1
536
M. M. GAMAL EL-DIN ET AL.
þ
N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
114.9, 112.2, 110.2, 56.1, 54.1, 53.6, 32.6, 25.7; MS m/z: 517.21 (M
þ 2).
1-yl)phenyl)-2-morpholino-acetamide (1b)
1
H NMR (400 MHz, CDCl ) d 9.33 (s, 1H), 8.56 (d, 2H, J¼ 4.8 Hz),
3
8
.03(s, 1H), 7.57 (d, 1H, J¼ 7.6 Hz), 7.51–7.45 (m, 2H), 7.36 (d, 1H, J
8.4 Hz), 7.29–7.27 (m, 2H), 7.14 (s, 1H), 7.09 (d, 1H, J ¼ 8.0 Hz),
N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
1-yl)phenyl)-3-morpholino-propanamide (1 h)
¼
13
3
.80 (m, 7H), 3.23 (s, 2H), 2.69–2.67 (m, 4H); C NMR (100 MHz,
1
CDCl ) d 168.1, 154.6, 150.1, 149.7, 140.8, 139.9, 138.7, 132.2,
3
H NMR (400 MHz, CDCl
3
) d 9.33 (s, 1H), 8.56 (d, 2H, J¼ 4.8 Hz),
1
6
30.5, 130.2, 127.6, 122.9, 122.8, 122.2, 117.9, 114.9, 112.3, 110.2, 8.03(s, 1H), 7.57 (d, 1H, J¼ 7.6 Hz), 7.51–7.45 (m, 2H), 7.46 (d, 1H,
þ
6.9, 62.4, 56.1, 50.8; MS m/z: 505.1 (M þ 2).
J¼ 8.4 Hz), 7.29–7.27 (m, 2H), 7.16 (s, 1H), 7.07 (d, 1H, J¼ 8.0 Hz),
13
3
.75 (m, 9H), 3.23 (s, 2H), 2.69–2.67 (m, 4H); C NMR (100 MHz,
CDCl ) d 168.1, 154.6, 150.1, 149.7, 140.8, 139.9, 138.7, 132.2,
30.5, 130.2, 127.6, 122.9, 122.8, 122.2, 117.9, 114.9, 112.3, 110.2,
3
N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
1
6
1-yl)phenyl)-2–(4-methyl-piperazin-1-yl)acetamide (1c)
þ
6.9, 62.4, 56.1, 50.8, 25.2; MS m/z: 518.43 (M þ 1).
1
H NMR (400 MHz, CDCl
3
) d 9.28 (s, 1H), 8.58 (d, 2H, J ¼ 8.4 Hz),
8
7
.22 (d, 2H, J¼ 3.6 Hz), 7.59–7.56 (m, 2H), 7.46 (t, 1H, J¼ 8.0 Hz),
N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
.38 (d, 1H, J¼ 8.0 Hz), 7.29–7.27 (m, 2H), 7.15–7.08 (m, 2H), 3.83
1-yl)phenyl)-3-(4-methyl-piperazin-1-yl)propanamide (1i)
(m, 3H), 3.31 (s, 2H), 2.94–2.90 (m, 8H), 2.63 (s, 3H); MS m/z:
þ
5
17.42 (M þ 1).
