Z.-X. Pan et al. / European Journal of Medicinal Chemistry 80 (2014) 278e284
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4.2.8. 4h: 6,8-dibromo-2-oxo-N-o-tolyl-2H-chromene-3-
carboxamide
362.1345. Anal. calcd for C17H19N3O6: C, 56.51; H, 5.30; N, 11.63%.
Found: C, 56.30; H, 5.47; N, 11.55%.
colorless crystals, yield, 78%; mp 235e236 ꢁC; 1H NMR
(400 MHz, CDCl3)
d
10.63 (s, 1H, eNHe), 8.91 (s, 1H, chromen C4e
4.2.14. 4n: 6-nitro-2-oxo-N-o-tolyl-2H-chromene-3-carboxamide
colorless crystals, yield, 78%; mp 247e248 ꢁC; 1H NMR
H), 8.23 (d, J ¼ 8.1 Hz, 1H, ArH), 8.02 (s, 1H, ArH), 7.81 (s, 1H, ArH),
7.28 (s, 1H, ArH), 7.23 (d, J ¼ 7.3 Hz, 1H, ArH), 7.12 (d, J ¼ 7.5 Hz, 1H,
(400 MHz, DMSO)
d 10.54 (s, 1H, eNHe), 9.11 (s, 1H, chromen C4e
ArH), 2.41 (s, 3H, Me). 13C NMR (101 MHz, CDCl3)
d: 160.72, 158.31,
H), 8.67 (d, J ¼ 2.3 Hz, 1H, ArH), 8.55 (dd, J ¼ 9.2, 2.4 Hz, 1H, ArH),
8.22 (d, J ¼ 8.1 Hz, 1H, ArH), 7.61 (d, J ¼ 9.1 Hz, 1H, ArH), 7.29 (d,
J ¼ 7.7 Hz, 1H, ArH), 7.24 (s, 1H, ArH), 7.13 (t, J ¼ 7.5 Hz, 1H, ArH),
150.29, 147.45, 139.69, 135.94, 131.28, 130.71, 128.67, 126.96, 125.41,
121.94, 120.99, 120.70, 118.25, 111.44, 18.14. TOF-HRMS: m/z
[M þ Na]þ calcd for C17H11Br2NO3: 437.08; found: 459.8988. Anal.
calcd for C17H11Br2NO3: C, 46.71; H, 2.54; N, 3.20%. Found: C, 46.66;
H, 2.79; N, 3.48%.
2.42 (s, 3H, Me). 13C NMR (101 MHz, DMSO-d6)
d 160.37, 158.88,
157.28, 146.97, 144.08, 135.97, 130.52, 128.46, 126.55, 126.21, 124.86,
121.58, 118.96, 117.88, 17.58.TOF-HRMS: m/z [M þ Na]þ calcd for
C17H12N2O5: 324.29; found: 347.0678. Anal. calcd for C17H12N2O5: C,
4.2.9. 4i: 6,8-dibromo-N-(2-methoxyphenyl)-2-oxo-2H-chromene-
3-carboxamide
62.96; H, 3.73; N, 8.64%. Found: C, 63.02; H, 3.56; N, 8.43%.
colorless crystals, yield, 81%; mp 237e238 ꢁC; 1H NMR
4.2.15. 4o: N-(2-methoxyphenyl)-6-nitro-2-oxo-2H-chromene-3-
carboxamide
(400 MHz, CDCl3) d 11.18 (s, 1H, eNHe), 8.87 (s,1H, chromen C4eH),
8.51 (d, J ¼ 8.0 Hz, 1H, ArH), 8.01 (s, 1H, ArH), 7.80 (s, 1H, ArH), 7.13
(t, J ¼ 7.8 Hz, 1H, ArH), 7.01 (t, J ¼ 7.8 Hz, 1H, ArH), 6.94 (d, J ¼ 8.1 Hz,
1H, ArH), 3.97 (s, 3H, OMe). TOF-HRMS: m/z [M þ H]þ calcd for
colorless crystals, yield, 80%; mp 288e289 ꢁC; 1H NMR
(400 MHz, DMSO)
d 11.09 (s, 1H, eNHe), 9.06 (s, 1H, chromen C4e
H), 8.65 (d, J ¼ 2.4 Hz, 1H, ArH), 8.52 (d, J ¼ 8.2 Hz, 2H, ArH), 7.58 (d,
J ¼ 9.1 Hz,1H, ArH), 7.14 (t, J ¼ 7.8 Hz,1H, ArH), 7.02 (t, J ¼ 7.8 Hz,1H,
ArH), 6.95 (d, J ¼ 8.1 Hz,1H, ArH), 3.98 (s, 3H, OMe). TOF-HRMS: m/z
[M þ H]þ calcd for C17H12N2O6: 340.29; found: 341.0754. Anal.
calcd for C17H12N2O6: C, 60.00; H, 3.55; N, 8.23%. Found: C, 60.21; H,
3.70; N, 8.21%.
