ethyl acetate 95:5 v/v followed by 70:30 v/v; Yield: 35%; 1H
ane:ethyl acetate 90:10 v/v followed by 55:45 v/v; Yield: 25%; 1H
NMR (CDCl3, 500 MHz)
d
7.46 (d, 4H, J ¼ 3.5 Hz), 7.43e7.39 (m, 1H),
NMR (CDCl3, 500 MHz)
d
8.04 (t, 1H, J ¼ 1.5 Hz), 7.96e7.94 (m, 1H),
7.36e7.32 (m, 7H), 7.19e7.16 (m, 2H), 6.87 (d,1H, J ¼ 7.5 Hz), 6.80 (d,
7.74 (dt, 1H, J ¼ 1.5, 8.0 Hz), 7.65 (t, 1H, J ¼ 3.0 Hz), 7.46 (d, 1H,
J ¼ 4.5 Hz), 7.39e7.35 (m, 4H), 7.33e7.31 (m, 1H), 7.21 (t, 1H,
J ¼ 8.0 Hz), 7.12e7.10 (m, 1H), 6.95 (d, 1H, J ¼ 4.5 Hz), 6.92e6.90 (m,
1H, J ¼ 4.5 Hz), 4.96 (s, 2H); 13C NMR (CDCl3, 125 MHz)
d 158.9,
149.0, 143.2, 137.2, 135.8, 130.5, 129.4, 129.3 (2C), 128.6 (2C), 127.9
(2C), 127.6 (2C), 123.1, 120.4, 117.6, 114.8, 113.2, 112.7, 69.9; LC/MS m/
z: 383.39 (Mþ þ 1); CHN analysis: calculated C:75.37%, H:4.74%,
N:7.32%; found: C:75.32%, H:4.69%, N:7.40%.
1H), 5.03 (s, 2H), 3.03 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d 159.2,
150.0, 142.0, 137.0, 134.1, 132.0, 130.5, 129.8, 128.7, 128.1 (2C), 127.7
(2C), 127.0 (2C), 121.0, 120.7, 117.4, 115.0, 114.2, 114.0, 70.2, 44.5; LC/
MS m/z: 461.33 (Mþ þ 1); CHN analysis: calculated C:65.20%,
H:4.38%, N:6.08%; found: C:65.37%, H:4.22%, N:6.04%.
4.4.23. 6-(3-(4-Fluorobenzyloxy)phenyl)-5-phenylimidazo[2,1-b]
thiazole (IIIb)
Purified by normal phase column chromatography, eluent hex-
4.4.28. 6-(3-(4-Fluorobenzyloxy)phenyl)-5-(3-(methylsulfonyl)
phenyl)imidazo[2,1-b]thiazole (IVb)
ane:ethyl acetate 95:5 v/v followed by 75:25 v/v; Yield: 40%; 1H
NMR (CDCl3, 500 MHz)
d
7.47e7.45 (m, 4H), 7.43e7.42 (m, 1H), 7.36
Purified by normal phase column chromatography, eluent hex-
(d, 1H, J ¼ 4.5 Hz), 7.33e7.29 (m, 3H), 7.18e7.15 (m, 2H), 7.05e7.01
ane:ethyl acetate 90:10 v/v followed by 55:45 v/v; Yield: 40%; 1H
(m, 2H), 6.85e6.83 (m, 1H), 6.81 (d, 1H, J ¼ 5.0 Hz), 4.92 (s, 2H); 13
C
NMR (CDCl3, 500 MHz) d 8.04e8.04 (m, 1H), 7.96e7.94 (m, 1H),
NMR (CDCl3, 125 MHz)
d
162.5 (d, J ¼ 244.4 Hz), 158.8, 149.0, 143.2,
7.74e7.73 (m, 1H), 7.65 (t, 1H, J ¼ 7.5 Hz), 7.45 (d, 1H, J ¼ 4.5 Hz),
7.38e7.35 (m, 2H), 7.28e7.28 (m, 1H), 7.19 (t, 1H, 8.0 Hz) 7.10e7.04
(m, 3H), 6.93 (d, 1H, J ¼ 4.5 Hz), 6.90e6.88 (m, 1H), 4.99 (s, 2H), 3.04
135.9, 133.0 (d, J ¼ 3.8 Hz), 130.6, 129.5, 129.4, 129.4, 129.3, 128.6,
123.1, 120.5, 117.6, 115.5 (d, J ¼ 21.3 Hz), 114.8, 113.2, 112.7, 69.3; LC/
MS m/z: 401.35 (Mþ þ 1); CHN analysis: calculated C:71.98%,
H:4.28%, N:7.00%; found: C:71.89%, H:4.13%, N:7.14%.
