6
H.-Q. Wu et al. / Bioorg. Med. Chem. xxx (2014) xxx–xxx
À
1
3
31.6, 132.8, 144.6, 155.3, 158.8, 165.2, 168.5; MS (ESI ) m/z
74.32 (MÀH) .
2H, J = 8.4 Hz, Ph), 7.61 (d, 2H, J = 8.4 Hz, Ph), 7.81 (d, 1H, J = 8.4 Hz,
Ph), 7.93 (d, 1H, J = 10.9 Hz, Ph), 8.18 (t, 1H, J = 8.1 Hz, Ph), 10.05 (s,
À
1
3
1
H, NH), 10.54 (s, 1H, NH); C NMR (DMSO-d
102.2, 106.1 (d, JC3-F = 8 Hz), 117.7 (d, JC4-F = 2 Hz), 118.4, 119.4 (d,
C-C-F = 23 Hz), 119.4, 122.5 (d, JC4-F = 2 Hz), 129.5 (d, JC4-F = 3 Hz),
130.9 (d, JC3-F = 11 Hz), 132.6, 144.6, 151.6(d, JC-F = 246 Hz), 158.4,
6
) d: 23.3, 64.1, 98.4,
5
.2.8. 2-((2-((4-Cyanophenyl)amino)-6-methylpyrimidin-4-
yl)oxy)-N-(4-fluorophenyl)acetamide (3h)
Yield 62%; white solid, mp 202.2–203.0 °C; H NMR (DMSO-d
d (ppm): 2.34 (s, 3H, CH ), 4.98 (s, 2H, CH ), 6.42 (s, 1H, Py), 7.13–
.17 (m, 2H, Ph), 7.50 (d, 2H, J = 8.7 Hz, Ph), 7.59–7.62 (m, 2H, Ph),
.83 (d, 2H, J = 8.8 Hz, Ph), 10.06 (s, 1H, NH), 10.30 (s, 1H, NH);
) d: 23.3, 64.1, 98.5, 102.1, 115.3 (d, JC-C-F = 23 Hz),
18.3, 119.4, 120.8(d, JC3-F = 8 Hz), 132.7, 133.8 (d, JC-F = 223 Hz),
J
1
6
)
À
À
3
2
167.2, 168.7, 168.9; MS (ESI ) m/z 383.37 (MÀH) .
7
7
1
3
C
5
.2.15. 2-((2-((4-Cyanophenyl)amino)-5-methylpyrimidin-4-
yl)oxy)-N-(4-fluorophenyl)acetamide (3o)
Yield 63%; white solid, mp 201.4–202.3 °C; H NMR (DMSO-d
d (ppm): 2.11 (s, 3H, CH ), 5.05 (s, 2H, CH ), 7.15 (t, 2H, J = 8.8 Hz,
Ph), 7.49 (d, 2H, J = 8.7 Hz, Ph), 7.60 (dd, 2H, J = 8.8, 5.0 Hz, Ph), 7.80
d, 2H, J = 8.7 Hz, Ph), 8.19 (s, 1H, Py), 9.92 (s, 1H, NH), 10.29 (s, 1H,
NMR (DMSO-d
1
1
m/z 376.19 (MÀH) .
6
1
6
)
À
34.9 (d, JC4-F = 3 Hz), 144.7, 158.4, 165.8, 168.6, 169.0; MS (ESI )
3
2
À
(
5
.2.9. N-(4-Chlorophenyl)-2-((2-((4-cyanophenyl)amino)-6-
1
3
NH); C NMR (DMSO-d
= 22 Hz), 117.9, 119.4, 120.9 (d, J
3 Hz), 140.6 (d, JC-F = 259 Hz), 144.8, 157.2, 157.7, 165.7, 166.7;
6
) d: 11.7, 64.2, 101.8, 108.7, 115.3 (d, JC-C-F
methylpyrimidin-4-yl)oxy)acetamide (3i)
Yield 59%; pale yellow solid, mp 208.4–210.1 °C; 1H NMR
C3-F = 8 Hz), 132.7, 134.9 (d, JC4-F
=
(
DMSO-d
6
) d (ppm): 2.33 (s, 3H, CH
H, Py), 7.36 (d, 2H, J = 8.8 Hz, Ph), 7.50 (d, 2H, J = 8.6 Hz, Ph),
.63 (d, 2H, J = 8.8 Hz, Ph), 7.82 (d, 2H, J = 8.7 Hz, Ph), 10.06 (s,
3 2
), 5.00 (s, 2H, CH ), 6.42 (s,
À
À
MS (ESI ) m/z 376.31 (MÀH) .
