V. Obermoser et al. / European Journal of Medicinal Chemistry 126 (2017) 590e603
601
(0.11 mmol), 0.073 g potassium hydroxide (1.31 mmol) and 1.5 mL
of ethylene glycol as solvent. Column chromatography: DCM/MeOH
(9:1). Off-white solid, yield: 0.025 g (0.05 mmol, 50%), mp
266e267 ꢀC.
ethylene glycol as solvent. Column chromatography: DCM/MeOH
(95:5). White solid, yield: 0.035
g
(0.07 mmol, 28%), mp
234e237 ꢀC.
1H-NMR (200 MHz, DMSO-d6):
d 7.78e7.53 (m, 4H), 7.52e7.24
1H-NMR (200 MHz, DMSO-d6):
d
12.69 (s, br, 1H), 9.45 (s, br, 1H),
(m, 8H), 7.23e7.02 (m, 3H), 5.57 (s, 2H), 2.89 (t, 3J ¼ 7.4 Hz, 2H),
7.78e7.64 (m, 2H), 7.60e7.22 (m, 9H), 7.14 (d, 3J ¼ 8.4 Hz, 2H), 6.83
(d, 3J ¼ 8.8 Hz, 2H), 5.54 (s, 2H), 2.85 (t, 3J ¼ 7.6 Hz, 2H), 1.93e1.68
(m, 2H), 0.97 (t, 3J ¼ 7.4 Hz, 3H); 13C-NMR (125 MHz, DMSO-d6):
1.93e1.69 (m, 2H), 0.99 (t, 3J ¼ 7.4 Hz, 3H); 13C-NMR (125 MHz,
DMSO-d6):
d 171.53, 156.45, 141.06, 138.76, 137.81, 136.39, 132.68,
126.84, 123.75, 119.64,110.32, 46.32, 29.06, 20.86,14.30; HRMS: m/z
d
170.04, 156.96, 156.08, 143.55, 140.82, 140.54, 134.82, 129.53,
calculated for C30H25N2O2Cl [M-H]-: 479.1521, found: 479.1524.
128.35, 126.73, 121.10, 116.10, 110.79, 50.79, 29.06, 20.84, 14.29;
HRMS: m/z calculated for C30H26N2O3 [MþH]þ: 463.2016, found:
463.2073.
4.1.10. 4’-((6-(4-Methoxyphenyl)-2-propyl-1H-benzo[d]imidazol-
1-yl)methyl)-[1,1’-biphenyl]-2-carbonic acid (36)
From 0.040 g 4’-((6-(4-methoxyphenyl)-2-propyl-1H-benzo[d]
4.1.6. 4’-((5-(3-Hydroxyphenyl)-2-propyl-1H-benzo[d]imidazol-1-
yl)methyl)-[1,1’-biphenyl]-2-carbonic acid (32)
imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile
(20)
(0.09 mmol), 0.049 g potassium hydroxide (0.87 mmol) and 3 mL of
ethylene glycol as solvent. Column chromatography: DCM/MeOH
(95:5). Yellowish solid, yield: 0.034 g (0.07 mmol, 81%), mp
209e212 ꢀC.
From 0.130 g 4’-((5-(3-hydroxyphenyl)-2-propyl-1H-benzo[d]
imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile
(26)
(0.29 mmol), 0.163 g potassium hydroxide (2.90 mmol) and 3 mL of
ethylene glycol as solvent. Column chromatography: DCM/MeOH
(9:1). White solid, yield: 0.046 g (0.10 mmol, 34%), mp 275e278 ꢀC.
1H-NMR (200 MHz, DMSO-d6):
d 7.76 (s,1H), 7.72e7.23 (m,10H),
7.14 (d, 3J ¼ 8.4 Hz, 2H), 7.01 (d, 3J ¼ 8.8 Hz, 2H), 5.60 (s, 2H), 3.79 (s,
3H), 2.84 (t, 3J ¼ 7.3 Hz, 2H), 1.90e1.68 (m, 2H), 0.96 (t, 3J ¼ 7.3 Hz,
3H); HRMS: m/z calculated for C31H28N2O3 [MþH]þ: 477.2173,
found: 477.2294.