(s, 3H); 13C NMR (CDCl3, 125 MHz)
d
162.6 (d, J ¼ 245.0 Hz), 150.1,
142.0, 134.0, 132.8 (d, J ¼ 3.8 Hz), 132.1, 130.5, 129.7, 129.5 (d,
J ¼ 8.8 Hz), 127.7, 126.9, 121.0, 120.8, 117.3, 115.6 (d, J ¼ 21.8 Hz),
115.0, 114.1, 113.8, 69.5, 44.5; LC/MS m/z: 479.35 (Mþ þ 1); CHN
analysis: calculated C:62.74%, H:4.00%, N:5.85%; found: C:62.69%,
H:3.92%, N:5.92%.
4.4.24. 6-(3-(Phenethyloxy)phenyl)-5-phenylimidazo[2,1-b]
thiazole (IIIc)
Purified by normal phase column chromatography, eluent hex-
ane:ethyl acetate 95:5 v/v followed by 75:25 v/v; Yield: 53%; 1H
NMR (CDCl3, 500 MHz)
d
7.46e7.42 (m, 4H), 7.40e7.35 (m, 2H),
4.4.29. 5-(3-(Methylsulfonyl)phenyl)-6-(3-(phenethyloxy)phenyl)
imidazo[2,1-b]thiazole (IVc)
7.32e7.29 (m, 2H), 7.23e7.21 (m, 4H), 7.17e7.13 (m, 2H), 6.82 (d, 1H,
J ¼ 4.5 Hz), 6.80e6.76 (m, 1H), 4.07 (t, 2H, J ¼ 7.5 Hz), 3.02 (t, 2H,
Purified by normal phase column chromatography, eluent hex-
J ¼ 7.5 Hz); 13C NMR (CDCl3, 125 MHz)
d 158.9, 148.9, 143.1, 138.5,
ane:ethyl acetate 90:10 v/v followed by 55:45 v/v; Yield: 34%; 1H
135.6, 130.5, 129.5, 129.4, 129.4, 129.1, 128.6, 128.5, 126.5, 123.1,
120.2, 117.6, 114.6, 113.1, 112.8, 68.6, 35.8; LC/MS m/z: 397.44
(Mþ þ 1); CHN analysis: calculated C:75.73%, H:5.08%, N:7.07%;
found: C:75.62%, H:5.05%, N:7.11%.
NMR (CDCl3, 500 MHz)
d
8.01 (s, 1H), 7.92 (d, 1H, J ¼ 8.0 Hz), 7.72 (d,
1H, J ¼ 7.5 Hz), 7.63 (t, 1H, J ¼ 8.0 Hz), 7.43 (d, 1H, J ¼ 4.5 Hz),
7.32e7.29 (m, 2H), 7.25e7.23 (m, 3H), 7.19e7.15 (m, 2H), 7.06 (d, 1H,
J ¼ 7.5 Hz), 6.90 (d, 1H, J ¼ 4.5 Hz), 6.82 (dd, 1H, J ¼ 2.0, 8.0 Hz), 4.12
(t, 2H, J ¼ 7.0 Hz), 3.05 (t, 2H, J ¼ 7.0 Hz), 2.96 (s, 3H); 13C NMR
4.4.25. 6-(3-(4-Fluorophenethyloxy)phenyl)-5-phenylimidazo[2,1-
b]thiazole (IIId)
(CDCl3, 125 MHz) d 159.1, 150.2, 144.9, 141.9, 138.4, 135.3, 134.1,
132.3, 130.4, 129.6, 129.1, 128.6, 127.7 (2C), 126.8 (2C), 126.6, 120.9,
120.5, 117.3, 114.6, 113.9, 113.6, 68.8, 44.4, 35.9; LC/MS m/z: 475.38
(Mþ þ 1); CHN analysis: calculated C:65.80%, H:4.67%, N:5.90%;
found: C:65.77%, H:4.60%, N:5.97%.
