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H. Xu et al. / European Journal of Medicinal Chemistry 198 (2020) 112360
4.8.17. 1-(2-(benzylselanyl)-2-(2,4-difluorophenyl)ethyl)-1H-
imidazole (A17)
112.06, 112.03, 104.76, 104.50, 104.24, 50.11, 35.67, 27.64, 27.62.
White solid; yield 81.33%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/
z): 379.0515 [MþH]þ (calcd. for C18H16N2F2Se); 1H NMR (400 MHz,
4.8.22. 1-(2-(2,4-difluorophenyl)-2-((4-fluorobenzyl)selanyl)
ethyl)-1H-imidazole (A22)
DMSO‑d6)
d
(ppm): 7.54e7.46 (m, 2H), 7.30 (d, J ¼ 5.2 Hz, 4H),
White solid; yield 79.47%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/
z): 397.0421 [MþH]þ (calcd. for C18H15N2F3Se); 1H NMR (400 MHz,
7.24e7.20 (m, 1H), 7.13 (ddd, J ¼ 10.8, 9.3, 2.6 Hz, 1H), 7.07e7.00 (m,
2H), 6.78 (d, J ¼ 1.1 Hz, 1H), 4.67e4.58 (m, 1H), 4.54e4.45 (m, 2H),
3.92 (d, J ¼ 11.5 Hz, 1H), 3.82 (d, J ¼ 11.5 Hz, 1H). 13C NMR (101 MHz,
DMSO‑d6) d (ppm): 7.54e7.46 (m, 2H), 7.35e7.30 (m, 2H), 7.16e7.09
(m, 3H), 7.06e7.00 (m, 2H), 6.79 (d, J ¼ 1.1 Hz, 1H), 4.67e4.59 (m,
DMSO)
d (ppm): 163.05, 161.34, 161.22, 160.60, 160.48, 158.88,
1H), 4.56e4.47 (m, 2H), 3.91 (d, J ¼ 11.8 Hz, 1H), 3.81 (d, J ¼ 11.7 Hz,
158.76, 139.11, 137.74, 130.76, 130.72, 130.67, 130.62, 129.34, 128.75,
127.27, 119.61, 112.26, 112.22, 112.05, 112.01, 104.76, 104.50, 104.24,
50.14, 35.58, 28.34.
1H). 13C NMR (101 MHz, DMSO)
d (ppm): 163.06, 162.93, 162.69,
161.32, 161.19, 160.61, 160.48, 160.27, 158.85, 158.73, 137.77, 135.47,
135.44, 131.25, 131.17, 130.75, 130.70, 130.65, 130.60, 128.76, 123.75,
123.71, 123.61, 123.58, 119.65, 115.78, 115.57, 112.26, 112.23, 112.05,
112.02, 104.76, 104.50, 104.24, 50.14, 35.57, 27.40.
4.8.18. 1-(2-((2,4-dichlorobenzyl)selanyl)-2-(2,4-difluorophenyl)
ethyl)-1H-imidazole (A18)
White solid; yield 88.66%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/
z): 446.9732 [MþH]þ (calcd. for C18H14N2F2Cl2Se); 1H NMR
4.8.23. 1-(2-((2-bromobenzyl)selanyl)-2-(2,4-difluorophenyl)
ethyl)-1H-imidazole (A23)
(400 MHz, DMSO‑d6)
d
(ppm): 7.61e7.48 (m, 3H), 7.45 (d, J ¼ 8.3 Hz,
White solid; yield 84.47%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/
z): 456.9618 [MþH]þ 478.9434 [MþNa]þ (calcd. for
1H), 7.38 (dd, J ¼ 8.3, 2.2 Hz, 1H), 7.14 (ddd, J ¼ 10.8, 9.3, 2.6 Hz, 1H),
7.09e7.00 (m, 2H), 6.79 (t, J ¼ 1.1 Hz, 1H), 4.69e4.61 (m, 2H),
4.61e4.51 (m, 1H), 3.98 (d, J ¼ 11.9 Hz, 1H), 3.90 (d, J ¼ 11.9 Hz, 1H).
