P. Wu et al. / European Journal of Medicinal Chemistry 46 (2011) 5540e5548
5545
H), 7.87 (d, 1H, J ¼ 8.5 Hz, aromatic H), 7.80 (d, 1H, J ¼ 8.5 Hz,
aromatic H), 7.72e7.66 (m, 3H, aromatic H), 7.60 (t, 2H, J ¼ 7.5 Hz,
aromatic H), 7.49 (t, 1H, J ¼ 7.5 Hz, aromatic H), 7.30e7.29 (m, 2H,
aromatic H), 6.64 (d, 1H, J ¼ 7.5 Hz, aromatic H), 5.09 (br s, 1H, OH,
also confirmed by hydrogen/deuterium exchange experiment). 13C
7.70 (dt, 1H, J ¼ 8.0 and 1.5 Hz, aromatic H), 7.47 (dt, 1H, J ¼ 8.0 and
1.5 Hz, aromatic H), 7.37 (d, 2H, J ¼ 8.5 Hz, aromatic H), 7.15 (d, 2H,
J ¼ 2.0 Hz, aromatic H), 6.29 (t, 1H, J ¼ 2.0 Hz, aromatic H), 3.86 (s,
6H, OCH3), 2.43 (s, 3H, CH3). ESI-MS (m/z): 436 [Mþ1]þ.
NMR (125 MHz, CDCl3):
d
156.26, 145.80, 142.70, 142.28, 140.08,
4.1.2.14. 2-(3,4,5-Trimethoxyphenylamino)-3-tosylquinoxaline
(28). Red solid, yield 21%, mp: 127e129 ꢀC. IR (KBr, cmꢁ1): 3452
(NH), 1636 (aromatic ring), 1384 (SO2). 1H NMR (500 MHz, CDCl3):
138.48, 136.31, 134.65, 133.48, 130.10, 129.90, 129.44 (2), 129.08 (2),
126.80, 126.78, 112.98, 110.86, 107.58. ESI-MS (m/z): 378 [Mþ1]þ.
d
9.52 (s, 1H, NH), 8.04 (d, 2H, J ¼ 8.0 Hz, aromatic H), 7.86 (d, 1H,
4.1.2.8. 2-(4-Fluorophenylamino)-3-(phenylsulfonyl)quinoxaline
(22). Orange solid, yield 28%, mp: 212e214 ꢀC. IR (KBr, cmꢁ1): 3449
(NH), 1623 (aromatic ring), 1384 (SO2). 1H NMR (500 MHz, CDCl3):
J ¼ 8.5 Hz, aromatic H), 7.70e7.68 (m, 2H, aromatic H), 7.47e7.43
(m, 1H, aromatic H), 7.40 (d, 2H, J ¼ 8.0 Hz, aromatic H), 7.24 (s, 2H,
aromatic H), 3.94 (s, 6H, OCH3), 3.87 (s, 3H, OCH3), 2.45 (s, 3H, CH3).
ESI-MS (m/z): 466 [Mþ1]þ.
d
9.48 (s, 1H, NH), 8.15 (d, 2H, J ¼ 7.5 Hz, aromatic H), 7.85e7.80 (m,
3H, aromatic H), 7.75 (d, 1H, J ¼ 8.5 Hz, aromatic H), 7.70 (t, 2H,
J ¼ 7.5 Hz, aromatic H), 7.61 (t, 2H, J ¼ 7.5 Hz, aromatic H), 7.47 (t,
1H, J ¼ 7.5 Hz, aromatic H), 7.13 (t, 2H, J ¼ 8.5 Hz, aromatic H). ESI-
MS (m/z): 380 [Mþ1]þ.
4.1.2.15. 2-(4-Aminophenylamino)-3-tosylquinoxaline
solid, yield 55%, mp: 190e191 ꢀC. IR (KBr, cmꢁ1): 3449 (NH), 1635
(aromatic ring), 1384 (SO2). 1H NMR (500 MHz, CDCl3):
9.51 (s, 1H,
(29). Red
d
NH), 8.02 (d, 2H, J ¼ 8.0 Hz, aromatic H), 7.88 (d, 1H, J ¼ 8.5 Hz,
aromatic H), 7.78 (d, 1H, J ¼ 8.5 Hz, aromatic H), 7.69 (t, 1H,
J ¼ 7.5 Hz, aromatic H), 7.45 (t, 1H, J ¼ 7.5 Hz, aromatic H), 7.37e7.36
(m, 3H, aromatic H), 7.24e7.17 (m, 2H, aromatic H), 6.50 (d, 1H,
J ¼ 8.0 Hz, aromatic H), 3.77 (br s, 2H, NH2) 2.43 (s, 3H, CH3). ESI-MS
(m/z): 391 [Mþ1]þ.
