X.-Q. Li et al. / European Journal of Medicinal Chemistry 101 (2015) 560e572
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AreH), 6.72 (d, 2H, J ¼ 8.8 Hz, AreH), 7.105 (t, 1H, J ¼ 7.2 Hz, AreH),
7.22 (d, 2H, J ¼ 8.0 Hz, AreH), 7.383 (d, 2H, J ¼ 8.0 Hz, AreH), 7.42 (d,
1H, J ¼ 8.4 Hz, AreH), 7.45 (d, 1H, J ¼ 8.0 Hz, AreH), 7.64 (s, 1H,
eCONHe), 7.66 (d, 3H, J ¼ 8.4 Hz, AreH). IR nmax (KBr): 3442.7,
2927.74, 1645.17, 1598.88, 1515.94, 1463.87, 1330.79, 1257.5, 1157.21,
1122.49, 1020.27, 831.26 cmꢂ1. ESI-MS (m/z): 600.792 [M ꢂ 1]þ.
1649.02, 1593.09, 1517.87, 1448.44, 1409.87, 1367.44, 1326.93,
1261.36, 1215.07, 1118.64, 1043.42, 908.41 cmꢂ1. LC-MS (m/z):
652.29 [M ꢂ 1]þ.
4.1.26. N-(4-(2-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)
ethyl)phenyl)-2-dodecanamidobenzamide (20)
The compound was synthesized following general procedure B
and E, purified by column chromatography on silica gel (5% MeOH/
CH2Cl2, Rf ¼ 0.5). The product was obtained as a light yellow
powder (87% yield), mp: 145e147 ꢀC. 1HNMR (400 MHz, CDCl3):
4.1.22. 2-(4-tert-Butylphenylsulfonamido)-N-(4-(2-(6,7-
dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-4,5-
dimethoxybenzamide (16)
Starting from 6-Nitroveratric acid, the compound was synthe-
sized following general procedure C and D, purified by column
chromatography on silica gel (10% MeOH/CH2Cl2, Rf ¼ 0.3). The
product was obtained as a light yellow powder (87% yield), mp:
d
(ppm) ¼ 0.87 (t, 3H, J ¼ 6.6 Hz, eCH2eCH3), 1.25e1.4 (m, 16H,
eCH2eCH2e), 1.71 (t, 2H, J ¼ 8.0 Hz, eCH2e), 2.35 (t, 2H, J ¼ 8.0 Hz,
eCH2eOe), 2.09 (s, 3H, eCOCH3), 2.76e2.95 (m, 8H, eCH2e), 3.66
(s, 2H, eNeCH2eAr), 3.84 (s, 6H, AreOCH3), 6.55 (s, 1H, AreH), 6.61
(s, 1H, AreH), 7.03 (t, 1H, J ¼ 8.0 Hz, AreH), 7.28 (d, 1H, J ¼ 8.0 Hz,
AreH), 7.37 (t, 1H, J ¼ 8.0 Hz, AreH), 7.54 (d, 1H, J ¼ 8.0 Hz,
AreH),7.58 (d, 2H, J ¼ 8.0 Hz, AreH), 8.44 (d, 1H, J ¼ 7.6 Hz),
8.47e8.51 (m, 1H, AreH), 10.64 (s, 1H, eNHe). IR nmax (KBr):
3894.01, 3743.57, 3620.14, 3278.76, 2921.96, 2850.59, 2364.57,
2322.13, 1658.67, 1596.95, 1515.94, 1446.51, 1409.87, 1323.08,
1257.5, 1130.21, 1014.49, 825.48 cmꢂ1. LC-MS (m/z): 612.5 [M ꢂ 1]þ.
153e155 ꢀC. 1HNMR (400 MHz, CDCl3):
d
(ppm) ¼ 1.18 (s, 9H,
eC(CH3)3), 2.75e2.92 (m, 8H, eCH2e), 3.68 (s, 2H, eNeCH2eAr),
3.82 (s, 6H, AreOCH3), 3.845 (s, 3H, AreOCH3), 3.851 (s, 3H,
AreOCH3), 6.52 (s, 1H, AreH), 6.57 (s, 1H, AreH), 6.90 (s, 1H, AreH),
7.14 (s, 1H, AreH), 7.18 (d, 2H, J ¼ 8.4 Hz, AreH), 7.30 (d, 2H,
J ¼ 8.8 Hz, AreH), 7.36 (d, 2H, J ¼ 8.0 Hz, AreH), 7.63 (d, 2H,
J ¼ 8.4 Hz, AreH). ESI-MS (m/z): 687.495 [M]þ.
