S.-X. Gu et al. / Bioorg. Med. Chem. 19 (2011) 4220–4226
4225
Calcd for C26H20FN3O5S: C, 61.77; H, 3.99, F 3.76; N, 8.31; S, 6.34.
Found: C, 61.72; H, 3.81; F, 3.79; N, 8.35; S, 6.29.
6.91–8.65 (m, 11H; Ph and Naph), 7.26 (s, 2H, SO2NH2), 9.36 (s,
1H, CONH); 13C NMR (100 MHz, DMSO-d6) d (ppm) 17.42, 67.58,
103.17 (d, JCF = 27.81 Hz), 107.65, 108.17 (d, JCF = 23.13 Hz),
116.40, 118.37, 122.85 (d, JCF = 10.73 Hz), 123.59, 123.77, 124.37,
127.62, 128.50, 128.89, 129.48, 130.98, 132.57, 132.57, 138.40,
134.80, 139.30 (d, JCF = 2.74 Hz), 140.29, 150.66 (d, JCF = 10.91 Hz),
152.59, 153.39, 159.68 (d, JCF = 240.26 Hz), 165.97; MS(ESI+) m/z
540.0 (35Cl), 541.9 (37Cl) (M+H)+; Anal. Calcd for C26H19ClFN3O5S:
C, 57.83; H, 3.55; Cl, 6.57, F 3.52; N, 7.78; S, 5.94. Found: C,
57.91; H, 3.53; Cl, 6.50, F 3.55; N, 7.81; S, 5.91
4.1.4.12. 2-(4-Fluoro-2-(1-chloro-2-naphthyloxy)phenoxy)-N-
(2-methyl-4-sulfamoylphenyl)acetamide
(12l). Yield:
69%;
white solid; mp 192.6–194.5 °C; 1H NMR (400 MHz, DMSO-d6) d
(ppm) 2.15 (s, 3H, CH3), 4.85 (s, 2H, OCH2), 6.89–8.18 (m, 12H;
Ph and Naph), 7.29 (s, 2H, SO2NH2), 9.35 (s, 1H, CONH); 13C NMR
(100 MHz, DMSO-d6)
d
(ppm) 17.49, 68.50, 107.58 (d,
JCF = 26.42 Hz), 111.00 (d, JCF = 22.52 Hz), 116.53 (d, JCF = 9.70 Hz),
118.28, 118.48, 123.14, 123.53, 123.87, 125.89, 127.67, 128.27,
128.53, 129.02, 130.76, 130.95, 131.02, 138.50, 140.26, 145.40 (d,
JCF = 10.65 Hz), 145.54 (d, JCF = 2.92 Hz), 149.61, 156.79 (d,
JCF = 239.59 Hz), 166.53; MS(ESIÀ) m/z 512.9 (35Cl), 514.9 (37Cl)
(MÀH)À, Anal. Calcd for C25H20ClFN2O5S: C, 58.31; H, 3.91; Cl,
6.88, F 3.69; N, 5.44; S, 6.23. Found: C, 58.39; H, 3.87; Cl, 6.79; F,
3.64; N, 5.47; S, 6.19.
4.1.4.17. 2-(4-Fluro-2-(1-chloro-3-methyl-2-naphthyloxy) phe-
noxy)-N-(2-methyl-4-sulfamoylphenyl)acetamide (12q). Yield:
62%; white solid; mp 190.4–192.2 °C; 1H NMR (400 MHz, DMSO-
d6) d (ppm) 2.26 (s, 3H, Ph-CH3), 2.32 (s, 3H, Naph-CH3), 4.94 (s,
2H, OCH2), 6.21–8.16 (m, 11H; Ph and Naph), 7.26 (s, 2H, SO2NH2),
9.57 (s, 1H, CONH); C13 NMR (100 MHz, DMSO-d6) d (ppm)
16.58,17.42,68.98, 101.83 (d, JCF = 27.60 Hz), 108.38 (d,
JCF = 20.85 Hz), 116.78 (d, JCF = 9.26 Hz), 122.75, 123.18, 123.44,
123.94, 126.77, 127.33, 127.68, 127.84, 129.19, 129.66, 130.54,
131.02, 131.78, 138.63, 140.13, 143.36 (d, JCF = 2.88 Hz), 146.73,
147.14 (d, JCF = 9.91 Hz), 156.95 (d, JCF = 239.12 Hz), 166.73;
MS(ESIÀ) m/z 527.0 (35Cl), 529.0 (37Cl) (MÀH)À, Anal. Calcd for
4.1.4.13. 2-(4-Fluoro-2-(1-chloro-6-bromo-2-naphthyloxy) phe-
noxy)-N-(2-methyl-4-sulfamoylphenyl)acetamide (12m). Yield:
56%; white solid; mp 198.8–201.2 °C; 1H NMR (400 MHz, DMSO-
d6) d (ppm) 2.14 (s, 3H, CH3), 4.83 (s, 2H, OCH2), 6.96–8.30 (m,
11H; Ph and Naph), 7.28 (s, 2H, SO2NH2), 9.37 (s, 1H, CONH); 13C
NMR (100 MHz, DMSO-d6)
