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JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
1073
The mixture was heated to 70 ꢀC for 4 h. After cooling to r.t. the 84.5, 119.9, 129.9, 133.2, 138.3, 157.0, 169.7; m/z (ESI positive)
355.8 [M þ H]þ.
solvents were removed under reduced pressure. The obtained
solid was dissolved in water (5.0 ml) and treated with ammonium
hydroxide (pH ¼10), then the reaction mixture stirred for 1 h at
90 ꢀC. The precipitated solid was filtered under vacuum, washed
with H2O (3 ꢁ 5.0 ml), then with n-Hexane (3 ꢁ 3.0 ml) and dried to
afford the titled compound.
N-(6-sulfamoylbenzo[d]thiazol-2-yl)acetamide (9)
A solution of 2 (1.0 g, 1.0 eq) in acetic acid (2.0 ml) was cooled to
0 ꢀC followed by drop-wise addition of acetic anhydride (1.2 eq).
The reaction mixture was refluxed for 3 h then excess of solvents
were removed under reduced pressure to obtain a residue which
was washed with Et2O (3 ꢁ 5 ml) to obtain titled compound.
White solid, 96% yield; dH (400 MHz, DMSO-d6) 2.27 (3H, s), 7.39
(2H, s, exchange with D2O, SO2NH2), 7.90 (2H, d, J 1.2), 8.50 (1H, t,
J 1.2), 12.59 (1H, s, exchange with D2O, NH); dC (100 MHz, DMSO-
d6) 23.7, 121.0, 121.4, 124.8, 132.4, 139.9, 151.7, 161.9, 170.7; m/z
(ESI positive) 272.0 [M þ H]þ.
Orange solid, 68% yield; dH (400 MHz, DMSO-d6) 7.35 (2H, s,
exchange with D2O, SO2NH2), 7.89 (1H, s), 8.17 (1H, s), 8.26 (2H, s,
exchange with D2O, NH2); dC (100 MHz, DMSO-d6) 110.7, 119.7,
127.6, 132.6, 138.1, 154.5, 170.9; m/z (ESI positive) 307.9 [M þ H]þ.
2-Amino-4-bromobenzo[d]thiazole-5-sulfonamide (6)
A suspension of 4 (0.2 g, 1.0 eq) in chloroform (4.0 ml) was treated
with a solution of Br2 (6.0 eq) in chloroform (1.0 ml) drop-wise.
The mixture was heated to 70 ꢀC for 12 h. After cooling to r.t. the
solvents were removed under reduced pressure. The obtained
solid was dissolved in water (5.0 ml) and treated with ammonium
hydroxide (pH ¼10), then the reaction mixture stirred for 1 h at
90 ꢀC. After cooling, the reaction mixture was extracted with
EtOAc (3 ꢁ 5 ml). The combined organic layers were washed with
H2O (3 ꢁ 5.0 ml), dried over Na2SO4, filtered and concentrated to
obtain a residue that was purified by silica gel column chromatog-
raphy eluting with EtOAc/n-Hexane 70% v/v to afford the titled
compound.
Orange solid, 19% yield; dH (400 MHz, DMSO-d6) 7.40 (1H, d, J
8.4), 7.66 (2H, s, exchange with D2O, SO2NH2), 7.69 (1H, d, J 8.4),
8.08 (2H, s, exchange with D2O, NH2); dC (100 MHz, DMSO-d6)
114.3, 120.6, 128.8, 129.8, 137.1, 152.9, 170.1; m/z (ESI negative)
305.7 [M-H]ꢂ.
N-(4-bromo-6-sulfamoylbenzo[d]thiazol-2-yl)acetamide (10)
A solution of 5 (0.1 g, 1.0 eq) in acetic acid (0.5 ml) was cooled to
0 ꢀC followed by drop-wise addition of acetic anhydride (1.2 eq)
then the mixture was refluxed for 3 h. The excess of solvents was
removed under reduced pressure. The obtained solid was treated
with sodium bicarbonate (1 N, 3.0 ml), then the reaction mixture
was extracted with EtOAc (3 ꢁ 5 ml). The combined organic layers
were washed with H2O (3 ꢁ 5.0 ml), dried over Na2SO4, filtered and
concentrated under reduced pressure to afford the titled
compound.
Orange solid, 93% yield; dH (400 MHz, DMSO-d6) 2.24 (3H, s),
7.44 (2H, s, exchange with D2O, SO2NH2), 8.05 (1H, s), 8.50 (1H, s),
12.59 (1H, s, exchange with D2O, NH); dC (100 MHz, DMSO-d6) 23.6,
114.1, 120.5, 127.5, 133.2, 140.8, 149.8, 162.7, 171.0; m/z (ESI posi-
tive) 349.8 [M þ H]þ.
