Y. Gao et al.
Bioorganic & Medicinal Chemistry 35 (2021) 116073
128.6, 127.5, 127.5, 125.8, 123.0, 120.8, 119.4, 112.5, 104.8, 55.9,
35.4, 26.6, 26.0; HRMS (ESI) calcd for C17H19N3 ([M+H]+) 266.1652,
found 266.1666.
113.2, 112.5, 112.2, 104.1, 55.3, 48.1; HRMS (ESI) calcd for C19H17N3O
([M+H]+) 304.1444, Found 304.1448.
2.2.13. 3-(1-(2-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (3m)
A white solid, yield 66%, mp: 170.5–172.0 ◦C. 1H NMR (400 MHz,
DMSO‑d6) δ 11.36 (s, 1H), 7.76 (s, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.44 (d,
J = 8.0 Hz, 1H), 7.29–7.20 (m, 2H), 7.20–7.13 (m, 2H), 7.07 (t, J = 7.5
Hz, 1H), 6.98 (d, J = 8.2 Hz, 1H), 6.83 (t, J = 7.5 Hz, 1H), 6.54 (dd, J =
7.5, 1.7 Hz, 1H), 5.21 (s, 2H), 3.75 (s, 3H). 13C NMR (100 MHz,
DMSO‑d6) δ 156.4, 138.8, 136.4, 129.3, 127.6, 127.4, 127.0, 126.9,
126.2, 124.2, 122.2, 120.9, 120.1, 119.4, 112.2, 111.1, 104.1, 55.8,
43.8; HRMS (ESI) calcd for C19H17N3O ([M+H]+) 304.1444, Found
304.1459.
2.2.6. 3-(1-benzyl-1H-imidazol-5-yl)-1H-indole (3f)
A light yellow crystal, yield 44%, mp: 136.5–137.6 ◦C. 1H NMR (400
MHz, CD3OD) δ 7.81 (s, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.1
Hz, 1H), 7.25–7.15 (m, 4H), 7.11–7.04 (m, 3H), 6.97 (d, J = 7.3 Hz, 2H),
5.22 (d, J = 2.5 Hz, 2H). 13C NMR (100 MHz, DMSO‑d6) δ 138.4, 138.2,
136.1, 128.7, 127.4, 126.6, 126.4, 126.4, 123.9, 121.9, 119.8, 119.0,
111.9, 103.7, 47.8; HRMS (ESI) calcd for C18H15N3 ([M+H]+) 274.1339,
found 274.1357.
2.2.7. 3-(1-(4-methylbenzyl)-1H-imidazol-5-yl)-1H-indole (3g)
A light yellow crystal, yield 57%, mp: 169.2–170.3 ◦C; 1H NMR (400
MHz, CD3OD) δ 7.76 (s, 1H), 7.43 (dd, J = 19.1, 8.0 Hz, 2H), 7.16 (t, J =
7.4 Hz, 1H), 7.07 (dd, J = 13.6, 5.3 Hz, 4H), 6.85 (d, J = 7.9 Hz, 2H),
4.88 (s, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, DMSO‑d6) δ 138.4, 136.6,
136.1, 135.2, 129.3, 127.3, 126.5, 126.5, 126.4, 123.9, 121.9, 119.8,
119.1, 111.9, 103.8, 47.7, 20.7; HRMS (ESI) calcd for C19H17N3
([M+H]+) 288.1495, found 288.1496.
2.2.14. 3-(1-(3-fluorobenzyl)-1H-imidazol-5-yl)-1H-indole (3n)
A light yellow solid, yield 34%, mp: 156.4–157.9 ◦C. 1H NMR (400
MHz, Acetone‑d6) δ 10.93 (s, 1H), 7.85 (s, 1H), 7.61 (d, J = 7.9 Hz, 1H),
7.50 (d, J = 8.1 Hz, 1H), 7.34–7.28 (m, 2H), 7.24–7.17 (m, 2H), 7.12 (t,
J = 7.5 Hz, 1H), 7.03–6.96 (m, 1H), 6.87 (d, J = 7.7 Hz, 1H), 6.79 (d, J =
10.0 Hz, 1H), 5.37 (s, 2H). 13C NMR (100 MHz, Acetone‑d6) δ 164.1,
161.7, 141.1 (d, J = 7.2 Hz), 138.3, 136.4, 130.6 (d, J = 8.4 Hz), 127.9,
127.0 (d, J = 14.8 Hz), 124.0, 122.4 (d, J = 2.9 Hz), 122.1, 119.9, 119.0,
114.1 (d, J = 21.2 Hz), 113.4 (d, J = 22.4 Hz), 111.8, 104.0, 47.6 (d, J =
2.0 Hz). 19F NMR (376 MHz, Acetone‑d6) δ ꢀ 114.2; HRMS (ESI) calcd
for C18H14FN3 ([M+H]+) 292.1245, Found 292.1258.