4.1.23. N-(4-(2-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)
ethyl)phenyl)-4,5-dimethoxy-2-(4-(trifluoromethyl)
4.1.27. 2-Cinnamamido-N-(4-(2-(6,7-dimethoxy-3,4-
dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)benzamide (21)
phenylsulfonamido)benzamide (17)
The compound was synthesized following general procedure B
and E, purified by column chromatography on silica gel (10% MeOH/
CH2Cl2, Rf ¼ 0.5). The product was obtained as a light yellow
powder (84% yield), mp: 94e95 ꢀC. 1HNMR (400 MHz, CDCl3):
Starting from 6-Nitroveratric acid, the compound was synthe-
sized following general procedure C and D, purified by column
chromatography on silica gel (10% MeOH/CH2Cl2, Rf ¼ 0.35). The
product was obtained as a light yellow powder (89% yield), mp:
d(ppm) ¼ 2.74e2.93 (m, 8H, eCH2e), 3.64 (s, 2H, eNeCH2eAr),
161e163 ꢀC. 1HNMR (400 MHz, CDCl3):
d
(ppm) ¼ 2.77e2.93 (m, 8H,
3.82 (s, 3H, AreOCH3), 3.83 (s, 3H, AreOCH3), 6.53 (s, 1H, AreH),
6.56 (d, 1H, J ¼ 16 Hz, eCH]CHe), 6.59 (s, 1H, AreH), 7.08 (t, 1H,
J ¼ 8.0 Hz, AreH), 7.28 (d, 2H, J ¼ 8.0 Hz, AreH), 7.36 (s, 1H, AreH),
7.37 (d, 2H, J ¼ 8.0 Hz, AreH), 7.47 (t, 1H, J ¼ 7.6 Hz, AreH),
7.54e7.59 (m, 4H, AreH), 7.71 (s,1H, AreH), 7.75 (s,1H, eCOeNHe),
8.18e8.21 (m, 1H, AreH), 8.68 (d, 1H, J ¼ 8.4 Hz, AreH), 11.0 (s, 1H,
eNHe). IR nmax (KBr): 3448.49, 3263.33, 2933.53, 2825.25, 1685.67,
eCH2e), 3.69 (s, 2H, eNeCH2eAr), 3.82 (s, 6H, AreOCH3), 3.85 (s,
3H, AreOCH3), 3.89 (s, 3H, AreOCH3), 5.28 (s, 1H, eSO2NHeAr),
6.52 (s, 1H, AreH), 6.57 (s, 1H, AreH), 6.87 (s, 1H, AreH), 7.18 (d, 2H,
J ¼ 7.6 Hz, AreH), 7.21 (s, 1H, AreH), 7.29 (d, 2H, J ¼ 7.6 Hz, AreH),
7.79 (d, 2H, J ¼ 8.4 Hz, AreH).
4.1.24. N-(4-(2-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)
ethyl)phenyl)-4,5-dimethoxy-2-(4-methylphenylsulfonamido)
benzamide (18)
1679.88, 1625.88, 1595.02, 1525.59, 1458.17, 1263.29, 966.27 cmꢂ1
.
ESI-MS (m/z): 560.517 [M ꢂ 1]þ.
Starting from 6-Nitroveratric acid, the compound was synthe-
sized following general procedure C and D, purified by column
chromatography on silica gel (10% MeOH/CH2Cl2, Rf ¼ 0.3). The
product was obtained as a light yellow powder (88% yield), mp:
4.1.28. N-(2-(4-(2-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-
yl)ethyl)phenylcarbamoyl)phenyl)-4-fluoro-2-nitrobenzamide (22)
The compound was synthesized following general procedure B
and E, purified by column chromatography on silica gel (6.7%
MeOH/CH2Cl2, Rf ¼ 0.4). The product was obtained as a yellow
powder (80% yield), mp: 192e194 ꢀC. 1HNMR (400 MHz, CDCl3):
171e173 ꢀC. 1HNMR (400 MHz, CDCl3):
d(ppm) ¼ 2.25 (s, 3H,
AreCH3), 2.28e2.94 (m, 8H, eCH2e), 3.70 (s, 2H, eNeCH2eAr),
3.821 (s, 3H, eAreOCH3), 3.828 (s, 3H, AreOCH3), 3.838 (s, 3H,
AreOCH3), 3.888 (s, 3H, AreOCH3), 6.52 (s, 1H, AreH), 6.58 (s, 1H,
AreH), 6.86 (s, 1H, AreH), 7.04 (d, 2H, J ¼ 8.4 Hz, AreH), 7.20 (s, 1H,
AreH), 7.22 (d, 2H, J ¼ 7.6 Hz, AreH), 7.34 (d, 2H, J ¼ 7.6 Hz, AreH),
7.56 (d, 2H, J ¼ 8.4 Hz, AreH).
