A.M. Schoepf, S. Salcher, P. Obexer et al.
European Journal of Medicinal Chemistry 216 (2021) 113285
7.61-7.54 (m, 4H, H4, H6, H20, H60), 7.29-7.22 (m, 3H, H30, H50, H700),
CH2CH2CH3). 13C NMR (101 MHz, acetone-d6):
d 169.3, 157.2, 142.3,
3
7.09-7.03 (m, 1H, H600), 6.99 (d, J ¼ 7.3 Hz, 1H, H500), 5.59 (s, 2H,
141.6, 141.1, 137.9, 136.8, 132.3, 132.2, 131.4, 130.4, 129.7, 128.3, 127.2,
124.4, 123.3, 122.3, 109.9, 52.1, 47.5, 21.5, 14.2. HRMS: m/z calculated
for C25H23ClN2O2 [MþH]þ: 419.1521, found: 419.1555.
NCH2), 2.89 (t, 3J ¼ 7.6 Hz, 2H, CH2CH2CH3), 2.59 (s, 3H, CH3), 1.94-
1.80 (m, 2H, CH2CH2CH3), 1.02 (t, 3J ¼ 7.4 Hz, 3H, CH2CH2CH3). 13
C
NMR (101 MHz, acetone-d6):
d 155.1, 145.5, 143.3, 139.0, 138.5,
136.2, 134.7, 134.1, 131.0, 130.1, 129.5, 129.0, 127.6, 122.7, 122.6, 119.1,
111.9, 108.2, 47.0, 21.8, 16.7, 14.3. HRMS: m/z calculated for C25H23N3
[MþH]þ: 366.1965, found: 366.1977.
4.1.2.11. Methyl 4’-((4-bromo-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carboxylate (3d). From 1d (0.10
g
0.4 mmol) in anhydrous DMF (1 ml), with NaH (0.01 g, 0.5 mmol) and
methyl 4’-(bromomethyl)-[1,10-biphenyl]-2-carboxylate (0.14 g,
0.5 mmol). Colorless solid, yield: 38%. 1H NMR (700 MHz, CD3OD):
4.1.2.6. 4’-((4-Methoxy-2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-
[1,10-biphenyl]-2-carbonitrile (2f). 1H NMR (400 MHz, acetone-d6):
d
7.78 (dd, 3J ¼ 7.7 Hz, 4J ¼ 1.4 Hz,1H, H3), 7.67 (d, 3J ¼ 7.8 Hz,1H, H7‘’),
d
7.87 (dd, 3J ¼ 7.7 Hz, 4J ¼ 1.2 Hz, 1H, H3), 7.79-7.73 (m, 1H, H5),
7.63 (d, 3J ¼ 8.3 Hz, 1H, H5‘’), 7.59-7.54 (m, 1H, H5), 7.48-7.43 (m, 1H,
H4), 7.39-7.33 (m, 2H, H6, H6‘’), 7.30 (d, 3J ¼ 8.3 Hz, 2H, H2‘, H6‘), 7.24
(d, 3J¼ 8.1Hz,2H, H3‘, H5‘),5.73(s, 2H, NCH2),3.59(s, 3H, CO2CH3), 3.16
(t, 3J ¼ 7.7 Hz, 2H, CH2CH2CH3), 1.85-1.78 (m, 2H, CH2CH2CH3),1.05 (t,
7.62-7.53 (m, 4H, H4, H6, H20, H60), 7.26 (d, 3J ¼ 8.6 Hz, 2H, H30, H50),
7.12-7.00 (m, 2H, H600, H700), 6.70 (dd, 3J ¼ 7.8 Hz, 4J ¼ 1.0 Hz, 1H,
H500), 5.58 (s, 2H, NCH2), 4.02 (s, 3H, OCH3), 2.87 (t, 3J ¼ 7.4 Hz, 2H,
CH2CH2CH3), 1.93-1.81 (m, 2H, CH2CH2CH3), 1.01 (t, 3J ¼ 7.4 Hz, 3H,
3J ¼ 7.4 Hz, 3H, CH2CH2CH3). 13C NMR (176 MHz, CD3OD):
d 170.5,
CH2CH2CH3). 13C NMR (101 MHz, acetone-d6):
d
154.3, 152.3, 145.4,
163.1, 157.7, 142.9, 135.7, 135.1, 132.6, 132.2, 131.7, 130.8, 130.3, 129.1,
138.9, 138.5, 134.7, 134.1, 131.0, 130.1, 129.0, 127.6, 123.5, 119.1, 111.9,
128.7,127.6,127.0,112.6, 52.4, 29.1, 22.6,14.1. HRMS: m/z calculated for
C
104.6, 103.7, 56.4, 47.0, 21.5, 14.2. HRMS: m/z calculated for
25H23BrN2O2 [MþH]þ: 463.1016, found: 463.1057.
