C.-T. Chen et al. / European Journal of Medicinal Chemistry 46 (2011) 6046e6056
6053
IR (KBr)
NMR (400 MHz, DMSO-d6)
(s, 2H), 7.15 (d, J ¼ 4.00 Hz, 1H), 7.65 (s, 1H), 7.77 (d, J ¼ 3.52 Hz,
1H), 8.21 (s, 1H), 12.82 (s, 1H); 13C NMR (50 MHz, CDCl3)
(ppm):
18.65, 28.61, 101.25, 102.12, 109.69, 115.02, 129.04, 131.12, 139.78,
142.43, 144.10, 153.08, 154.31, 161.99, 200.86; MS (EI, 70 eV) m/z:
337.0 (Mþ).
n
(cmꢄ1): 1658 (C]O, acetyl), 1637 (C]O, amide); 1H
(ppm): 2.59 (s, 3H), 2.62 (s, 3H), 6.17
132.67, 143.99, 154.30, 155.09, 161.13, 203.30; MS (EI, 70 eV) m/z:
d
337.0 (Mþ).
d
5.2.2.11. N-(6-Acetylbenzo[d][1,3]dioxol-5-yl)selenophene-3-carbox-
amide (6a). Yield: 63.0%; white solid; mp: 192e193 ꢀC; IR (KBr)
n
(cmꢄ1): 1664 (C]O, acetyl), 1635 (C]O, amide); 1H NMR
(400 MHz, DMSO-d6) (ppm): 2.63 (s, 3H), 6.17 (s, 2H), 7.66 (s, 1H),
7.81 (d, J ¼ 5.09 Hz, 1H), 8.30 (s, 1H), 8.33 (dd, J ¼ 5.28, 2.15 Hz, 1H),
8.96 (s, 1H), 12.74 (s, 1H); 13C NMR (50 MHz, CDCl3)
(ppm): 28.65,
d
5.2.2.5. N-(6-Acetylbenzo[d][1,3]dioxol-5-yl)-5-methylthiophene-2-
d
carboxamide (3e). Yield: 85.6%; yellow solid; mp: 210e211 ꢀC; IR
101.44, 102.13, 109.74, 115.22, 128.99, 131.39, 135.72, 139.77, 140.77,
(KBr)
(400 MHz, DMSO-d6)
6.99 (d, J ¼ 3.52 Hz, 1H), 7.60 (d, J ¼ 3.91 Hz, 1H), 7.65 (s, 1H), 8.22 (s,
1H), 12.83 (s, 1H); 13C NMR (50 MHz, CDCl3)
(ppm): 15.78, 28.58,
n
(cmꢄ1): 1664 (C]O, acetyl), 1639 (C]O, amide); 1H NMR
142.51, 153.09, 162.11, 200.89; MS (EI, 70 eV) m/z: 337.3 (Mþ).
d
(ppm): 2.53 (s., 3H), 2.63 (s, 3H), 6.17 (s, 2H),
5.2.2.12. N-(6-Acetylbenzo[d][1,3]dioxol-5-yl)thiophene-3-carbox-
d
amide (6b). Yield: 80.8%; white solid; mp: 202e203 ꢀC; IR (KBr)
n
101.32, 102.11, 109.67, 115.01, 126.46, 129.36, 137.44, 139.74, 142.43,
(cmꢄ1): 1668 (C]O, acetyl), 1637 (C]O, amide); 1H NMR
(400 MHz, DMSO-d6) (ppm): 2.63 (s, 3H), 6.17 (s, 2H), 7.55 (d,
146.77, 153.06, 160.77, 200.86; MS (EI, 70 eV) m/z: 303.4 (Mþ).
d
J ¼ 4.69 Hz, 1H), 7.66 (s, 1H), 7.75 (dd, J ¼ 5.09, 2.74 Hz, 1H), 8.27 (d,
5.2.2.6. N-(6-Acetylbenzo[d][1,3]dioxol-5-yl)-5-methylfuran-2-car-
J ¼ 1.96 Hz,1H), 8.29 (s,1H),12.74 (s, 1H); 13C NMR (50 MHz, DMSO-
boxamide (3f). Yield: 49.8%; white solid; mp: 154e156 ꢀC; IR (KBr)
d6) d (ppm): 29.33, 100.70, 102.90, 111.18, 116.20, 126.30, 128.69,
n
(cmꢄ1): 3468(NeH), 1672 (C]O, acetyl), 1637 (C]O, amide); 1H
130.73, 138.07, 138.49, 142.96, 152.68, 161.15, 202.13; MS (EI, 70 eV)
NMR (400 MHz, DMSO-d6)
2H), 6.38 (d, J ¼ 3.13 Hz, 1H), 7.16 (d, J ¼ 3.52 Hz, 1H), 7.65 (s, 1H),
8.30 (s, 1H),12.84 (s, 1H); 13C NMR (50 MHz, CDCl3)
(ppm): 13.98,
d
(ppm): 2.41 (s, 3H), 2.62 (s, 3H), 6.16 (s,
m/z: 289.0 (Mþ).
