Y. Hu et al.
Bioorganic Chemistry 107 (2021) 104575
4.1.27. Synthesis of (E)-N-(4-((2-((2-butyl-4-chloro-1-(2-fluorobenzyl)-
1H-imidazol-5-yl)methylene)hydrazinyl) sulfonyl)phenyl)acetamide (6a)
Compound 6a was prepared according to the procedure described for
compound 4a, starting from intermediate 9a (1.47 g, 5.00 mmol), and
compound 3 (1.15 g, 5.00 mmol). The pure product 6a was obtained as
white solid. Yield: 76.2%; mp: 200–202 ◦C; 1H NMR (600 MHz,
DMSO‑d6) δ: 11.35 (s, 1H, SO2NH), 10.28 (s, 1H, NHCOCH3), 7.84 (s,
1H, NCH), 7.60 (d, J = 8.9 Hz, 2H, Ph-2,6-H), 7.51 (d, J = 8.9 Hz, 2H,
Ph-3,5-H), 7.06 (t, J = 8.8 Hz, 2H, Im-N-CH2-Ph-3,4-H), 6.91 (m, J = 8.6,
5.5 Hz, 2H, Im-N-CH2-Ph-5,6-H), 5.47 (s, 2H, Im-N-CH2), 2.52 (d, J =
7.9 Hz, 2H, CH2CH2CH2CH3), 2.09 (s, 3H, COCH3), 1.48–1.40 (m, 2H,
CH2CH2CH3), 1.22 (m, J = 14.7, 7.3 Hz, 2H, CH2CH3), 0.77 (t, J = 7.3
Hz, 3H, CH2CH3) ppm; 13C NMR (150 MHz, DMSO‑d6) δ: 169.4, 163.0,
160.6, 152.0, 143.8, 136.3, 133.2, 132.7, 132.4, 128.6, 128.5, 120.3,
118.9, 115.9, 115.7, 47.4, 29.1, 26.1, 24.6, 22.0, 14.0 ppm.
4.1.31. Synthesis of (E)-N-(4-((2-((2-butyl-4-chloro-1-(2-chlorobenzyl)-
1H-imidazol-5-yl)methylene) hydrazinyl)sulfonyl)phenyl) acetamide (6c)
Compound 6c was prepared according to the procedure described for
compound 4a, starting from intermediate 9c (1.55 g, 5.00 mmol), and
compound 3 (1.15 g, 5.00 mmol). The pure product 6c was obtained as
white solid. Yield: 70.9%; mp: 210–212 ◦C; 1H NMR (600 MHz,
DMSO‑d6) δ: 11.27 (s, 1H, SO2NH), 10.24 (s, 1H, NHCOCH3), 7.83 (s,
1H, NCH), 7.55 (s, 1H, Im-N-CH2-Ph-3-H), 7.54–7.51 (m, 2H, Ph-2,6-H),
7.37–7.33 (m, 2H, Ph-3,5-H), 7.30 (m, J = 7.8, 1.3 Hz, 1H, Im-N-CH2-
Ph-4-H), 7.18 (m, J = 7.6, 1.0 Hz, 1H, Im-N-CH2-Ph-5-H), 6.23 (d, J =
6.8 Hz, 1H, Im-N-CH2-Ph-6-H), 5.56 (s, 2H, Im-N-CH2), 2.46 (t, J = 7.6
Hz, 2H, CH2CH2CH2CH3), 2.09 (s, 3H, COCH3), 1.50–1.42 (m, 2H,
CH2CH2CH3), 1.25–1.16 (m, 2H, CH2CH3), 0.75 (t, J = 7.3 Hz, 3H,
CH2CH3) ppm; 13C NMR (150 MHz, DMSO‑d6) δ: 169.4, 152.1, 143.6,
136.0, 134.3, 132.6, 132.4, 131.4, 129.9, 129.3, 128.3, 128.0, 126.2,
120.7, 118.8, 46.5, 28.9, 25.8, 24.6, 22.0, 14.0 ppm.