C
25H23N3O [MþH]þ: 382.1914, found: 382.1930.
4.1.2.12. Methyl 4’-((4-methyl-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carboxylate (3e). 1H NMR (400 MHz,
4.1.2.7. 4’-((4-Nitro-2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-
[1,10-biphenyl]-2-carbonitrile (2g). 1H NMR (400 MHz, acetone-d6):
acetone-d6):
d
7.76 (dd, 3J ¼ 7.7 Hz, 4J ¼ 1.4 Hz, 1H, H3), 7.61-7.55 (m,
d
8.01 (dd, 3J ¼ 8.0 Hz, 4J ¼ 0.9 Hz, 1H, H3), 7.93-7.85 (m, 2H, H5,
1H, H5), 7.50-7.43 (m, 1H, H4), 7.39 (dd, 3J ¼ 7.9 Hz, 4J ¼ 1.4 Hz, 1H,
H6), 7.27 (d, 3J ¼ 8.3 Hz, 2H, H2‘, H6‘), 7.22 (d, 3J ¼ 7.7 Hz, 1H, H7‘’),
7.16 (d, 3J ¼ 8.5 Hz, 2H, H3‘, H5‘), 7.08-7.02 (m, 1H, H6‘’), 6.98 (d,
3J ¼ 7.2 Hz, 1H, H5‘‘), 5.53 (s, 2H, NCH2), 3.56 (s, 3H, CO2CH3), 2.88 (t,
3J ¼ 7.6 Hz, 2H, CH2CH2CH3), 2.59 (s, 3H, CH3), 1.93-1.79 (m, 2H,
CH2CH2CH3), 1.02 (t, 3J ¼ 7.4 Hz, 3H, CH2CH2CH3). 13C NMR
H500), 7.80-7.73 (m, 1H, H4), 7.63-7.55 (m, 4H, H6, H20, H60, H700),
7.41-7.35 (m, 1H, H600), 7.31 (d, 3J ¼ 8.3 Hz, 2H, H30, H5’), 5.77 (s, 2H,
NCH2), 3.01 (t, 3J ¼ 7.6 Hz, 2H, CH2CH2CH3), 1.97-1.83 (m, 2H,
CH2CH2CH3), 1.03 (t, 3J ¼ 7.4 Hz, 3H, CH2CH2CH3). 13C NMR
(101 MHz, acetone-d6):
d 160.4, 145.3, 139.9, 139.5, 138.9, 138.0,
137.4, 134.7, 134.1, 131.0, 130.3, 129.1, 127.7, 122.0, 119.0, 118.9, 117.1,
111.9, 47.4, 21.6, 14.2. HRMS: m/z calculated for C24H20N4O2
[MþH]þ: 397.1659, found: 397.1678.
(101 MHz, acetone-d6): d 169.3, 155.1, 143.3, 142.4, 141.4, 137.3,
136.3, 132.3, 132.1, 131.4, 130.4, 129.6, 129.5, 128.2, 127.1, 122.6,
122.5, 108.2, 52.1, 47.1, 21.7, 16.7, 14.3. HRMS: m/z calculated for
C
26H26N2O2 [MþH]þ: 399.2067, found: 399.2104.
