A.B. Popov et al. / European Journal of Medicinal Chemistry 207 (2020) 112802
15
(Mr ¼ 477.92): C 60.32, H 4.85, N 11.72; found: C 60.03, H 4.98, N
for C23H21N5O2 ꢁ HCl ꢁ 3H2O (Mr ¼ 489.95): C 56.38, H 5.76, N
12.07.
14.29; found: C 56.03, H 5.39, N 14.57.
4.2.8.6. 2-[3-Fluoro-4-(2-oxoethoxy-2-phenyl)phenyl]-5-(imidazo-
lin-2-yl)-1H-benzo[d]imidazole hydrochloride (15c). According to
the above-mentioned procedure, from 10c (150 mg, 0.55 mmol)
compound 15c was obtained as brown solid (183.6 mg, 78%,
4.2.8.10. 5-(Imidazolin-2-yl)-2-[4-(2-morpholinoethoxy)phenyl]1-
1H-benzo[d]imidazole hydrochloride (l7a). According to the above-
mentioned procedure, from 12a (150 mg; 0.64 mmol) compound
17a was obtained as brown solid (248.5 mg, 74%,
m.p. ¼ 206e210 ꢂC). 1H NMR (300 MHz, DMSO‑d6) (
d/ppm): 10.66
m.p. ¼ 203e207 ꢂC). 1H NMR (600 MHz, DMSO‑d6) (
d/ppm): 11.82
(2H, s, CNH), 8.34 (1H, s, H4), 8.05 (2H, d, J ¼ 7.4 Hz, Ph), 7.97e7.67
(5H, m, Ph), 7.59 (2H, t, J ¼ 7.4 Hz, Ph), 7.11 (1H, d, J ¼ 8.6 Hz, Ph),
5.71 (2H, s, OCH2), 4.01 (4H, s, CH2CH2), 3.95 (3H, s, OCH3). 13C NMR
(1H, s, NH), 10.96 (2H, s, CNH), 8.49e8.44 (3H, m, H4, Ph), 8.04 (1H,
dd, J ¼ 8.6, 1.3 Hz, H6), 7.89 (1H, d, J ¼ 8.6 Hz, H7), 7.28 (2H, d,
J ¼ 8.9 Hz, Ph), 4.61 (2H, t, J ¼ 5.1 Hz, CH2CH2), 4.02 (4H, s, CH2CH2),
3.96e3.87 (6H, m, CH2-morpholine, CH2CH2), 3.64e3.40 (4H, m, CH2-
(75 MHz, DMSO‑d6) (d/ppm): 194.2 (CO), 165.5 (CNH), 153.7 (C2),
149.7 (Ph-q), 149.0 (Ph-q), 134.3 (Ph-q), 133.9 (Ph), 128.9 (Ph), 127.9
(Ph), 122.3 (Ph), 122.0 (Ph), 120.0 (C6), 115.1 (C5), 113.4 (Ph, C7),
110.7 (Ph), 70.6 (OCH2), 55.9 (OCH3), 44.2 (CH2CH2). Anal. calcd. for
CH2CH2). 13C NMR (151 MHz, DMSO‑d6) (
d/ppm): 165.2
morpholine,
(CNH), 159.6 (Ph-q), 154.0 (C2), 129.0 (Ph), 122.6 (C6), 121.3 (Ph-q),
115.5 (C5), 115.2 (Ph), 115.0 (C4, C7), 62.9 (CH2-morpholine), 62.4
(CH2CH2), 54.5 (CH2CH2), 51.5 (CH2-morpholine), 44.0 (CH2CH2).
C
25H22N4O3 ꢁ HCl ꢁ 2.25H2O (Mr ¼ 503.46): C 59.64, H 5.51, N
11.13; found: C 60.06, H 5.21, N 11.37.
4.2.8.11. 5-(Imidazolin-2-yl)-2-[3-fluoro-4-(2-morpholinoethoxy)
4.2.8.7. 5-(Imidazolin-2-yl)-2-[4-(pyridin-2-ylmethoxy)phenyl]-1H-
benzo[d]imidazole hydrochloride (16a). According to the above-
mentioned procedure, from 11a (150 mg; 0.70 mmol) compound
16a was obtained as white solid (175.0 mg, 46%,
phenyl]1-1H-benzo[d]imidazole
dihydrochloride
(l7b).