4.1.28. Synthesis of (E)-4-amino-N′-((2-butyl-4-chloro-1-(2-
fluorobenzyl)-1H-imidazol-5-yl)methylene) benzenesulfonohydrazide (7a)
Hybrid 7a was prepared according to the procedure described for
compound 5a, starting from compound 6a (0.46 g, 1.00 mmol), and
hydrochloric acid (0.5 mL). The pure product 7a was obtained as white
solid. Yield: 61.2%; mp: 137–139 ◦C; 1H NMR (600 MHz, DMSO‑d6) δ:
7.68 (s, 1H, NCH), 7.20 (d, J = 8.7 Hz, 2H, Ph-2,6-H), 7.12–7.07 (m, 2H,
Im-N-CH2-Ph-3,4-H), 7.03–6.98 (m, 2H, Im-N-CH2-Ph-5,6-H), 6.43 (d, J
= 8.6 Hz, 2H, Ph-3,5-H), 5.76 (s, 2H, NH2), 5.53 (s, 2H, Im-N-CH2), 2.52
(d, J = 8.0 Hz, 2H, CH2CH2CH2CH3), 1.46 (m, J = 15.2, 7.5 Hz, 2H,
CH2CH2CH3), 1.23 (m, J = 14.9, 7.4 Hz, 2H, CH2CH3), 0.81–0.77 (m,
3H, CH2CH3) ppm; 13C NMR (150 MHz, DMSO‑d6) δ: 163.0, 160.6,
152.4, 150.4, 133.7, 129.1, 129.0, 127.1, 121.7, 116.0, 115.8, 115.6,
112.8, 112.7, 47.1, 29.3, 26.1, 22.1, 14.0 ppm; HRMS (ESI) calcd. for
4.1.32. Synthesis of (E)-4-amino-N′-((2-butyl-4-chloro-1-(2-
chlorobenzyl)-1H-imidazol-5-yl)methylene) benzenesulfonohydrazide (7c)
Hybrid 7c was prepared according to the procedure described for
compound 5a, starting from compound 6c (0.52 g, 1.00 mmol), and
hydrochloric acid (0.5 mL). The pure product 7c was obtained as yellow
solid. Yield: 61.1%; mp: 176–178 ◦C; 1H NMR (600 MHz, DMSO‑d6) δ:
11.06 (s, 1H, SO2NH), 7.84 (s, 1H, NCH), 7.56 (m, J = 8.0, 1.1 Hz, 1H,
Im-N-CH2-Ph-3-H), 7.38–7.33 (m, 1H, Im-N-CH2-Ph-4-H), 7.22 (m, J =
7.6, 1.1 Hz, 1H, Im-N-CH2-Ph-5-H), 7.14–7.10 (m, 2H, Ph-2,6-H), 6.46
(d, J = 8.7 Hz, 2H, Ph-3,5-H), 6.28 (d, J = 6.7 Hz, 1H, Im-N-CH2-Ph-6-
H), 5.59 (s, 2H, Im-N-CH2), 2.46 (t, J = 7.6 Hz, 2H, CH2CH2CH2CH3),
1.47 (m, J = 15.2, 7.5 Hz, 2H, CH2CH2CH3), 1.21 (m, J = 14.9, 7.4 Hz,
2H, CH2CH3), 0.75 (t, J = 7.3 Hz, 3H, CH2CH3) ppm; 13C NMR (150
MHz, DMSO‑d6) δ: 151.8, 135.3, 134.4, 132.1, 131.5, 130.2, 129.9,
129.4, 129.2, 128.1, 126.4, 124.8, 120.9, 113.8, 46.5, 28.9, 25.8, 22.0,
14.0 ppm; HRMS (ESI) calcd. for C21H23Cl2N5O2S [M+H]+, 480.1022;
found, 480.1024.
