188
Y. Kim et al. / European Journal of Medicinal Chemistry 123 (2016) 180e190
ArH), 3.78 (s, OCH3), 3.42 (s, CH2), 2.26 (s, N(CH3)2); 13C NMR
(CDCl3, 100 MHz) 156.77, 137.47, 137.20, 132.42, 132.31, 131.05,
5.1.2.13. 1-((20,6-dimethoxy-[1,10-biphenyl]-3-yl)methyl)-4-
d
methylpiperidine (2m). 8% Yield (as an oil): 1H NMR (300 MHz,
129.30, 129.11, 129.09, 128.59, 120.31, 110.99, 63.60, 55.63, 45.35;
HRMS (ESIþ) calcd for C16H19ClNOþ [MþH]þ 276.1150, found
276.1151.
CDCl3)
d
7.40e7.30 (m, 3ArH), 7.24 (d, J ¼ 1.8 Hz, ArH), 7.08e6.97 (m,
3ArH), 3.82 (s, OCH3, OCH3), 3.63 (s, CH2), 3.03 (d, J ¼ 11.1 Hz, 2H
piperidine), 2.15e2.07 (2H piperidine), 1.67 (d, J ¼ 9.3 Hz, 2H
piperidine), 1.42e1.32 (m, 3H piperidine), 0.98 (d, J ¼ 4.8 Hz, CH3);
5.1.2.7. 1-(6-Chloro-20-methoxy-[1,1'-biphenyl]-3-yl)-N-methyl-
13C NMR (CDCl3, 75 MHz)
d 157.04, 156.42, 133.07, 131.59, 129.94,
methanamine (2g). 72% Yield (as an oil): 1H NMR (400 MHz, CDCl3)
128.65, 128.29, 127.69, 127.38, 120.37, 111.22, 110.94, 62.25, 55.80,
55.73, 53.25, 33.68, 30.53, 21.77; HRMS (ESIþ) calcd for C21H28NOþ2
[MþH]þ 326.2115, found 326.2117.
d
7.39e7.33 (m, 2ArH), 7.23e7.21 (m, 2ArH), 7.16 (dd, J ¼ 7.2, 1.6 Hz,
ArH), 6.99 (td, J ¼ 7.2, 0.8 Hz, ArH), 6.95 (d, J ¼ 8.4 Hz, ArH), 3.76 (s,
OCH3), 3.73 (s, CH2), 2.44 (s, NCH3); 13C NMR (CDCl3, 100 MHz)
d
156.75, 138.41, 137.64, 132.41, 131.39, 130.98, 129.34, 129.22,
5.1.2.14. 1-(20,6-dimethoxy-[1,10-biphenyl]-3-yl)-N,N-dimethylme-
128.57, 128.26, 120.34, 110.98, 55.63, 55.29, 35.99; HRMS (ESIþ)
thanamine (2n). 13% Yield (as an oil): 1H NMR (300 MHz, CDCl3)
calcd for C15H17ClNOþ [MþH]þ 262.0993, found 262.0993.
d
7.39e7.21 (m, 4ArH), 7.06e6.96 (m, 3ArH), 3.81 (s, OCH3), 3.80 (s,
OCH3), 3.50 (s, CH2), 2.32 (s, N(CH3)2); 13C NMR (CDCl3, 75 MHz)
157.07, 156.37, 132.66, 131.54, 129.55, 129.49, 128.61, 127.78,
5.1.2.8. 1-((20-methoxy-6-methyl-[1,1'-biphenyl]-3-yl)methyl)-4-(2-
d
methoxyphenyl)piperazine (2h). 83% Yield (as an oil): 1H NMR
127.56, 120.36, 111.19, 110.99, 63.36, 55.82, 55.73, 44.82; HRMS
(400 MHz, CDCl3)
d
7.35e7.30 (m, ArH), 7.23e7.12 (m, 4ArH),
(ESIþ) calcd for C17H22NOþ2 [MþH]þ 272.1645, found 272.1645.