According to the above-mentioned procedure, from 12b (150 mg,
0.59 mmol) compound 17b was obtained as brown solid (301.4 mg,
74%, m.p. ¼ 204e208 ꢂC). 1H NMR (300 MHz, DMSO‑d6) (
d/ppm):
m.p. ¼ 208e211 ꢂC). 1H NMR (600 MHz, DMSO‑d6) (
d/ppm): 11.03
12.00 (1H, bs, NH), 10.99 (2H, s, CNH), 8.50 (1H, s, H4), 8.44e8.25
(2H, m, Ph), 8.04 (1H, dd, J ¼ 8.6, 1.4 Hz, H6), 7.86 (1H, d, J ¼ 8.6 Hz,
H7), 7.53 (1H, t, J ¼ 8.7 Hz, Ph), 4.75e4.68 (2H, m, CH2CH2), 4.01
(4H, s, CH2CH2), 3.98e3.80 (4H, m, CH2- morpholine), 3.70e3.61 (2H,
m, CH2-morpholine), 3.56e3.45 (2H, m, CH2-morpholine) 3.33e3.18 (2H,
(2H, s, CNH), 8.80 (1H, d, J ¼ 4.9 Hz, H6’), 8.54-8.51 (3H, m, H4, Ph),
8.31-8.22 (1H, m, H4’), 8.14-8.07 (1H, m, H6), 7.92 (1H, d, J ¼ 8.2 Hz,
H7), 7.90 (1H, d, J ¼ 7.8 Hz, H3’), 7.73 (1H, dd, J ¼ 7.1, 5.1 Hz, H5’),
7.41 (2H, d, J ¼ 8.8 Hz, Ph), 5.54 (2H, s, OCH2), 4.03 (4H, s, CH2CH2).
13C NMR (75 MHz, DMSO‑d6) (
d
/ppm): 164.8 (CNH), 161.1 (Ph-q),
m, CH2CH2). 13C NMR (75 MHz, DMSO‑d6) (
d/ppm): 165.1 (CNH),
154.2 (C2’), 152.8 (C2), 146.8 (C6’), 139.7 (Ph), 138.9 (Ph), 135.3 (Ph-
q), 129.9 (C4’), 124.0 (C3’), 123.0 (C5’), 118.53, 117.0 (C5), 115.6 (C4),
115.6 (Ph), 114.4 (C7), 69.0 (OCH2), 44.2 (CH2CH2). Anal. calcd. for
151.5 (d, JCF ¼ 244.9 Hz, Ph-q), 152.8 (C2), 147.7 (JCF ¼ 10.0 Hz, Ph-q),
124.3 (JCF ¼ 1.5 Hz, Ph), 122.9 (C6), 121.9 (JCF ¼ 7.5 Hz, Ph-q), 116.5
(C4), 115.8 (C5), 115.7 (Ph), 115.0 (d, JCF ¼ 20.6 Hz, Ph), 114.7 (C7),
63.8 (CH2CH2), 62.9 (CH2-morpholine), 54.4 (CH2CH2), 51.5 (CH2-
C
22H19N5O ꢁ HCl ꢁ 2H2O (Mr ¼ 441.46): C 59.79, H 5.47, N 15.85;
found: C 59.41, H 5.26, N 16.17.
morpholine),
22H24FN5O2 ꢁ 2HCl ꢁ 2.5H2O (Mr ¼ 527.42): C 50.10, H 5.92, N
13.28; found: C 50.03, H 5.71, N 13.72.
44.0
(CH2CH2).
Anal.
calcd.
for
C
4.2.8.8. 5-(Imidazolin-2-yl)-2-[3-fluoro-4-(pyridin-2-ylmethoxy)
phenyl]-1H-benzo[d]imidazole hydrochloride (l6b). According to the
above-mentioned procedure, from 11b (150 mg, 0.65 mmol) com-
pound 16b was obtained as brown solid (187.2 mg, 74%,
4.2.8.12. 5-(Imidazolin-2-yl)-2-[3-methoxy-4-(2-morpholinoethoxy)
phenyl]1-1H-benzo[d]imidazole fdihydrochloride (l7c).
m.p. ¼ 200e203 ꢂC). 1H NMR (300 MHz, DMSO‑d6) (
d
/ppm): 10.91
According to the above-mentioned procedure, from 12c (150 mg;
0.56 mmol) compound 17c was obtained as yellow solid (237.7 mg,
(2H, s, CNH), 8.74 (1H, d, J ¼ 4.5 Hz, H6’), 8.48 (1H, s, H4), 8.39 (1H,
dd, J ¼ 12.3, 1.9 Hz, H6), 8.28 (1H, d, J ¼ 8.7 Hz, H7), 8.14 (1H, td,
J ¼ 7.8, 1.5 Hz, Ph), 8.01 (1H dd, J ¼ 8.5, 1.5 Hz, H4’), 7.88 (1H, d,
J ¼ 8.6 Hz, H3’), 7.79 (1H, d, J ¼ 7.9 Hz, Ph), 7.65e7.51 (2H, m, Ph;
H5’), 5.52 (2H, s, OCH2), 4.02 (4H, s, CH2CH2). 13C NMR (75 MHz,
87%, m.p. ¼ 217e223 ꢂC). 1H NMR (300 MHz, DMSO‑d6) (
d
/ppm): 1H
NMR (300 MHz, DMSO) d 12.08 (1H, bs, NH),10.97 (2H, s, CNH), 8.50
(1H, s, H4), 8.24 (1H, d, J ¼ 1.8 Hz, Ph), 8.15e8.01 (2H, m, Ph, H6),
7.87 (1H, d, J ¼ 8.6 Hz, H7), 7.31 (1H, d, J ¼ 8.6 Hz, Ph), 4.63 (2H, t,
J ¼ 5.1 Hz, CH2CH2), 4.02 3H, s, OCH3), 3.97e3.88 (8H, m, CH2CH2,
DMSO‑d6) (d/ppm): 165.1 (CNH), 154.9 (C2’), 154.1 (C2), 151.5 (d,
JCF ¼ 245.1 Hz, Ph-q),152.7 (C2), 148.7 (d, JCF ¼ 10.5 Hz, Ph-q), 147.4
(C6’), 139.8 (Ph), 136.4 (Ph-q), 124.8 (d, JCF ¼ 3.1 Hz, Ph), 124.6 (C4’),
124.3 (C3’), 123.5 (C6), 123.1 (C5’), 118.2 (C5), 116.8 (C4), 115.8 (C7),
115.4 (d, JCF ¼ 21.2 Hz, Ph), 70.0 (OCH2), 44.4 (CH2CH2).). Anal. calcd.