Purified by normal phase column chromatography, eluent hex-
ane:ethyl acetate 95:5 v/v followed by 75:25 v/v; Yield: 28%; 1H
NMR (CDCl3, 500 MHz)
d 7.48e7.43 (m, 4H), 7.41e7.35 (m, 2H),
7.22e7.13 (m, 5H), 7.00e6.96 (m, 2H), 6.84 (d, 1H, J ¼ 4.5 Hz),
6.79e6.76 (m,1H), 4.06 (t, 2H, J ¼ 7.0 Hz), 2.99 (t, 2H, J ¼ 7.0 Hz); 13
C
4.4.30. 6-(3-(4-Fluorophenethyloxy)phenyl)-5-(3-(methylsulfonyl)
phenyl)imidazo[2,1-b]thiazole (IVd)
NMR (CDCl3, 125 MHz)
d
161.8 (d, J ¼ 242.7 Hz), 158.9, 148.9, 134.2
(d, J ¼ 3.4 Hz), 130.6 (d, J ¼ 7.6 Hz), 130.34, 129.5, 129.5, 129.4, 128.7,
128.6, 127.6, 123.1, 120.2, 117.7, 115.3 (d, J ¼ 20.9 Hz), 114.7, 113.1,
113.0, 68.6, 35.0; LC/MS m/z: 415.27 (Mþ þ 1); CHN analysis:
calculated C:72.44%, H:4.62%, N:6.76%; found: C:72.50%, H:4.55%,
N:6.68%.
Purified by normal phase column chromatography, eluent hex-
ane:ethyl acetate 90:10 v/v followed by 55:45 v/v; Yield: 30%; 1H
NMR (CDCl3, 500 MHz)
d
8.02 (s, 1H), 7.94 (d,1H, J ¼ 8.0 Hz), 7.72 (d,
1H, 8.0 Hz), 7.64 (t, 1H, J ¼ 7.5 Hz), 7.44 (d, 1H, J ¼ 4.5 Hz), 7.22e7.20
(m, 3H), 7.15 (t, 1H, J ¼ 8.0 Hz), 7.03e6.97 (m, 3H), 6.92 (d, 1H,
4.5 Hz), 6.82e6.80 (m, 1H), 4.12 (t, 2H, J ¼ 7.0 Hz), 3.04e3.00 (m,
4.4.26. 2-(3-(5-Phenylimidazo[2,1-b]thiazol-6-yl)phenoxy)-1-
phenylethanone (IIIe)
5H); 13C NMR (CDCl3, 125 MHz)
d
161.8 (d, J ¼ 242.5 Hz), 159.2,
149.9, 142.0, 134.1, 134.1 (d, J ¼ 3.8 Hz), 131.9, 130.6, 130.5, 129.7,
128.7, 128.2, 127.8 (2C), 127.7 (2C), 127.1, 121.0, 120.5, 117.4, 115.4 (d,
J ¼ 21.3 Hz), 115.0, 114.2, 113.8, 68.7, 44.4, 35.1; LC/MS m/z: 493.34
(Mþ þ 1); CHN analysis: calculated C:63.40%, H:4.30%, N:5.69%;
found: C:63.30%, H:4.24%, N:5.77%.
Purified by normal phase column chromatography, eluent hex-
ane:ethyl acetate 95:5 v/v followed by 75:25 v/v; Yield: 55%; 1H
NMR (CDCl3, 500 MHz)
J ¼ 7.5 Hz), 7.49 (t, 2H, J ¼ 7.5 Hz), 7.43e7.40 (m, 4H), 7.36e7.35 (m,
d
7.93 (d, 2H, J ¼ 7.5 Hz), 7.61 (t, 1H,
17