7.02e6.87 (m, 5ArH), 6.83 (dd, J ¼ 8.0, 1.6 Hz, ArH), 3.84 (s, OCH3),
3.75 (s, OCH3), 3.57 (s, CH2), 3.08 (brs, 4H piperazine), 2.67 (brs, 4H
5.1.2.15. 1-(20,6-dimethoxy-[1,10-biphenyl]-3-yl)-N-methylmethan-
piperazine), 2.12 (s, ArCH3); 13C NMR (CDCl3, 100 MHz)
d
156.64,
amine (2o). 24% Yield (as an oil): 1H NMR (300 MHz, CDCl3)
d
1H
7.66 (d, J ¼ 7.8 Hz, ArH), 7.30e7.16 (m,
3ArH), 6.95e6.88 (m, 3ArH), 4.04 (s, CH2), 3.66 (s, OCH3), 3.61 (s,
OCH3), 2.47 (s, NCH3); 13C NMR (CDCl3, 75 MHz)
157.41, 156.90,
152.30, 141.53, 138.39, 135.55, 134.93, 131.15, 131.12, 129.50, 128.68,
128.52, 128.31, 126.11, 122.77, 120.96, 120.41, 118.23, 111.15, 110.69,
62.89, 55.39, 55.33, 53.27, 50.71, 19.60; HRMS (ESIþ) calcd for
NMR (300 MHz, CDCl3) d
d
C
26H31N2Oþ2 [MþH]þ 403.2380, found 403.2377.
133.58, 131.48, 130.87, 128.79, 127.69, 127.01, 123.05, 120.41, 111.76,
111.09, 55.60, 55.52, 51.17, 31.07; HRMS (ESIþ) calcd for C16H20NOþ2
[MþH]þ 258.1489, found 258.1491.
5.1.2.9. 1-((20-methoxy-6-methyl-[1,1'-biphenyl]-3-yl)methyl)-4-
methylpiperidine (2i). 64% Yield (as an oil): 1H NMR (400 MHz,
CDCl3)
d
7.34e7.30 (m, ArH), 7.22e7.11 (m, 4ArH), 6.99 (t, J ¼ 7.2 Hz,
5.1.2.16. 1-(2-methoxyphenyl)-4-((7-(2-methoxyphenyl)benzo[d]
ArH), 6.94 (d, J ¼ 8.0 Hz, ArH), 3.75 (s, OCH3), 3.48 (s, CH2), 2.88 (d,
J ¼ 11.2 Hz, 2H piperidine), 2.12 (s, ArCH3), 1.93 (t, J ¼ 10.8 Hz, 2H
piperidine), 1.58 (d, J ¼ 12.4 Hz, 2H piperidine), 1.38e1.18 (m, 3H
piperidine), 0.90 (d, J ¼ 6.0 Hz, CH3); 13C NMR (CDCl3, 100 MHz)
[1,3]dioxol-5-yl)methyl)piperazine (3a). 54% Yield (as an oil): 1H
NMR (300 MHz, CDCl3) d 7.45e7.35 (m, 2ArH), 7.09e6.88 (m, 8ArH),
6.00 (s, OCH2O), 3.90 (s, OCH3), 3.87 (s, OCH3), 3.60 (s, CH2), 3.14
(brs, 4H piperazine), 2.73 (brs, 4H piperazine); 13C NMR (CDCl3,
d
156.65, 138.27, 135.43, 135.31, 131.16, 131.10, 130.93, 129.40, 128.48,
75 MHz) d 156.77, 152.33, 147.59, 144.30, 141.52, 131.09, 129.21,
128.26, 120.41, 110.71, 63.23, 55.41, 53.88, 34.36, 30.80, 21.95, 19.60;
125.10, 124.52, 122.81, 121.00, 120.61, 119.57, 118.25, 111.44, 111.22,
108.50, 100.82, 62.96, 55.73, 55.35, 53.15, 50.71; HRMS (ESIþ) calcd
for C26H29N2Oþ4 [MþH]þ 433.2122, found 433.2120.
HRMS (ESIþ) calcd for C21H28NOþ [MþH]þ 310.2165, found 310.2166.
5.1.2.10. 1-(20-methoxy-6-methyl-[1,1'-biphenyl]-3-yl)-N,N-dime-
thylmethanamine (2j). 42% Yield (as an oil): 1H NMR (400 MHz,
5.1.2.17. 1-((7-(2-methoxyphenyl)benzo[d][1,3]dioxol-5-yl)methyl)-
CDCl3)
d
7.33e7.29 (m, ArH), 7.21e7.16 (m, 2ArH), 7.14 (dd, J ¼ 7.2,
4-methylpiperidine (3b). 61% Yield (as an oil): 1H NMR (300 MHz,
1.6 Hz, ArH), 7.10 (brs, ArH), 6.98 (td, J ¼ 7.6, 1.2 Hz, ArH), 6.96 (d,
CDCl3) d 7.43e7.35 (m, 2ArH), 7.08e7.01 (m, 3ArH), 6.93 (brs, ArH),
J ¼ 8.0 Hz, ArH), 3.74 (s, OCH3), 3.41 (s, CH2), 2.14 (s, N(CH3)2), 2.11
5.99 (s, OCH2O), 3.88 (brs, CH2), 3.85 (s, OCH3), 3.20 (d, J ¼ 9.6 Hz,
(s, ArCH3); 13C NMR (CDCl3, 100 MHz)
d 156.62, 138.47, 135.65,
2H piperidine), 2.31 (brs, 2H piperidine), 1.73e1.45 (m, 5H piperi-
135.55, 131.13, 130.92, 130.85, 129.49, 128.51, 128.08, 120.40, 110.67,
64.05, 55.40, 45.32, 19.60; HRMS (ESIþ) calcd for C17H22NOþ
[MþH]þ 256.1696, found 256.1694.