1H-NMR (200 MHz, DMSO-d6):
d 12.84 (s, br, 1H), 9.53 (s, 1H),
7.85e7.68 (m, 2H), 7.66e7.30 (m, 7H), 7.29e7.02 (m, 5H), 6.77 (d,
3J ¼ 9.2 Hz, 1H), 5.60 (s, 2H), 2.90 (t, 3J ¼ 7.4 Hz, 2H), 1.95e1.69 (m,
2H), 1.02 (t, 3J ¼ 7.3 Hz, 3H); 13C-NMR (50 MHz, DMSO-d6):
d 170.13,
158.28,156.44,143.49,143.21,140.64,136.52,135.49,134.89,132.95,
131.32, 130.95, 130.36, 129.62, 128.26, 127.85, 126.61, 121.58, 118.26,
116.93, 114.25, 110.90, 46.39, 41.29, 29.14, 20.31, 14.36; HRMS: m/z
calculated for C30H26N2O3 [MþH]þ: 463.2016, found: 463.2069.
4.1.11. 4’-((6-(3-Methoxyphenyl)-2-propyl-1H-benzo[d]imidazol-1-
yl)methyl)-[1,1’-biphenyl]-2-carbonic acid (37)
From 0.068 g 4’-((6-(3-methoxyphenyl)-2-propyl-1H-benzo[d]
imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile
(21)
(0.15 mmol), 0.083 g potassium hydroxide (1.49 mmol) and 4 mL of
ethylene glycol as solvent. Column chromatography: DCM/MeOH
(9:1). White solid. yield: 0.050 g (0.11 mmol, 70%), mp 223e227 ꢀC.
4.1.7. 4’-((5-(4-Chlorophenyl)-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carbonic acid (33)
From 0.050
g
4’-((5-(4-chlorophenyl)-2-propyl-1H-benzo[d]
(17)
1H-NMR (200 MHz, DMSO-d6):
d 7.84 (s, 1H), 7.72e7.58 (m, 2H),
imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile
7.56e7.06 (m, 11H), 6.89 (d, 3J ¼ 8.8 Hz, 1H), 5.62 (s, 2H), 3.81 (s,
(0.11 mmol), 0.061 g potassium hydroxide (1.08 mmol) and 2 mL of
ethylene glycol as solvent. Column chromatography: DCM/MeOH
(9:1). White solid, yield: 0.035 g (0.07 mmol, 69%), mp 252e253 ꢀC.
3H), 2.84 (t, 3J ¼ 7.5 Hz, 2H), 1.89e1.66 (m, 2H), 0.96 (t, 3J ¼ 7.5 Hz,
3H); 13C-NMR (125 MHz, DMSO-d6):
d 170.01, 160.17, 156.40, 142.97,
142.60, 140.52, 134.63, 129.52, 126.73, 119.13, 113.02, 112.75, 108.90,
1H-NMR (200 MHz, DMSO-d6):
d
7.82 (d, 4J ¼ 2.0 Hz, 1H), 7.65 (s,
55.56, 46.12, 29.11, 20.77, 14.28; HRMS: m/z calculated for
1H), 7.56 (d, 3J ¼ 8.2 Hz, 1H), 7.51e7.21 (m, 10H), 7.09 (d, 3J ¼ 8.0 Hz,
C
31H28N2O3 [MþH]þ: 477.2173, found: 477.2230.
2H), 5.55 (s, 2H), 2.82 (t, 3J ¼ 7.4 Hz, 2H), 1.90e1.65 (m, 2H), 0.96 (t,
3J ¼ 7.3 Hz, 3H); 13C-NMR (125 MHz, DMSO-d6):
d
170.13, 156.58,
4.1.12. 4’-((6-(4-Hydroxyphenyl)-2-propyl-1H-benzo[d]imidazol-1-
yl)methyl)-[1,1’-biphenyl]-2-carbonic acid (38)
143.54, 140.58, 140.52, 133.21, 129.23, 129.07, 126.73, 121.44, 117.09,
111.12, 46.31, 29.06, 20.79, 14.27; HRMS: m/z calculated for
C
From 0.053 g 4’-((6-(4-hydroxyphenyl)-2-propyl-1H-benzo[d]
30H25N2O2Cl [M-H]-: 479.1521, found: 479.1526.
imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile
(27)
(0.12 mmol), 0.078 g potassium hydroxide (1.40 mmol) and 3 mL of
ethylene glycol as solvent. Column chromatography: DCM/MeOH
(9:1). Yellowish solid, yield: 0.022 g (0.05 mmol, 40%), mp
227e230 ꢀC.
