Z. Yu et al. / European Journal of Medicinal Chemistry 106 (2015) 50e59
57
1H NMR (400 MHz, CDCl3):
d
8.69 (d, J ¼ 1.6 Hz, 1H), 8.45e8.38 (m,
4.2.19. 2-[4-(2-Bromobenzoyl)phenoxy]-N-(6-methylpyridin-3-yl)
acetamide (7f1)
2H), 8.23 (dd, J ¼ 7.2, 1.2 Hz, 1H), 7.85 (d, J ¼ 8.8 Hz, 2H), 7.68 (d,
J ¼ 8.0 Hz, 2H), 7.33 (dd, J ¼ 8.4, 4.8 Hz, 1H), 7.28 (d, J ¼ 7.2 Hz, 2H),
7.07 (d, J ¼ 8.8 Hz, 2H), 4.73 (s, 2H), 2.45 (s, 3H) ppm; HPLC
tR ¼ 7.09 min purity 98%; ESI-MS: 347.13 [MþH]þ.
Started from 6f and 5-amino-2-methylpyridine. White solid,
47 mg, yield ¼ 73%. 1H NMR (400 MHz, CDCl3):
8.54 (d, J ¼ 2.4 Hz,
d
1H), 8.35 (s,1H), 8.07 (dd, J ¼ 8.4, 2.4 Hz,1H), 7.84 (d, J ¼ 8.8 Hz, 2H),
7.65 (d, J ¼ 7.6 Hz, 1H), 7.43 (td, J ¼ 7.2, 0.8 Hz, 1H), 7.37e7.33 (m,
2H), 7.17 (d, J ¼ 8.4 Hz, 1H), 7.05 (d, J ¼ 8.8 Hz, 2H), 4.70 (s, 2H), 2.54
(s, 3H) ppm; HPLC tR ¼ 7.09 min purity 99%; ESI-MS: 425.07
[MþH]þ.
4.2.13. 2-(4-(4-Fluorobenzoyl)phenoxy)-N-(pyridin-3-yl)acetamide
(7m)
White solid, 187 mg, yield ¼ 53%. 1H NMR (400 MHz, CDCl3):
d
8.72 (d, J ¼ 2.4 Hz, 1H), 8.44e8.40 (m, 2H), 8.30e8.23 (m, 1H), 7.85
4.2.20. 2-[4-(2-Bromobenzoyl)phenoxy]-N-(6-methoxypyridin-3-
yl)acetamide (7f2)
(d, J ¼ 8.8 Hz, 2H), 7.83e7.77 (m, 2H), 7.35 (dd, J ¼ 8.4, 4.8 Hz, 1H),
7.17 (t, J ¼ 8.8 Hz, 2H), 7.09 (d, J ¼ 8.8 Hz, 2H), 4.74 (s, 2H) ppm;
HPLC tR ¼ 6.89 min purity 99%; ESI-MS: 351.13 [MþH]þ.
Started from 6f and 5-amino-2-methoxypyridine. White solid,
50 mg, yield ¼ 94%. 1H NMR (400 MHz, CDCl3):
d 8.31e8.20 (m, 2H),
7.91 (dd, J ¼ 7.8, 2.0 Hz, 1H), 7.83 (d, J ¼ 8.4 Hz, 2H), 7.64 (d,
J ¼ 7.6 Hz, 1H), 7.42 (t, J ¼ 7.2 Hz, 1H), 7.37e7.32 (m, 2H), 7.04 (d,
J ¼ 8.8 Hz, 2H), 6.75 (d, J ¼ 8.8 Hz,1H), 4.69 (s, 2H), 3.92 (s, 3H) ppm;
HPLC tR ¼ 9.06 min purity 98%; ESI-MS: 441.07 [MþH]þ.
4.2.14. 2-[4-(4-Chlorobenzoyl)phenoxy]-N-(pyridin-3-yl)acetamide
(7n) [19]
White solid, 903 mg, yield ¼ 98%. 1H NMR (400 MHz, DMSO):
d
10.41 (s, 1H), 8.79 (d, J ¼ 2.4 Hz, 1H), 8.30 (dd, J ¼ 4.4, 1.2 Hz, 1H),
8.07 (dt, J ¼ 8.0, 1.6 Hz, 1H), 7.77 (d, J ¼ 8.8 Hz, 2H), 7.72 (dd, J ¼ 8.8,
2.0 Hz, 2H), 7.62 (d, J ¼ 8.4 Hz, 2H), 7.38 (dd, J ¼ 8.4, 4.8 Hz, 1H), 7.17
(d, J ¼ 8.8 Hz, 2H), 4.89 (s, 2H) ppm; HPLC tR ¼ 7.27 min purity
100%; ESI-MS: 367.13 [MþH]þ.
