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W. Lu et al. / Bioorg. Med. Chem. 22 (2014) 2707–2713
(d, J = 4 Hz, 1H), 6.92–6.88 (m, 1H), 6.75 (d, J = 4 Hz, 1H), 6.68 (d,
J = 6 Hz, 1H), 6.60–6.56 (m, 1H), 3.81 (s, 3H).
Compound 5b was prepared following the same procedure as
5a. Then it was purified by silica gel column chromatography
(petroleum/AcOEt = 3:1 to 1:3).
d 7.62 (d, J = 6 Hz, 2H), 7.52 (d, J = 4 Hz, 2H), 7.50 (d, J = 4 Hz, 1H),
7.35 (d, J = 4 Hz, 1H), 7.28 (s, 1H), 7.17 (d, J = 4 Hz, 1H), 6.99 (d,
J = 4 Hz, 1H), 6.94–6.90 (m, 1H), 6.80 (d, J = 8 Hz, 1H), 6.76 (d,
J = 4 Hz, 1H), 6.61–6.57 (m, 1H), 4.76 (s, 2H), 3.87 (s, 3H).
5.1.6.6.
(2E)-N-(2-Aminophenyl)-3-(3-{2-[(2-fluorophenyl)
(IF15).
5.1.6. (2E)-N-(2-Aminophenyl)-3-[3-(2-{[3-bromo-5-(trifluoro-
methyl)phenyl]amino}-2-oxoethoxy)-4-methoxyphenyl]acryl-
amide (IF18)
amino]-2-oxoethoxy}-4-methoxyphenyl)acrylamide
Mp: 193–194 °C. EI-MS (m/z): 435.1 (M+). 1H NMR (400 MHz,
(CD3)2SO) d 7.98 (d, J = 8 Hz, 1H), 7.49 (d, J = 8 Hz, 1H), 7.35–7.28
(m, 4 H), 7.20 (d, J = 2 Hz, 1H), 7.18 (d, J = 2 Hz, 1H), 7.11 (d,
J = 4 Hz, 1H), 6.93 (d, J = 2 Hz, 1H), 6.77 (d, J = 4 Hz, 1H), 6.74 (s,
1H), 6.58 (d, J = 8 Hz, 1H), 4.83 (s, 2H), 3.87 (s, 3H).
To a suspension of 5a (0.85 g, 3 mmol) in dehydrated acetone
(70 mL) was added anhydrous potassium carbonate (1.30 g,
9 mmol). The mixture was stirred at room temperature for
30 min and then 2-chloro-N-(3-bromo-5(trifluoromethyl)acetam-
ide (3.33 g, 15 mmol) was added. The reaction mixture was re-
fluxed for another 10 h. Filtration and evaporation of acetone
was done in vacuum. The residue was extracted with EtOAc
(120 mL). The combined layers were washed with water, 2 M
NaOH, 2 M HCl and brine, dried over Na2SO4 and solvent was re-
moved. The crude product was purified by silica gel column chro-
matography (PE/AcOEt = 3:1 to 1:3) to yield (IF18) as white solid
(0.98 g, 58.0%). Mp: 193–195 °C. EI-MS (m/z): 563.0 (M+). 1H
NMR (400 MHz, (CD3)2SO) d 8.22 (s, 1H), 8.08 (s, 1H), 7.69 (s,
1H), 7.49 (d, J = 8 Hz, 1H), 7.33–7.28 (m, 2H), 7.29 (d, J = 4 Hz,
1H), 7.11 (d, J = 4 Hz, 1H), 6.91 (d, J = 6 Hz, 1H), 6.76 (s, 1H), 6.74
(d, J = 2 Hz, 1H), 6.58 (d, J = 8 Hz, 1H), 4.80 (s, 2H), 3.86 (s, 3H).
Compounds (IF10–IF27) were prepared following the proce-
dure described above.
5.1.6.7. (2E)-N-(2-Aminophenyl)-3-(3-{2-[(3-fluorophenyl)ami
no]-2-oxoethoxy}-4-methoxyphenyl)acrylamide
(IF16). Mp:
199–201 °C. EI-MS (m/z): 435.1 (M+). 1H NMR (400 MHz, (CD3)2-
SO) d 7.65 (d, J = 6 Hz, 1H), 7.48 (d, J = 8 Hz, 1H), 7.39 (d, J = 2 Hz,
1H), 7.39–7.37 (m, 1H), 7.33 (d, J = 4 Hz, 1H), 7.28 (d, J = 4 Hz,
1H), 7.27 (s, 1H), 7.10 (d, J = 4 Hz, 1H), 6.94–6.90 (m, 2H), 6.76
(s, 1H), 6.73 (d, J = 4 Hz, 1H), 6.58 (d, J = 8 Hz, 1H), 4.77 (s,
2H), 3.86 (s, 3H).