C
C
17H11Br2NO4: 453.08; found: 451.9141. Anal. calcd for
17H11Br2NO4: C, 45.07; H, 2.45; N, 3.09%. Found: C, 44.98; H, 2.51;
N, 3.32%.
4.2.10. 4j: 6,8-dibromo-2-oxo-N-m-tolyl-2H-chromene-3-
carboxamide
colorless crystals, yield, 85%; mp 253e254 ꢁC; 1H NMR
4.2.16. 4p: 6-nitro-2-oxo-N-m-tolyl-2H-chromene-3-carboxamide
colorless crystals, yield, 83%; mp 253e254 ꢁC; 1H NMR
(400 MHz, CDCl3)
d 10.59 (s, 1H, eNHe), 8.89 (s, 1H, chromen C4e
H), 8.02 (s, 1H, ArH), 7.81 (s, 1H, ArH), 7.54 (s, 2H, ArH), 7.28 (d,
(400 MHz, DMSO) d 10.53 (s, 1H, eNHe), 9.08 (s, 1H, chromen C4e
J ¼ 7.8 Hz, 1H, ArH), 7.00 (d, J ¼ 7.6 Hz, 1H, ArH), 2.39 (s, 3H, Me). 13
C
H), 8.66 (d, J ¼ 2.5 Hz, 1H, ArH), 8.54 (dd, J ¼ 9.1, 2.5 Hz, 1H, ArH),
7.57 (dd, J ¼ 23.2, 9.1 Hz, 3H, ArH), 7.29 (d, J ¼ 7.8 Hz, 1H, ArH), 7.01
(d, J ¼ 7.6 Hz, 1H, ArH), 2.39 (s, 3H, Me). 13C NMR (101 MHz, DMSO-
NMR (101 MHz, CDCl3) d: 160.47, 158.32, 150.35, 147.34, 139.68,
139.23, 137.35, 131.27, 129.10, 126.16, 121.37, 121.00, 120.60, 118.21,
117.89, 111.42, 21.66. TOF-HRMS: m/z [M
Na]þ calcd for
17H11Br2NO3: 437.08; found: 459.8998. Anal. calcd for
17H11Br2NO3: C, 46.71; H, 2.54; N, 3.20%. Found: C, 46.89; H, 2.59;
þ
d6) d: 159.38, 159.35, 157.26, 145.87, 144.01, 138.41, 137.77, 128.93,
C
C
128.26, 125.99, 125.20, 122.44, 120.36, 118.86, 117.87, 117.05, 21.13.
TOF-HRMS: m/z [M þ H]þ calcd for C17H12N2O5: 324.29; found:
325.0826. Anal. calcd for C17H12N2O5: C, 62.96; H, 3.73; N, 8.64%.
Found: C, 62.84; H, 3.77; N, 8.80%.
N, 3.11%.
4.2.11. 4k: 6,8-dibromo-2-oxo-N-(3-(trifluoromethyl)phenyl)-2H-
chromene-3-carboxamide
4.2.17. 4q: 6-nitro-2-oxo-N-(3-(trifluoromethyl)phenyl)-2H-
chromene-3-carboxamide
colorless crystals, yield, 80%; mp 198e199 ꢁC; 1H NMR
(400 MHz, CDCl3)
H), 8.06 (d, J ¼ 16.8 Hz, 2H, ArH), 7.93e7.77 (m, 2H, ArH), 7.62e7.37
(m, 2H, ArH). 13C NMR (101 MHz, DMSO-d6)
: 160.51, 158.74,
d
10.80 (s, 1H, eNHe), 8.90 (s, 1H, chromen C4e
colorless crystals, yield, 77%; mp 238e239 ꢁC; 1H NMR
(400 MHz, CDCl3)
d 10.73 (s, 1H, eNHe), 9.10 (s, 1H, chromen C4e
d
H), 8.68 (d, J ¼ 2.6 Hz, 1H, ArH), 8.57 (dd, J ¼ 9.1, 2.6 Hz, 1H, ArH),
8.07 (s, 1H, ArH), 7.90 (d, J ¼ 8.0 Hz, 1H, ArH), 7.62 (d, J ¼ 9.1 Hz, 1H,
ArH), 7.52 (t, J ¼ 8.0 Hz, 1H, ArH), 7.46 (d, J ¼ 7.6 Hz, 1H, ArH). TOF-
HRMS: m/z [M þ Na]þ calcd for C17H9F3N2O5: 378.26; found:
401.0346. Anal. calcd for C17H9F3N2O5: C, 53.98; H, 2.40; N, 7.41%.
Found: C, 54.05; H, 2.62; N, 7.33%.
150.41, 147.91, 140.03, 137.94, 131.87, 131.87, 131.55, 129.80, 123.76,
121.86, 120.86, 120.05, 118.39, 117.57, 111.52. TOF-HRMS: m/z
[M þ Na]þ calcd for C17H8Br2F3NO3: 491.05; found: 512.8715. Anal.
calcd for C17H8Br2F3NO3: C, 41.58; H, 1.64; N, 2.85%. Found: C, 41.33;
H, 1.80; N, 3.02%.
4.2.12. 4l: 6,8-dibromo-2-oxo-N,N-diphenyl-2H-chromene-3-
carboxamide
4.2.18. 4r: N,N-dihexyl-2-oxo-2H-chromene-3-carboxamide
colorless crystals, yield, 75%; mp 197e198 ꢁC; 1H NMR
(400 MHz, CDCl3) d 7.77 (s, 1H, chromen C4eH), 7.61e7.49 (m, 2H,
colorless crystals, yield, 69%; mp 241e242 ꢁC; 1H NMR
(400 MHz, DMSO)
d
8.34 (s, 1H, chromen C4eH), 8.17 (s, 1H, ArH),
ArH), 7.39e7.28 (m, 2H, ArH), 3.47 (s, 2H), 3.24e3.15 (m, 2H), 1.72e
1.61 (m, 2H), 1.55 (s, 2H), 1.35 (s, 6H), 1.23e1.14 (m, 6H), 0.90 (s, 3H),
7.99 (s, 1H, ArH), 7.33 (s, 10H, ArH). TOF-HRMS: m/z [M þ H]þ calcd
for
C
22H13Br2NO3: 499.05; found: 499.9308. Anal. calcd for
0.79 (t, J ¼ 6.6 Hz, 3H). 13C NMR (101 MHz, CDCl3)
d: 157.33, 156.70,
C
22H13Br2NO3: C, 52.94; H, 2.63; N, 2.81%. Found: C, 53.14; H, 2.45;
144.43, 139.85, 128.81, 127.18, 124.19, 118.56, 118.21, 48.94, 45.12,
31.70, 31.46, 28.66, 27.33, 26.70, 26.45, 22.74, 22.60, 14.19, 14.06.
TOF-HRMS: m/z [M þ H]þ calcd for C22H31NO3: 357.49; found:
358.2381. Anal. calcd for: C22H31NO3: C, 73.91; H, 8.74; N, 3.92%.
Found: C, 74.02; H, 8.55; N, 4.01%.
N, 3.06%.
4.2.13. 4m: N-(3-morpholinopropyl)-6-nitro-2-oxo-2H-chromene-
3-carboxamide
colorless crystals, yield, 72%; mp 180e181 ꢁC; 1H NMR
(400 MHz, DMSO)
d
9.00 (s, 2H, eNHe and ArH), 8.75 (s, 1H,
4.2.19. 4s: 6,8-dibromo-N-tert-butyl-2-oxo-2H-chromene-3-
carboxamide
chromen C4eH), 8.55e8.48 (m, 1H, ArH), 7.73 (d, J ¼ 9.1 Hz, 1H,
ArH), 3.59 (s, 4H), 3.42e3.36 (m, 2H), 2.35 (s, 6H), 1.78e1.61 (m,
2H). TOF-HRMS: m/z [M þ H]þ calcd for C17H19N3O6: 361.35; found:
colorless crystals, yield, 82%; mp 184e185 ꢁC; 1H NMR
(400 MHz, CDCl3) d 8.75 (s, 1H, eNHe), 8.61 (s, 1H, chromen C4eH),