d
5.2.2.13. N-(6-Acetylbenzo[d][1,3]dioxol-5-yl)furan-3-carboxamide
28.54, 101.61, 102.09, 108.76, 109.67, 115.46, 116.60, 139.14, 142.51,
146.55, 152.82, 155.76, 157.19, 200.43; MS (EI, 70 eV) m/z: 287.4
(Mþ).
(6c). Yield: 13.2%; yellow solid; mp: 171e172 ꢀC; IR (KBr) (cmꢄ1):
n
3462 (NeH), 1670 (C]O, acetyl), 1639 (C]O, amide); 1H NMR
(400 MHz, DMSO-d6) (ppm): 2.61 (s, 3H), 6.16 (s, 2H), 6.86 (s, 1H),
7.64 (s, 1H), 7.87 (s, 1H), 8.22 (s, 1H), 8.35 (s, 1H), 12.52 (s, 1H); 13C
NMR (50 MHz, DMSO-d6) (ppm): 29.28, 100.74, 102.89, 108.53,
d
5.2.2.7. N-(2-Acetyl-3,4-dimethoxyphenyl)selenophene-2-carbox-
d
amide (3g). Yield: 61.2%; brown needle crystal; mp: 109e110 ꢀC; IR
111.09, 116.16, 123.67, 138.26, 142.98, 145.56, 146.59, 152.62, 160.86,
(KBr)
n
(cmꢄ1): 3439 (NeH), 3307 (OCH3), 1685 (C]O, acetyl), 1643
202.03; MS (EI, 70 eV) m/z: 273.1 (Mþ).
(C]O, amide); 1H NMR (400 MHz, DMSO-d6)
d
(ppm): 2.46 (s, 3H),
3.80 (s, 3H), 3.86 (s, 3H), 7.08e7.19 (m, 2H), 7.44 (dd, J ¼ 5.28,
5.2.2.14. N-(2-Acetyl-3,4-dimethoxyphenyl)selenophene-3-carbox-
4.11 Hz, 1H), 8.06 (d, J ¼ 3.52 Hz, 1H), 8.46 (d, J ¼ 5.09 Hz, 1H), 10.13
amide (6d). Yield: 75.0%; brown cubi crystal; mp: 141e143 ꢀC; IR
(s, 1H); 13C NMR (50 MHz, CDCl3)
d
(ppm): 33.21, 56.28, 61.54,
(KBr)
n
(cmꢄ1): 3325 (OCH3), 1685 (C]O, acetyl), 1656 (C]O,
117.08, 117.36, 122.21, 130.04, 130.45, 131.04, 136.99, 146.85, 148.74,
amide); 1H NMR (400 MHz, DMSO-d6)
d (ppm): 2.47 (s, 3H), 3.80 (s,
149.62, 161.30, 204.68; MS (EI, 70 eV) m/z: 353.1 (Mþ).
3H), 3.85 (s, 3H), 7.07e7.20 (m, 2H), 7.77 (d, J ¼ 5.48 Hz, 1H), 8.22
(dd, J ¼ 5.48, 2.35 Hz, 1H), 8.92 (s, 1H), 9.96 (s, 1H); 13C NMR
5.2.2.8. N-(2-Acetyl-4-methoxyphenyl)selenophene-2-carboxamide
(50 MHz, CDCl3) d (ppm): 33.18, 56.29, 61.54, 117.03, 117.50, 122.44,
(3h). Yield: 78.4%; yellow solid; mp: 143e144 ꢀC; IR (KBr)
n
(cmꢄ1):
128.81, 131.11, 131.47, 135.06, 140.60, 148.70, 149.53, 161.58, 204.67;
3466 (NeH), 1653 (C]O, acetyl), 1637 (C]O, amide); 1H NMR
(400 MHz, DMSO-d6) (ppm): 2.64 (s, 3H), 3.82 (s, 3H), 7.25 (dd,
MS (EI, 70 eV) m/z: 353.1 (Mþ).
