R.-H. Guo et al. / European Journal of Medicinal Chemistry 46 (2011) 307e319
317
(4H, m), 4.44e4.33 (2H, m), 4.17 (2H, t, J ¼ 6.4 Hz), 2.99 (1H, m),
2.73 (3H, m); 13C NMR (CDCl3, 100 MHz)
170.9, 164.0, 158.4, 147.2,
136.0, 134.2, 132.9, 130.7, 130.5, 130.4, 130.2, 129.6 (2C), 129.0, 128.1,
127.3, 125.5, 121.1, 120.98, 117.7, 115.4 (2C), 63.2, 62.6, 34.6, 28.1;
ESIMS: m/z 504 [M þ Na]þ, HRESIMS: calc for C26H21NO4Cl2Na
[M þ Na]þ 504.0745, found 504.0758.
5.1.10.27. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
droquinolin-3-yl]ethyl-3-[3-(trifluoro methyl) phenyl]acrylate
(46). White amorphous power, yield 91% (after chromatography
with CHCl3/MeOH, 70:1); 1H NMR (CDCl3, 400 MHz)
13.19 (1H,
d
d
br.s), 7.69e7.42 (10H, m), 7.25 (1H, dd, J ¼ 7.2, 1.6 Hz), 6.86 (1H, d,
J ¼ 2.0 Hz), 4.42 (1H, d, J ¼ 16.0 Hz), 4.46 (2H, t, J ¼ 6.8 Hz), 3.07e3.00
(1H, m), 2.83e2.76 (1H, m); 13C NMR (CDCl3,100 MHz)
d 166.2,163.9,
5.1.10.22. 2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
147.3,142.8,136.0,135.1,134.1,133.0,130.9,130.7,130.5,130.4,130.2,
129.4,129.0,128.2,127.3,126.6,126.6,125.5,124.5,124.5,121.1,120.0,
117.7, 62.6, 28.2; ESIMS: m/z 554 [M þ Na]þ, HRESIMS: calc for
C27H19NO3Cl2F3 [M þ H]þ 532.0694, found 532.0693.
droquinolin-3-yl]ethylcinnamate (41). White amorphous power,
yield 50% (after chromatography with petroleum ether/acetone,
90:10); 1H NMR (CDCl3, 400 MHz)
d
7.63e7.26 (12H, m), 6.86 (1H, d,
J ¼ 2.0 H z), 6.36 (1H, d, J ¼ 16 Hz), 4.46 (2H, t, J ¼ 6.4 Hz), 3.04 (1H,
m), 2.77 (1H, m); 13C NMR (CDCl3, 100 MHz)
166.7, 163.8, 147.1,
d
5.1.10.28. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
144.7, 135.9, 134.3, 134.1, 132.9, 130.8, 130.5, 130.3, 130.2, 130.17,
129.1, 128.8 (2C), 128.1, 127.9 (2C), 127.2, 125.5, 121.4, 118.0, 117.6,
62.3, 28.2; FABMS: m/z 464 [M þ H] þ, HRESIMS: calc for
C26H19NO3Cl2Na [M þ Na]þ 486.0639, found 486.0636.
droquinolin-3-yl]ethyl-3-[4-(trifluoro
(47). White amorphous power, yield 34% (after chromatography
with CHCl3/MeOH, 70:1); 1H NMR (CDCl3, 400 MHz)
13.03 (1H,
methyl)
phenyl]acrylate
d
br.s), 7.63e7.42 (10H, m), 7.24 (1H, dd, J ¼ 7.5, 1.6 Hz), 6.86 (1H, d,
J ¼ 2.0 Hz), 6.42 (1H, d, J ¼ 16.1 Hz), 4.45 (2H, t, J ¼ 6.7 Hz), 3.06e3.00
5.1.10.23. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
(1H, m), 2.82e2.75 (1H, m); 13C NMR (CDCl3,100 MHz)
d 166.2,163.8,
droquinolin-3-yl]ethyl-3-(3-fluorophenyl)
amorphous power, yield 76% (after chromatography with CHCl3/
MeOH, 70:1); 1H NMR (CDCl3, 500 MHz)
13.23 (1H, br.s),
acrylate
(42). White
147.4,142.8,137.7,135.8,134.1,132.9,130.7,130.6,130.4,130.3,129.0,
128.4, 128.1 (2C), 127.3, 125.9, 125.8 (2C), 125.7, 125.6, 121.2, 120.6,
117.7, 62.7, 28.1; ESIMS: m/z 554 [M þ Na]þ, HRESIMS: calc for
C27H18NO3Cl2F3Na [M þ Na]þ 554.0513, found 554.0529.
