620 Prabu et al.
Asian J. Chem.
2
1
956.3 (-CH), 2875.3 (-C≡N), 1627.8 (-C=O), 1534.1 (-C=N),
EXPERIMENTAL
All chemicals used for the synthesis of the desired comp-
170.6 (-C=C). ESI-MS: Calculated 435.53, Found 436.2
+
(
M+1) . Anal. calcd. (%) for C24
H
25
N
3
O S: C, 66.18; H, 5.79;
3
ounds were obtained from Loba Chime, Spectrochem, India
and Merck. The FT-IR analysis of the synthesized compounds
were recorded in FTIR 8300, KBr press, Shimadzu. Mass studies
of the synthesized compounds were performed by using the
N, 9.65; S, 7.36: Found (%): C, 66.18; H, 5.79; N, 9.65; S,
.36; Found (%): C, 66.71; H, 5.77; N, 9.62; S, 7.38.
-(3-Cyano-4-isobutoxyphenyl)-N-(4-fluorobenzyl)-4-
7
2
1
methylthiazole-5-carboxamide (8c): H NMR (300 MHz,
CDCl ), δ ppm: 8.02-8.12 (2H, m, Ar-H); 7.26-7.33 (2H, m,
Ar-H); 6.98-7.08 (2H, m, Ar-H); 6.12 (1H, m, Ar-H), 4.57-
1
instrument SHIMADZU QP 500. H NMR spectra were acquired
3
on a Bruker 300 MHz spectrometer in CDCl
3
and DMSO-d
6
using TMS as an internal standard. The microwave reactions
were carried out in a biotage microwave synthesizer.
Biological assay: The antibacterial activities of all test
compounds were carried out by disc diffusion method. The
concentrations of the test compounds were fixed at 100 and
4
2
ν
1
.59 (2H, d, -CH
.17-2.20 (1H, m, -CH); 1.07-1.09 (6H, d, -CH
2
); 3.88-3.90 (2H, d, -CH
2
); 2.75 (3H, s, -CH
3
);
3
). FT-IR (KBr,
–1
max, cm ): 2958.3 (-CH), 2872.5 (-C≡N), 1644.0 (-C=O),
535.1 (-C=N), 1171.5 (-C=C). ESI-MS: Calculated 423.50,
+
Found 424.2 (M+1) . Anal. calcd. (%) for C23
H
22
N
3
O SF: C,
2
2
00 µg. The standard drug is used as streptomycin. The target
6
5.23; H, 5.24; N, 9.92; S, 7.57; Found (%): C, 65.25; H, 5.22;
N, 9.91; S, 7.58.
-(3-Cyano-4-isobutoxyphenyl)-N-(3,4-dichlorobenzyl)-
microorganisms were cultured in Muller-Hinton broth (MHB).
After 24 h, the suspensions were adjusted to standard sub culture
dilution. The petri-dishes containing Muller Hinton agar (MHA)
medium were cultured with diluted bacterial strain. Disc made
of Whatman no.1, diameter 6 mm was presterilized and was
maintained in the aseptic chamber. Each concentration was
injected into the sterile disc papers. Then, prepared discs were
placed on the culture medium. Standard drug streptomycin
2
1
4
-methylthiazole-5-carboxamide (8d): H NMR (300 MHz,
CDCl ), δ ppm: 8.16-8.18 (2H, m, Ar-H); 7.39 -7.46 (2H, m,
Ar-H); 7.23-7.27 (1H, d, Ar-H); 7.05 (1H, d, Ar-H); 4.56 (2H,
d, -CH ); 3.91 (2H, d, -CH ); 2.77 (3H, s, -CH ); 2.16-2.24
1H, m, -CH); 1.07-1.09 (6H, d, -CH ). FT-IR (KBr, νmax, cm ):
3
2
2
3
–1
(
3
2
1
960.2 (-CH), 2875.34 (-C≡N), 1635.44 (-C=O), 1531.2 (-C=N),
(
10 µg) was used as a positive reference standard to determine
167.6 (-C=C). ESI-MS: Calculated 474.40, Found 474.1
the sensitivity of each microbial species tested. Then the inocu-
lated plates were incubated at 37 ºC for 24 h. The diameter of
the clear zone around the disc was measured and expressed in
millimeters as its antibacterial activity.
+
(M+1) .Anal. calcd. (%) for C23
H
21
N O
3
2
SCl : C, 58.23; H, 4.46;
2
N, 8.86; S, 6.76; Found (%): C, 58.24; H, 4.47; N, 8.89; S,
.78.
N-(2-Chlorobenzyl)-2-(3-cyano-4-isobutoxyphenyl)-4-
6
General procedure for the synthesis of febuxostat amide
derivatives (8a-j): Compound 7 (0.2 g, 0.632 mmol) was
dissolved in acetonitrile (2 mL). To that solution, TBTU (0.243
g, 0.757 mmol) and triethylamine (0.132 mL, 0.948 mmol)
was added and stirred for 30 min under nitrogen atmosphere.
The amine (0.632 mmol) was added and stirred for 3 h at room
temperature. The completion of the reaction was monitored
by TLC and extracted with ethyl acetate. The organic layer was
washed with sodium bicarbonate solution, water, brine solution,
which was separated and dried over anhydrous sodium sulphate.
