22 Letters in Drug Design & Discovery, 2015, Vol. 12, No. 1
Yao et al.
Hz), 9.33 (s, 1H), 10.21 (s, 1H). MS (ESI): 409.0
(C25H21N5O, [M+H]+); Anal. Calcd for C25H21N5O: C, 73.68;
H, 5.21; N, 17.22%; Found: C, 73.69; H, 5.19; N, 17.19%.
[M+H]+). Anal. Calcd for C25H20ClN5O: C, 67.99; H, 4.55;
N, 15.88%; Found: C, 67.95; H, 4.56; N, 15.85%.
a7:(E)-3-(4-chlorophenyl)-N-(4-methyl-3-(4-(pyridin-3-yl)-
pyrimidin-2-ylamino)phenyl) Acrylamide
a2:(E)-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylami-
no)phenyl)-3-(2-(trifluoromethyl) phenyl) Acrylamide
1
Light yellow solid; Yield: 85.7%; m.p. 273-275 °C. H
1
White solid; Yield: 84.5%; m.p. 284-286 °C. H NMR
NMR (DMSO, 300 MHz) ꢀ: 2.22 (s, 3H), 7.99-7.81 (d, 1H,
J = 8.4 Hz), 7.20-7.21 (d, 1H, J = 3.6 Hz), 7.40-7.49 (m,
2H), 7.56-7.58 (m, 4H), 7.74-7.76 (d, 2H, J = 4.8 Hz), 8.00
(s, 1H), 8.47-8.53 (m, 2H), 8.69-8.70 (d, 1H, J = 2.4 Hz),
9.02 (s, 1H), 9.30 (s, 1H), 10.21 (s, 1H). MS (ESI): 443.0
(C25H20ClN5O, [M+H]+). Anal. Calcd for C25H20ClN5O: C,
67.92; H, 4.58; N, 15.85%; Found: C, 67.95; H, 4.56; N,
15.84%.
(DMSO, 300 MHz) ꢀ: 2.23 (s, 3H), 6.89-6.93 (d, 1H,
J = 12.0 Hz), 7.21-7.19 (d, 1H, J = 5.4 Hz), 7.41-7.55 (m,
4H), 7.63-7.90 (m, 4H), 8.03 (d, 1H, J = 1.8 Hz), 8.48-8.66
(m, 2H), 8.70 (d, 1H, J = 2.4 Hz), 8.98 (s, 1H), 9.27 (s, 1H),
10.32 (s, 1H). MS (ESI): 476.5 (C26H20F3N5O, [M+H]+);
Anal. Calcd for C26H20F3N5O:C, 65.66; H, 4.29; N, 14.75%;
Found: C, 65.68; H, 4.24; N, 14.73%.
a3:(E)-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylami-
no)phenyl)-3-(3-(trifluoromethyl) phenyl) Acrylamide
a8:(E)-3-(2-chloro-5-(trifluoromethyl)phenyl)-N-(4-methyl-
3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl) Acrylamide
1
White solid; Yield: 80.5%; m.p. 281-282 °C. H NMR
1
Light brown solid; Yield: 80.8%; m.p. 267-270 °C. H
(DMSO, 300 MHz) ꢀ: 2.23 (s, 3H), 6.89-6.93 (d, 1H,
J = 12.0 Hz), 7.21-7.19 (d, 1H, J = 6.0 Hz), 7.41-7.55 (m,
4H), 7.63-7.90 (m, 4H), 8.03 (d, 1H, J = 1.8 Hz), 8.58-8.66
(m, 2H), 8.80-8.81 (d, 1H, J = 3.6 Hz), 8.98 (s, 1H), 9.21 (s,
1H), 10.15 (s, 1H). MS (ESI): 476.4 (C26H20F3N5O,
[M+H]+); Anal. Calcd for C26H20F3N5O: C,65.67; H, 4.25; N,
14.76%; Found: C, 65.68; H, 4.24; N, 14.75%.
NMR (DMSO, 300 MHz) ꢀ: 2.21 (s, 3H), 7.04 (d, 1H,
J = 1.2 Hz), 7.21 (d, 1H, J = 1.8 Hz), 7.50-7.57 (m, 3H),
7.75-7.84 (m, 3H), 8.03 (m, 2H), 8.47-8.53 (m, 2H), 8.67-
8.69 (m, 1H), 8.95 (s, 1H), 9.27 (d, 1H, J = 1.2 Hz), 10.27 (s,
1H). MS (ESI): 510.9 (C26H19ClF3N5O, [M+H]+). Anal.
Calcd for C26H19ClF3N5O: C, 61.27; H, 3.76; N, 13.78%;
Found: C, 61.24; H, 3.76; N, 13.73%.
a4:(E)-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylam-
ino)phenyl)-3-(4-(trifluoromethyl) phenyl) Acrylamide
a9:(E)-3-(3,5-dichlorophenyl)-N-(4-methyl-3-(4-(pyridin-3-
yl)pyrimidin-2-ylamino)phenyl) Acrylamide
1
Yellow solid; Yield: 81.9%; m.p. 288-291 °C. H NMR
1
Light yellow solid; Yield: 82.8%; m.p. 252-253 °C. H
(DMSO, 300 MHz) ꢀ: 2.18 (s, 3H), 6.91-6.95 (d, 1H,
J = 12.3 Hz), 7.14-7.17 (d, 1H, J = 8.4 Hz), 7.44-7.51 (m,
3H), 7.58-7.63 (d, 1H, J = 15.6 Hz), 7.73-7.82 (m, 4H), 7.96
(s, 1H), 8.44-8.48 (t, 2H, J = 12.3 Hz), 8.64-8.65 (d, 1H,
J = 3.6 Hz), 8.97 (s, 1H), 9.24 (s, 1H), 10.25 (s, 1H). MS
(ESI): 476.5 (C26H20F3N5O, [M+H]+); Anal. Calcd for
C26H20F3N5O: C, 65.68; H, 4.27; N, 14.74%; Found: C,
65.70; H, 4.27; N, 14.73%.