for C22H18FN5O ꢁ HCl ꢁ 1.75H2O (Mr ¼ 455.40): C 58.02, H 4.98, N
15.38; found: C 57.63, H 5.26, N 15.57.
CH2-morpholine), 3.65e3.40 (4H, m, CH2-morpholine
,
CH2CH2),
3.32e3.20 (2H, m, CH2-morpholine). 13C NMR (151 MHz, DMSO‑d6) (
d/
ppm): 165.0 (CNH), 153.3 (C2), 149.8 (Ph-q), 149.4 (Ph-q), 123.3
(Ph), 121.0 (C6), 120.5 (Ph-q), 116.2 (C5), 115.9 (C4), 114.4 (Ph, C7),
111.9 (Ph), 63.6 (CH2CH2), 62.8 (CH2-morpholine), 56.2 (OCH3), 54.5
(CH2CH2), 51.5 (CH2-morpholine), 44.0 (CH2CH2). Anal. calcd. for
C
23H27N5O3 ꢁ 2HCl ꢁ 2H2O (Mr ¼ 530.44): C 52.08, H 6.27, N 13.20;
4.2.8.9. 5-(Imidazolin-2-yl)-2-[3-methoxy-4-(pyridin-2-ylmethoxy)
phenyl]-1H-benzo[d]imidazole hydrochloride (l6c). According to the
above-mentioned procedure, from 11c (150 mg; 0.62 mmol) com-
pound 16c was obtained as brown solid (181.7 mg; 73%,
found: C 52.43, H 5.98, N 13.11.
4.2.8.13. 2-{4-[2-(Diethylamino)ethoxy]phenyl}-5-(imidazolin-2-yl)-
1H-benzo[d]imidazole dihydrochloride (l8a). According to the
above-mentioned procedure, from 13a (150 mg, 0.68 mmol) com-
pound 18a was obtained as brown solid (126.8 mg, 49%,
m.p. ¼ 265e268 ꢂC). 1H NMR (600 MHz, DMSO‑d6) (
d/ppm): 10.67
(2H, s, CNH), 8.60 (1H, d, J ¼ 4.6 Hz, H6’), 8.35 (1H, s, H4), 7.96 (1H, s,
Ph), 7.92e7.81 (3H, m, Ph; H4’; H6), 7.77 (1H, d, J ¼ 8.2 Hz, H7), 7,56
(1H, d, J ¼ 7.9 Hz, H3’), 7.37 (1H, dd, J ¼ 7.2, 5.1 Hz, H5’), 7.24 (1H, d,
J ¼ 8.5 Hz, Ph), 5.27 (2H, s, OCH2), 4.01 (4H, s, CH2CH2), 3.94 (3H, s,
m.p. ¼ 214e218 ꢂC). 1H NMR (300 MHz, DMSO‑d6) (
d/ppm): 10.98
(3H, s, CNH), 8.54e8.40 (3H, m, Ph, H4), 8.06 (1H, dd, J ¼ 8.6, 1.3 Hz,
H6), 7.90 (1H, d, J ¼ 8.6 Hz, H7), 7.28 (2H, d, J ¼ 8.9 Hz, Ph), 4.56 (2H,
t, J ¼ 4.8 Hz, CH2CH2), 4.02 (4H, s, CH2CH2), 3.63e3.44 (2H, m,
CH2CH2), 3.29e3.10 (4H, m, CH2CH3), 1.28 (6H, t, J ¼ 7.2 Hz,
OCH3). 13C NMR (75 MHz, DMSO‑d6) (
d/ppm): 165.4 (CNH), 156.4
(C2), 149.8 (Ph-q), 149.2 (Ph-q), 149.1 (C6’), 137.1 (Ph), 123.1 (C4’),
122.3 (C6), 122.2 (C5), 121.8 (C5’), 120.1 (C3’), 115.1 (Ph-q), 113.4 (C4/
C7),110.6 (Ph), 70.9 (OCH2), 55.9 (OCH3), 44.2 (CH2CH2). Anal. calcd.
CH2CH3). 13C NMR (75 MHz, DMSO‑d6) (
d/ppm): 164.9 (CNH), 160.6
(Ph-q), 153.2 (C2), 129.8 (Ph), 123.9 (C6), 120.5 (Ph-q), 116.8 (C5),