d
(ppm) 17.50, 68.40, 108.04 (d,
C26H22ClFN2O5S: C, 59.03; H, 4.19; Cl, 6.70, F 3.59; N, 5.30; S,
JCF = 25.80 Hz), 111.38 (d, JCF = 22.50 Hz), 116.46 (d, JCF = 9.50 Hz),
118.17, 118.99, 123.58, 123.59, 123.85, 125.50, 127.67, 128.23,
129.78, 130.31, 131.00, 131.11, 131.77, 138.50, 140.28, 144.94 (d,
JCF = 10.00 Hz), 145.69 (d, JCF = 2.90 Hz), 150.20, 156.76 (d,
JCF = 238.20 Hz), 166.48; MS(ESIÀ) m/z 590.9 (35Cl+79Br), 592.9
6.06. Found: C, 59.08; H, 4.13; Cl, 6.72, F 3.54; N, 5.35; S, 6.09.
4.1.4.18. 2-(4-Fluro-2-(8-fluoro-2-naphthyloxy)phenoxy)-N-(2-
methyl-4-sulfamoylphenyl)acetamide (12r). Yield: 55%; white
solid; mp 190.8–192.3 °C; 1H NMR (400 MHz, DMSO-d6) d (ppm)
2.11 (s, 3H,CH3), 4.80 (s, 2H, OCH2), 7.12–8.05 (m, 12H; Ph and
Naph), 7.26 (s, 2H, SO2NH2), d (ppm) 9.29 (s, 1H, CONH); 13C
(
35Cl+81Br, 37Cl+79Br), 594.9 (37Cl+81Br) (MÀH)À; Anal. Calcd for
C25H19BrClFN2O5S: C, 50.56; H, 3.22; Br, 13.46; Cl, 5.97, F 3.20; N,
4.72; S, 5.40. Found: C, 50.64; H, 3.20; Br, 13.42; Cl, 5.90; F, 3.23;
N, 4.68; S, 5.38.
NMR (100 MHz, DMSO-d6) d (ppm) 17.44, 68.28, 103.48 (d,
JCF = 5.30 Hz), 109.69 (d, JCF = 25.45 Hz), 110.48 (d, JCF = 19.19 Hz),
111.88 (d, JCF = 22.64 Hz), 116.46 (d, JCF = 9.57 Hz), 119.59, 123.52
(d, J CF = 16.11 Hz), 123.57, 123.77, 123.89 (d, JCF = 3.57 Hz),
124.53 (d, JCF = 8.08 Hz), 127.60, 130.26 (d, JCF = 2.58 Hz), 130.99,
131.04 (d, JCF = 4.82 Hz), 138.45, 140.26, 144.34 (d, JCF = 10.93 Hz),
146.47 (d, JCF = 3.06 Hz), 155.70, 156.74 (d, JCF = 238.3 Hz), 157.26
(d, JCF = 246.9 Hz), 166.40; MS(ESIÀ) m/z 497.0 (MÀH)À, Anal.