4.1.2.8. Methyl
4’-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-
[1,10-biphenyl]-2-carboxylate (3a). 1H NMR (400 MHz, DMSO‑d6):
4.1.2.13. Methyl 4’-((4-methoxy-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carboxylate (3f). From 1f (0.70 g,
3.7 mmol) in anhydrous DMF (3 ml), with NaH (0.11 g, 4.4 mmol)
d
7.72 (dd, 3J ¼ 7.7 Hz, 4J ¼ 1.2 Hz,1H, H3), 7.63-7.56 (m, 2H, H5, H4‘’),
7.52-7.44 (m, 2H, H4, H7‘’), 7.38 (dd, 3J ¼ 7.7 Hz, 4J ¼ 0.9 Hz, 1H, H6),
7.24 (d, 3J ¼ 8.2 Hz, 2H, H2‘, H6‘), 7.20-7.11 (m, 4H, H3‘, H5‘, H5‘’,
H6‘‘), 5.54 (s, 2H, NCH2), 3.54 (s, 3H, CO2CH3), 2.84 (t, 3J ¼ 7.5 Hz, 2H,
CH2CH2CH3), 1.85-1.71 (m, 2H, CH2CH2CH3), 0.96 (t, 3J ¼ 7.4 Hz, 3H,
and
methyl
4’-(bromomethyl)-[1,10-biphenyl]-2-carboxylate
(1.24 g, 4.0 mmol). Colorless solid, yield: 34%. 1H NMR (400 MHz,
acetone-d6):
d
7.76 (dd, 3J ¼ 7.7 Hz, 4J ¼ 1.4 Hz, 1H, H3), 7.62-7.55 (m,
CH2CH2CH3). 13C NMR (101 MHz, DMSO‑d6):
d
168.4, 155.1, 142.4,
1H, H5), 7.50-7.43 (m, 1H, H4), 7.40 (dd, 3J ¼ 7.5 Hz, 4J ¼ 1.4 Hz, 1H,
H6), 7.27 (d, 3J ¼ 8.3 Hz, 2H, H2‘, H6‘), 7.16 (d, 3J ¼ 8.5 Hz, 2H, H3‘,
H5‘), 7.11-7.05 (m, 1H, H6‘’), 7.01 (dd, 3J ¼ 8.1 Hz, 4J ¼ 1.0 Hz, 1H,
H7‘’), 6.69 (dd, 3J ¼ 7.8 Hz, 4J ¼ 0.9 Hz, 1H, H5‘’), 5.53 (s, 2H, NCH2),
4.01 (s, 3H, OCH3), 3.56 (s, 3H, CO2CH3), 2.86 (t, 3J ¼ 7.4 Hz, 2H,
CH2CH2CH3), 1.92-1.80 (m, 2H, CH2CH2CH3), 1.01 (t, 3J ¼ 7.4 Hz, 3H,
140.7, 139.7, 136.2, 135.4, 131.5, 130.7, 130.5, 129.3, 128.5, 127.5,
126.4, 121.7, 121.3, 118.5, 110.1, 51.8, 45.7, 28.6, 20.3, 13.8. HRMS: m/z
calculated for C25H24N2O2 [MþH]þ: 385.1911, found: 385.1934.
4.1.2.9. Methyl
4’-((4-fluoro-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carboxylate (3b). 1H NMR (400 MHz,
CH2CH2CH3). 13C NMR (101 MHz, acetone-d6):
d 169.4, 154.3, 152.3,
acetone-d6):
d
7.77 (dd, 3J ¼ 7.7 Hz, 4J ¼ 1.1 Hz, 1H, H3), 7.62-7.56 (m,
142.4,141.4, 138.5,137.3, 134.1, 132.3,132.1, 131.4, 130.4,129.6,128.2,
127.1, 123.4, 104.6, 103.7, 56.4, 52.1, 47.1, 21.5, 14.3. HRMS: m/z
calculated for C26H26N2O3 [MþH]þ: 415.2016, found: 415.2056.