d
7.60e7.44 (6H, m), 7.33e7.03 (5H, m), 6.86 (1H, s), 6.50 (1H, d,
J ¼ 16.0 Hz), 4.46 (2H, t, J ¼ 6.9 Hz), 3.07e3.02 (1H, m), 2.81e2.76
(1H, m); 13C NMR (CDCl3,125 MHz)
d
166.3,164.0,162.0,147.1,143.2,
5.1.10.29. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
136.6, 136.0, 134.2, 133.0, 130.7, 130.4, 130.4, 130.2, 129.2, 128.1,
127.2, 125.5, 123.9, 121.1, 119.5, 117.6, 117.2, 117.0, 114.2, 62.6, 28.2;
ESIMS: m/z 504 [M þ Na]þ, HRESIMS: calc for C26H19NO3Cl2F
[M þ H]þ 482.0726, found 482.0716.
droquinolin-3-yl]ethyl-3-(benzo[d][1,3] dioxol-5-yl)acrylate (48). White
amorphous power, yield 60% (after chromatography with CHCl3/
MeOH, 98:2); 1H NMR (CDCl3, 500 MHz)
d 7.41 (2H, m), 7.32e7.23 (5H,
m), 7.15 (1H, d, J ¼ 8.8 Hz), 7.07 (1H, d, J ¼ 7.5, 1.5 Hz), 6.63 (2H, m),
5.99 (1H, d, J ¼ 15.9 Hz), 5.82 (2H, s), 3.17 (2H, m), 2.77e2.72 (1H, m),
5.1.10.24. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
droquinolin-3-yl]ethyl-3-(2-methoxyphenyl) acrylate (43). White
amorphous power, yield 60% (after chromatography with CHCl3/
2.53e2.47 (1H, m); 13C NMR (CDCl3, 100 MHz)
d 167.7, 163.0, 150.1,
148.7, 147.4, 145.1, 136.2, 134.4, 133.1, 131.1, 130.7, 130.6, 130.4, 129.0,
128.3, 127.6, 125.9, 124.8, 121.4, 117.4, 115.9, 108.8, 106.7, 106.6, 101.9,
MeOH,100:1); 1H NMR (CDCl3, 400 MHz)
d
13.16 (1H, br.s), 7.91 (1H,
62.6, 28.6; ESIMS: m/z 530 [M
þ
Na]þ, HRESIMS: calc for
d, J ¼ 16.0 Hz),7.60e7.26 (8H, m), 6.94e6.87 (3H, m), 6.46 (1H, d,
C27H19NO5Cl2Na [M þ Na]þ 530.0537, found 530.0543.
J ¼ 16.0 Hz), 4.47 (2H, m), 3.84 (3H, s), 3.08e3.03 (1H, m), 2.78e2.78
(1H, m); 13C NMR (CDCl3, 100 MHz)
d
167.2,163.9, 158.2, 147.2, 140.1,
5.1.10.30. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
droquinolin-3-yl]ethyl-3-(3,4-dimethoxy phenyl)acrylate (49). White
amorphous power, yield 60% (after chromatography with CHCl3/
135.9, 134.2, 132.9, 131.4, 130.8, 130.4, 130.3, 130.1, 129.2, 128.8,
128.1, 127.2, 125.4, 123.3, 121.2, 120.6, 118.6, 117.8, 111.0, 62.2, 55.4,
28.3; ESIMS: m/z 516 [M þ Na]þ, HRESIMS: calc for C27H21NO4Cl2Na
[M þ Na]þ 516.0745, found 516.0759.
MeOH, 98:2); 1H NMR (CDCl3, 400 MHz)
d 13.18 (1H, br.s), 7.59e6.80
(11H, m), 6.24 (1H, d, J ¼ 16.0 Hz), 4.43 (2H, t, J ¼ 6.8 Hz), 3.88 (3H, s),
3.86 (3H, s), 3.05e2.99 (1H, m), 2.80e2.74 (1H, m); 13C NMR (CDCl3,
5.1.10.25. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
droquinolin-3-yl]ethyl-3-(3-methoxyphenyl) acrylate (44). White
amorphous power, yield 70% (after chromatography with CHCl3/
100 MHz) d 166.9, 163.9, 151.0, 149.1, 147.1, 144.8, 144.6, 136.0, 134.1,
132.9, 130.7, 130.4, 130.3, 130.2,129.2, 128.0, 127.2, 125.4, 122.5,121.1,
117.7, 115.7, 115.4, 110.9, 62.2, 55.9, 51.6, 28.2; ESIMS: m/z 546
[M þ Na]þ, HRESIMS: calc for C28H23NO5Cl2Na [M þ Na]þ 546.0850,
found 546.0855.