Calcd for C25H22F2N2O5S: C, 60.23; H, 4.04, F 7.62; N, 5.62; S,
6.43. Found: C, 60.18; H, 4.12, F 7.57; N, 5.64; S, 6.46.
4.1.4.14. 2-(4-Chloro-2-(6-cyano-2-naphthyloxy)phenoxy)-N-(2-
methyl-4-sulfamoylphenyl)acetamide (12n). Yield: 58%; light
yellow solid; mp 244.3–246.1 °C; 1H NMR (400 MHz, DMSO-d6) d
(ppm) 2.10 (s, 3H, CH3), 4.83 (s, 2H, OCH2), 7.28–8.09 (m, 12H;
Ph and Naph), 7.26 (s, 2H, SO2NH2), 9.37 (s, 1H, CONH); 13C NMR
(100 MHz, DMSO-d6)
d (ppm) 17.52, 67.66, 106.75, 110.82,
119.30, 119.96, 120.11, 122.49, 123.67, 123.76, 123.85, 125.35,
126.99, 127.70, 128.31, 128.49, 130.88, 131.08, 134.21, 135.70,
138.46, 140.29, 143.75, 149.14, 157.62, 166.24; MS(ESIÀ) m/z
520.0 (35Cl), 521.9 (37Cl) (MÀH)À; Anal. Calcd for C26H20ClN3O5S:
C, 59.83; H, 3.86; Cl, 6.79; N, 8.05; S, 6.14. Found: C, 59.78; H, 3.90;
Cl, 6.76; N, 8.08; S, 6.12
4.1.4.19. 2-(4-Chloro-2-(1-chloro-3-methyl-2-naphthyloxy) phe-
noxy)-N-(2-methyl-4-sulfamoylphenyl)acetamide (12s). Yield:
65%; white solid; mp 223.6–225.1 °C; 1H NMR (400 MHz, DMSO-
d6) d (ppm) 2.28 (s, 3H, Ph-CH3), 2.31 (s, 3H, Naph-CH3), 4.99 (s,
2H, OCH2), 6.34–8.15 (m, 11H; Ph and Naph), 7.28 (s, 2H, SO2NH2),
9.60 (s, 1H, CONH); C13 NMR (100 MHz, DMSO-d6) d (ppm) 16.58,
17.50, 68.34, 113.57, 116.65, 122.45, 122.76, 123.17, 123.46,
123.97, 125.41, 126.83, 127.40, 127.72, 127.88, 129.24, 129.66,
130.59, 131.00, 131.78, 138.66, 140.16, 145.97, 146.73, 146.91,
166.55; MS(ESI+) m/z 545.1 (35Cl+35Cl), 547.0 (35Cl+37Cl), 549.0
4.1.4.15. 2-(4-Fluro-2-(1-bromo-6-cyano-2-naphthyloxy) phen-
oxy)-N-(2-methyl-4-sulfamoylphenyl)acetamide
(12o). Yield:
68%; light yellow solid; mp 221.5–222.9 °C; 1H NMR (400 MHz,
DMSO-d6) d (ppm) 2.10 (s, 3H, CH3), 4.88 (s, 2H, OCH2), 6.89–
8.63 (m, 11H; Ph and Naph), 7.26 (s, 2H, SO2NH2), 9.34 (s, 1H,
CONH); 13C NMR (100 MHz, DMSO-d6) d (ppm) 17.46, 67.59,
103.20 (d, JCF = 27.75 Hz), 107.63, 108.13 (d, JCF = 23.06 Hz),
118.77, 119.16, 122.85 (d, JCF = 10.03 Hz), 123.60, 123.77, 127.00,
127.61, 128.72, 129.18, 130.34, 133.94, 134.80, 138.38, 139.45 (d,
JCF = 2.98 Hz), 140.30, 150.63 (d, JCF = 10.77 Hz), 154.00, 154.75,
159.66 (d, JCF = 241.67 Hz), 165.98; MS(ESIÀ) m/z 581.9 (79Br),
583.8 (81Br) (MÀH)À; Anal. Calcd for C26H19BrFN3O5S: C, 53.43;
H, 3.28; Br, 13.67, F 3.25; N, 7.19; S, 5.49. Found: C, 53.37; H,
3.30; Br, 13.62, F 3.28; N, 7.14; S, 5.42.
(
37Cl+37Cl) (M+H)+; Anal. Calcd for C26H22Cl2N2O5S: C, 57.25; H,
4.07; Cl, 13.00; N, 5.14; S, 5.88. Found: C, 57.32; H, 4.03; Cl,
13.03; N, 5.09; S, 5.84
4.1.4.20. 2-(4-Chloro-2-(3-methyl-2-naphthyloxy)phenoxy)-N-
(2-methyl-4-sulfamoylphenyl)acetamide
(12t). Yield:
67%;
white solid; mp 206.7–208.4 °C; 1H NMR (400 MHz, DMSO-d6) d
(ppm) 2.12 (s, 3H, Ph-CH3), 2.44 (s, 3H, Naph-CH3), 4.85 (s, 2H,
OCH2), 7.08–7.80 (m, 12H; Ph and Naph), 7.27 (s, 2H, SO2NH2),
9.35 (s, 1H, CONH); C13 NMR (100 MHz, DMSO-d6) d (ppm)
16.51, 17.46, 68.02, 111.84, 116.67, 120.59, 123.59, 123.85,
124.65, 124.83, 125.44, 125.75, 126.78, 126.88, 127.66, 128.32,
129.58, 129.95, 131.02, 132.60, 138.52, 140.29, 145.77, 148.51,
153.96, 166.40; MS(ESIÀ) m/z 509.0 (35Cl), 511.0 (37Cl) (MÀH)À,
4.1.4.16. 2-(4-Fluro-2-(1-chloro-6-cyano-2-naphthyloxy) phen-
oxy)-N-(2-methyl-4-sulfamoylphenyl)acetamide (12p). Yield:
73%; light yellow solid; mp 210.8–212.6 °C; 1H NMR (400
MHz, DMSO-d6) d (ppm) 2.11 (s, 3H, CH3), 4.88 (s, 2H, OCH2),