2-Amino-4-iodobenzo[d]thiazole-6-sulfonamide (7)
N-(5-sulfamoylbenzo[d]thiazol-2-yl)acetamide (11)
A solution of 2 (0.3 g, 1.0 eq) in methanol (3.0 ml) was treated
with iodine monochloride (4.0 eq) in methanol (1.0 ml) drop-wise.
The mixture was heated to reflux temperature for 12 h. After cool-
ing to room temperature, the reaction mixture was extracted with
EtOAc (3 ꢁ 5.0 ml). The combined organic layers were washed with
H2O (3 ꢁ 5.0 ml), dried over Na2SO4, filtered and concentrated to
obtain a residue that was purified by silica gel column chromatog-
raphy eluting with EtOAc/n-Hexane 70% v/v to afford the titled
compound.
Dark orange solid, 31% yield; dH (400 MHz, DMSO-d6) 7.31 (2H,
s, exchange with D2O, SO2NH2), 8.06 (1H, d, J 2.0), 8.16 (1H, d, J
2.0), 8.21 (2H, s, exchange with D2O, NH2); dC (100 MHz, DMSO-d6)
84.4, 119.9, 129.9, 133.1, 138.3, 157.0, 169.7; m/z (ESI positive)
355.9 [M þ H]þ.
A solution of 4 (0.1 g, 1.0 eq) in acetic acid (0.5 ml) was cooled to
0 ꢀC followed by drop-wise addition of acetic anhydride (1.2 eq)
then the mixture was refluxed for 3 h. The excess of solvents was
removed under reduced pressure. The obtained solid was treated
with sodium bicarbonate (1 N, 3 ml), then the reaction mixture was
extracted with EtOAc (3 ꢁ 5 ml). The combined organic layers were
washed with H2O (3 ꢁ 5.0 ml), dried over Na2SO4, filtered and con-
centrated under reduced pressure to afford the titled compound.
White solid, 89% yield; dH (400 MHz, DMSO-d6) 2.27 (3H, s), 7.66
(1H, t, J 7.8), 7.71 (2H, s, exchange with D2O, SO2NH2), 8.80 (1H,
dd, J 7.8, 1.0), 7.98 (1H, dd, J 7.8, 1.0), 12.45 (1H, s, exchange with
D2O, NH); dC (100 MHz, DMSO-d6) 23.6, 122.7, 124.6, 127.1, 128.8,
138.6, 150.9, 161.5, 170.6; m/z (ESI positive) 272.0 [M þ H]þ.
2-((6-Sulfamoylbenzo[d]thiazol-2-yl)carbamoyl)benzoic acid (12)
A solution of 2 (0.3 g, 1.0 eq) in dry DMF (3.0 ml) was treated with
phthalic anhydride (1.0 eq), then the mixture was refluxed for 4 h.
The reaction mixture was extracted with EtOAc (3 ꢁ 5.0 ml). The
combined organic layers were washed with H2O (3 ꢁ 5.0 ml), dried
over Na2SO4, filtered and concentrated under reduced pressure to
afford the corresponding pure mixture of 2 isomers in (50:50) as
2-Amino-4-iodobenzo[d]thiazole-5-sulfonamide (8)
A solution of 4 (0.2 g, 1.0 eq) in methanol (3.0 ml) was treated
with a solution of iodine monochloride (4.0 eq) in methanol
(1.0 ml) drop-wise. The mixture was heated to reflux temperature
for 12 h. After cooling to room temperature, the reaction mixture
was extracted with EtOAc (3 ꢁ 5 ml). The combined organic layers
were washed with H2O (3 ꢁ 5.0 ml), dried over Na2SO4, filtered and
concentrated to obtain a residue that was purified by silica gel
column chromatography eluting with EtOAc/n-Hexane 70% v/v to
afford the titled compound.
1
evidenced by H NMR integration.
White solid, 100% yield; dH (400 MHz, DMSO-d6) 7.41 (2H, s,
exchange with D2O, SO2NH2), 7.51 (2H, s, exchange with D2O,
SO2NH2), 7.67–7.77 (4H, m), 7.93–8.03 (7H, m), 8.11–8.13 (2H, m),
8.22 (1H, d, J 8.4), 8.56 (1H, s, exchange with D2O, NH), 8.71 (1H, d,
J 1.6, exchange with D2O, NH); dC (100 MHz, DMSO-d6) 121.0,
Dark orange solid, 16% yield; dH (400 MHz, DMSO-d6) 7.25 (1H,
d, J 8.0), 7.63 (2H, s, exchange with D2O, SO2NH2), 7.87 (1H, d, J
8.0), 8.03 (2H, s, exchange with D2O, NH2); dC (100 MHz, DMSO-d6) 121.2, 121.5, 123.4, 124.8, 125.0, 125.1, 129.0, 130.6, 130.8, 131.3,