M. Bozdag et al. / Bioorg. Med. Chem. 23 (2015) 7751–7764
7759
2-(4-Chlorobenzamido)-5-nitro-N-(4-sulfamoylphenyl)benza-
mide 6d: yield 60%; silica gel TLC Rf = 0.35 (Ethyl acetate/n-hexane
50% v/v); mp 299–300 °C (decomp.); dH (400 MHz, DMSO-d6) 7.36
(2H, s, exchange with D2O, SO2NH2), 7.70 (2H, d, J 8.4), 7.90 (4H,
m), 7.97 (2H, d, J 8.4), 8.53 (1H, dd, J 2.8, 9.2), 8.63 (1H, d, J 9.2),
8.81 (1H, d, J 2.8),11.15 (1H, s, exchange with D2O, NH), 11.85
(1H, s, exchange with D2O, NH); dC (100 MHz, DMSO-d6) 121.8,
122.8, 124.3, 125.8, 127.5, 128.4, 130.0, 130.2, 133.5, 138.4,
140.5, 142.1, 142.9, 144.9, 165.2, 166.8; m/z (ESI negative) 473.0
[MꢁH]ꢁ.
2-Benzamido-N-(4-sulfamoylphenethyl)benzamide 6f: yield
47%, silica gel TLC Rf = 0.11 (Ethyl acetate/n-hexane 50% v/v); mp
258–259 °C; dH (400 MHz, DMSO-d6) 3.00 (2H, t, J 6.8), 3.62 (2H,
q, J 6.8), 7.23 (1H, t, J 8.0), 7.33 (2H, s, exchange with D2O, SO2NH2),
7.49 (2H, d, J 8.4), 7.59–7.70 (4H, m), 7.78 (3H, m),7.97 (2H, m),
8.67 (1H, d, J 8.0), 9.02 (1H, t, J 6.8, exchange with D2O, NH),
12.55 (1H, s, exchange with D2O, NH); dC (100 MHz, DMSO-d6)
35.3, 41.3, 121.2, 121.2, 123.8, 126.6, 127.9, 129.0, 129.9, 130.1,
133.0, 133.2, 135.5, 140.3, 143.1, 144.5, 165.3, 169.6; m/z (ESI
negative)422.17 [MꢁH]ꢁ.
4.1.21. Synthesis of 2-(4-fluorobenzamido)-5-nitro-N-(4-sulfa-
4.1.23. Synthesis of 2-(4-chlorobenzamido)-N-(4-sulfamoyl-
moylphenyl)benzamide 6e
phenethyl)benzamide 6g
SO2NH2
O
N
SO2NH2
SO2NH2
O
O
O2N
O
O
N
+
+
H
DMA, 160 o
C
N
NH
NH2
F
Cl
O
NH2
Cl
5a
4f
5b
4b
6g
SO2NH2
O
O2N
4(2-Aminoethyl)benzenesulfonamide 5b (0.2 g, 1.0 equiv) was
treated with 4b (1.0 equiv) in dry DMA (10 ml) according to the
general procedure c, previously reported. Reaction was quenched
with slush and obtained precipitate was filtered and washed with
Et2O (3 ꢀ 10 ml), and dried under vacuum to obtain the title com-
pound 6g as a white solid.
N
H
NH
AcOH, reflux
O
F
6e
2-(4-Chlorobenzamido)-N-(4-sulfamoylphenethyl)benzamide
6g: yield 75%, silica gel TLC Rf = 0.63 (Ethyl acetate/n-hexane 80% v/v);
mp 272–273 °C (decomp.); dH (400 MHz, DMSO-d6) 3.00 (2H, t, J
6.8), 3.61 (2H, q, J 6.8), 7.25 (1H, t, J 8.0), 7.32 (2H, s, exchange with
D2O, SO2NH2), 7.49 (2H, d, J 8.4), 7.61 (1H, t, J 8.0), 7.72 (2H, d, J
8.4), 7.80 (3H, m), 7.97 (2H, d, J 8.4), 8.64 (1H, d, J 8.0), 9.04 (1H,
t, J 6.8, exchange with D2O, NH), 12.59 (1H, s, exchange with
D2O, NH); dC (100 MHz, DMSO-d6) 35.3, 41.3, 121.3, 121.3, 124.0,
126.6, 129.0, 129.8, 130.0, 130.1, 133.2, 134.2, 137.8, 140.1,
143.1, 144.5, 164.3, 169.5; m/z (ESI negative) 456.17 [MꢁH]ꢁ.