The evaporation of solvent yielded target compounds (yield:
1
methylthiazole-5-carboxamide (8e): H NMR (500 MHz,
DMSO-d ), δ ppm: 8.81-8.83 (1H,t, -NH); 8.25-8.26 (2H, m,
Ar-H); 7.46-7.47 (1H, d,Ar-H); 7.35-7.39 (4H, m,Ar-H); 4.50-
6
4
2
.52 (2H, d, -CH
.08-2.09 (1H, m, -CH); 1.01-1.02 (6H, d, -CH
), δ ppm: 16.85, 17.05, 18.61, 22.12, 27.54,
5.08, 101.53, 113.95, 115.37, 127.14, 128.69, 128.80, 131.21,
2
); 4.00-4.01 (2H, t, -CH
2
); 2.62 (3H, s, -CH
3
);
13
3
). C NMR (75
MHz, DMSO-d
6
7
1
2
1
–1
32.82, 151.14, 155.14, 161.05, 161.81. FT-IR (KBr, νmax, cm ):
960.2 (-CH), 2873.4 (-C≡N), 1626.7 (-C=O), 1542.8 (-C=N),
156.1 (-C=C). ESI-MS: Calculated 439.95, Found 440.1
+
(M+1) .Anal. calcd. (%) for C23
H
22
N
3
O SCl; C, 62.79; H, 5.04;
2
8
5 %) (Scheme-I).
Spectral data
N-Benzyl-2-(3-cyano-4-isobutoxyphenyl)-4-methyl-
N, 9.55; S, 7.29; Found (%): C, 62.81; H, 5.06; N, 9.58; S,
7.32.
N-(3,5-Bis(trifluoromethyl)benzyl)-2-(3-cyano-4-
1
1
isobutoxyphenyl)-4-methylthiazole-5-carboxamide (8f): H
thiazole-5-carboxamide (8a): H NMR (300 MHz, CDCl
δ ppm: 8.09-8.12 (2H, m, Ar-H); 7.27-7.36 (5H, m, Ar-H);
.00-7.02 (1H, d, Ar-H); 4.62 (2H, d, -CH ); 3.88-3.90 (2H, d,
CH ); 2.74 (3H, s, -CH ); 2.24-2.25 (1H, m, -CH); 1.07-1.10
6H, d, -CH ). FT-IR (KBr, νmax, cm ): 2965.98 (-CH), 2222.56
-C≡N), 1636.3 (-C=O), 1527.35 (-C=N), 1174.44 (-C=C).
3
),
NMR (500 MHz, DMSO-d
.25-8.26 (1H, d, Ar-H); 8.17-8.20 (1H, m, Ar-H); 8.02-8.03
3H, d,Ar-H); 7.37-7.39 (1H, m,Ar-H); 4.62-4.63 (2H, d, -CH );
4.00-4.01 (2H, d, -CH ); 2.61 (3H, s, -CH ); 2.07-2.09 (1H,
6
), δ ppm: 8.95-8.97 (1H,t, -NH);
8
(
7
2
2
-
(
(
2
3
–1
2
3
3
13
m, -CH); 1.01-1.02 (6H, d, -CH
3
). C NMR (75 MHz, DMSO-d
6
),
+
δ ppm: 16.99, 18.66, 27.54, 42.21, 75.08, 101.53, 113.91,
ESI-MS: Calculated 405.51, Found 406.2 (M+1) .Anal. calcd.
S: C, 68.12; H, 5.72; N, 10.36; S, 7.91;
Found (%): C, 68.14; H, 5.71; N, 10.35; S, 7.90.
-(3-Cyano-4-isobutoxyphenyl)-N-(4-methoxybenzyl)-
120.70, 125.38, 128.19, 131.24, 132.83, 142.83, 155.33, 161.25,
(
%) for C23
H
23
N O
3 2
–1
1
61.84, 163.98. FT-IR (KBr, νmax, cm ): 2964.05 (-CH), 2878.24
(-C≡N), 1617.98 (-C=O), 1534.1 (-C=N), 1167.69 (-C=C).
2
+
1
ESI-MS: Calculated 541.50, Found 543.1 (M+1) .Anal. calcd.
SF ; C, 55.45; H, 3.91; N, 7.76; S, 5.92;
Found (%): C, 55.47; H, 3.94; N, 7.77; S, 5.95.
-(3-Cyano-4-isobutoxyphenyl)-N-(3-methoxybenzyl)-
4
-methylthiazole-5-carboxamide (8b): H NMR (300 MHz,
CDCl ), δ ppm: 8.02-8.12 (2H, m, Ar-H); 7.26-7.30 (2H, m,
Ar-H); 6.98-7.01 (1H, m, Ar-H); 6.88-6.91 (1H, m, Ar-H);
.04 (1H, m, Ar-H), 4.54-4.56 (2H, d, -CH ); 3.87-3.90 (2H,
d, -CH ); 3.81 (3H, s, -CH ); 2.71 (3H, s, -CH ); 2.09-2.16
1H, m, -CH); 1.07-1.09 (6H, d, -CH ). FT-IR (KBr, νmax, cm ):
(
%) for C25
H
21
N O
3 2
6
3
2
6
2
1
4
-methylthiazole-5-carboxamide (8g): H NMR (300 MHz,
2
3
3
–1
CDCl ), δ ppm: 8.20-8.28 (3H, m, Ar-H); 7.91-7.94 (1H, m,
3
(
3