Journal of Medicinal Chemistry
Article
2.24 (s, 6H). 13C NMR (150 MHz, DMSO-d6) δ 160.9, 156.8, 155.2,
148.0, 146.9, 144.5, 133.5, 131.4, 130.8, 129.8, 128.3, 127.0, 122.3,
121.4, 117.7, 19.9. MS (m/z): calcd for C19H19N4O3S+ [M + H]+,
383.11; found, 383.11. Purity >99%, tR = 5.0 min.
(E)-4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-N-(pyridin-2-yl)-
benzenesulfonamide (4, MS435). Following a similar procedure as
compound 3, compound 4 was prepared as an orange powder (80%).
1H NMR (600 MHz, DMSO-d6) δ 12.2 (br s, 1H), 9.33 (br s, 1H),
(E)-N-(5-Bromopyridin-2-yl)-4-((4-hydroxy-3,5-dimethylphenyl)-
diazenyl)benzenesulfonamide (11). 1H NMR (600 MHz, MeOD-d4)
δ 7.89−7.80 (m, 4H), 7.58 (s, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.04 (d, J
= 8.4 Hz, 2H), 2.27 (s, 6H). 13C NMR (150 MHz, MeOD-d4) δ 160.6,
157.9, 148.5, 142.6, 139.6, 134.6, 130.7, 127.5, 126.6, 125.5, 125.0,
120.2, 18.1. MS (m/z): calcd for C19H18BrN4O3S+ [M + H]+, 462.03;
found, 462.00. Yield: 55%, purity >99%, tR = 5.6 min.
(E)-4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-N-(5-methoxy-
pyridin-2-yl)benzenesulfonamide (12). 1H NMR (600 MHz, DMSO-
d6) δ 10.85 (s, 1H), 9.35 (s, 1H), 7.99 (d, J = 8.4 Hz, 2H), 7.92−7.85
(m, 3H), 7.59 (s, 2H), 7.37 (m, 1H), 7.11 (m, 1H), 3.73 (s, 3H), 2.26
(s, 6H). MS (m/z): calcd for C20H21N4O4S+ [M + H]+, 413.13; found,
413.12. Yield: 57%, purity >99%, tR = 6.2 min.
(E)-4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-N-(4-
methoxyphenyl)benzenesulfonamide (13). 1H NMR (600 MHz,
CDCl3) δ 7.86 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.65 (s,
2H), 6.98 (d, J = 9.0 Hz, 2H), 6.77 (d, J = 9.0 Hz, 1H), 6.28 (s, 1H),
5.10 (s, 1H), 3.76 (s, 3H), 2.34 (s, 6H). MS (m/z): calcd for
C21H22N3O4S+ [M + H]+, 412.13; found, 412.13. Yield: 57%, purity
>99%, tR = 6.3 min.
(E)-4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-N-(4-
(trifluoromethyl)phenyl)benzenesulfonamide (14). 1H NMR (600
MHz, DMSO-d6) δ 11.02 (s, 1H), 9.38 (s, 1H), 7.98 (d, J = 8.4 Hz,
2H), 7.92 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.59 (s, 2H),
7.31 (d, J = 8.4 Hz, 2H), 2.26 (s, 6H). MS (m/z): calcd for
C21H19F3N3O3S+ [M + H]+, 450.11; found, 450.13. Purity >95%, tR =
6.5 min.
8.00 (d, J = 8.4 Hz, 1H), 7.98−7.93 (m, 2H), 7.87 (d, J = 8.4 Hz, 2H),
7.74 (t, J = 8.4 Hz, 1H), 7.57 (s, 2H), 7.20 (d, J = 9.0 Hz, 1H), 6.85 (t,
J = 6.6 Hz, 1H), 2.14 (s, 6H). 13C NMR (150 MHz, DMSO-d6) δ
158.3, 154.3, 154.0, 145.4, 143.7, 141.8, 141.6, 128.6, 125.6, 124.3,
122.8, 120.0, 114.8, 17.1. MS (m/z): calcd for C19H19N4O3S+ [M +
H]+, 383.11; found, 383.11. Purity >99%, tR = 2.1 min.
(Chromatography was performed on a 2.1 × 50 mm Acquity BEH
C-18 column using acetonitrile as solvent A and water containing
0.025% TFA as solvent B at a flow rate of 0.5 mL/min. The gradient
program was as follows: 90% B (0−0.5 min), 90−10% B (0.5−3 min),
and 10% B (3−6 min).)