C
18H15N2F2BrSe); 1H NMR (400 MHz, DMSO‑d6)
d (ppm): 7.61e7.50
(m, 3H), 7.43 (dd, J ¼ 7.6, 1.8 Hz, 1H), 7.33 (td, J ¼ 7.5, 1.3 Hz, 1H),
7.19e7.12 (m, 2H), 7.09e7.01 (m, 2H), 6.79 (t, J ¼ 1.1 Hz, 1H), 4.67 (d,
J ¼ 8.8 Hz, 2H), 4.58e4.49 (m, 1H), 4.00 (d, J ¼ 11.7 Hz, 1H), 3.93 (d,
13C NMR (101 MHz, DMSO)
d (ppm): 163.14, 163.02, 161.37, 161.25,
160.69, 160.57, 158.90, 158.78, 137.81, 136.37, 134.22, 132.77, 132.48,
130.77, 130.72, 130.67, 130.62, 129.49, 128.77, 127.93, 123.51, 119.67,
112.26, 112.23, 112.05, 112.02, 104.80, 104.55, 104.29, 50.12, 36.09,
25.23.
J ¼ 11.7 Hz, 1H). 13C NMR (101 MHz, DMSO)
d (ppm): 163.12, 162.99,
161.40, 161.28, 160.67, 160.54, 158.93, 158.81, 138.71, 137.79, 133.33,
131.31, 130.79, 130.74, 130.69, 130.64, 129.49, 128.77, 128.40, 124.16,
123.61, 123.58, 123.48, 123.44, 119.65, 112.27, 112.23, 112.06, 112.02,
104.80, 104.54, 104.28, 50.16, 36.01, 28.77.
4.8.19. 1-(2-((2-chlorobenzyl)selanyl)-2-(2,4-difluorophenyl)
ethyl)-1H-imidazole (A19)
White solid; yield 86.25%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/
z): 413.0121 [MþH]þ (calcd. for C18H15N2F2ClSe); 1H NMR
4.8.24. 1-(2-((4-bromobenzyl)selanyl)-2-(2,4-difluorophenyl)
ethyl)-1H-imidazole (A24)
(400 MHz, DMSO‑d6)
d
(ppm): 7.58e7.49 (m, 2H), 7.42 (dd, J ¼ 7.1,
White solid; yield 82.15%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/z):
456.9616 [MþH]þ (calcd. for C18H15N2F2BrSe); 1H NMR (400 MHz,
2.2 Hz, 2H), 7.31e7.23 (m, 2H), 7.15 (ddd, J ¼ 10.8, 9.3, 2.7 Hz, 1H),
7.08e7.00 (m, 2H), 6.79 (d, J ¼ 1.2 Hz, 1H), 4.71e4.61 (m, 2H),
4.58e4.49 (m, 1H), 3.99 (d, J ¼ 11.6 Hz, 1H), 3.92 (d, J ¼ 11.7 Hz, 1H).
DMSO‑d6) d (ppm): 7.54e7.46 (m, 4H), 7.27e7.22 (m, 2H), 7.13 (ddd,
J ¼ 10.8, 9.3, 2.6 Hz, 1H), 7.06e7.00 (m, 2H), 6.79 (t, J ¼ 1.1 Hz, 1H),
4.63 (dd, J ¼ 15.3, 11.4 Hz, 1H), 4.57e4.48 (m, 2H), 3.89 (d,
J ¼ 11.8 Hz, 1H), 3.79 (d, J ¼ 11.8 Hz, 1H). 13C NMR (101 MHz, DMSO)
13C NMR (101 MHz, DMSO)
d (ppm): 163.12, 162.99, 161.39, 161.27,
160.67, 160.54, 158.92, 158.80, 137.79, 137.02, 133.30, 131.35, 130.77,
130.72, 130.67, 130.62, 130.05, 129.30, 128.77, 127.80, 123.62, 123.59,
123.48, 123.45, 119.64, 112.26, 112.22, 112.05, 112.01, 104.79, 104.53,
104.27, 50.16, 35.98, 25.91.
d
(ppm): 163.08, 162.96, 161.31, 161.19, 160.63, 160.51, 158.85,
158.73, 138.87, 137.78, 131.78, 131.48, 130.76, 130.70, 130.66, 130.61,
128.76, 123.68, 123.64, 123.54, 123.50, 120.23, 119.67, 112.27, 112.24,
112.06, 112.03, 104.77, 104.51, 104.25, 50.11, 35.66, 27.49.
