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Z. Brzozowski et al. / European Journal of Medicinal Chemistry 56 (2012) 282e291
4.1.6. General procedure for the preparation of 1-sustituted 1,4-dihy-
dro-4-oxo-3-pyridinesulfonamides (21e31)
(d, J ¼ 8.3 Hz,1H, H-6, pyrid.), 8.38 (d, Jmeta ¼ 2.2 Hz,1H, H-2, pyrid.),
10.79 (s, 1H, NH) ppm. Anal. (C15H15 N3O6S) C, H, N.
A
mixture of 4-methoxy-3-pyridinesulfonamide 1 (0.76 g,
4 mmol) and the corresponding chloride derivatives ReCOeCH2Cl
(4.3 mmol) in dry acetonitrile (20 ml) was stirred at room temper-
ature for 30 h, followed at reflux for 55 h. After cooling to room
temperature and standing overnight the precipitate was filtered off,
washed with acetonitrile (4 ꢃ 1 ml) and dried. In this manner the
following 1,4-dihydro-3-pyridinesulfonamides were obtained.
4.1.6.6. 1,4-Dihydro-1-[(4-sulfamoylphenylcarbamoyl)methyl]-4-oxo-
3-pyridinesulfonamide (26). Starting from 4-(chloracetylamino)
benzenesulfonamide (1.07 g), the title compound 26 was obtained
(1.2 g, 77.6%): m.p. 310e311 ꢀC dec; IR (KBr) 3365, 3315, 3300, 3260,
3225 (NHCO, SO2NH2), 1695, 1650 (C]O), 1365, 1340, 1185, 1168
(SO2) cmꢁ1 1H NMR (DMSO-d6)
; d 5.03 (s, 2H, CH2), 6.38 (d,
J ¼ 7.4 Hz, 1H, H-5, pyrid.), 6.84 (s, 2H, Py-SO2NH2), 7.29 (s, 3H,
4.1.6.1. 1,4-Dihydro-1-[(2,6-dimethylphenylcarbamoyl)methyl]-4-oxo-
3-pyridinesulfonamide (21). Starting from N-chloroacetyl-2,6-
dimethylaniline (0.85 g), the title compound 21 was obtained
(1.0 g, 74%): m.p. 328e329 ꢀC dec; IR (KBr) 3325, 3270, 3235
(NHC]O, SO2NH2), 1700, 1670, 1650 (C]O), 1335, 1160 (SO2)
PhSO2NH2 and H-6, pyrid.), 7.72e7.83 (m, 4H, Ph), 8.39 (s, 1H, H-2,
pyrid.), 10.79 (s, 1H, NH) ppm; 13C NMR (DMSO-d6)
d 59.49, 119.38,
129.66, 142.06, 142.92, 143.99, 164.48, 164.99, 165.67, 171.67,
172.74 ppm. Anal. (C13H14 N4O6S2) C, H, N.
cmꢁ1; 1H NMR (DMSO-d6)
d
2.16 (s, 6H, 2 ꢃ CH3), 5.06 (s, 2H, CH2),
4.1.6.7. 1-[(2-Chlorobenzenesulfonamidocarbonyl)methyl]-1,4-dihy-
dro-4-oxo-3-pyridinesulfonamide (27). Starting from 2-chloro-N-
chlorocetylbenzenesulfonamide 18a (1.15 g), the title compound 27
was obtained (1.3 g, 80%): m.p. 271e272 ꢀC dec; IR (KBr) 3395, 3235
(SO2NH2 and SO2NH), 1725, 1645 (C]O) 1365, 1340, 1330, 1160,
6.38 (d, J ¼ 7.6 Hz, 1H, H-5, pyrid.), 6.84 (s, 2H, SO2NH2), 7.07 (s, 3H,
H-3, H-4 and H-5, Ph), 7.79 (dd, Jortho ¼ 7.6 Hz, Jmeta ¼ 2.2 Hz, 1H,
H-6, pyrid.), 8.40 (d, Jmeta ¼ 2.2 Hz, 1H, H-2, pyrid.), 9.69 (s, 1H, NH)
ppm; 13C NMR (DMSO-d6)
d 18.39, 57.43, 119.65, 126.97, 128.00,
129.83, 134.48, 135.34, 142.80, 143.72, 165,13, 172.66 ppm. Anal.
(C15H17N3O4S) C, H, N.