2.2.8. 3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (3h)
A light yellow solid, yield 50%, mp: 150.1–152.0 ◦C. 1H NMR (400
MHz, CD3OD) δ 7.76 (s, 1H), 7.44 (dd, J = 11.9, 8.0 Hz, 2H), 7.20–7.15
(m, 1H), 7.13 (s, 1H), 7.10–7.05 (m, 2H), 6.90 (d, J = 8.7 Hz, 2H),
6.82–6.75 (m, 2H), 5.13 (s, 2H), 4.89 (s, 3H). 13C NMR (100 MHz,
DMSO‑d6) δ 158.8, 138.4, 136.4, 130.2, 128.3, 127.6, 126.7, 126.7,
124.3, 122.1, 120.0, 119.3, 114.3, 112.2, 104.1, 55.3, 47.6; HRMS (ESI)
calcd for C19H17N3O ([M+H]+) 304.1444, found 304.1442.
2.2.15. 3-(1-(2-fluorobenzyl)-1H-imidazol-5-yl)-1H-indole (3o)
A yellow solid, yield 45%, mp: 150.8–151.5 ◦C. 1H NMR (400 MHz,
DMSO‑d6) δ 11.37 (s, 1H), 7.81 (s, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.42 (d,
J = 8.1 Hz, 1H), 7.34–7.25 (m, 2H), 7.19–7.12 (m, 3H), 7.10–7.02 (m,
2H), 6.74–6.68 (m, 1H), 5.34 (s, 2H). 13C NMR (100 MHz, DMSO‑d6) δ
161.0, 158.6, 138.8, 136.4, 130.1 (d, J = 8.1 Hz), 128.9 (d, J = 4.0 Hz),
127.9, 126.9 (d, J = 9.0 Hz), 125.3 (d, J = 14.4 Hz), 125.1 (d, J = 3.5
Hz), 124.5, 122.2, 120.1, 119.3, 115.7 (d, J = 20.7 Hz), 112.3, 103.9,
42.5 (d, J = 4.8 Hz). 19F NMR (376 MHz, DMSO‑d6) δ ꢀ 118.4 (d, J = 9.3
Hz); HRMS (ESI) calcd for C18H14FN3 ([M+H]+) 292.1245, Found
292.1239.
2.2.9. 3-(1-(4-fluorobenzyl)-1H-imidazol-5-yl)-1H-indole (3i)
A white solid, yield 43%, mp: 182.1–182.8 ◦C. 1H NMR (400 MHz,
CD3OD) δ 7.82 (s, 1H), 7.44–7.40 (m, 2H), 7.17 (t, J = 7.5 Hz, 1H), 7.12
(s, 1H), 7.09–7.04 (m, 2H), 6.94 (d, J = 7.0 Hz, 4H), 5.19 (s, 2H). 13
C
NMR (100 MHz, DMSO‑d6) δ 161.3 (d, JC-F = 244.2 Hz, 1C), 138.3,
136.0, 134.2, 134.2, 128.6, 128.5, 127.5, 126.4, 124.0, 121.8, 119.7,
118.9, 115.5, 115.3, 111.8, 103.6, 47.1; HRMS (ESI) calcd for
C
18H14FN3 ([M+H]+) 292.1245, found 292.1244.
2.2.16. 3-(1-(4-chlorobenzyl)-1H-imidazol-5-yl)-1H-indole (3p)
A gray solid, yield 30%, mp: 204.7–206.5 ◦C. 1H NMR (400 MHz,
DMSO‑d6) δ 11.39 (s, 1H), 7.86 (s, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.44 (d,
J = 8.1 Hz, 1H), 7.32 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 2.7 Hz, 1H), 7.16
(q, J = 7.6, 6.0 Hz, 2H), 7.06 (t, J = 7.5 Hz, 1H), 6.97 (d, J = 8.1 Hz, 2H),
5.30 (s, 2H). 13C NMR (100 MHz, DMSO‑d6) δ 138.8, 137.6, 136.4,
132.4, 129.0, 128.7, 127.9, 126.9, 126.8, 124.4, 122.2, 120.1, 119.3,
112.3, 103.9, 47.6; HRMS (ESI) calcd for C18H14ClN3 ([M+H]+)
308.0949, Found 308.0964.