d
J ¼ 9.00, 2.74 Hz, 1H), 7.43e7.53 (m, 2H), 7.97 (d, J ¼ 3.52 Hz, 1H),
5.2.2.15. N-(2-Acetyl-4-methoxyphenyl)selenophene-3-carboxamide
8.25 (d, J ¼ 9.00 Hz, 1H), 8.51 (d, J ¼ 5.48 Hz, 1H), 11.71 (s, 1H); 13C
(6e). Yield: 52.1%; yellow solid; mp: 96e97 ꢀC; IR (KBr)
n
(cmꢄ1):
NMR (50 MHz, DMSO-d6)
d
(ppm): 29.30, 56.03, 116.41, 120.24,
3439 (NeH), 1672 (C]O, acetyl), 1645 (C]O, amide); 1H NMR
(400 MHz, DMSO-d6) (ppm): 2.67 (s, 3H), 3.84 (s, 3H), 7.28 (dd,
123.18, 126.72, 131.10, 131.22, 132.37, 139.11, 146.76, 155.27, 161.26,
d
203.23; MS (EI, 70 eV) m/z:323.0 (Mþ).
J ¼ 9.00, 2.74 Hz, 1H), 7.51 (d, J ¼ 2.74 Hz, 1H), 7.81 (dd, J ¼ 5.48,
1.17 Hz, 1H), 8.31 (dd, J ¼ 5.48, 2.35 Hz, 1H), 8.35 (d, J ¼ 9.00 Hz, 1H),
5.2.2.9. N-(2-Acetyl-3,4-dimethoxyphenyl)-5-methylselenophene-2-
8.95 (s, 1H), 11.63 (s, 1H); 13C NMR (50 MHz, CDCl3)
d (ppm): 28.62,
carboxamide (3i). Yield: 43.8%; yellow needle crystal; mp:
55.73, 116.93, 120.40, 122.15, 122.81, 128.94, 131.36, 134.92, 135.27,
116e117 ꢀC; IR (KBr)
n
(cmꢄ1): 3350 (NeH), 1666 (C]O, acetyl),
140.91, 154.27, 161.83, 202.90; MS (EI, 70 eV) m/z: 323.3 (Mþ).
1649 (C]O, amide); 1H NMR (400 MHz, DMSO-d6)
d (ppm): 2.43 (s,
3H), 2.54 (s, 3H), 3.78 (s, 3H), 3.84 (s, 3H), 7.02e7.17 (m, 3H), 7.83 (d,
5.2.3. General procedure for the synthesis of quinolin-4-ones
(4aeg, 4iej, 4l, 7aed and 7f) [7]
J ¼ 3.91 Hz, 1H), 9.99 (s, 1H); 13C NMR (50 MHz, CDCl3)
d (ppm):
18.63, 33.19, 56.29, 61.53, 117.10, 117.32, 122.17, 128.88, 130.47,
131.20, 143.90, 148.59, 149.56, 153.89, 161.37, 204.65; MS (EI, 70 eV)
m/z: 367.1 (Mþ).
Compound 3aej or 6aee (1 equiv) was added into 100 mL 1,4-
dioxane at room temperature, and then NaOH powder (5 equiv)
was added. The reaction mixtures were stirred for 16 h under
reflux. The mixtures were evaporated, added into 10% NH4Cl aq
solution (100 mL), and stirred for 30 min. The residues were
washed with water to neutral pH, and then, recrystallization gave
the pure compound.
5.2.2.10. N-(2-Acetyl-4-methoxyphenyl)-5-methylselenophene-2-
carboxamide (3j). Yield: 84.8%; yellow solid; mp: 160e161 ꢀC; IR
(KBr)
n
(cmꢄ1): 3458 (NeH), 1660 (C]O, acetyl), 1635 (C]O,
amide); 1H NMR (400 MHz, DMSO-d6)
d
(ppm): 2.58 (s, 3H), 2.66 (s,
3H), 3.84 (s, 3H), 7.14 (d, J ¼ 3.13 Hz, 1H), 7.27 (dd, J ¼ 9.00, 2.74 Hz,
5.2.3.1. 6,7-Methylenedioxy-2-(selenophen-2-yl)quinolin-4-one
1H), 7.50 (d, J ¼ 2.74 Hz, 1H), 7.79 (d, J ¼ 3.91 Hz, 1H), 8.29 (d,
(4a). Yield: 58.6%; yellow solid; mp: >350 ꢀC; IR (KBr)
n
(cmꢄ1): 3396
(ppm): 6.17 (s,
2H), 7.19 (s, 2H), 7.36 (s, 1H), 7.44 (br. s, 1H), 7.84 (br. s, 1H), 8.23 (br. s,
J ¼ 9.00 Hz,1H),11.70 (s,1H); 13C NMR (50 MHz, DMSO-d6)
d
(ppm):
(NeH), 1637 (C]O); 1H NMR (400 MHz, DMSO-d6)
d
18.70, 29.30, 56.03, 116.47, 120.36, 122.39, 126.25, 129.87, 131.21,