Y. Wang et al. / European Journal of Medicinal Chemistry 123 (2016) 80e89
87
þ
1
[
(
MþH] ; H NMR (400 MHz, DMSO)
d
11.33 (s,1H), 9.77 (s, 1H), 9.29
5.1.6.21. (E)-5-chloro-2-(2-(2-chlorobenzylidene)hydrazinyl)-N-(2-
s, 1H), 8.30 (s, 1H), 8.09 (s, 1H), 7.86 (d, J ¼ 7.7 Hz, 2H), 7.65 (d,
(isopropylsulfonyl)phenyl)pyrimidin-4-amine (6u). White solid;
ꢀ
þ 1
J ¼ 8.1 Hz, 2H), 7.40e7.35 (m, 3H), 3.51 (hept, J ¼ 6.7 Hz, 1H), 2.53 (s,
yield: 76%; M.p.: 244e246 C; MS (ESI) m/z (%): 464.0 [MþH] ; H
13
3
1
(
1
H), 1.20 (d, J ¼ 6.7 Hz, 6H); C NMR (101 MHz, DMSO)
55.95, 155.38, 141.70, 140.04, 139.03, 135.52, 132.18, 131.48, 127.12
2C), 126.33 (2C), 123.56, 123.48, 122.92, 105.55, 55.48, 15.36 (2C),
4.89. Anal. calcd. for C21 22ClN (%): C, 52.99; H, 4.66; N,14.71.
Found (%): C, 53.00; H, 4.63; N, 14.74.
d
158.01,
NMR (400 MHz, DMSO) 11.60 (s, 1H), 9.78 (s, 1H), 9.22 (s, 1H), 8.52
d
(s, 1H), 8.34 (s, 1H), 8.08 (d, J ¼ 7.9 Hz, 1H), 7.91e7.78 (m, 2H),
7.52e7.48 (m, 2H), 7.43e7.37 (m, 2H), 3.50 (hept, J ¼ 6.8 Hz, 1H),
1
3
H
5
O
2
S
2
1.20 (d, J ¼ 6.8 Hz, 6H); C NMR (101 MHz, DMSO)
d 157.84, 155.99,
155.45, 138.90, 137.84, 135.41, 132.83, 132.75, 131.51, 130.87, 130.38,
28.03, 126.53, 123.69 (2C), 123.03, 106.21, 55.46, 15.35 (2C). Anal.
calcd. for C20 S (%): C, 51.73; H, 4.12; N, 15.08. Found (%):
1
5
.1.6.16. (E)-5-chloro-N-(2-(isopropylsulfonyl)phenyl)-2-(2-(4-
2 5 2
H19Cl N O
(
methylsulfonyl)benzylidene)hydrazinyl)pyrimidin- 4-amine (6p).
C, 51.75; H, 4.10; N, 15.10.
ꢀ
White solid; yield: 80%; M.p.: 275e277 C; MS (ESI) m/z(%): 508.1
þ
1
[
(
(
1
(
MþH] ; H NMR (400 MHz, DMSO)
d
11.60 (s, 1H), 9.75 (s, 1H), 9.18
5.1.6.22. (E)-5-chloro-N-(2-(isopropylsulfonyl)phenyl)-2-(2-(3-(tri-
fluoromethyl)benzylidene)hydrazinyl)pyrimidin
s, 1H), 8.29 (s, 1H), 8.14 (s, 1H), 7.96e7.82 (m, 6H), 7.35 (s, 1H), 3.45
-4-amine
(6v).
13
ꢀ
s, 1H), 3.20 (s, 3H), 1.15 (s, 6H); C NMR (101 MHz, DMSO)
55.96, 155.49, 140.83, 140.50, 139.95, 138.88, 135.59, 131.51, 128.07
2C), 127.10 (2C), 123.73, 122.99, 106.39, 55.47, 44.02, 15.35 (2C).