2.2.10. 3-(1-(3-methylbenzyl)-1H-imidazol-5-yl)-1H-indole (3j)
A yellow solid, yield 39%, mp:145.9–146.6 ◦C. 1H NMR (400 MHz,
Acetone‑d6) δ 10.84 (s, 1H), 7.77 (s, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.50
(d, J = 8.1 Hz, 1H), 7.29–7.27 (m, 1H), 7.22–7.16 (m, 3H), 7.15–7.08
(m, 2H), 7.05 (d, J = 7.6 Hz, 1H), 6.89–6.82 (m, 2H), 5.27 (s, 2H), 2.22
(s, 3H). 13C NMR (100 MHz, DMSO‑d6) δ 138.7, 138.5, 138.2, 136.4,
129.0, 128.4, 127.7, 127.4, 126.9, 126.8, 124.3, 123.9, 122.2, 120.1,
119.4, 112.2, 104.1, 48.1, 21.4; HRMS (ESI) calcd for C19H17N3
([M+H]+) 288.1495, Found 288.1489.
2.2.17. 3-(1-(4-bromobenzyl)-1H-imidazol-5-yl)-1H-indole (3q)
A light yellow solid, yield 38%, mp: 211.5–213.0 ◦C. 1H NMR (400
MHz, DMSO‑d6) δ 11.34 (s, 1H), 7.84 (s, 1H), 7.52 (d, J = 8.1 Hz, 1H),
7.46 (d, J = 7.9 Hz, 2H), 7.42 (d, J = 8.6 Hz, 1H), 7.28 (s, 1H), 7.14 (d, J
= 5.2 Hz, 2H), 7.06 (d, J = 7.5 Hz, 1H), 6.90 (d, J = 8.0 Hz, 2H), 5.28 (s,
2H). 13C NMR (100 MHz, DMSO‑d6) δ 138.8, 138.0, 136.4, 132.0, 129.0,
128.0, 126.8, 124.4, 122.3, 120.9, 120.1, 119.4, 112.3, 103.9, 47.7;
HRMS (ESI) calcd for C18H14BrN3 ([M+H]+) 352.0444, Found
352.0440.
2.2.11. 3-(1-(2-methylbenzyl)-1H-imidazol-5-yl)-1H-indole (3k)
A yellow solid, yield 87%, mp: 176.7–178.1 ◦C. 1H NMR (400 MHz,
DMSO‑d6) δ 11.31 (s, 1H), 7.70 (s, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.41 (d,
J = 8.0 Hz, 1H), 7.19–7.16 (m, 4H), 7.15–7.11 (m, 2H), 7.11–7.06 (m,
2H), 5.26 (s, 2H), 2.17 (s, 3H). 13C NMR (100 MHz, DMSO‑d6) δ 138.6,
136.7, 136.4, 135.2, 130.5, 127.7, 127.6, 127.2, 126.7, 126.7, 126.1,
123.9, 122.2, 120.1, 119.4, 112.2, 104.1, 46.5, 18.9; HRMS (ESI) calcd
for C19H17N3 ([M+H]+) 288.1495, Found 288.1502.
2.2.18. 3-(1-(4-(trifluoromethyl)benzyl)-1H-imidazol-5-yl)-1H-indole
(3r)
2.2.12. 3-(1-(3-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (3l)
A white solid, yield 80%, mp: 152.6–154.5 ◦C. 1H NMR (400 MHz,
Acetone‑d6) δ 10.60 (s, 1H), 7.76 (s, 1H), 7.62 (dd, J = 7.9, 1.0 Hz, 1H),
7.51–7.46 (m, 1H), 7.28 (d, J = 2.6 Hz, 1H), 7.23–7.08 (m, 4H),
6.84–6.76 (m, 1H), 6.65–6.61 (m, 1H), 6.59 (t, J = 2.0 Hz, 1H), 5.30 (s,
2H), 3.67 (s, 3H). 13C NMR (100 MHz, DMSO‑d6) δ 159.8, 140.2, 138.8,
136.4, 130.2, 127.7, 126.8, 126.8, 124.3, 122.2, 120.1, 119.4, 118.9,
A light yellow solid, yield 25%, mp: 203.5–204.5 ◦C. 1H NMR (400
MHz, DMSO‑d6) δ 11.34 (s, 1H), 7.90 (s, 1H), 7.64 (d, J = 8.1 Hz, 2H),
7.52 (d, J = 7.9 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.27 (d, J = 7.2 Hz,
1H), 7.17–7.12 (m, 4H), 7.08–7.02 (m, 1H), 5.42 (s, 2H). 13C NMR (100
MHz, DMSO‑d6) δ 143.3, 138.9, 136.4, 127.9, 127.4, 126.9, 126.7,
126.0, 126.0, 125.9, 124.4, 122.3, 120.1, 119.3, 112.3, 103.8, 47.8. 19
F
4