4.2.21. 2-[4-(2-Bromobenzoyl)phenoxy]-N-(6-chloropyridin-3-yl)
acetamide (7f3)
Started from 6f and 5-amino-2-chloropyridine. Yellow solid,
51 mg, yield ¼ 82%. 1H NMR (400 MHz, CDCl3):
8.47 (d, J ¼ 2.8 Hz,
d
1H), 8.30 (s,1H), 8.21 (dd, J ¼ 8.8, 2.8 Hz,1H), 7.85 (d, J ¼ 8.0 Hz, 2H),
7.65 (d, J ¼ 8.0 Hz, 1H), 7.43e7.32 (m, 4H), 7.05 (d, J ¼ 8.8 Hz, 2H),
4.71 (s, 2H) ppm; HPLC tR ¼ 9.65 min purity 100%; ESI-MS: 445.07
[MþH]þ.
4.2.15. 2-[4-(2-Bromo-3-fluorobenzoyl)phenoxy]-N-(5-
methoxypyridin-3-yl)acetamide (7o)
White solid, 69 mg, yield ¼ 25%. 1H NMR (400 MHz, CDCl3):
d
8.68 (d, J ¼ 2.0 Hz, 1H), 8.42 (d, J ¼ 4.4 Hz, 1H), 8.37 (s, 1H), 8.22 (d,
J ¼ 8.4 Hz, 1H), 7.85 (d, J ¼ 8.4 Hz, 2H), 7.44e7.39 (m, 1H), 7.33 (dd,
J ¼ 8.2, 4.8 Hz,1H), 7.26 (t, J ¼ 8.0 Hz,1H), 7.13 (d, J ¼ 7.6 Hz,1H), 7.07
(d, J ¼ 8.8 Hz, 2H), 4.72 (s, 2H) ppm; HPLC tR ¼ 7.25 min purity 98%;
ESI-MS: 429.07 [MþH]þ.
4.2.22. 2-[4-(2-Bromobenzoyl)phenoxy]-N-(5-methylpyridin-3-yl)
acetamide (7f4)
Started from 6f and 3-amino-5-methylpyridine. White solid,
55 mg, yield ¼ 86%. 1H NMR (400 MHz, CDCl3):
8.47 (d, J ¼ 2.0 Hz,
d
1H), 8.40 (s, 1H), 8.24 (s, 1H), 8.04 (s, 1H), 7.83 (dd, J ¼ 7.8, 2.0 Hz,
2H), 7.65 (dd, J ¼ 7.2, 0.8 Hz, 1H), 7.43 (td, J ¼ 7.0, 1.2 Hz, 1H),
7.37e7.33 (m, 2H), 7.05 (d, J ¼ 8.8 Hz, 2H), 4.71 (s, 2H), 2.36 (s, 3H)
ppm. HPLC tR ¼ 7.18 min purity 99%; ESI-MS: 425.07 [MþH]þ.
4.2.16. 2-[4-(2-Bromo-5-fluorobenzoyl)phenoxy]-N-(5-
methoxypyridin-3-yl)acetamide (7p)
White solid, 108 mg, yield ¼ 39%. 1H NMR (400 MHz, CDCl3):
d
8.67 (s, 1H), 8.43 (d, J ¼ 4.4 Hz, 1H), 8.28 (s, 1H), 8.21 (d, J ¼ 8.4 Hz,
4.2.23. 2-[4-(2-Bromobenzoyl)phenoxy]-N-(5-methoxypyridin-3-
yl)acetamide (7f5)
1H), 7.86 (d, J ¼ 8.8 Hz, 2H), 7.61 (dd, J ¼ 8.4, 4.8 Hz, 1H), 7.33 (dd,
J ¼ 8.0, 4.8 Hz, 1H), 7.14e7.03 (m, 4H), 4.73 (s, 2H) ppm; 13C NMR
Started from 6f and 3-amino-5-methoxypyridine. White solid,
(101 MHz, CDCl3):
d 192.9, 165.9, 162.9, 161.3, 160.4, 146.1, 142.1,
274 mg, yield ¼ 100%. 1H NMR (400 MHz, CDCl3):
d 8.78 (s, 1H), 8.23
141.7, 134.9, 134.8, 133.7, 132.9, 130.1, 127.7, 123.8, 118.7, 118.4, 116.2,
116.0, 114.9, 113.7, 67.5 ppm; HPLC tR ¼ 7.22 min purity 100%; ESI-
MS: 429.07 [MþH]þ.
(d, J ¼ 1.6 Hz,1H), 8.09 (d, J ¼ 2.4 Hz,1H), 7.90 (t, J ¼ 2.4 Hz,1H), 7.80
(dt, J ¼ 9.2, 2.0 Hz, 2H), 7.63 (dd, J ¼ 7.8, 1.2 Hz, 1H), 7.41 (td, J ¼ 7.8,
1.2 Hz, 1H), 7.34 (td, J ¼ 7.8, 2.0 Hz, 1H), 7.30 (dd, J ¼ 7.6, 2.0 Hz, 1H),
7.02 (dt, J ¼ 8.8, 2.4 Hz, 2H), 4.70 (s, 2H), 3.85 (s, 3H) ppm. HPLC
tR ¼ 7.44 min purity 99%; ESI-MS: 441.07 [MþH]þ.