Sulfanilamide 5a (0.1 g, 1.0 equiv) was treated with 4f
(1.0 equiv) in glacial acetic acid (3 ml) according to the general
procedure c, previously reported. Reaction was quenched with
slush and obtained precipitate was filtered and washed with
Et2O (3 ꢀ 10 ml), and dried under vacuum to obtain the title com-
pound 6e as a white solid.
2-(4-Fluorobenzamido)-5-nitro-N-(4-sulfamoylphenyl)benza-
mide 6e: yield 73%; silica gel TLC Rf = 0.35 (Ethyl acetate/n-hexane
50% v/v); mp >300 °C; dH (400 MHz, DMSO-d6) 7.36 (2H, s,
exchange with D2O, SO2NH2), 7.48 (2H, m), 7.89 (4H, m), 8.05
(2H, m), 8.55 (1H, dd, J 2.4, 9.2), 8.63 (1H, d, J 9.2), 8.81 (1H, d, J
2.4),11.15 (1H, s, exchange with D2O, NH), 11.82 (1H, s, exchange
4.1.24. Synthesis of 2-(4-fluorobenzamido)-N-(4-sulfamoyl-
phenethyl)benzamide 6h
2
with D2O, NH); dC (100 MHz, DMSO-d6) 116.9 (d, JC–F 22), 121.8,
3
122.6, 124.0, 125.8, 127.4, 128.4, 131.1 (d, JC–F 9), 140.6, 142.1,
1
142.8, 145.1, 165.1, 165.5 (d, JC–F 248), 166.8; dF (376 MHz,
SO2NH2
DMSO-d6) ꢁ107.0 (1F, s); m/z (ESI negative) 457.0 [MꢁH]ꢁ.
SO2NH2
O
O
O
4.1.22. Synthesis of 2-benzamido-N-(4-sulfamoylphenethyl)
benzamide 6f
N
+
H
N
DMA,160 o
C
NH
F
O
NH2
F
SO2NH2
5b
4c
6h
SO2NH2
O
O
O
4(2-Aminoethyl)benzenesulfonamide 5b (0.4 g, 1.0 equiv) was
treated with 4c (1.0 equiv) in dry DMA (20 ml) according to the
general procedure c, previously reported. Reaction was quenched
with slush and extracted with ethyl acetate (3 ꢀ 20 ml) and the
combined organic layers were washed with H2O (3 ꢀ 20 ml), dried
over Na2SO4, filtered and concentrated in vacuum to give the title
compound 6h as a white solid.
2-(4-Fluorobenzamido)-N-(4-sulfamoylphenethyl)benzamide
6h: yield 94%; silica gel TLC Rf = 0.37 (Ethyl acetate/n-hexane 50%
v/v); mp 242–243 °C; dH (400 MHz, DMSO-d6) 3.00 (2H, t, J 6.8),
3.61 (2H, q, J 6.8), 7.24 (1H, t, J 7.8), 7.32 (2H, s, exchange with
D2O, SO2NH2), 7.48 (4H, m), 7.60 (1H, d, J 7.8), 7.78 (3H, m), 8.00
N
+
H
DMA, 160 o
C
N
NH
O
NH2
5b
4a
6f
4(2-Aminoethyl)benzenesulfonamide 5b (0.2 g, 1.0 equiv) was
treated with 4a (1.0 equiv)in dry DMA (10 ml) according to the
general procedure c, previously reported. Reaction was quenched
with slush and obtained precipitate was filtered and washed with
Et2O (3 ꢀ 10 ml) and dried under vacuum to obtain the title com-
pound 6f as a white solid.