X.-D. Ma et al. / Bioorg. Med. Chem. 19 (2011) 4704–4709
4707
mixture was poured into water (30 mL) and extracted twice with
3.2.6. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
EtOAc (2 ꢀ 30 mL). The combined organic layers were washed with
2 N HC1, dried over MgSO4, filtered, and concentrated in vacuo to
give the crude product which was crystallized from acetonitrile
to give 7a–t as white solids in yield of 73–93%.
2-[hydroxyl(3-chlorphenyl)methyl]phenoxyl}acetamide (7f)
Yield 87.1%; mp 181.1–182.5 °C; 1H NMR (DMSO-d6) d (ppm):
2.25 (s, 3H, CH3), 4.73–4.85 (m, 2H, CH2), 5.94 (d, 1H, J = 4.4 Hz,
OH), 6.10 (d, 1H, J = 4.4 Hz, CH), 7.31 (s, 2H, NH2), 7.00–7.74 (m,
10H, PhH), 9.56 (s, 1H, NH); 13C NMR (DMSO-d6) d: 17.8, 67.6,
68.1, 114.0, 123.5, 123.8, 124.4, 125.2, 126.6, 127.0, 127.5 (2C,
127.48, 127.50), 127.7, 127.9, 131.8, 136.3, 137.0, 138.6, 140.5,
144.3, 153.0, 166.6; MS (ESIꢁ) m/z 493 [MꢁH]ꢁ; Anal. Calcd for
3.2.1. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-[4-chloro-
2-(hydroxyphenylmethyl)phenoxyl]acetamide (7a)
Yield 91.7%; mp 185.3–186.4 °C; 1H NMR (DMSO-d6) d (ppm):
2.25 (s, 3H, CH3), 4.74–4.85 (m, 2H, CH2), 6.00 (d, 1H, J = 4.4 Hz,
OH), 6.15 (d, 1H, J = 4.0 Hz, CH), 7.31 (s, 2H, NH2), 7.00–7.75 (m,
11H, PhH), 9.59 (s, 1H, NH); 13C NMR (DMSO-d6) d: 17.8, 67.9,
68.1, 114.0, 123.8, 124.4, 125.2, 126.4 (2C), 126.6, 126.9, 127.6,
127.7, 127.9, 128.0 (2C), 131.8, 136.2, 138.6, 140.5, 144.4, 153.1,
166.6; MS (ESIꢁ) m/z 459 [MꢁH]ꢁ; Anal. Calcd for C22H21ClN2O5S:
C, 57.33; H, 4.59; Cl, 7.69; N, 6.08; S, 6.96. Found: C, 57.30; H, 4.58;
Cl, 7.70; N, 6.10; S, 6.98.
C22H20Cl2N2O5S: C, 53.34; H, 4.07; Cl, 14.31; N, 5.65; S, 6.47. Found:
C, 53.33; H, 4.04; C, 14.32; N, 5.66; S, 6.45.
3.2.7. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(3-fluorophenyl)methyl]phenoxyl}acetamide (7g)
Yield 85.4%; mp 157.8–158.9 °C; 1H NMR (DMSO-d6) d (ppm):
2.27 (s, 3H, CH3), 4.78–4.88 (m, 2H, CH2), 6.15 (m, 2H, OH, CH),
7.31 (s, 2H, NH2), 6.98–7.74 (m, 10H, PhH), 9.64 (s, 1H, NH); 13C
NMR (DMSO-d6) d: 17.8, 67.4, 67.6, 113.0 (JC-F = 22.2 Hz), 113.6
(JC-F = 20.4 Hz), 114.1, 122.3 (JC-F = 2.8 Hz), 123.8, 124.4, 125.3,
126.6, 127.7, 127.8, 129.9 (JC-F = 4.0 Hz), 131.8, 135.6, 138.6,
140.6, 147.5 (JC-F = 7.1 Hz), 153.0, 162.0 (JC-F = 241.1 Hz), 166.6;
MS (ESIꢁ) m/z 477 [MꢁH]ꢁ; Anal. Calcd for C22H20ClFN2O5S: C,
55.17; H, 4.21; Cl, 7.40; F, 3.97; N, 5.85; S, 6.70. Found: C, 55.15;
H, 4.20; Cl, 7.43; F, 3.95; N, 5.82; S, 6.73.