4.2.17. 2-[(9-Oxo-9H-fluoren-3-yl)oxy]-N-(pyridin-3-yl)acetamide
(7q)
Started from 4q and 3-aminopyridine. Yellow solid, 170 mg,
4.2.24. 2-[4-(2-Bromobenzoyl)phenoxy]-N-(4-methylpyridin-3-yl)
acetamide (7f6)
yield ¼ 51%. 1H NMR (400 MHz, DMSO):
d 10.52 (s, 1H), 8.89 (d,
J ¼ 2.4 Hz, 1H), 8.37 (dd, J ¼ 4.8, 1.2 Hz, 1H), 8.17 (d, J ¼ 8.4 Hz, 1H),
7.81 (d, J ¼ 7.2 Hz, 1H), 7.65e7.55 (m, 3H), 7.53e7.47 (m, 2H), 7.39(t,
J ¼ 7.2 Hz, 1H), 6.95 (dd, J ¼ 8.0, 2.0 Hz, 1H), 4.95 (s, 2H) ppm; HPLC
tR ¼ 6.73 min purity 99%; ESI-MS: 331.07 [MþH]þ.
Started from 6f and 3-amino-4-methylpyridine. White solid,
90 mg, yield ¼ 70%. 1H NMR (400 MHz, CDCl3):
d 8.92 (s, 1H), 8.34
(d, J ¼ 4.4 Hz, 1H), 8.28 (s, 1H), 7.84 (d, J ¼ 8.8 Hz, 2H), 7.64 (d,
J ¼ 7.6 Hz, 1H), 7.43 (td, J ¼ 7.2, 0.8 Hz, 1H), 7.35 (td, J ¼ 7.8, 2.0 Hz,
1H), 7.33 (dd, J ¼ 7.4, 2.0 Hz, 1H), 7.16 (d, J ¼ 4.8 Hz, 1H), 7.05 (d,
J ¼ 8.8 Hz, 2H), 4.76 (s, 2H), 2.25 (s, 3H) ppm. HPLC tR ¼ 7.05 min
purity 100%; ESI-MS: 425.13 [MþH]þ.
4.2.18. 2-[(1-Bromonaphthalen-2-yl)oxy]-N-(pyridin-3-yl)
acetamide (7r) [22]
White solid, 235 mg, yield ¼ 74%. 1H NMR (400 MHz, CDCl3):
d
9.07 (s br, 1H), 8.77 (d, J ¼ 2.4 Hz, 1H), 8.42 (dd, J ¼ 4.8, 1.2 Hz, 1H),
4.2.25. 2-[4-(2-Bromobenzoyl)phenoxy]-N-(4-methoxypyridin-3-
yl)acetamide (7f7)
8.28 (ddd, J ¼ 8.4 Hz, 1.2, 1.2 Hz, 1H), 8.24 (d, J ¼ 8.8 Hz, 1H), 7.89 (d,
J ¼ 8.8 Hz, 1H), 7.84 (d, J ¼ 8.0 Hz, 1H), 7.65 (dd, J ¼ 6.8, 0.8 Hz, 1H),
7.49 (dd, J ¼ 7.2, 0.8 Hz, 1H), 7.34 (dd, J ¼ 8.4, 3.6 Hz, 1H), 7.25 (d,
Started from 6f and 3-amino-4-methoxypyridine. Yellow solid,
35 mg, yield ¼ 72%. 1H NMR (400 MHz, CDCl3):
d 9.48 (s,1H), 8.66 (s,
J ¼ 8.4 Hz, 1H), 4.83 (s, 2H); 13C NMR (101 MHz, CDCl3):
d
166.2,
1H), 8.33 (d, J ¼ 5.2 Hz, 1H), 7.85 (d, J ¼ 8.8 Hz, 2H), 7.65 (d,
J ¼ 8.0 Hz, 1H), 7.44e7.32 (m, 3H), 7.05 (d, J ¼ 8.8 Hz, 2H), 6.85 (d,
J ¼ 5.6 Hz, 1H), 4.72 (s, 2H), 3.95 (s, 3H) ppm. HPLC tR ¼ 7.13 min
purity 99%; ESI-MS: 441.13 [MþH]þ.
151.2, 145.9, 141.4, 134.0, 132.8, 130.6, 129.8, 128.4, 128.3, 127.0,
126.3,125.5, 123.8, 114.7, 109.9, 69.0 ppm. HPLC tR ¼ 7.95 min purity
99%; ESI-MS: 357.00 [MþH]þ.