Anal. calcd. for C21 22ClN (%): C, 49.65; H, 4.37; N, 13.79.
Found (%):C, 49.63; H, 4.35; N, 13.76.
d
157.82,
White solid; yield: 73%; M.p.: 217e219 C; MS (ESI) m/z (%): 498.0
þ
1
[MþH] ; H NMR (400 MHz, DMSO)
d 11.57 (s, 1H), 9.78 (s, 1H), 9.21
(s, 1H), 8.34 (s, 1H), 8.21 (s, 1H), 8.07 (s, 1H), 7.96 (d, J ¼ 5.5 Hz, 1H),
7.87 (d, J ¼ 7.4 Hz, 1H), 7.80e7.69 (m, 3H), 7.39 (t, J ¼ 7.4 Hz, 1H),
H
5 4 2
O S
13
3.50 (hept, J ¼ 6.8 Hz, 1H), 1.20 (d, J ¼ 6.8 Hz, 6H); C NMR
(101 MHz, DMSO) d 157.90, 155.97, 155.49, 140.29, 138.91, 136.79,
5
.1.6.17. (E)-5-chloro-N-(2-(isopropylsulfonyl)phenyl)-2-(2-(2-
135.06, 131.52, 130.91, 130.45, 130.22, 129.90, 125.97, 124.00, 123.57,
123.27, 122.98, 106.13, 55.42, 15.35 (2C). Anal. calcd. for
C H19ClF N O S (%): C, 50.66; H, 3.85; N, 14.07. Found (%):C, 50.64;
21 3 5 2
methoxybenzylidene)hydrazinyl)pyrimidin-4-amine
solid; yield: 78%; M.p.: 294e296 C; MS (ESI) m/z (%): 460.1
(6q). White
ꢀ
þ
1
[
(
MþH] ; H NMR (400 MHz, DMSO)
d
11.35 (s,1H), 9.77 (s, 1H), 9.30
H, 3.87; N, 14.09.
s, 1H), 8.48 (s, 1H), 8.29 (s, 1H), 7.95 (d, J ¼ 7.1 Hz, 1H), 7.86 (d,
J ¼ 8.0 Hz, 1H), 7.81 (t, J ¼ 7.9 Hz, 1H), 7.38 (t, J ¼ 7.7 Hz, 2H),
.14e7.04 (m, 2H), 3.86 (s, 3H), 3.51 (hept, J ¼ 6.8 Hz, 1H), 1.20 (d,
J ¼ 6.8 Hz, 6H). Anal. calcd. for C21 22ClN S (%): C, 54.84; H, 4.82;
N, 15.23. Found (%): C, 54.82; H, 4.87; N, 15.25.
5.1.6.23. (E)-5-chloro-2-(2-(2,4-difluorobenzylidene)hydrazinyl)-N-
(2-(isopropylsulfonyl)phenyl)pyrimidin-4- amine (6w). White solid;
7
ꢀ
þ 1
H
5
O
3
yield: 77%; M.p.: 229e231 C; MS (ESI) m/z (%): 466.1 [MþH] ; H
NMR (400 MHz, DMSO) 11.51 (s, 1H), 9.78 (s, 1H), 9.22 (s, 1H), 8.32
s, 1H), 8.28 (s, 1H), 8.02e7.96 (m, 1H), 7.87e7.83 (m, 2H), 7.43e7.25
(m, 3H), 3.50 (hept, J ¼ 6.8 Hz, 1H), 1.20 (d, J ¼ 6.8 Hz, 6H). Anal.
calcd. for C20 18ClF S (%): C, 51.56; H, 3.89; N,15.03. Found (%):
C, 51.53; H, 3.86; N, 15.00.