1
H NMR (400 MHz, CDCl ) d 8.49 (d, 2H, J¼ 6.4 Hz), 8.29 (s, 1H),
3
8
7
.15 (s, 1H), 7.49 (dd, 8H, J¼ 1.2, 8.0 Hz), 7.36 (t, 1H, J¼ 8.0 Hz),
.28 (d, 1H, J¼ 4.8 Hz), 7.21 (d, 2H, J¼ 6.4 Hz), 7.07 (s, 1H), 7.03
N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
(
3
dd, 1H, J¼ 1.6, 8.0 Hz), 3.73 (s, 3H), 2.73–2.51 (m, 12H), 2.31 (s,
1-yl)phenyl)-2–(4-ethyl-piperazin-1-yl)acetamide (1d)
1
3
3
H); C NMR (100 MHz, CDCl ) d 170.7, 154.6, 149.9, 149.6, 140.6,
1
H NMR (400 MHz, CDCl ) d 9.29 (s, 1H), 8.58 (brs, 2H), 8.15 (d, 2H, 139.9, 139.8, 132.3, 130.1, 129.6, 127.6, 122.9, 122.6, 121.4, 120.1,
3
J¼ 5.2 Hz), 7.59–7.56 (m, 2H), 7.47 (t, 1H, J ¼ 8.0 Hz), 7.38 (d, 1H, 117.6, 114.1, 112.3, 110.2, 56.0, 55.1, 53.4, 53.1, 45.8, 32.5; MS m/z:
þ
J¼ 8.0 Hz), 7.16–7.08 (m, 4H), 3.83 (m, 3H), 3.27 (s, 2H), 2.83–2.50 529.9 (M þ 1).
13
(
m, 10H), 1.25 (t, 3H, J¼ 7.6 Hz); C NMR (100 MHz, CDCl
3
) d
1
1
2
69.0, 155.0, 150.1, 149.9, 139.9, 138.9, 132.1, 130.3, 130.0, 127.5,
22.3, 121.5, 120.3, 117.9, 114.8, 112.3, 110.2, 61.7, 56.1, 52.4, 52.2, N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
þ
9.7; MS m/z: 531.0 (M þ 1).
1-yl)phenyl)-3-(4-ethyl-piperazin-1-yl)propanamide (1j)
1
H NMR (400 MHz, CDCl ) d 8.56 (d, 2H, J¼ 6.4 Hz), 8.29 (s, 1H),
3
8
7
(
3
1
1
.15 (s, 1H), 7.49(dd, 8H, J¼ 1.2, 8.0 Hz), 7.36 (t, 1H, J¼ 8.0 Hz),
.28 (d, 1H, J¼ 4.8 Hz), 7.21 (d, 2H, J¼ 6.4 Hz), 7.07 (s, 1H), 7.03
N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
1-yl)phenyl)-2–(4-phenyl-piperazin-1-yl)acetamide (1e)
dd, 1H, J¼ 1.6, 8.0 Hz), 3.73 (s, 3H), 2.73–2.51 (m, 12H), 2.31 (s,
1
H NMR (400 MHz, CDCl ) d 8.48 (d, 2H, J ¼ 4.8 Hz), 8.13 (brs, 1H),
13
3
3
H); C NMR (100 MHz, CDCl ) d 170.7, 154.6, 149.9, 149.6, 140.6,
7
6
.63 (brs, 1H), 7.51–7.28 (m, 3H), 7.28–7.18 (m, 6H), 7.06 (s, 1H),
.98 (d,1H, J ¼ 8.0 Hz), 6.88–6.83 (m, 3H), 3.71 (s, 3H), 3.25–3.24
39.9, 139.8, 132.3, 130.1, 129.6, 127.6, 122.9, 122.6, 121.4, 120.1,
17.6, 114.1, 112.3, 110.2, 56.0, 55; MS m/z: 545.9 (M þ 2).
þ
13
3
(m, 4H), 2.81 (s, 2H), 2.11–1.99 (m, 4H); C NMR (100 MHz, CDCl )
d 170.7, 155.0, 149.6, 139.9, 138.1, 132.1, 130.9, 130.3, 130.0, 129.3,
1
6
28.9, 127.7, 123.0, 121.5, 120.3, 117.9, 116.5, 114.9, 112.3, 110.2,
1.7, 56.1, 52.4; MS m/z: 579.9 (M þ 2).