C
21H23ClFN5O2S [M+H]+, 464.1318; found, 464.1319.
4.1.29. Synthesis of (E)-N-(4-((2-((2-butyl-4-chloro-1-(4-fluorobenzyl)-
1H-imidazol-5-yl)methylene)hydrazinyl) sulfonyl)phenyl)acetamide (6b)
Compound 6b was prepared according to the procedure described
for compound 4a, starting from intermediate 9b (1.47 g, 5.00 mmol),
and compound 3 (1.15 g, 5.00 mmol). The pure product 6b was obtained
as white solid. Yield: 75.1%; mp: 190–192 ◦C; 1H NMR (600 MHz,
DMSO‑d6) δ: 11.30 (s, 1H, SO2NH), 10.26 (s, 1H, NHCOCH3), 7.83 (s,
1H, NCH), 7.60–7.56 (m, 2H, Ph-2,6-H), 7.45–7.41 (m, 2H, Ph-3,5-H),
7.33 (m, J = 7.4, 1.5 Hz, 1H, Im-N-CH2-Ph-6-H), 7.26–7.19 (m, 1H, Im-
N-CH2-Ph-2-H), 7.04 (m, J = 7.6, 1.0 Hz, 1H, Im-N-CH2-Ph-5-H), 6.47
(m, J = 7.6, 6.6 Hz, 1H, Im-N-CH2-Ph-3-H), 5.56 (s, 2H, Im-N-CH2), 2.52
(m, J = 3.8, 1.9 Hz, 2H, CH2CH2CH2CH3), 2.09 (s, 3H, COCH3), 1.46 (m,
J = 15.3, 7.5 Hz, 2H, CH2CH2CH3), 1.26–1.16 (m, 2H, CH2CH3), 0.77 (t,
J = 7.3 Hz, 3H, CH2CH3) ppm; 13C NMR (150 MHz, DMSO‑d6) δ: 169.4,
161.0, 158.5, 152.1, 143.7, 136.1, 132.5, 129.8, 128.4, 127.4, 125.2,
123.9, 120.6, 118.9, 115.9, 42.9, 29.0, 25.9, 24.6, 22.0, 14.0 ppm.
4.1.33. Synthesis of (E)-N-(4-((2-((2-butyl-4-chloro-1-(4-chlorobenzyl)-
1H-imidazol-5-yl)methylene) hydrazinyl)sulfonyl)phenyl) acetamide (6d)
Compound 6d was prepared according to the procedure described
for compound 4a, starting from intermediate 9d (1.55 g, 5.00 mmol),
and compound 3 (1.15 g, 5.00 mmol). The pure product 6d was obtained
as white solid. Yield: 74.4%; mp: 208–210 ◦C; 1H NMR (600 MHz,
DMSO‑d6) δ: 11.35 (s, 1H, SO2NH), 10.28 (s, 1H, NHCOCH3), 7.83 (s,
1H, NCH), 7.64–7.60 (m, 2H, Ph-2,6-H), 7.53–7.49 (m, 2H, Ph-3,5-H),
7.30–7.26 (m, 2H, Im-N-CH2-Ph-3,5-H), 6.87 (d, J = 8.5 Hz, 2H, Im-N-
CH2-Ph-2,6-H), 5.47 (s, 2H, Im-N-CH2), 2.53–2.51 (m, 2H,
CH2CH2CH2CH3), 2.09 (s, 3H, COCH3), 1.45 (m, J = 15.3, 7.5 Hz, 2H,
CH2CH2CH3), 1.26–1.17 (m, 2H, CH2CH3), 0.77 (t, J = 7.3 Hz, 3H,
CH2CH3) ppm; 13C NMR (150 MHz, DMSO‑d6) δ: 169.4, 152.0, 143.8,
136.2, 136.0, 132.7, 132.4, 129.0, 128.6, 128.3, 120.4, 118.9, 47.5,
29.1, 26.0, 24.7, 22.0, 14.0 ppm.