d
(
5
.1.6.18. (E)-5-chloro-N-(2-(isopropylsulfonyl)phenyl)-2-(2-(3-
methoxybenzylidene)hydrazinyl)pyrimidin-4-amine
solid; yield: 84%; M.p.: 203e204 C; MS (ESI) m/z (%): 460.2
(6r). White
H
2 5 2
N O
ꢀ
þ
1
[
(
2
MþH] ; H NMR (400 MHz, DMSO)
s, 1H), 8.31 (s, 1H), 8.10 (s, 1H), 7.93e7.76 (m, 2H), 7.39 (t, J ¼ 7.0 Hz,
H), 7.28 (d, J ¼ 7.7 Hz, 2H), 6.97 (d, J ¼ 8.0 Hz, 1H), 3.82 (s, 3H), 3.51
d 11.39 (s, 1H), 9.76 (s, 1H), 9.24
5.1.6.24. (E)-5-chloro-N-(2-(isopropylsulfonyl)phenyl)-2-(2-(3,4,5-
trimethoxybenzylidene)hydrazinyl)pyrimidin-4-
amine
(6x).
13
ꢀ
(
hept, J ¼ 6.6 Hz, 1H), 1.20 (d, J ¼ 6.6 Hz, 6H); C NMR (101 MHz,
DMSO) 160.04, 158.01, 155.96, 155.43, 141.94, 138.99, 137.06,
35.31, 131.49, 130.37, 123.64, 123.56, 122.97, 119.49, 115.31, 111.54,
05.73, 55.65, 55.44, 15.36 (2C). Anal. calcd. for C21 22ClN S (%):
C, 54.84; H, 4.82; N, 15.23. Found (%): C, 54.85; H, 4.84; N, 15.26.
White solid; yield: 86%; M.p.: 227e229 C; MS (ESI) m/z (%): 520.0
þ
1
d
[MþH] ; H NMR (400 MHz, DMSO)
d 11.33 (s,1H), 9.68 (s,1H), 9.06
1
1
(s, 1H), 8.31 (s, 1H), 8.07 (s, 1H), 7.86 (dd, J ¼ 7.9, 1.3 Hz, 1H), 7.76 (t,
H
5 3
O
J ¼ 7.9 Hz, 1H), 7.36 (t, J ¼ 7.6 Hz, 1H), 6.98 (s, 2H), 3.84 (s, 6H), 3.70
13
(s, 3H), 3.51 (hept, J ¼ 6.8 Hz, 1H), 1.20 (d, J ¼ 6.8 Hz, 6H); C NMR
(
101 MHz, DMSO) d 157.99, 155.94, 155.49, 153.65 (2C), 142.48,
5
.1.6.19. (E)-5-chloro-2-(2-(2-fluorobenzylidene)hydrazinyl)-N-(2-
139.03, 138.86, 135.24, 131.48, 131.06, 123.93, 123.58, 123.07, 105.61,
104.11 (2C), 60.59, 56.40 (2C), 55.30, 15.35 (2C). Anal. calcd. for
(
isopropylsulfonyl)phenyl)pyrimidin-4-amine (6s). White solid;
ꢀ
þ 1
yield: 90%; M.p.: 245e247 C; MS (ESI) m/z (%): 448.3 [MþH] ; H
NMR (400 MHz, DMSO) 11.52 (s, 1H), 9.79 (s, 1H), 9.24 (s, 1H), 8.35
s, 1H), 8.33 (s, 1H), 7.98 (t, J ¼ 7.2 Hz, 1H), 7.87e7.82 (m, 2H),
.48e7.36 (m, 3H), 7.31e7.26 (m,1H), 3.51 (hept, J ¼ 6.6 Hz,1H),1.20
C
23
5 5
H26ClN O S (%): C, 53.13; H, 5.04; N,13.47. Found (%): C, 53.10; H,
d
5.07; N, 13.45.
(
7
5.1.6.25. (E)-5-chloro-N-(2-(isopropylsulfonyl)phenyl)-2-(2-(1-(4-
methoxyphenyl)ethylidene)hydrazinyl)pyrimidin -4-amine (7a).