d(ppm) ¼ 2.74e2.91 (m, 8H, eCH2e), 3.64 (s, 2H, eNeCH2eAr),
3.83 (s, 3H, AreOCH3), 3.84 (s, 3H, AreOCH3), 6.53 (s, 1H, AreH),
6.60 (s, 1H, AreH), 7.23 (t, 1H, J ¼ 5.2 Hz, AreH), 7.25 (s, 1H, AreH),
7.39e7.42 (m, 1H, AreH), 7.44 (s, 1H, AreH), 7.45 (s, 1H, AreH),
7.52e7.53 (m, 1H, AreH), 7.58 (t, 1H, J ¼ 4.8 Hz, AreH), 7.69 (t, 1H,
J ¼ 4.0 Hz, AreH), 7.70e7.72 (m, 1H, AreH), 7.75 (dd, 1H, J ¼ 2.0 Hz,
6.0 Hz), 8.02 (s, 1H, eNHe), 8.70 (d, 1H, J ¼ 1.6 Hz), 11.45 (s, 1H,
eNHe). IR nmax (KBr): 3739.72, 3577.71, 3350.12, 3209.33, 3066.61,
2954.74, 2927.74, 2823.59, 2748.37, 2316.35, 1731.96, 1679.88,
1662.52, 1515.94, 1448.44, 1353.94, 1311.5, 1253.64, 1016.42, 939.27,
767.62 cmꢂ1. ESI-MS (m/z): 597.47 [M ꢂ 1]þ.
4.1.25. (9H-Fluoren-9-yl)methyl 2-(4-(2-(6,7-dimethoxy-3,4-
dihydroisoquinolin-2(1H)-yl)ethyl)phenylcarbamoyl)
phenylcarbamate (19)
The compound was synthesized following general procedure B
and E, purified by column chromatography on silica gel (4% MeOH/
CH2Cl2, Rf ¼ 0.5). The product was obtained as a yellow powder
(76% yield), mp: 124e125 ꢀC. 1HNMR (400 MHz, CDCl3):
4.1.29. N-(2-(4-(2-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-
yl)ethyl)phenylcarbamoyl)phenyl)furan-2-carboxamide (23)
The compound was synthesized following general procedure B
and E, purified by column chromatography on silica gel (10% MeOH/
CH2Cl2, Rf ¼ 0.4). The product was obtained as a light yellow
powder (82% yield), mp: 170e172 ꢀC. 1HNMR (400 MHz, CDCl3):
d
(ppm) ¼ 2.8e3.5 (m, 8H, eCH2e), 3.78 (s, 3H, AreOCH3), 3.80 (s,
3H, AreOCH3), 3.90 (s, 2H, eNeCH2eAr), 4.22 (s, 1H, eCH¼), 4.37
(s, 2H, eCH2eOe), 6.45 (s, 1H, AreH), 6.55 (s, 1H, AreH), 7.03 (s, 1H,
AreH), 7.10 (d, 1H, J ¼ 8.0 Hz, AreH), 7.34e7.40 (m, 4H, AreH),
7.54e7.60 (m, 5H, AreH), 7.71 (d, 4H, J ¼ 8.0 Hz, AreH), 8.25 (s, 1H,
AreH), 8.87 (s, 1H, eNHe), 10.50 (s, 1H, eNHeCOe). IR nmax (KBr):
3988.52, 3743.57, 3446.56, 2925.81, 2852.52, 2335.64, 1730.03,
d
(ppm) ¼ 2.73e2.98 (m, 8H, eCH2e), 3.64 (s, 2H, eNeCH2eAr),
3.82 (s, 3H, AreOCH3), 3.83 (s, 3H, AreOCH3), 6.51e6.52 (m, 1H,