4.8.20. 1-(2-((4-chlorobenzyl)selanyl)-2-(2,4-difluorophenyl)
ethyl)-1H-imidazole (A20)
4.8.25. 1-(2-(2,4-difluorophenyl)-2-((3,5-dimethoxybenzyl)selanyl)
ethyl)-1H-imidazole (A25)
White solid; yield 86.68%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/
z): 413.0123 [MþH]þ (calcd. for C18H15N2F2ClSe); 1H NMR
White solid; yield 85.25%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/
z): 439.0686 [MþH]þ 461.0508 [MþNa]þ (calcd. for
(400 MHz, DMSO‑d6)
d (ppm): 7.53e7.47 (m, 2H), 7.37e7.29 (m,
4H), 7.13 (ddd, J ¼ 10.8, 9.3, 2.6 Hz, 1H), 7.06e7.01 (m, 2H), 6.79 (t,
J ¼ 1.1 Hz, 1H), 4.63 (dd, J ¼ 15.3, 11.4 Hz, 1H), 4.56e4.49 (m, 2H),
3.91 (d, J ¼ 11.8 Hz, 1H), 3.81 (d, J ¼ 11.8 Hz, 1H). 13C NMR (101 MHz,
C d (ppm): 7.56e7.43
20H20N2F2O2Se); 1H NMR (400 MHz, DMSO‑d6)
(m, 2H), 7.19e7.09 (m, 1H), 7.09e6.97 (m, 2H), 6.78 (q, J ¼ 1.3 Hz,
1H), 6.47e6.34 (m, 3H), 4.62 (dd, J ¼ 12.2, 8.7 Hz, 1H), 4.57e4.45 (m,
2H), 3.90e3.84 (m, 1H), 3.75 (d, J ¼ 11.6 Hz, 1H), 3.72 (d, J ¼ 2.3 Hz,
DMSO)
d (ppm): 163.08, 161.32, 161.20, 160.63, 160.50, 158.85,
158.73, 138.44, 137.78, 131.76, 131.12, 130.75, 130.70, 130.66, 130.61,
128.85, 128.77, 123.69, 123.65, 123.55, 123.51, 119.66, 112.27, 112.23,
112.06, 112.02, 104.77, 104.51, 104.25, 50.12, 35.65, 27.44.
6H). 13C NMR (101 MHz, DMSO)
d (ppm): 160.87, 160.82, 160.60,
141.47, 137.80, 137.74, 130.80, 130.75, 130.70, 128.73, 123.76, 123.66,
123.62, 119.57, 112.26, 112.02, 107.30, 104.75, 104.49, 104.23, 99.27,
55.60, 50.17, 35.64, 28.55.
4.8.21. 1-(2-(2,4-difluorophenyl)-2-((3-fluorobenzyl)selanyl)ethyl)-
1H-imidazole (A21)
4.8.26. 1-(2-(2,4-difluorophenyl)-2-((3-methoxybenzyl)selanyl)
ethyl)-1H-imidazole (A26)
White solid; yield 86.46%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/
z): 397.0423 [MþH]þ (calcd. for C18H15N2F3Se); 1H NMR (400 MHz,
White solid; yield 76.18%; m.p.: 225.1e228.3 ꢀC. ESI-HRMS(m/z):
409.0619 [MþH]þ (calcd. for C19H18N2F2OSe); 1H NMR (400 MHz,
DMSO‑d6)
d
(ppm): 7.54e7.47 (m, 2H), 7.33 (td, J ¼ 8.1, 6.2 Hz, 1H),
7.17e7.09 (m, 3H), 7.08e7.00 (m, 3H), 6.79 (d, J ¼ 1.1 Hz, 1H), 4.63
DMSO‑d6)
d
(ppm): 7.54e7.45 (m, 2H), 7.21 (dd, J ¼ 8.4, 7.4 Hz, 1H),
(dd, J ¼ 15.8, 11.7 Hz, 1H), 4.56e4.48 (m, 2H), 3.93 (d, J ¼ 11.8 Hz,
7.14 (ddd, J ¼ 10.6, 9.2, 2.6 Hz,1H), 7.07e7.00 (m, 2H), 6.90e6.83 (m,
2H), 6.82e6.75 (m, 2H), 4.67e4.57 (m, 1H), 4.55e4.44 (m, 2H), 3.90
(d, J ¼ 11.5 Hz, 1H), 3.79 (d, J ¼ 11.5 Hz, 1H), 3.73 (s, 3H). 13C NMR
1H), 3.83 (d, J ¼ 11.8 Hz, 1H). 13C NMR (101 MHz, DMSO)
d (ppm):
163.71, 162.96, 161.29, 161.21, 160.63, 160.51, 158.74, 142.38, 142.31,
137.77, 130.84, 130.76, 130.67, 130.62, 128.76, 125.45, 125.42, 123.68,
123.65, 123.51, 119.62, 116.05, 115.83, 114.16, 113.95, 112.28, 112.24,
(101 MHz, DMSO)
d (ppm): 163.05, 161.23, 160.60, 160.48, 159.72,
158.88, 158.76, 140.70, 137.74, 130.78, 130.73, 130.68, 130.63, 129.99,