1
7
1
9
1
H, NH), 10.40 (s, 1H, NH); 1 C NMR (DMSO-d
3
5.2.16. 2-((2-((4-Cyanophenyl)amino)-5-methylpyrimidin-4-
6
) d: 23.3, 64.1,
yl)oxy)-N-(2-fluorophenyl)acetamide (3p)
8.5, 102.1, 118.3, 119.4, 120.6, 127.0, 128.7, 132.7, 137.4, 144.7,
1
À
À
Yield 47%; white solid, mp 199.4–200.1 °C; H NMR (DMSO-d
6
)
58.4, 166.1, 168.6, 168.9; MS (ESI ) m/z 392.12 (MÀH) .
d (ppm): 2.11 (s, 3H, CH
.18 (s, 1H, Py), 9.93 (s, 1H, NH), 10.04 (s, 1H, NH); C NMR
DMSO-d ) d: 11.6, 64.2, 101.8, 108.7, 115.4 (d, JC-C-F = 19 Hz),
3 2
), 5.14 (s, 2H, CH ), 7.14–7.85 (m, 8H, Ph),
13
8
5
.2.10. N-(4-Bromophenyl)-2-((2-((4-cyanophenyl)amino)-6-
(
6
methylpyrimidin-4-yl)oxy)acetamide (3j)
Yield 59%; white solid, mp 209.4–210.9 °C; H NMR (DMSO-d
d (ppm): 2.33 (s, 3H, CH ), 4.99 (s, 2H, CH ), 6.42 (s, 1H, Py), 7.49 (d,
H, J = 8.8 Hz, Ph), 7.50 (d, 2H, J = 8.8 Hz, Ph), 7.57 (d, 2H, J = 8.8 Hz,
Ph), 7.82 (d, 2H, J = 8.7 Hz, Ph), 10.07 (s, 1H, NH), 10.40 (s, 1H, NH);
1
1
1
1
18.0, 119.4, 123.6, 124.3 (d, JC4-F = 3 Hz), 125.3 (d, JC3-F = 8 Hz),
25.5 (d, JC3-F = 11 Hz), 132.6, 144.8, 153.3 (d, JC-F = 243 Hz),
57.2, 157.7, 166.3, 166.6; MS (ESI ) m/z 376.34 (MÀH) .
6
)
3
2
À
À
2
1
3
5
.2.17. N-(4-Chlorophenyl)-2-((2-((4-cyanophenyl)amino)-5-
C NMR (DMSO-d
6
) d: 23.3, 64.1, 98.5, 102.1, 115.0, 118.3, 119.4,
methylpyrimidin-4-yl)oxy)acetamide (3q)
Yield 54%; white solid, mp 210.3–212.1 °C; H NMR (DMSO-d
d (ppm): 2.11 (s, 3H, CH ), 5.06 (s, 2H, CH ), 7.37 (d, 2H, J = 8.7 Hz,
Ph), 7.49 (d, 2H, J = 8.6 Hz, Ph), 7.62 (d, 2H, J = 8.7 Hz, Ph), 7.79 (d,
1H, J = 8.5 Hz, Ph), 8.19 (s, 1H, Py), 9.94 (s, 1H, NH), 10.40 (s, 1H,
1
21.0, 131.6, 132.7, 137.9, 144.7, 158.4, 166.1, 168.6, 168.9; MS
1
À
À
6
)
(
ESI ) m/z 436.06 (MÀH) .
3
2
5
.2.11. N-(3-Chlorophenyl)-2-((2-((4-cyanophenyl)amino)-6-
2
methylpyrimidin-4-yl)oxy)acetamide (3k)
Yield 57%; white solid, mp 204.8–206.1 °C; H NMR (DMSO-d
d (ppm): 2.33 (s, 3H, CH ), 5.01 (s, 2H, CH ), 6.41 (s, 1H, Py), 7.10–
.83 (m, 8H, Ph), 10.05 (s, 1H, NH), 10.44 (s, 1H, NH); C NMR
DMSO-d ) d: 23.3, 64.1, 98.5, 102.1, 117.5, 118.3, 118.6, 119.3,
23.2, 130.4, 132.7, 133.1, 139.9, 144.7, 158.4, 166.3, 168.6,
1
3
1
NH); C NMR (DMSO-d
6
) d: 11.7, 64.2, 101.8, 108.7, 117.9, 119.4,
6
)
1
1
20.6, 127.0, 128.7, 132.7, 137.5, 144.8, 157.2, 157.7, 166.0,
66.6; MS (ESI ) m/z 392.17 (MÀH) .
3
2
À
À
13
7
(
6
5
.2.18. N-(3-Chlorophenyl)-2-((2-((4-cyanophenyl)amino)-5-
1
1
À
À
methylpyrimidin-4-yl)oxy)acetamide (3r)
Yield 50%; white solid, mp 214.4–216.1 °C; H NMR (DMSO-d
d (ppm): 2.11 (s, 3H, CH ), 5.07 (s, 2H, CH ), 7.12–7.78 (m, 8H, Ph),
.18 (s, 1H, Py), 9.92 (s, 1H, NH), 10.44 (s, 1H, NH); C NMR
DMSO-d ) d: 11.7, 64.2, 101.8, 108.7, 117.5, 118.0, 118.6, 119.4,
23.2, 130.4, 132.7, 133.1, 139.9, 144.8, 157.2, 157.8, 166.3,
68.9; MS (ESI ) m/z 392.36 (MÀH) .
