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M. J. Tozer et al. / Bioorg. Med. Chem. 10 (2002) 425–432
Hz), 1.63 (2H, quin., J=7.5 Hz), 1.46 (2H, quin., J=7.2
Hz).
Found: C 49.84, H 5.26, N 9.08%; C19H24ClN3O6S
requires: C 49.83, H 5.28, N 9.18%.
5-(1H-Imidazol-4-yl)pentane-1-sulfonic acid 4-chloroben-
zylamide (16). A solution of compound (13, m=3) (146
mg, 0.25 mmol) in trifluoroacetic acid (3.5 mL) was left
to stand overnight under ambient conditions. The sol-
vent was evaporated and the residue purified by flash
column chromatography (1:10:90 ammonia (880)/
methanol/dichloromethane) was isolated as a white
solid (73 mg, 84%): 1H NMR (300 MHz, MeOH-d4)
7.59 (1H, d), 7.35 (4H, m), 6.78 (1H, s), 4.20 (2H, s),
2.93 (2H, m), 2.58 (2H, t, J=7.5 Hz), 1.74 (2H, quin.,
J=7.8 Hz), 1.62(2H, quin., J=7.8 Hz), 1.39 (2H, quin.,
J=7.8 Hz). The maleate salt was prepared by lyophili-
sation of an equimolar solution of the product and
maleic acid in water/dioxan. Found: C 49.70, H 5.24, N
9.18%; C19H24ClN3O6S requires: C 49.83, H 5.28, N
9.18%.
5-(1H-Imidazol-4-yl)pentane-1-sulfonicacid benzylamide
1
(20). H NMR (300 MHz, MeOH-d4) 7.55 (1H, s), 7.30
(5H, m), 6.75 (1H, s), 4.22 (2H, s), 2.86 (2H, m), 2.55
(2H, t, J=7.5 Hz), 1.68 (2H, quin., J=7.8 Hz), 1.56
(2H, quin., J=7.5 Hz), 1.34 (2H, quin., J=7.5 Hz). The
maleate salt was prepared by lyophilisation of an equi-
molar solution of the product and maleic acid in water/
dioxan. Found:
C19H25N3O6S requires: C 53.89, H 5.95, N 9.92%.
C
53.87,
H
6.03,
N
10.03%;
5-(1H-Imidazol-4-yl)pentane-1-sulfonicacid 4-bromoben-
1
zylamide (21). H NMR (300 MHz, CDCl3) 7.47 (3H,
m), 7.24 (2H, m), 6.74 (1H, s), 4.50 (2H, br s), 4.23 (2H,
s), 2.91 (2H, t, J=7.5 Hz), 2.58 (2H, t, J=7.5 Hz), 1.72
(2H, quin., J=7.5 Hz), 1.59 (2H, quin., J=7.2Hz), 1.34
(2H, quin., J=7.2Hz). The maleate salt was prepared
by lyophilisation of an equimolar solution of the pro-
duct and maleic acid in water/dioxan. Found: C 45.51,
H 4.85, N 8.28%; C19H24BrN3O6S requires: C 45.42, H
4.82, N 8.36%.
The following reverse sulfonamides were prepared in
similar fashion. For the syntheses of compounds 18, 19
and 21 the vinylsulfonamide intermediates, analogous
to 12, were hydrogenated in the presence of 5% rho-
dium-on-alumina.
5-(1H-Imidazol-4-yl)pentane-1-sulfonicaicd 4-fluoroben-
1
zylamide (22). H NMR (300 MHz, CDCl3) 7.52(1H,
4-(1H-Imidazol-4-yl)butane-1-sulfonic acid 4-chloroben-
zylamide (15). 1H NMR (300 MHz, MeOH-d4) 7.57
(1H, s), 7.34 (4H, s), 6.79 (1H, s), 4.19 (2H, s), 2.97 (2H,
m), 2.58 (2H, t, J=6.9 Hz), 1.72(4H, m). The maleate
salt was prepared by lyophilisation of an equimolar
solution of the product and maleic acid in water/dioxan.
Found: C 48.95, H 5.00, N 9.47%; C18H22ClN3O6S
requires: C 48.70, H 5.00, N 9.47%.
s), 7.33 (2H, m), 7.04 (2H, m), 6.76 (1H, s), 5.12 (1H, br
s), 4.27 (2H, s), 2.93 (2H, t, J=7.5 Hz), 2.61 (2H, t,
J=7.5 Hz), 1.80 (2H, quin., J=7.8 Hz), 1.65 (2H, quin.,
J=7.5 Hz), 1.45 (2H, quin., J=7.8 Hz). The maleate
salt was prepared by lyophilisation of an equimolar
solution of the product and maleic acid in water/dioxan.