NMR (DMSO, 300 MHz) ꢀ: 2.21 (s, 3H), 6.91-6.95 (d, 1H,
J = 12.3 Hz), 7.19-7.21 (d, 1H, J = 6.3 Hz), 7.35-7.70 (m,
7H), 7.98-7.99 (d, 1H, J = 1.8 Hz), 8.45-8.53 (m, 2H), 8.68-
8.70 (m, 1H), 8.95 (s, 1H), 9.27 (d, 1H, J = 1.8 Hz), 10.16 (s,
1H). MS (ESI): 477.4 (C25H19Cl2N5O, [M+H]+). Anal. Calcd
for C25H19Cl2N5O: C, 63.10; H, 4.04; N, 14.75%; Found: C,
63.03; H, 4.02; N, 14.70%.
a10:(E)-3-(2-methoxyphenyl)-N-(4-methyl-3-(4-(pyridin-3-
yl)pyrimidin-2-ylamino)phenyl) Acrylamide
a5:(E)-3-(2-chlorophenyl)-N-(4-methyl-3-(4-(pyridin-3-
yl)pyrimidin-2-ylamino)phenyl) Acrylamide
1
Light yellow solid; Yield: 85.2%; m.p. 245-247 °C. H
1
Champagne solid ; Yield: 82.6% ; m.p. 255-256 °C. H
NMR (DMSO, 300 MHz) ꢀ: 2.21 (s, 3H), 3.89 (s, 3H), 6.87
(d, 1H, J = 1.2 Hz), 7.01-7.03 (t, 1H, J = 8.4 Hz), 7.09-7.11
(d, 1H, J = 6.3 Hz), 7.18-7.19 (d, 1H, J = 4.8 Hz), 7.40-7.45
(m, 3H), 7.52-7.57 (m, 2H), 7.78-7.80 (d, 1H, J = 8.4 Hz),
7.99 (s, 1H), 8.48-8.53 (m, 2H), 8.69-8.70 (d, 1H, J = 3.3
Hz), 8.97 (s, 1H), 9.27 (d, 1H, J = 1.2 Hz), 10.12 (s, 1H). MS
(ESI): 438.5 (C26H23N5O2, [M+H]+). Anal. Calcd for
C26H23N5O2: C, 71.41; H, 5.33; N, 16.06%; Found: C, 71.38;
H, 5.30; N, 16.01%.
NMR (DMSO, 300 MHz) ꢀ: 2.29 (s, 3H), 6.88-6.90 (d, 1H,
J = 9.0 Hz), 7.19-7.21 (d, 1H, J = 6.3 Hz), 7.39-7.42 (t, 4H,
J = 8.1 Hz), 7.50-7.59 (m, 2H), 7.76-7.78 (m, 1H), 7.84-7.88
(d, 1H, J = 12.0 Hz), 8.00 (s, 1H), 8.47-8.54 (m, 2H), 8.69-
8.70 (d, 1H, J = 2.4 Hz), 8.98 (s, 1H), 9.27 (d, 1H, J = 1.2
Hz), 10.21 (s, 1H). MS (ESI): 443.7 (C25H20ClN5O,
[M+H]+). Anal. Calcd for C25H20ClN5O: C, 68.11; H, 4.55;
N, 15.91%; Found: C, 68.05; H, 4.56; N, 15.85%.
a6:(E)-3-(3-chlorophenyl)-N-(4-methyl-3-(4-(pyridin-3-
yl)pyrimidin-2-ylamino)phenyl) Acrylamide
a11:(E)-3-(3-methoxyphenyl)-N-(4-methyl-3-(4-(pyridin-3-
yl)pyrimidin-2-ylamino)phenyl) Acrylamide
1
White solid; Yield: 82.9%; m.p. 228-229 °C. H NMR
1
White solid; Yield: 84.7%; m.p. 234-236 °C. H NMR
(DMSO, 300 MHz) ꢀ: 2.22 (s, 3H), 6.88-6.92 (d, 1H,
J = 12.0 Hz), 7.19-7.21 (d, 1H, J = 6.3 Hz), 7.39-7.42 (t, 4H,
J = 8.4 Hz), 7.50-7.59 (m, 2H), 7.76-7.88 (m, 1H), 7.84-7.88
(d, 1H, J = 12.3 Hz), 8.01 (s, 1H), 8.47-8.53 (m, 2H), 8.69-
8.70 (d, 1H, J = 2.4 Hz), 8.97 (s, 1H), 9.27-9.28 (d, 1H,
J = 3.0 Hz), 10.27 (s, 1H). MS (ESI): 443.3 (C25H20ClN5O,
(DMSO, 300 MHz) ꢀ: 2.21 (s, 3H), 3.80 (s, 3H), 6.81-6.85
(d, 1H, J = 12.3 Hz), 6.69-7.00 (m, 1H), 7.18-7.38 (m, 3H),
7.40-7.44 (m, 3H), 7.51-7.57 (m, 2H), 7.98-8.00 (t, 1H,
J = 6.3 Hz), 8.45-8.52 (m, 2H), 8.68-8.70 (m, 1H), 8.94 (s,
1H), 9.27 (d, 1H, J = 1.8 Hz), 10.11 (s, 1H). MS (ESI): 438.8
(C26H23N5O2, [M+H]+). Anal. Calcd for C26H23N5O2: C,