1155 (SO2) cmꢁ1 1H NMR (DMSO-d6)
; d 4.95 (s, 2H, CH2), 6.30 (d,
J ¼ 7.6 Hz, 1H, H-5, pyrid.), 6.77 (br s, 3H, SO2NH2 and SO2NH), 7.58
(dd, Jortho ¼ 7.6 Hz, Jmeta ¼ 2.2 Hz, 1H, H-6, pyrid.), 7.67e7.72 (m, 3H,
H-3, H-4 and H-5, Ph), 8.09 (d, J ¼ 7.5 Hz, H-6, Ph), 8.33 (d,
4.1.6.2. 1-[(4-Chlorophenylcarbamoyl)methyl]-1,4-dihydro-4-oxo-3-
pyridinesulfonamide
(22). Starting
from
N-chlorocetyl-4-
Jmeta ¼ 2.2 Hz, 1H, H-2, pyrid.) ppm; 13C NMR (DMSO-d6)
d 57.50,
chloroaniline (0.88 g), the title compound 22 was obtained
119.54, 127.98, 129.89, 131.27, 132.13, 132.32, 135.62, 136.52, 142.87,
143.67, 166.81, 172.59 ppm. Anal. (C13H12 ClN3O6S2) C, H, N.
(1.05 g, 76.8%): m.p. 290e291 ꢀC dec; IR (KBr) 3365, 3380, 3270
(NHC]O, SO2NH2), 1700, 1645 (C]O), 1330, 1160 (SO2) cmꢁ1 1H
;
NMR (DMSO-d6)
d
4.99 (s, 2H, CH2), 6.37 (d, J ¼ 7.6 Hz, 1H, H-5,
4.1.6.8. 1-[(4-Chlorobenzenesulfonamidocarbonyl)methyl]-1,4-dihy-
dro-4-oxo-3-pyridinesulfonamide (28). Starting from 4-chloro-N-
chlorocetylbenzenesulfomide 18b (1.15 g), the title compound 28
was obtained (1.25 g, 77%): m.p. 285e286 ꢀC dec; IR (KBr) 3405,
3185 (SO2NH2 and SO2NH),1740,1645 (C]O),1345,1175,1150 (SO2)
pyrid.), 6.84 (s, 2H, SO2NH2), 7.39 (d, J ¼ 8.9 Hz, 2H, H-2, and H-6,
Ph), 7.77 (d, J ¼ 8.9 Hz, 2H, H-3 and H-5, Ph), 7.81 (dd, Jortho ¼ 7.6 Hz,
Jmeta ¼ 2.2 Hz, 1H, H-6, pyrid.), 8.37 (d, Jmeta ¼ 2.2 Hz, 1H, H-2,
pyrid.), 10.52 (s, 1H, NH) ppm; 13C NMR (DMSO-d6)
d 57.97, 119.52,
120.90, 127.48, 129.13, 129.84, 137.75, 142.94, 143.88, 165.72,
172.69 ppm. Anal. (C12H12 ClN3O4S) C, H, N.
cmꢁ1; 1H NMR (DMSO-d6)
d
4.88 (s, 2H, CH2), 6.31(d, J ¼ 7.5 Hz, 1H,
H-5, pyrid.), 6.81 (br s, 3H, SO2NH2 and SO2NH), 7.65 (dd,
Jortho ¼ 7.5 Hz, Jmeta ¼ 2.1 Hz, 1H, H-6, pyrid.), 7.73 (d, J ¼ 8.5 Hz, 2H,
4-ClPh), 7.94 (d, J ¼ 8.5 Hz, 2H, 4-ClPh), 8.30 (d, Jmeta ¼ 2.1 Hz,1H, H-
4.1.6.3. 1-[(4-Chloro-3-nitrophenylcarbomoyl)methyl]-1,4-dihydro-4-
oxo-3-pyridinesulfonamide (23). Starting from N-chloroacetyl-4-
chloro-3-nitroaniline (1.07 g), the title compound 23 was obtained
(1.3 g, 84%): m.p. 284e285 ꢀC dec; IR (KBr) 3360, 2265, 3175 (NHC]
2, pyrid.) ppm; 13C NMR (DMSO-d6)
d 57.55, 119.53, 129.67, 129.91,
138.14, 139.18, 142.82, 143.68, 166.11, 166.89, 172.61 ppm. Anal.
(C13H12 ClN3O6S2) C, H, N.
O, SO2NH2), 1715, 1651 (C]O), 1335, 1165 (SO2) cmꢁ1 1H NMR
;
(DMSO-d6)
d
5.02 (s, 2H, CH2), 6.37 (d, J ¼ 7.8 Hz,1H, H-5, pyrid.), 6.82
4.1.6.9. 1,4-Dihydro-1-[(4-nitrobenzenesulfonamidocarbonyl)methyl]-
4-oxo-3-pyridinesulfonamide (29). Starting from N-chloracetyl-4-
nitrobenzenesulfonamide 18c (1.2 g), the title compound 29 was
obtained (1.3 g, 78%): m.p. 275e276 ꢀC dec; IR (KBr) 3370, 3270
(SO2NH2 and SO2NH), 1735, 1650 (C]O), 1365, 1350, 1170,1160 (SO2)
(s, 2H, SO2NH2), 7.73e7.79 (m, 3H, arom.) 8.37 (s,1H, H-2, Ph), 8.39 (s,
1H, H-2, pyrid.),10.94 (s,1H, NH) ppm. Anal. (C13H11 ClN4O6S) C, H, N.