4.1.2.9. 2-(4-Chlorophenylamino)-3-(phenylsulfonyl)quinoxaline
(23). Yellow solid, yield 16%, mp: 203e205 ꢀC. IR (KBr, cmꢁ1): 3452
(NH), 1636 (aromatic ring), 1384 (SO2). 1H NMR (500 MHz, CDCl3):
d
9.57 (s, 1H, NH), 8.15 (d, 2H, J ¼ 8.0 Hz, aromatic H), 7.86e7.83 (m,
3H, aromatic H), 7.78 (d,1H, J ¼ 8.0 Hz, aromatic H), 7.70 (t,1H, J ¼ 8.
Hz, aromatic H), 7.63e7.58 (m, 3H, aromatic H), 7.49 (t, 1H,
J ¼ 8.0 Hz, aromatic H), 7.39 (d, 2H, J ¼ 8.5 Hz, aromatic H). ESI-MS
(m/z): 396 [Mþ1]þ.
4.1.2.16. 2-(3-Aminophenylamino)-3-tosylquinoxaline
solid, yield 22%, mp: 129e131 ꢀC. IR (KBr, cmꢁ1): 3452 (NH), 1628
(aromatic ring), 1384 (SO2). 1H NMR (500 MHz, CDCl3):
9.51 (s, 1H,
(30). Red
d
4.1.2.10. 2-(4-Trifluoromethylphenylamino)-3-(phenylsulfonyl)qui-
noxaline (24). Yellow solid, yield 20%, mp: 208e209 ꢀC. IR (KBr,
cmꢁ1): 3450 (NH), 1627 (aromatic ring), 1384 (SO2). 1H NMR
NH), 8.02 (d, 2H, J ¼ 8.0 Hz, aromatic H), 7.88 (d, 1H, J ¼ 8.5 Hz,
aromatic H), 7.78 (d, 1H, J ¼ 8.5 Hz, aromatic H), 7.69 (t, 1H,
J ¼ 7.5 Hz, aromatic H), 7.45 (t, 1H, J ¼ 7.5 Hz, aromatic H), 7.37e7.36
(m, 3H, aromatic H), 7.24e7.17 (m, 2H, aromatic H), 6.50 (d, 1H,
J ¼ 6.5 Hz, aromatic H), 3.77 (br s, 2H, NH2) 2.43 (s, 3H, CH3). ESI-MS
(m/z): 391 [Mþ1]þ.
(500 MHz, CDCl3):
d 9.80 (s, 1H, NH, also confirmed by hydrogen/
deuterium exchange experiment), 8.17 (d, 2H, J ¼ 8.5 Hz, aromatic
H), 8.05 (d, 2H, J ¼ 8.5 Hz, aromatic H), 7.90 (d, 1H, J ¼ 8.5 Hz,
aromatic H), 7.83 (d, 1H, J ¼ 8.5 Hz, aromatic H), 7.77 (t, 1H,
J ¼ 7.5 Hz, aromatic H), 7.72e7.67 (m, 3H, aromatic H), 7.62 (t, 2H,
J ¼ 7.5 Hz, aromatic H), 7.54 (t, 1H, J ¼ 7.5 Hz, aromatic H). 13C NMR
4.1.2.17. 2-(3-Hydroxyphenylamino)-3-tosylquinoxaline
(31). Yellow solid, yield 18%, mp: 188e191 ꢀC. IR (KBr, cmꢁ1):
(125 MHz, CDCl3):
d 145.43, 142.38, 141.92, 138.27, 136.61, 134.77,
3449 (NH), 3335 (OH), 1614 (aromatic ring), 1386 (SO2). 1H NMR
133.70, 129.94, 129.48 (2), 129.18 (2), 127.35, 126.91, 126.46, 126.44,
(500 MHz, CDCl3):
d
9.60 (s, 1H, NH), 8.02 (d, 2H, J ¼ 8.5 Hz,
126.40, 126.37, 125.49, 119.92 (2). ESI-MS (m/z): 430 [Mþ1]þ.
aromatic H), 7.88 (d, 1H, J ¼ 8.5 Hz, aromatic H), 7.80 (d, 1H,
J ¼ 8.5 Hz, aromatic H), 7.71e7.68 (m, 2H, aromatic H), 7.48 (t, 1H,
J ¼ 7.5 Hz, aromatic H), 7.38 (d, 2H, J ¼ 8.5 Hz, aromatic H),
7.30e7.28 (m, 2H, aromatic H), 6.64 (d, 1H, J ¼ 7.5 Hz, aromatic
H), 5.01 (br s, 1H, OH), 2.44 (s, 3H, CH3). ESI-MS (m/z): 392
[Mþ1]þ.