N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
þ
1-yl)phenyl)-3-(4-phenyl-piperazin-1-yl)propanamide (1k)
1
H NMR (400 MHz, CDCl ) d 8.58 (d, 2H, J¼ 6.0 Hz), 8.34 (s, 1H),
3
2-(4-Benzylpiperazin-1-yl)-N-(3–(3-(4-chloro-3-methoxyphenyl)-4-
8.21 (s, 1H), 7.58 (d, 1H, J¼ 7.2 Hz), 7.43 (t, 1H, J¼ 8.0 Hz),
7.35–7.28 (m, 2H), 7.14 (s, 1H), 7.08 (dd, 1H, J¼ 2.0, 8.0 Hz),
(
pyridin-4-yl)-1H-pyrazol-1-yl)phenyl)acetamide (1f)
1
3
1
6.96–6.93 (m, 6H), 3.79 (s, 3H), 2.96–2.65 (m, 12H); C NMR
H NMR (400 MHz, CDCl ) d 8.57 (d, 2H, J¼ 5.6 Hz), 7.78–7.75 (m,
3
(100 MHz, CDCl
3
) d 169.7, 155.1, 151.9, 150.9, 150.8, 146.9, 142.9,
4
H), 7.59–7.53 (m, 4H), 7.45 (t, 2H, J¼ 4.0 Hz), 7.40 (d, 1H,
1
40.0, 132.0, 130.3, 129.3, 127.5, 123.1, 122.4, 121.5, 120.5, 120.3,
J¼ 8.4 Hz), 7.14–7.07 (m, 2H), 3.84 (s, 3H), 3.31 (s, 2H), 3.10 (brs,
þ
117.6, 117.2, 116.4, 114.5, 112.2, 110.2, 56.1, 53.1, 52.4, 32.5; MS
4
H), 2.36 (brs, 4 H), 2.32 (brs, 2H); MS m/z: 593.9 (M þ 2).
þ
m/z: 593.43 (M þ 1).
Compounds 1 g–m were prepared from 9 b and appropriate
acid chloride as reported in the synthesis of 1a.
3-(4-Benzylpiperazin-1-yl)-N-(3–(3-(4-chloro-3-methoxyphenyl)-4-
N-(3-(3-(4-Chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-
(pyridin-4-yl)-1H-pyrazol-1-yl)phenyl)propanamide (1 l)
1
-yl)phenyl)-3-(piperidin-1-yl)propanamide (1 g)
1
H NMR (400 MHz, CDCl
3
) d 8.57 (d, 2H, J¼ 6.0 Hz), 8.36 (s, 1H),
1
H NMR (400 MHz, CDCl
3
) d 8.59 (brs, 1H), 8.36 (s, 1H), 8.19 (s, 1H), 8.21 (s, 1H), 7.58 (dd, 1H, J¼ 1.2, 9.2 Hz), 7.43 (t, 1H, J¼ 8.0 Hz),
7
.57 (d, 1H, J¼ 8.0 Hz), 7.44 (t, 1H, J¼ 8.0 Hz), 7.36 (d, 2H, 7.33–7.29 (m, 5H), 7.16–7.11 (m, 2H), 3.79 (s, 3H), 3.58 (s, 2H),
1
3
J¼ 8.0 Hz), 7.32–7.29 (m, 3H), 7.17 (s, 1H), 7.10 (d, 1H, J¼ 7.6 Hz), 2.81–2.58 (m, 12H); C NMR (100 MHz, CDCl ) d 170.9, 156.9,
3
1
3
3
.83 (s, 3H), 3.22 (s, 2H), 2.84–2.67 (m, 6H), 1.79–1.28 (m, 8H);
C
150.9, 150.8, 146.9, 142.9, 140.0, 137.6, 132.5, 130.3, 129.1, 127.6,
NMR (100 MHz, CDCl ) d 170.7, 154.9, 150.1, 149.9, 149.8, 140.1, 123.0, 121.5, 120.2, 117.6, 114.3, 112.3, 110.2, 62.9, 56.1, 53.1, 52.3,
3
þ
1
39.9, 132.6, 130.5, 130.2, 129.6, 127.6, 122.7, 120.5, 120.2, 117.7, 32.6; MS m/z: 608.1 (M þ 1).