5.1.6.8.
methyl)phenyl]amino}-2-oxoethoxy)-4-methoxyphenyl]acrylam-
ide (IF17).
Mp: 231–233 °C. EI-MS (m/z):553.3 (M+). 1H NMR
(400 MHz, (CD3)2SO) d 8.38 (s, 2H), 7.83 (s, 1H), 7.49 (d, J = 8 Hz,
1H), 7.33–7.29 (m, 2H), 7.30 (d, J = 4 Hz, 1H), 7.12 (d, J = 4 Hz, 1H),
6.91 (d, J = 8 Hz, 1H), 6.76 (d, J = 4 Hz, 1H), 6.76 (s, 1H), 6.57 (d,
J = 8 Hz, 1H), 4.83 (s, 2H), 3.86 (s, 3H).
(2E)-N-(2-Aminophenyl)-3-[3-(2-{[3,5-bis(trifluoro-
5.1.6.1.
(2E)-N-(2-Aminophenyl)-3-(3-{2-[(3-chloro-4-fluoro-
phenyl)amino]-2-oxoethoxy}-4-methoxyphenyl)acrylamide
(IF10). Mp: 191–193 °C. EI-MS (m/z): 469.1. (M+). 1H NMR
(400 MHz, (CD3)2SO) d 7.99 (d, J = 6 Hz, 1H), 7.91 (d, J = 4 Hz,
1H), 7.59–7.55 (m, 1H), 7.50 (s, 1H), 7.42 (d, J = 4 Hz, 1H),
7.40 (d, J = 6 Hz, 1H), 7.21–7.19 (m, 1H), 6.91 (d, J = 6 Hz, 1H),
6.76 (s, 1H), 6.73 (d, J = 4 Hz, 1H), 6.58 (d, J = 6 Hz, 1H), 4.94
(s, 2H), 3.86 (s, 3H).
5.1.6.9. (2E)-N-(2-Amino-4-methylphenyl)-3-(3-{2-[(3-chloro-4-
fluorophenyl)amino]-2-oxoethoxy}-4-methoxyphenyl)
amide (IF19).
NMR (400 MHz, (CD3)2SO)
J = 4 Hz, 1H), 7.40 (d, J = 6 Hz, 1H), 7.26 (s, 2H), 7.17 (d, J = 4 Hz,
1H), 7.10 (d, J = 4 Hz, 1H), 6.75 (d, J = 2 Hz, 1H), 6.65 (d, J = 4 Hz,
1H), 6.56 (s, 1H), 6.39 (d, J = 4 Hz, 1H), 4.76 (s, 2H), 3.86 (s, 3H),
2.16 (s, 3H).
acryl-
Mp: 170–171 °C. EI-MS (m/z): 483.1 (M+). 1H
d 7.98 (d, J = 4 Hz, 1H), 7.44 (d,
5.1.6.2. (2E)-N-(2-Aminophenyl)-3-[4-methoxy-3-(2-oxo-2-{[3-
(trifluoromethyl)phenyl]amino}ethoxy)phenyl]acrylamide
(IF11). Mp: 188–189 °C. EI-MS (m/z): 485.1 (M+). 1H NMR
(400 MHz, (CD3)2SO) d 8.15 (s, 1H), 7.87 (d, J = 4 Hz, 1H), 7.61–
7.57 (m, 1H), 7.49 (d, J = 8 Hz, 1H), 7.46 (d, J = 6 Hz, 1H), 7.33 (d,
J = 2 Hz, 1H), 7.29 (s, 1H), 7.28 (d, J = 2 Hz, 1H), 7.11 (d, J = 4 Hz,
1H), 6.93–6.89 (m, 1H), 6.77–6.73 (m, 2H), 6.57 (d, J = 6 Hz, 1H),
4.80 (s, 2H), 3.86 (s, 3H).
5.1.6.10. (2E)-N-(2-Amino-4-methylphenyl)-3-[4-methoxy-3-(2-
oxo-2-{[3-(trifluoromethyl)phenyl]amino}ethoxy)phenyl] acryl-
amide (IF20).