Found: C 51.50, H 5.60, N 9.41%; C19H24FN3O6S
requires: C 51.69, H 5.48, N 9.52%.
6-(1H-Imidazol-4-yl)hexane-1-sulfonic acid 4-chloroben-
zylamide (17). 1H NMR (300 MHz, MeOH-d4) 7.56
(1H, d), 7.35 (4H, m), 6.76 (1H, s), 4.20 (2H, s), 2.92
(2H, m), 2.58 (2H, t, J=7.5 Hz), 1.72(2H, m), 1.62(2H,
m), 1.35 (4H, m). The maleate salt was prepared by
lyophilisation of an equimolar solution of the product
and maleic acid in water/dioxan. Found: C 50.67, H
5.63, N 9.01%; C20H26ClN3O6S requires: C 50.90, H
5.55, N 8.90%.
5-(1H-Imidazol-4-yl)pentane-1-sulfonicaicd 4-trifluoro-
1
methylbenzylamide (23). H NMR (300 MHz, DMSO-
d6) 11.45 (1H, br s), 7.71 (2H, d, J=8.1 Hz), 7.65 (1H,
br s), 7.56 (2H, d, J=8.1 Hz), 7.51 (1H, s), 6.71 (1H, s),
4.23 (2H, d, J=6.0 Hz), 2.95 (2H, m), 2.45 (2H, t,
J=7.5 Hz), 1.63 (2H, m), 1.53 (2H, m), 1.34 (2H, m).
The maleate salt was prepared by lyophilisation of an
equimolar solution of the product and maleic acid in
water/dioxan. Found: C 44.07, H 5.29, N 7.61%;
C20H24F3N3O6S.2.8H2O requires: C 44.30, H 5.51, N
7.75%.
5-(1H-Imidazol-4-yl)pentane-1-sulfonic acid 2-chloroben-
zylamide (18). 1H NMR (300 MHz, MeOH-d4) 7.56
(1H, s), 7.50 (1H, m), 7.39 (1H, m), 7.31 (2H, m), 6.75
(1H, s), 4.22 (2H, s), 2.92 (2H, m), 2.56 (2H, t, J=7.5
Hz), 1.74 (2H, quin., J=7.5 Hz), 1.60 (2H, quin., J=7.5
Hz), 1.38 (2H, quin., J=7.5 Hz). The maleate salt was
prepared by lyophilisation of an equimolar solution of
the product and maleic acid in water/dioxan. Found: C
49.59, H 5.30, N 8.95%; C19H24ClN3O6S requires: C
49.83, H 5.28, N 9.18%.
5-(1H-Imidazol-4-yl)pentane-1-sulfoniciadc 4-methyl-
benzylamide (24). 1H NMR (300 MHz, DMSO-d6)
11.40 (1H, br s), 7.60 (1H, br s), 7.52(1H, t, J=6.3 Hz),
7.47 (1H, s), 7.20 (2H, d, J=8.1 Hz), 7.12(2H, d, J=8.1
Hz), 6.68 (1H, s), 4.06 (2H, d, J=6.0 Hz), 2.83 (2H, m),
2.43 (2H, t, J=7.5 Hz), 2.26 (3H, s), 1.60 (2H, quin.,
J=7.8 Hz), 1.49 (2H, quin., J=7.5 Hz), 1.27 (2H, quin.,
J=7.5 Hz). The maleate salt was prepared by lyophili-
sation of an equimolar solution of the product and
maleic acid in water/dioxan. Found: C 51.73, H 6.44, N
9.17%; C19H27N3O6S.1.4H2O requires: C 51.83, H 6.50,
N 9.07%.
5-(1H-Imidazol-4-yl)pentane-1-sulfonic acid 3-chloroben-
zylamide (19). 1H NMR (300 MHz, MeOH-d4) 7.56
(1H, s), 7.41 (1H, m), 7.31 (3H, m), 6.77 (1H, s), 4.22
(2H, s), 2.93 (2H, m), 2.58 (2H, t, J=7.2Hz), 1.75 (2H,
m), 1.62(2H, quin., J=7.5 Hz), 1.39 (2H, m). The mal-
eate salt was prepared by lyophilisation of an equimolar
solution of the product and maleic acid in water/dioxan.
(E)-4-(1H-Imidazol-4-yl)but-1-ene-1-sulfoniicdac 4-
chlorobenzylamide (25). A solution of compound (12,
m=2) (85 mg, 0.15 mmol) in trifluoroacetic acid (2 mL)