4.1.30. Synthesis of (E)-4-amino-N′-((2-butyl-4-chloro-1-(4-
fluorobenzyl)-1H-imidazol-5-yl)methylene) benzenesulfonohydrazide (7b)
Hybrid 7b was prepared according to the procedure described for
compound 5a, starting from compound 6b (0.46 g, 1.00 mmol), and
hydrochloric acid (0.5 mL). The pure product 7b was obtained as white
solid. Yield: 60.7%; mp: 122–124 ◦C; 1H NMR (600 MHz, DMSO‑d6) δ:
7.66 (s, 1H, NCH), 7.34 (m, J = 7.4, 1.6 Hz, 1H, Im-N-CH2-Ph-6-H), 7.24
(m, J = 9.3, 6.7, 1.0 Hz, 1H, Im-N-CH2-Ph-2-H), 7.14–7.10 (m, 2H, Ph-
2,6-H), 7.06 (m, J = 7.6, 1.1 Hz, 1H, Im-N-CH2-Ph-5-H), 6.58 (t, J = 7.1
Hz, 1H, Im-N-CH2-Ph-3-H), 6.38–6.34 (m, 2H, Ph-3,5-H), 5.67 (s, 2H,
NH2), 5.63 (d, J = 6.2 Hz, 2H, Im-N-CH2), 2.49–2.44 (m, 2H,
CH2CH2CH2CH3), 1.45 (m, J = 15.2, 7.5 Hz, 2H, CH2CH2CH3), 1.21 (m,
J = 14.9, 7.4 Hz, 2H, CH2CH3), 0.77 (t, J = 7.3 Hz, 3H, CH2CH3) ppm;
13C NMR (150 MHz, DMSO‑d6) δ: 161.0, 158.6, 152.3, 150.6, 129.7,
128.9, 127.8, 127.1, 125.1, 124.5, 122.0, 115.6, 112.8, 112.7, 42.4,
29.1, 25.9, 22.1, 14.0 ppm; HRMS (ESI) calcd. for C21H23ClFN5O2S [M
+ Na]+, 486.1137; found, 486.1140.
4.1.34. Synthesis of (E)-4-amino-N′-((2-butyl-4-chloro-1-(4-
chlorobenzyl)-1H-imidazol-5-yl)methylene) benzenesulfonohydrazide (7d)
Hybrid 7d was prepared according to the procedure described for
compound 5a, starting from compound 6d (0.52 g, 1.00 mmol), and
hydrochloric acid (0.5 mL). The pure product 7d was obtained as white
solid. Yield: 62.5%; mp: 133–135 ◦C; 1H NMR (600 MHz, DMSO‑d6) δ:
7.59 (s, 1H, NCH), 7.33–7.30 (m, 2H, Ph-2,6-H), 7.18–7.15 (m, 2H, Im-
N-CH2-Ph-3,5-H), 6.96 (d, J = 8.5 Hz, 2H, Im-N-CH2-Ph-2,6-H), 6.40 (d,
J = 8.7 Hz, 2H, Ph-3,5-H), 5.61 (s, 2H, NH2), 5.54 (s, 2H, Im-N-CH2),
2.48 (d, J = 7.6 Hz, 2H, CH2CH2CH2CH3), 1.48–1.44 (m, 2H,
CH2CH2CH3), 1.23 (d, J = 7.4 Hz, 2H, CH2CH3), 0.80–0.78 (m, 3H,
CH2CH3) ppm; 13C NMR (150 MHz, DMSO‑d6) δ: 151.5, 149.3, 136.9,
132.2, 129.1, 128.8, 128.7, 127.1, 126.1, 122.7, 112.7, 47.1, 29.3, 26.1,
22.1, 14.1 ppm; HRMS (ESI) calcd. for C21H23Cl2N5O2S [M+H]+,
480.1022; found, 480.1009.
13