4.1.6.4. 1,4-Dihydro-1-[(3-nitrophenylcarbamoyl)methyl]-4-oxo-3-
pyridinesulfonamide
nitroaniline (0.8 g), the title compound 24 was obtained (1.0 g,
71%): m.p. 267e269 ꢀC dec; IR (KBr) 3360, 3325, 3225 (NHC]O,
SO2NH2),1705, 1655 (C]O), 1350, 1160 (SO2) cmꢁ1; 1H NMR (DMSO-
(24). Starting
from
N-chloracetyl-3-
cmꢁ1; 1H NMR (DMSO-d6)
d
4.90 (s, 2H, CH2), 6.32 (d, J ¼ 7.6 Hz, 1H,
H-5, pyrid.), 6.79 (br s, 3H, SO2NH2 and SO2NH), 7.67 (dd,
Jortho ¼ 7.6 Hz, Jmeta ¼ 2.1 Hz, 1H, H-6, pyrid.), 8.18 (d, J ¼ 8.9 Hz, 2H,
4-O2NPh), 8.29 (d, Jmeta ¼ 2.1 Hz, 1H, H-2, pyrid.), 8.45 (d, J ¼ 8.9 Hz,
2H, 4-O2NPh) ppm. Anal. (C13H12N4O8S2) C, H, N.
d6)
d
5.05 (s, 2H, CH2), 6.38 (d, J ¼ 7.6 Hz, 1H, H-5, pyrid.), 6.85 (s, 2H,
SO2NH2), 7.64 (t, J ¼ 8.1 Hz, 1H, H-5, Ph), 7.81 (dd, Jortho ¼ 7.6 Hz,
Jmeta ¼ 2.1 Hz, 1H, H-6, pyrid.), 7.87e7.97 (m, 2H, H-4 and H-5, Ph),
8.40 (d, Jortho ¼ 2.1 Hz,1H, H-2, pyrid.), 8.60 (t, Jmeta ¼ 2.0 Hz,1H, H-2,
Ph), 10.91 (s, 1H, NH), ppm. Anal. (C13H12N4O6S) C, H, N.
4.1.6.10. 1,4-Dihydro-1-[(p-toluenesulfonylhydrazinocarbonyl)methyl]-
4-oxo-3-pyridinesulfonamide (30). Starting from N0-(chloroacetyl)-p-
toluenesulfonylhydrazide 19 (1.12 g), the title compound 30 was
obtained (1.17 g, 73,9%): m.p. 270e271 ꢀC dec; IR (KBr) 3365, 3300,
3245 (HNeNH), 1705, 1685, 1650 (C]O), 1340, 1160 (SO2) cmꢁ1; 1H
4.1.6.5. 1,4-Dihydro-1-[(2-methoxcarbonylphenylcarbamoyl)methyl]-
4-oxo-3-pyridinesulfonamide (25). Starting from methyl N-chlor-
acetylanthranilate (0.98 g), the title compound 25 was obtained
(1.2 g, 82.1%): m.p. 254e255 ꢀC dec; IR (KBr) 3330, 3280, 3175
NMR (DMSO-d6)
d 2.36 (s, 3H, CH3), 4.73 (s, 2H, CH2), 6.31 (d,
J ¼ 7.6 Hz,1H, H-5, pyrid.), 6.82 (s, 2H, SO2NH2), 7.35 (d, J ¼ 8.1 Hz, 2H,
H-3 and H-5, Ph), 7.54 (dd, Jortho ¼ 7.6 Hz, Jmeta ¼ 2.2 Hz, 1H, H-6,
pyrid.), 7.69 (d, J ¼ 8.1 Hz, 2H, H-2 and H-6, Ph), 8.15 (d, Jmeta ¼ 2.2 Hz,
1H, H-2, pyrid.), 9.95 (s, 1H, SO2NHeN), 10.48 (s, 1H, COeNHeN)
(NHC]O, SO2NH2), 1700, 1690, 1650 (C]O), 1335, 1170 (SO2) cmꢁ1
;
1H NMR (DMSO-d6)
d 3.86 (s, 3H, CO2CH3), 5.11 (s, 2H, CH2), 6.40 (d,
J ¼ 7.6 Hz, 1H, H-5, pyrid.), 6.85 (s, 2H, SO2NH2), 7.22e7.30 (m, 1H,
Ph), 7.59e7.68 (m,1H, Ph), 7.80 (dd, Jortho ¼ 7.6 Hz, Jmeta ¼ 2.2 Hz,1H,
H-6, pyrid.), 7.92 (dd, Jortho ¼ 7.8 Hz, Jmeta ¼ 1.4 Hz, 1H, H-3, Ph), 8.11
ppm; 13C NMR (DMSO-d6)
d 21.31, 55.89, 119.60, 127.90, 129.74,
129.88, 135.73, 142.51, 143.31, 143.89, 165.63, 172.58 ppm. Anal.
(C14H16N4O6S2) C, H, N.