Journal of Medicinal Chemistry
Page 8 of 17
and finally C. 54% yield over three steps. 1H-
124.3, 124.6, 126.6, 128.7, 130.7, 134.7, 135.7,
149.6, 157.1, 157.4, 168.3. HRMS-ESI (m/z):
[M+H]+ calculated for C19H11Cl4NO3, 441.9566;
found 441.9407. Purity by HPLC was found to be
100%.
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NMR (500 MHz, Acetone-d6) δ 7.05 (d, J = 9.0
Hz, 2H), 7.10 (d, J = 9.0 Hz, 2H), 7.41 (d, J =
9.0 Hz, 2H), 7.67 (d, J = 2.4 Hz, 1H), 7.79, (d, J
= 9.0 Hz, 2H), 8.04 (d, J = 2.3 Hz, 1H), 10.01 (s,
1H), 13.06 (s, 1H). 13C-NMR (125 MHz,
Acetone-d6) δ 117.8, 120.2, 120.9, 123.5, 124.2,
124.5, 126.4, 128.7, 130.7, 134.1, 134.5, 154.9,
157.3, 157.5, 168.2. HRMS-ESI (m/z): [M+H]+
calculated for C19H12Cl3NO3, 407.9955; found
407.9800. Purity by HPLC was found to be
100%.
N-(2-bromo-4-(4-chlorophenoxy)phenyl)-3,5-
dichloro-2-hydroxybenzamide (2). Procedures A,
then B and finally C. 75% yield over three steps.
1H-NMR (500 MHz, Acetone-d6) δ 7.14 (d, J =
8.7 Hz, 3H), 7.37 (d, J = 2.5 Hz, 1H), 7.46 (d, J =
8.8 Hz, 2H), 7.71 (s, 1H), 7.82 (d, J = 8.8 Hz,
1H), 8.08 (s, 1H), 9.96 (s, 1H), 12.61 (s, 1H).
13C-NMR (125 MHz, Acetone-d6) δ 118.1, 119.0,
121.2, 121.9, 123.3, 124.1, 124.3, 127.1, 129.7,
130.0, 131.0, 131.6, 134.6, 156.2, 156.7, 157.1,
168.0. HRMS-ESI (m/z): [M+H]+ calculated for
C19H11BrCl3NO3, 485.9061; found 485.8909.
Purity by HPLC was found to be 100%.
N-(3-bromo-4-(4-chlorophenoxy)phenyl)-3,5-
dichloro-2-hydroxybenzamide (3). Procedures A,
then B and finally C. 62% yield over three steps.
1H-NMR (500 MHz, Acetone-d6) δ 7.00 (dt, J =
2.3, 9.0 Hz, 2H), 7.19 (d, J = 8.8 Hz, 1H), 7.41
(dt, J = 2.3, 9.0 Hz, 2H), 7.70 (d, J = 2.4 Hz,
1H), 7.80 (dd, J = 2.6, 8.9 Hz, 1H), 8.04 (d, J =
2.4 Hz, 1H), 8.22 (d, J = 2.6 Hz, 1H), 10.07 (s,
1H), 12.79 (s, 1H). 13C-NMR (125 MHz,
3,5-dichloro-N-(4-(4-chlorophenoxy)-3-
iodophenyl)-2-hydroxybenzamide (5). Procedures
A, then B and finally C. 52% yield over three
steps. 1H-NMR (500 MHz, Acetone-d6) δ 6.99 (d,
J = 8.95 Hz, 2H), 7.09 (d, J = 8.8 Hz, 1H), 7.41
(d, J = 9.0 Hz, 2H), 7.84 (dd, J = 2.5, 8.8 Hz,
1H), 8.04 (d, J = 2.4 Hz, 1H), 8.38 (d, J = 2.5 Hz,
1H), 10.01 (s, 1H), 12,83 (s, 1H). 13C-NMR (125
MHz, Acetone-d6) δ 89.3, 117.8, 120.0, 121.1,
123.6, 124.2, 124.3, 126.6, 128.7, 130.8, 133.6,
134.7, 135.8, 153.9, 157.1, 157.4, 168.3. HRMS-
ESI (m/z): [M+H]+ calculated for C19H11Cl3INO3,
533.8922; found 533.8758. Purity by HPLC was
found to be 100%.