(E)-4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-N-(4-
(trifluoromethyl)benzyl)benzenesulfonamide (5). 1H NMR (600
MHz, MeOD-d4) δ 7.93 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 8.4 Hz,
2H), 7.62 (s, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H),
4.20 (s, 2H), 2.30 (s, 6H). 13C NMR (150 MHz, MeOD-d4) δ 160.5,
157.7, 148.6, 144.7, 144.0, 132.1, 131.9, 130.8, 130.5, 127.9, 127.6 (d),
126.6, 125.1, 48.7, 18.1. IR (neat): ν 3498 (−OH), 3247 (−NH−),
1616 (−CN−), 1591 (−NN−), 1382 (−SO2−). MS (m/z):
calcd for C22H21F3N3O3S+ [M + H]+, 464.12; found, 464.12. Purity
>99%, tR = 6.5 min. mp 195.7 °C.
(E)-4-(4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-
1
phenylsulfonamido)benzamide (15). H NMR (600 MHz, DMSO-
d6) δ 10.81 (br s, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz,
1H), 8.00 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.84−7.77 (m,
2H), 7.75−7.66 (m, 2H), 7.28−7.20 (m, 2H), 7.14 (d, J = 8.4 Hz,
2H), 2.48 (s, 6H). 13C NMR (150 MHz, DMSO-d6) δ 170.3, 160.0,
153.0, 149.5, 143.5, 142.6, 132.8, 132.0, 131.3, 130.9, 128.6, 126.8,
122.1, 121.8, 16.5. MS (m/z): calcd for C21H21N4O4S+ [M + H]+,
425.13; found, 425.14. Yield: 24%, purity >99%, tR = 5.4 min.
(E)-N-(5-Fluoropyridin-2-yl)-4-((4-hydroxy-3,5-dimethylphenyl)-
diazenyl)benzenesulfonamide (16). 1H NMR (600 MHz, DMSO-d6)
δ 9.47 (br s, 1H), 8.15 (d, J = 2.4 Hz, 1H), 8.02 (d, J = 7.8 Hz, 2H),
7.88 (d, J = 7.8 Hz, 2H), 7.64 (dt, J = 7.8, 2.4 Hz, 1H), 7.56 (s, 2H),
7.11 (dd, J = 7.8, 2.4 Hz, 1H), 2.23 (s, 6H). 13C NMR (150 MHz,
DMSO-d6) δ 161.2, 159.9, 158.3, 157.6, 150.9, 148.1, 144.0, 131.7,
129.4, 128.3, 127.1, 125.6, 117.1, 19.8. MS (m/z): calcd for
C19H18FN4O3S+ [M + H]+, 401.11; found, 401.08. Yield: 78%, purity
>99%, tR = 5.3 min.
The following compounds were synthesized following Scheme 1.
(E)-4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-N-methyl-N-(pyr-
idin-2-yl)benzenesulfonamide (6). 1H NMR (600 MHz, MeOD-d4) δ
8.16−8.12 (m, 1H), 8.10 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H),
7.63 (s, 2H), 7.04 (t, J = 6.6 Hz, 1H), 6.86 (d, J = 7.2 Hz, 1H), 6.63 (t,
J = 7.2 Hz, 1H), 2.30 (s, 6H), 2.18 (s, 3H). 13C NMR (150 MHz,
DMSO-d6) δ 161.1, 156.9, 155.6, 148.3, 146.7, 143.1, 140.9, 130.7,
127.8, 126.8, 122.1, 115.1, 114.1, 31.5, 18.1. MS (m/z): calcd for
C20H21N4O3S+ [M + H]+, 397.13; found, 397.13. Yield: 31%, purity
>99%, tR = 4.8 min.
(E)-4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-N-(3-
(trifluoromethyl)phenyl)benzenesulfonamide (7). 1H NMR (600
MHz, CDCl3) δ 7.90 (m, 4H), 7.65 (s, 2H), 7.38 (m, 3H), 7.29 (br s,
1H), 6.82 (s, 1H), 5.10 (s, 1H), 2.34 (s, 6H). MS (m/z): calcd for
C21H19F3N3O3S+ [M + H]+, 450.11; found, 450.11. Yield: 68%, purity
>99%, tR = 6.5 min.
(E)-N-(4-Fluorophenyl)-4-((4-hydroxy-3,5-dimethylphenyl)-
1
(E)-N-(4-Chloropyridin-2-yl)-4-((4-hydroxy-3,5-dimethylphenyl)-
diazenyl)benzenesulfonamide (17). H NMR (600 MHz, CDCl3) δ
1
diazenyl)benzenesulfonamide (8). H NMR (600 MHz, DMSO-d6)
10.31 (br s, 1H), 9.40 (br s, 1H), 8.00−7.79 (m, 4H), 7.59 (s, 2H),
7.21−7.07 (m, 4H), 2.25 (s, 6H). MS (m/z): calcd for
C20H19FN3O3S+ [M + H]+, 400.11; found, 400.12. Yield: 76%, purity
>99%, tR = 6.4 min.