1
6
)
5
.2.12. 2-((2-((4-Cyanophenyl)amino)-6-methylpyrimidin-4-
3
2
13
8
yl)oxy)-N-(4-nitrophenyl)acetamide (3l)
Yield 57%; yellow solid, mp 213.4–214.9 °C; H NMR (DMSO-d
d (ppm): 2.33 (s, 3H, CH ), 5.01 (s, 2H, CH ), 6.43 (s, 1H, Py), 7.50 (d,
H, J = 8.6 Hz, Ph), 7.80 (d, 2H, J = 8.7 Hz, Ph), 7.84 (d, 2H, J = 9.1 Hz,
Ph), 7.82 (d, 2H, J = 9.1 Hz, Ph), 10.07 (s, 1H, NH), 10.97 (s, 1H, NH);
1
(
6
6
)
1
1
3
2
À
À
66.6; MS (ESI ) m/z 392.34 (MÀH) .
2
1
3
6
C NMR (DMSO-d ) d: 23.3, 64.2, 98.4, 102.1, 118.3, 118.8, 119.3,
5
.2.19. N-(2-Chlorophenyl)-2-((2-((4-cyanophenyl)amino)-5-
1
25.0, 132.7, 142.3, 144.6, 144.7, 158.4, 167.0, 168.7, 168.9; MS
methylpyrimidin-4-yl)oxy)acetamide (Vs)
Yield 47%; white solid, mp 209.9–211.5 °C; H NMR (DMSO-d
d (ppm): 2.13 (s, 3H, CH ), 5.14 (s, 2H, CH ), 7.17–7.87 (m, 8H, Ph),
.21 (s, 1H, Py), 9.66 (s, 1H, NH), 9.95 (s, 1H, NH); C NMR (DMSO-
À
À
(
ESI ) m/z 403.13 (MÀH) .
1
6
)
3
2
5
.2.13. N-(4-Cyanophenyl)-2-((2-((4-cyanophenyl)amino)-6-
1
3
8
methylpyrimidin-4-yl)oxy)acetamide (3m)
Yield 63%; white solid, mp 207.7–209.1 °C; H NMR (DMSO-d
d (ppm): 2.33 (s, 3H, CH ), 5.04 (s, 2H, CH ), 6.42 (s, 1H, Py), 7.47–
.81 (m, 8H, Ph), 10.05 (s, 1H, NH), 10.72 (s, 1H, NH); C NMR
DMSO-d ) d: 23.3, 64.2, 98.5, 102.2, 105.2, 118.3, 118.9, 119.1,
19.4, 132.7, 133.3, 142.7, 144.6, 158.4, 166.8, 168.7, 168.9; MS
d
1
1
6
) d: 11.7, 64.3, 101.9, 108.8, 118.1, 119.5, 125.0, 125.7, 126.3,
1
6
)
27.5, 129.4, 132.8, 134.1, 139.9, 144.9, 157.2, 157.7, 166.3,
3
2
À
À
66.4; MS (ESI ) m/z 392.33 (MÀH) .
13
7
(
1
6
5
.2.20. N-(4-Bromophenyl)-2-((2-((4-cyanophenyl)amino)-5-
À
À
methylpyrimidin-4-yl)oxy)acetamide (3t)
(
ESI ) m/z 401.38 (MÀH) .
Yield 49%; pale yellow solid, mp 217.2–219.1 °C; 1H NMR
(DMSO-d ) d (ppm): 2.11 (s, 3H, CH ), 5.06 (s, 2H, CH ), 7.48–
5
.2.14. N-(4-Cyano-2-fluorophenyl)-2-((2-((4-
6
3
2
cyanophenyl)amino)-6-methylpyrimidin-4-yl)oxy)acetamide
3n)
Yield 52%; white solid, mp 208.8–210.1 °C; H NMR (DMSO-d
d (ppm): 2.33 (s, 3H, CH ), 5.04 (s, 2H, CH ), 6.42 (s, 1H, Py), 7.50 (d,
7.78 (d, 8H, Ph), 8.19 (s, 1H, Py), 9.92 (s, 1H, NH), 10.38 (s, 1H,
1
3
(
NH); C NMR (DMSO-d ) d: 11.7, 64.2, 101.8, 108.7, 115.0, 117.9,
6
1
6
)
119.4, 121.0, 131.6, 132.7, 137.9, 144.8, 157.2, 157.7, 166.0,
À
À
3
2
166.6; MS (ESI ) m/z 436.27 (MÀH) .