dine), 0.95 (d, J ¼ 11.1 Hz, CH3); 13C NMR (CDCl3, 75 MHz)
d 162.33,
156.69, 147.81, 145.12, 131.04, 129.37, 125.99, 124.60, 120.64, 119.63,
111.47, 109.63, 101.03, 61.66, 55.72, 52.48, 32.56, 30.00, 21.37; HRMS
(ESIþ) calcd for C21H26NOþ3 [MþH]þ 340.1907, found 340.1909.
5.1.2.11. 1-(20-methoxy-6-methyl-[1,1'-biphenyl]-3-yl)-N-methyl-
methanamine (2k). 75% Yield (as an oil): 1H NMR (400 MHz, CDCl3)
5.1.2.18. 1-(7-(2-methoxyphenyl)benzo[d][1,3]dioxol-5-yl)-N,N-
d
7.34e7.30 (m, ArH), 7.22e7.08 (m, 4ArH), 6.98 (td, J ¼ 7.6, 12 Hz,
ArH), 6.94 (d, J ¼ 8.0 Hz, ArH), 3.75 (s, CH2), 3.74 (s, OCH3), 2.45 (s,
NCH3), 2.10 (s, ArCH3); 13C NMR (CDCl3, 100 MHz)
156.57, 138.74,
dimethylmethanamine (3c). 40% Yield (as an oil): 1H NMR
(300 MHz, CDCl3)
6.90e6.87 (m, 2ArH), 6.00 (s, OCH2O), 3.86 (s, OCH3), 3.53 (s, CH2),
2.36 (s, N(CH3)2); 13C NMR (CDCl3, 75 MHz)
156.75, 147.69, 144.64,
d 7.43e7.35 (m, 2ArH), 7.08e7.02 (m, 2ArH),
d
135.92, 135.86, 131.05, 130.66, 130.14, 129.78, 128.61, 127.34, 120.46,
110.63, 55.38, 55.30, 35.44, 19.59; HRMS (ESIþ) calcd for C16H20NOþ
[MþH]þ 242.1539, found 242.1542.
d
131.06, 130.25, 129.29, 124.94, 120.62, 119.68, 111.45, 108.64, 100.93,
63.39, 55.73, 44.35; HRMS (ESIþ) calcd for C17H20NO3þ [MþH]þ
286.1438, found 286.1436.
5.1.2.12. 1-((20,6-dimethoxy-[1,10-biphenyl]-3-yl)methyl)-4-(2-
methoxyphenyl)piperazine (2l). 26% Yield (as an oil): 1H NMR
5.1.2.19. 1-(7-(2-methoxyphenyl)benzo[d][1,3]dioxol-5-yl)-N-meth-
(300 MHz, CDCl3)
d
7.40e7.29 (m, 4ArH), 7.09e6.96 (m, 6ArH), 6.90
ylmethanamine (3d). 41% Yield (as an oil): 1H NMR (300 MHz,
(d, J ¼ 7.5 Hz, ArH), 3.91 (s, OCH3), 3.83 (s, OCH3, OCH3), 3.63 (s,
CDCl3)
6.89 (s, ArH), 5.98 (s, OCH2O), 3.86 (s, OCH3), 3.77 (s, CH2), 2.50 (s,
CH3); 13C NMR (CDCl3, 75 MHz)
156.73, 147.75, 144.54, 131.93,
d 7.42e7.35 (m, 2ArH), 7.08e7.01 (m, 2ArH), 6.93 (s, ArH),
CH2), 3.15 (brs, 4H piperazine), 2.74 (brs, 4H piperazine); 13C NMR
(CDCl3, 75 MHz)
d
157.09, 156.26, 152.36, 141.58, 132.70, 131.60,
d
129.58, 128.60, 127.89, 127.48, 122.79, 121.02, 120.37, 118.26, 111.23,
110.97, 62.59, 55.86, 55.74, 55.37, 53.22, 50.73; HRMS (ESIþ) calcd
for C26H31N2Oþ3 [MþH]þ 419.2329, found 419.2330.
131.05, 129.32, 124.88, 123.82, 120.64, 119.91, 111.40, 107.78, 100.93,
55.73, 55.27, 35.03; HRMS (ESIþ) calcd for C16H18NO3þ [MþH]þ
272.1281, found 272.1284.