1H, H5), 7.49-7.44 (m, 1H, H4), 7.40 (dd, 3J ¼ 7.7 Hz, 4J ¼ 0.9 Hz, 1H,
H6), 7.31-7.26 (m, 3H, H2‘, H6‘, H7‘’), 7.21-7.12 (m, 3H, H3‘, H5‘, H6‘’),
6.96-6.89 (m, 1H, H5‘‘), 5.59 (s, 2H, NCH2), 3.56 (s, 3H, CO2CH3), 2.91
(t, 3J ¼ 7.6 Hz, 2H, CH2CH2CH3), 1.93-1.82 (m, 2H, CH2CH2CH3), 1.02
(t, 3J ¼ 7.4 Hz, 3H, CH2CH2CH3). 13C NMR (101 MHz, acetone-d6):
4.1.2.14. Methyl
4’-((4-nitro-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carboxylate (3g). From 1g (0.80 g,
3.9 mmol) in anhydrous DMF (3 ml), with NaH (0.11 g, 4.7 mmol)
d
169.3, 156.7, 142.4, 141.6, 136.8, 132.3, 132.2, 131.4, 130.4, 129.7,
128.3, 127.2, 123.2, 123.1, 107.8, 107.7, 107.2, 107.2, 52.1, 47.4, 21.4,
14.2. HRMS: m/z calculated for C25H23FN2O2 [MþH]þ: 403.1816,
found: 403.1845.
and
methyl
4’-(bromomethyl)-[1,10-biphenyl]-2-carboxylate
(1.31 g, 4.3 mmol). Colorless solid, yield: 20%. 1H NMR (400 MHz,
acetone-d6):
d
8.00 (dd, 3J ¼ 8.0 Hz, 4J ¼ 0.9 Hz, 1H, H500), 7.89 (dd,
3J ¼ 8.1 Hz, 4J ¼ 0.9 Hz, 1H, H700), 7.77 (dd, 3J ¼ 7.5 Hz, 4J ¼ 1.2 Hz, 1H,
H3), 7.62-7.56 (m, 1H, H5), 7.50-7.44 (m, 1H, H4), 7.42-7.35 (m, 2H,
H6, H600), 7.30 (d, 3J ¼ 8.3 Hz, 2H, H20, H60), 7.21 (d, 3J ¼ 8.5 Hz, 2H,
H30, H50), 5.71 (s, 2H, NCH2), 3.57 (s, 3H, CO2CH3), 3.00 (t, 3J ¼ 7.6 Hz,
2H, CH2CH2CH3), 1.95-1.83 (m, 2H, CH2CH2CH3), 1.03 (t, J ¼ 7.4 Hz,
4.1.2.10. Methyl 4’-((4-chloro-2-propyl-1H-benzo[d]imidazol-1-yl)
methyl)-[1,1’-biphenyl]-2-carboxylate (3c). 1H NMR (400 MHz,
acetone-d6):
d
7.77 (dd, 3J ¼ 7.7 Hz, 4J ¼ 1.1 Hz, 1H, H3), 7.62-7.56 (m,
1H, H5), 7.50-7.44 (m, 1H, H4), 7.43-7.38 (m, 2H, H6, H7‘’), 7.29 (d,
3J ¼ 8.3 Hz, 2H, H2‘, H6‘), 7.25-7.13 (m, 4H, H3‘, H5‘, H5‘’, H6‘‘), 5.60
(s, 2H, NCH2), 3.56 (s, 3H, CO2CH3), 2.92 (t, 3J ¼ 7.6 Hz, 2H,
CH2CH2CH3), 1.94-1.81 (m, 2H, CH2CH2CH3), 1.02 (t, 3J ¼ 7.4 Hz, 3H,
3H, CH2CH2CH3). 13C NMR (101 MHz, acetone-d6):
d 169.3, 160.4,
142.3, 141.8, 139.9, 139.5, 137.4, 136.3, 132.2, 131.4, 130.5, 129.8,
128.3, 127.2, 121.9, 118.9, 117.2, 52.1, 47.6, 21.6, 14.2. HRMS: m/z
8