MeOH, 95:5); 1H NMR (CDCl3, 500 MHz)
d 7.60e7.42 (6H, m), 7.27
(3H, m), 7.05 (1H, d, J ¼ 7.5 Hz), 6.97 (1H, s), 6.90 (1H, dd, J ¼ 7.5,
2.5 Hz), 6.86 (1H, d, J ¼ 2.0 Hz), 6.35 (1H, d, J ¼ 16.0 Hz), 4.50 (2H, t,
J ¼ 5.2 Hz), 3.80 (3H, s), 3.03 (1H, m), 2.77 (1H, m); 13C NMR (CDCl3,
5.1.10.31. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
droquinolin-3-yl]ethyl-3-(pyridin-3-yl) acrylate (50). White amor-
phous power, yield 70% (after chromatography with CHCl3/MeOH,
125 MHz) d 166.6, 163.8, 159.8, 147.2, 144.6, 135.9, 135.7, 134.1, 132.9,
130.7, 130.5,130.4,130.2,129.8, 129.1, 128.2,127.2,125.5,121.2, 120.6,
118.3, 117.7, 116.1, 112.8, 62.4, 55.2, 28.2; ESIMS: m/z 516 [M þ Na]þ,
HRESIMS: calc for C27H22NO4Cl2 [Mþ H]þ 494.0925, found 494.0932.
25:1); 1H NMR (CDCl3, 400 MHz)
d 13.19 (1H, br.s), 8.85 (1H, s), 8.58
(1H, d, J ¼ 4.4 Hz), 7.73 (1H, d, J ¼ 6.8 Hz), 7.60e7.26 (8H, m), 6.85
(1H, d, J ¼ 1.6 Hz), 6.36 (1H, d, J ¼ 16.0 Hz), 4.46 (2H, t, J ¼ 6.7 Hz),
5.1.10.26. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
droquinolin-3-yl]ethyl-3-(4-methoxyphenyl) acrylate (45). White
amorphous power, yield 60% (after chromatography with CHCl3/
3.03 (1H, m), 2.75 (1H, m); 13C NMR (CDCl3,100 MHz)
d 166.0,164.0,
150.9, 149.5, 147.1, 140.9, 136.0, 134.1, 134.1, 132.9, 130.7, 130.4, 130.3,
130.2, 130.1, 129.1, 128.1, 127.2, 125.5, 123.7, 121.0, 120.2, 117.6, 62.8,
28.2; ESIMS: m/z 465 [M þ H]þ, HRESIMS: calc for C25H19N2O3Cl2
[M þ H]þ 465.0772, found 465.0767.
MeOH, 70:1); 1H NMR (CDCl3, 500 MHz)
d 13.28 (1H, br.s),
7.60e7.38 (8H, m), 7.28 (1H, d, J ¼ 8.0 Hz), 6.86 (3H, m), 6.24 (1H, d,
J ¼ 16.0 Hz), 4.45 (2H, m), 3.81 (3H, s), 3.08e3.03 (1H, m), 2.80e2.74
(1H, m); 13C NMR (CDCl3, 125 MHz)
d
167.1, 164.0, 161.3, 147.0, 144.3,
5.1.10.32. (E)-2-[6-Chloro-4-(2-chlorophenyl)-2-oxo-1,2-dihy-
droquinolin-3-yl]ethyl-but-2-enoate (51). White amorphous power,
yield 60% (after chromatography with CHCl3/MeOH, 98:2); 1H
136.0, 134.2, 132.9, 130.8, 130.4, 130.3, 130.1, 129.6 (2C), 129.3, 128.0,
127.2, 127.0, 125.4, 121.1, 117.7, 115.5, 114.2 (2C), 62.3, 55.3, 28.2;
ESIMS: m/z 516 [M þ Na]þ, HRESIMS: calc for C27H21NO4Cl2Na
[M þ Na]þ 516.0745, found 516.0754.
NMR (CDCl3, 500 MHz)
7.25 (1H, dd, J ¼ 9.0, 1.5 Hz), 6.94e6.87 (2H, m), 5.77 (1H, m), 4.38
d
7.59 (1H, d, J ¼ 7.9 Hz), 7.51e7.42 (4H, m),