4.1.8. 4’-((5-(3-Chlorophenyl)-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carbonic acid (34)
From 0.140
g
4’-((5-(3-chlorophenyl)-2-propyl-1H-benzo[d]
(18)
imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile
1H-NMR (200 MHz, DMSO-d6):
d 9.47 (s, 1H), 7.74e7.58 (m, 3H),
(0.30 mmol), 0.255 g potassium hydroxide (4.50 mmol) and 4 mL of
ethylene glycol as solvent. Column chromatography: DCM/MeOH
7.54e7.32 (m, 7H), 7.31e7.20 (m, 1H), 7.13 (d, 3J ¼ 8.4 Hz, 2H), 6.83
(d, 3J ¼ 8.8 Hz, 2H), 5.58 (s, 2H), 2.84 (t, 3J ¼ 7.6 Hz, 2H), 1.90e1.66
(m, 2H), 0.97 (t, 3J ¼ 7.4 Hz, 3H); 13C-NMR (125 MHz, DMSO-d6):
(95:5). White solid, yield: 0.040
g
(0.08 mmol, 28%), mp
178e180 ꢀC.
d 171.54, 157.10, 155.88, 141.80, 136.54, 134.99, 132.26, 130.79,
1H-NMR (200 MHz, DMSO-d6):
d
7.91 (s,1H), 7.78e7.23 (m,12H),
130.29, 129.64, 129.17, 128.40, 127.68, 126.64, 120.63, 119.05, 116.10,
7.14 (d, 3J ¼ 7.8 Hz, 2H), 5.57 (s, 2H), 2.87 (t, 3J ¼ 7.6 Hz, 2H),
107.88, 46.06, 29.08, 19.67, 14.28; HRMS: m/z calculated for
1.93e1.69 (m, 2H), 0.99 (t, 3J ¼ 7.4 Hz, 3H); 13C-NMR (125 MHz,
C
30H26N2O3 [M-H]-: 461.1865, found: 461.1895.
DMSO-d6):
d 171.52, 156.05, 143.90, 143.52, 135.85, 131.12, 129.20,
127.03, 126.06, 121.61, 117.33, 111.17, 46.29, 29.05, 20.80, 14.28;
HRMS: m/z calculated for C30H25N2O2Cl [M-H]-: 479.1521, found:
479.1567.
4.1.13. 4’-((6-(3-Hydroxyphenyl)-2-propyl-1H-benzo[d]imidazol-1-
yl)methyl)-[1,1’-biphenyl]-2-carbonic acid (39)
From 0.075 g 4’-((6-(3-hydroxyphenyl)-2-propyl-1H-benzo[d]
imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile
(28)
4.1.9. 4’-((5-(2-Chlorophenyl)-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carbonic acid (35)
(0.17 mmol), 0.095 g potassium hydroxide (1.69 mmol) and 3 mL of
ethylene glycol as solvent. Column chromatography: DCM/MeOH
(9:1). Beige solid, yield: 0.030 g (0.05 mmol, 39%), mp 257 ꢀC.
From 0.110
imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile
(0.24 mmol), 0.134 g potassium hydroxide (2.38 mmol) and 4 mL of
g
4’-((5-(2-chlorophenyl)-2-propyl-1H-benzo[d]
(19)
1H-NMR (200 MHz, DMSO-d6):
d 9.48 (s,1H), 7.75 (s,1H), 7.64 (d,
3J ¼ 8.4 Hz, 2H), 7.52e6.95 (m, 11H), 6.72 (dd, 4J < 1.0 Hz, 3J ¼ 7.4 Hz,