13
(
1
1
5
4
d, J ¼ 6.6 Hz, 6H); C NMR (101 MHz, DMSO)
57.88, 155.96, 155.44, 138.94, 135.41, 134.64, 131.49, 131.28, 131.20,
26.11, 125.37, 123.63, 123.21, 123.12, 123.00, 116.56, 116.36, 106.04,
5.47, 15.35 (2C). Anal. calcd. for C20 19ClFN S (%): C, 53.63; H,
d
161.94, 159.47,
ꢀ
White solid; yield: 83%; M.p.: 80e83 C; MS (ESI) m/z (%): 474.1
[MþH] ; H NMR (400 MHz, DMSO)
þ
1
d 10.22 (s, 1H), 9.78 (s, 1H),
H
5
O
2
9.39 (d, J ¼ 7.3 Hz, 1H), 8.30 (s, 1H), 7.86e7.82 (m, 3H), 7.79 (t,
J ¼ 7.9 Hz, 1H), 7.37 (t, J ¼ 7.6 Hz, 1H), 7.02 (d, J ¼ 8.8 Hz, 2H), 3.80 (s,
.28; N, 15.64. Found (%): C, 53.65; H, 4.26; N, 15.60.
3
H), 3.49 (hept, J ¼ 6.8 Hz, 1H), 2.27 (s, 3H), 1.18 (d, J ¼ 6.8 Hz, 6H);
1
3
5
.1.6.20. (E)-2-(2-(3-bromobenzylidene)hydrazinyl)-5-chloro-N-(2-
C NMR (101 MHz, DMSO) d 160.25, 158.89, 155.79, 155.35, 147.25,
(
isopropylsulfonyl)phenyl)pyrimidin-4-amine (6t). White solid;
139.14, 135.41, 131.66, 131.45, 127.53 (2C), 123.47, 123.23, 122.89,
114.19 (2C), 105.41, 55.73, 55.52, 15.36 (2C), 13.84. Anal. calcd. for
C H24ClN O S (%): C, 55.75; H, 5.10; N, 14.78. Found (%): C, 55.77;
22 5 3
ꢀ
þ 1
yield: 76%; M.p.: 217e218 C; MS (ESI) m/z (%): 508.0 [MþH] ; H
NMR (400 MHz, DMSO) 11.53 (s, 1H), 9.79 (s, 1H), 9.26 (s, 1H), 8.32
s, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.93e7.84 (m, 2H), 7.64 (d,
J ¼ 7.7 Hz, 1H), 7.57 (d, J ¼ 8.2 Hz,1H), 7.44e7.38 (m, 2H), 3.50 (hept,
d
(
H, 5.13; N, 14.75.
13
J ¼ 6.8 Hz, 1H), 1.20 (d, J ¼ 6.8 Hz, 6H); C NMR (101 MHz, DMSO)
5.1.6.26. (E)-5-chloro-2-(2-(1-(4-fluorophenyl)ethylidene)hydra-
d
157.91, 155.97, 155.44, 140.01, 138.97, 138.16, 135.30, 131.95, 131.53,
31.47, 128.23, 126.31, 123.69, 123.59, 122.98, 122.72, 106.01, 55.47,
zinyl)-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-
amine
(7b).
ꢀ
1
1
1
White solid; yield: 83%; M.p.: 196e198 C; MS (ESI) m/z (%): 461.8
þ
1
5.36 (2C). Anal. calcd. for C20
H19BrClN
5
O
2
S (%): C, 47.21; H, 3.76; N,
[MþH] ; H NMR (400 MHz, DMSO)
d 10.36 (s, 1H), 9.81 (s, 1H),
3.76. Found (%): C, 47.23; H, 3.74; N, 13.74.
9.36 (d, J ¼ 8.1 Hz, 1H), 8.34 (s, 1H), 7.96e7.93 (m, 2H), 7.86 (dd,