4.1.2.11. 2-Phenylamino-3-tosylquinoxaline (25). Yellow solid, yield
13%, mp: 162e164 ꢀC. IR (KBr, cmꢁ1): 3449 (NH), 1636 (aromatic
ring), 1384 (SO2). 1H NMR (500 MHz, CDCl3):
d 9.58 (s, 1H, NH),
8.03 (d, 2H, J ¼ 8.5 Hz, aromatic H), 7.89e7.87 (m, 3H, aromatic
H), 7.78e7.76 (m, 1H, aromatic H), 7.70 (dt, 1H, J ¼ 8.0 and 1.0 Hz,
aromatic H), 7.47 (dd, 1H, J ¼ 8.0 and 1.0 Hz, aromatic H), 7.44 (dt,
2H, J ¼ 8.5 and 2.0 Hz, aromatic H), 7.38 (d, 2H, J ¼ 8.5 Hz,
aromatic H), 7.17 (t, 1H, J ¼ 7.5 Hz, aromatic H), 2.44 (s, 3H, CH3).
ESI-MS (m/z): 376 [Mþ1]þ.
4.1.2.18. 2-(4-Fluorophenylamino)-3-tosylquinoxaline (32). Orange
solid, yield 24%, mp: 183e185 ꢀC. IR (KBr, cmꢁ1): 3447 (NH), 1620
(aromatic ring), 1384 (SO2). 1H NMR (500 MHz, CDCl3):
d 9.50 (s, 1H,
NH), 8.03 (d, 2H, J ¼ 8.5 Hz, aromatic H), 7.86e7.80 (m, 3H, aromatic
H), 7.74 (d, 1H, J ¼ 8.5 Hz, aromatic H), 7.69 (dt, 1H, J ¼ 8.5 and
1.5 Hz, aromatic H), 7.46 (dt,1H, J ¼ 8.5 and 1.5 Hz, aromatic H), 7.38
(d, 2H, J ¼ 8.5 Hz, aromatic H), 7.13 (t, 2H, J ¼ 8.5 Hz, aromatic H),
2.44 (s, 3H, aromatic CH3). ESI-MS (m/z): 394 [Mþ1]þ.
4.1.2.12. 2-(4-Methoxyphenylamino)-3-tosylquinoxaline (26). Red
solid, yield 24%, mp: 164e166 ꢀC. IR (KBr, cmꢁ1): 3455 (NH), 1636
(aromatic ring),1386 (SO2). 1H NMR (500 MHz, CDCl3):
d 9.39 (s, 1H,
NH), 8.03 (d, 2H, J ¼ 8.5 Hz, aromatic H), 7.86 (d, 1H, J ¼ 8.0 Hz,
aromatic H), 7.76 (d, 2H, J ¼ 8.5 Hz, aromatic H), 7.71 (d, 1H,
J ¼ 8.0 Hz, aromatic H), 7.67 (dt, 1H, J ¼ 8.0 and 1.0 Hz, aromatic H),
7.43 (dt, 1H, J ¼ 8.0 and 1.0 Hz, aromatic H), 7.38 (d, 2H, J ¼ 8.5 Hz,
aromatic H), 6.97 (d, 2H, J ¼ 8.5 Hz, aromatic H), 3.85 (s, 3H, OCH3),
2.44 (s, 3H, CH3). ESI-MS (m/z): 406 [Mþ1]þ.
4.1.2.19. 2-(4-Chlorophenylamino)-3-tosylquinoxaline (33). Yellow
solid, yield 28%, mp: 200e201 ꢀC. IR (KBr, cmꢁ1): 3455 (NH), 1637
(aromatic ring), 1386 (SO2). 1H NMR (500 MHz, CDCl3):
d 9.59 (s, 1H,
NH), 8.02 (d, 2H, J ¼ 8.5 Hz, aromatic H), 7.87 (t, 3H, J ¼ 8.5 Hz,
aromatic H), 7.77 (d, 1H, J ¼ 8.5 Hz, aromatic H), 7.71 (t, 1H,
J ¼ 8.0 Hz, aromatic H), 7.48 (t, 1H, J ¼ 8.0 Hz, aromatic H),
7.38e7.36 (m, 4H, aromatic H), 2.44 (s, 3H, aromatic CH3). ESI-MS
(m/z): 410 [Mþ1]þ.
4.1.2.13. 2-(3,5-Dimethoxyphenylamino)-3-tosylquinoxaline
(27). Orange solid, yield 38%, mp: 168e169 ꢀC. IR (KBr, cmꢁ1): 3450
(NH), 1637 (aromatic ring), 1384 (SO2). 1H NMR (500 MHz, CDCl3):
d
9.58 (s, 1H, NH), 8.02 (d, 2H, J ¼ 8.5 Hz, aromatic H), 7.87 (dd, 1H,
4.1.2.20. 2-(4-Trifluoromethylphenylamino)-3-tosylquinoxaline
(34). Yellow solid, yield 14%, mp: 200e202 ꢀC. IR (KBr, cmꢁ1): 3452
J ¼ 8.5 and 1.0 Hz, aromatic H), 7.77 (d, 1H, J ¼ 8.5 Hz, aromatic H),