δ 9.39 (br s, 1H), 8.18 (d, J = 1.8 Hz, 1H), 8.04 (d, J = 7.8 Hz, 2H),
7.89 (d, J = 7.8 Hz, 2H), 7.79 (dd, J = 9.0, 1.8 Hz, 1H), 7.56 (s, 2H),
7.08 (d, J = 9.0 Hz, 1H), 7.01 (d, J = 5.6 Hz, 1H), 2.23 (s, 6H). 13C
NMR (150 MHz, DMSO-d6) δ 161.2, 157.7, 153.2, 149.3, 148.2,
143.9, 141.7, 131.8, 128.3, 127.1, 125.6, 121.8, 116.7, 19.8. MS (m/z):
calcd for C19H18ClN4O3S+ [M + H]+, 417.08; found, 417.08. Yield:
87%, purity >99%, tR = 5.3 min.
(E)-6-(4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-
phenylsulfonamido)nicotinic Acid (9). 1H NMR (600 MHz, DMSO-
d6) δ 9.31 (br s, 1H), 8.24−8.14 (m, 2H), 8.03 (d, J = 8.4 Hz, 2H),
7.88 (d, J = 8.4 Hz, 2H), 7.72 (s, 1H), 7.57 (s, 2H), 7.50 (s, 1H), 7.27
(d, J = 4.8 Hz, 2H), 2.24 (s, 6H). 13C NMR (150 MHz, MeOD-d4) δ
169.0, 161.2, 157.3, 156.1, 148.1, 145.0, 131.4, 128.4, 127.1, 125.5,
122.3, 117.7, 114.8, 19.9. MS (m/z): calcd for C20H18N4O5S [M]+,
426.11; found, 426.11. Yield: 24%, purity >99%, tR = 5.1 min.
(E)-N-(5-Chloropyridin-2-yl)-4-((4-hydroxy-3,5-dimethylphenyl)-
diazenyl)benzenesulfonamide (10). 1H NMR (600 MHz, DMSO-d6)
δ 9.36 (br s, 1H), 8.03 (d, J = 7.8 Hz, 4H), 7.89 (d, J = 7.8 Hz, 2H),
7.57 (s, 2H), 7.16 (s, 1H), 7.01 (d, J = 5.6 Hz, 1H), 2.24 (s, 6H). 13C
NMR (150 MHz, DMSO-d6) δ 161.1, 157.4, 156.6, 149.2, 148.2,
145.1, 131.7, 131.3, 128.3, 127.1, 125.6, 119.9, 115.8, 19.8. MS (m/z):
calcd for C19H18ClN4O3S+ [M + H]+, 417.08; found, 417.07. Yield:
87%, purity >99%, tR = 5.3 min.
(E)-4-((4-Hydroxy-3,5-dimethylphenyl)diazenyl)-2-methoxy-N-
(pyridin-2-yl)benzenesulfon-amide (18). 1H NMR (600 MHz,
DMSO-d6) δ 9.31 (br s, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.96 (d, J =
4.8 Hz, 1H), 7.70 (t, J = 7.8 Hz, 1H), 7.58 (s, 2H), 7.47−7.41 (m,
2H), 7.18 (d, J = 8.4 Hz, 1H), 6.85 (t, J = 6.6 Hz, 1H), 3.8 (s, 3H),
2.24 (s, 6H). 13C NMR (150 MHz, DMSO-d6) δ 160.6, 158.7, 156.6
(m), 148.0, 143.2, 140.9, 133.9, 131.4, 128.4, 127.1, 122.3, 117.5,
117.0, 114.9, 114.1, 31.5, 18.1. MS (m/z): calcd for C20H21N4O4S+ [M
+ H]+, 413.13; found, 413.13. Yield: 31%, purity >99%, tR = 4.8 min.
The following compounds were synthesized following Scheme 2.
(E)-4-((3,5-Dichloro-4-hydroxyphenyl)diazenyl)-N-(pyridin-2-yl)-
1
benzenesulfonamide (19). H NMR (600 MHz, MeOD-d4) δ 8.08
(d, J = 8.4 Hz, 1H), 8.02−7.94 (m, 3H), 7.93 (s, 2H), 7.74 (t, J = 7.8
Hz, 2H), 7.30 (d, J = 9.0 Hz, 1H), 6.89 (t, J = 6.6 Hz, 1H). 13C NMR
(150 MHz, DMSO-d6) δ 158.0, 156.5, 156.0, 146.7, 146.5, 142.9,
142.5, 131.3, 131.0, 126.8 (m), 125.9, 118.1, 115.7. MS (m/z): calcd
for C17H13Cl2N4O3S+ [M + H]+, 423.01, 425.01; found, 423.01,
425.01. Yield: 75%, purity >95%, tR = 5.9 min.
(E)-4-((3-Bromo-4-hydroxy-5-methylphenyl)diazenyl)-N-(pyridin-
1
2-yl)benzenesulfonamide (20). H NMR (600 MHz, DMSO-d6) δ
9260
dx.doi.org/10.1021/jm401334s | J. Med. Chem. 2013, 56, 9251−9264