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3,5-dichloro-N-(4-(4-chlorophenoxy)-3-
fluorophenyl)-2-hydroxybenzamide (6).
Procedures A, then B and finally C. 69% yield
over three steps. 1H-NMR (500 MHz, Acetone-
d6) δ 7.03 (d, J = 8.9 Hz, 2H), 7.25 (t, J = 8.9 Hz,
1H), 7.40 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 8.8 Hz,
1H), 7.69 (d, J = 2.4 Hz, 1H), 7.88 (dd, J = 2.3,
12.8 Hz, 1H), 8.02 (d, 2.25 Hz, 1H), 10.11 (s,
1H), 12.77 (s, 1H). 13C-NMR (125 MHz,
Acetone-d6) δ 111.5, 111.7, 119.0, 119.1, 119.2,
123.4, 123.7, 124.3, 126.5, 128.5, 130.7, 134.7,
135.8, 135.9, 153.7, 155.7, 157.3, 157.5, 168.3.
HRMS-ESI (m/z): [M+H]+ calculated for
C19H11Cl3FNO3, 425.9861; found 425.9701.
Purity by HPLC was found to be 100%.
3,5-dichloro-N-(4-(4-chlorophenoxy)-3-
methoxyphenyl)-2-hydroxybenzamide (7).
Procedures A, then B and finally C. 57% yield
over three steps. 1H-NMR (500 MHz, Acetone-
d6) δ 3.80 (s, 3H), 6.89 (dt, J = 3.5, 9.1 Hz, 2H),
7.12 (d, 8.65 Hz, 1H), 7.32 (dt, J = 3.5, 9.1 Hz,
2H), 7.40 (dt, J = 2.8, 8.7 Hz, 1H), 7.66 (t, J =
2.6 Hz, 1H), 7.70 (d, J = 2.4 Hz, 1H), 8.04 (d, J =
2.3 Hz, 1H), 10.08 (s, 1H), 12.98 (s, 1H). 13C-
NMR (125 MHz, Acetone-d6) δ 56.3, 108.2,
115.1, 117.9, 118.4, 123.0, 123.6, 124.2, 126.5,
127.2, 130.3, 134.5, 136.1, 141.8, 152.8, 157.4,
158.4, 168.2. HRMS-ESI (m/z): [M+H]+
calculated for C20H14Cl3NO4, 438.0061; found
437.9902. Purity by HPLC was found to be
100%.
Acetone-d6) δ 115.4, 117.8, 119.9, 122.4, 123.4,
123.7, 124.3, 126.6, 127.6, 128.7, 130.7, 134.7,
135.8, 150.8, 157.0, 157.4, 168.3. HRMS-ESI
(m/z): [M+H]+ calculated for C19H11BrCl3NO3,
485.9061; found 485.8906. Purity by HPLC was
found to be 100%.
3,5-dichloro-N-(3-chloro-4-(4-
chlorophenoxy)phenyl)-2-hydroxybenzamide (4).
Procedures A, then B and finally C. 39% yield
over three steps. 1H-NMR (500 MHz, Acetone-
d6) δ 7.00 (dt, J = 2.2, 9 Hz, 2H), 7.21 (d, J = 8.9
Hz, 1H), 7.41 (dt, J = 2.2, 9 Hz, 2H), 7.70 (d, J =
2.4 Hz, 1H), 7.75 (dd, J = 2.6, 8.9 Hz, 1H), 8.04
(d, J = 2.5 Hz, 1H), 8.07 (d, J = 2.6 Hz, 1H),
10.09 (s, 1H), 12.78 (s, 1H). 13C-NMR (125
MHz, Acetone-d6) δ 117.8, 119.7, 122.7, 123.7,
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