NMR (400 MHz, (CD3)2SO) d 8.15 (s, 1H), 7.87 (d, J = 4 Hz, 1H), 7.59
(d, J = 8 Hz, 1H), 7.47 (d, J = 4 Hz, 1H), 7.45 (d, J = 4 Hz, 1H), 7.28 (s,
1H), 7.27 (d, J = 4 Hz, 1H), 7.17 (d, J = 4 Hz, 1H), 7.10 (d, J = 4 Hz,
1H), 6.76–6.70 (m, 1H), 6.56 (s, 1H), 6.39 (d, J = 4 Hz, 1H), 4.79 (s,
2H), 3.86 (s, 3H), 2.17 (s, 3H).
Mp: 192–194 °C. EI-MS (m/z): 499.1 (M+). 1H
5.1.6.3. (2E)-N-(2-Aminophenyl)-3-(3-{2-[(3,4-dichlorophenyl)
amino]-2-oxoethoxy}-4-methoxyphenyl)acrylamide (IF12).
Mp: 209–210 °C. EI-MS (m/z): 485.0 (M+). 1H NMR (400 MHz,
(CD3)2SO) d 8.06 (s, 1H), 7.61 (d, J = 4 Hz, 1H), 7.59 (d, J = 8 Hz,
1H), 7.51 (d, J = 4 Hz, 1H), 7.33 (d, J = 6 Hz, 1H), 7.28 (d,
J = 4 Hz, 1H), 7.27 (s, 1H), 7.10 (d, J = 4 Hz, 1H), 6.93–6.89 (m,
2H), 6.73 (d, J = 4 Hz, 1H), 6.57 (d, J = 6 Hz, 1H), 4.77 (s, 2H),
3.86 (s, 3H).
5.1.6.11. (2E)-N-(2-Amino-4-methylphenyl)-3-(3-{2-[(3,4-dichlo-
rophenyl)amino]-2-oxoethoxy}-4-methoxyphenyl)acrylamide
(IF21).
(400 MHz, (CD3)2SO) d 8.05 (s, 1H), 7.61 (d, J = 4 Hz, 1H), 7.59
(d, J = 6 Hz, 1H), 7.46 (d, J = 8 Hz, 1H), 7.27 (d, J = 4 Hz, 1H), 7.26
(s, 1H), 7.17 (d, J = 4 Hz, 1H), 7.10 (d, J = 4 Hz, 1H), 6.72 (d,
J = 4 Hz, 1H), 6.56 (s, 1H), 6.39 (d, J = 4 Hz, 1H), 4.77 (s, 2H),
3.86 (s, 3H), 2.17 (s, 3H).
Mp: 178–180 °C. EI-MS (m/z): 500.3 (M+). 1H NMR
5.1.6.4. (2E)-N-(2-Aminophenyl)-3-(4-methoxy-3-{2-[(4-meth
oxyphenyl)amino]-2-oxoethoxy}phenyl)acrylamide
(IF13).
Mp: 190–191 °C. EI-MS (m/z): 447.1 (M+). 1H NMR (400 MHz,
(CD3)2SO) d 7.56 (d, J = 4 Hz, 2H), 7.48 (d, J = 8 Hz, 1H), 7.33 (d,
J = 4 Hz, 1H), 7.28 (s, 1H), 7.27 (d, J = 4 Hz, 1H), 7.10 (d, J = 4 Hz,
1H), 6.93 (d, J = 2 Hz, 1H), 6.91 (d, J = 4 Hz, 2H), 6.77–6.73 (m,
2H), 6.58 (d, J = 8 Hz, 1H), 4.72 (s, 2H), 3.86 (s, 3H), 3.73 (s, 3H).
5.1.6.12. (2E)-N-(2-Amino-4-methylphenyl)-3-(4-methoxy-3-{2-
[(4-methoxyphenyl)amino]-2-oxoethoxy}phenyl)acrylamide
(IF22).
Mp: 184–186 °C. EI-MS (m/z): 461.2 (M+). 1H NMR
(400 MHz, (CD3)2SO) d 7.56 (d, J = 6 Hz, 2H), 7.49 (d, J = 2 Hz, 1H),
7.27 (s, 1H), 7.26 (d, J = 4 Hz, 1H), 7.18 (d, J = 4 Hz, 1H), 7.10 (d,
J = 6 Hz, 1H), 6.74 (d, J = 6 Hz, 1H), 6.56 (s, 1H), 6.39 (d, J = 4 Hz,
1H), 4.71 (s, 2H), 3.87 (s, 3H), 3.73 (s, 3H), 2.17 (s, 3H).
5.1.6.5. (2E)-N-(2-Aminophenyl)-3-(3-{2-[(4-bromophenyl)ami-
no]-2-oxoethoxy}-4-methoxyphenyl)acrylamide
(IF14).
Mp:
217–219 °C. EI-MS (m/z): 497.1 (M+). 1H NMR (400 MHz, (CD3)2SO)