3.2.2. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(2-methylphenyl)methyl]phenoxyl}acetamide (7b)
Yield 93.2%; mp 195.5–196.4 °C; 1H NMR (DMSO-d6) d (ppm):
2.23 (s, 3H, CH3), 2.29 (s, 3H, CH3), 4.72–4.86 (m, 2H, CH2), 5.85
(d, 1H, J = 4.8 Hz, OH), 6.29 (d, 1H, J = 4.8 Hz, CH), 7.32 (s, 2H,
NH2), 7.06–7.72 (m, 10H, PhH), 9.49 (s, 1H, NH); 13C NMR
(DMSO-d6) d: 17.8, 18.9, 65.4, 67.8, 114.2, 123.8, 124.5, 125.2,
125.7, 128.6, 127.0, 127.4, 127.8, 127.9, 130.1, 131.9, 135.3,
136.3, 138.6, 140.8, 141.6, 153.7, 166.7; MS (ESIꢁ) m/z 473
[MꢁH]ꢁ; Anal. Calcd for C23H23ClN2O5S: C, 58.16; H, 4.88; Cl,
7.46; N, 5.90; S, 6.75. Found: C, 58.15; H, 4.90; Cl, 7.45; N, 5.89;
S, 6.73.
3.2.8. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(3-nitrophenyl)methyl]phenoxyl}acetamide (7h)
Yield 78.9%; mp 189.9–190.7 °C; 1H NMR (DMSO-d6) d (ppm):
2.28 (s, 3H, CH3), 4.81–4.90 (m, 2H, CH2), 6.29 (s, 1H, CH), 6.44 (s,
1H, OH), 7.73 (s, 2H, NH2), 7.04–8.30 (m, 10H, PhH), 9.80 (s, 1H,
NH); 13C NMR (DMSO-d6) d: 18.0, 67.5, 67.6, 114.2, 120.9, 122.0,
123.9, 124.6, 125.4, 126.6, 127.8, 128.2, 129.7, 132.1, 133.3, 136.1,
138.8, 140.6, 146.7, 147.8, 153.1, 166.7; MS (ESIꢁ) m/z 504 [MꢁH]
ꢁ; Anal. Calcd for C22H20ClN3O7S: C, 52.23; H, 3.98; Cl, 7.01; N,
8.31; S, 6.34. Found: C, 52.20; H, 3.95; Cl, 7.06; N, 8.34; S, 6.31.
3.2.3. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(3-methylphenyl)methyl]phenoxyl}acetamide (7c)
Yield 90.5%; mp 193.4–194.7 °C; 1H NMR (DMSO-d6) d (ppm):
2.24 (s, 3H, CH3), 2.25 (s, 3H, CH3), 4.73–4.85 (m, 2H, CH2), 5.95
(s, 1H, OH), 6.10 (s, 1H, CH), 7.31 (s, 2H, NH2), 6.99–7.74 (m, 10H,
PhH), 9.54 (s, 1H, NH); 13C NMR (DMSO-d6) d: 17.8, 21.1, 67.6,
68.1, 114.0, 123.5, 123.8, 124.4, 125.2, 126.6, 127.0, 127.5, 127.6,
127.7, 127.9, 131.8, 136.3, 137.0, 138.6, 140.6, 144.3, 153.0,
166.6; MS (ESIꢁ) m/z 473 [MꢁH]ꢁ; Anal. Calcd for C23H23ClN2O5S:
C, 58.16; H, 4.88; Cl, 7.46; N, 5.90; S, 6.75. Found: C, 58.15; H, 4.89;
Cl, 7.45; N, 5.90; S, 6.75.
3.2.9. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(2,3-dimethylphenyl)methyl]phenoxyl}acetamide
(7i)
Yield 91.7%; mp 173.4–174.3 °C; 1H NMR (DMSO-d6) d (ppm):
2.15 (s, 3H, CH3), 2.18 (s, 3H, CH3), 2.23 (s, 3H, CH3), 4.75–4.89
(m, 2H, CH2), 5.83 (s, 1H, OH), 6.33 (s, 1H, CH), 7.33 (s, 2H, NH2),
7.01–7.71 (m, 9H, PhH), 9.65 (s, 1H, NH); 13C NMR (DMSO-d6) d:
14.5, 17.9, 20.2, 65.5, 67.7, 114.1, 123.7, 123.8, 124.4, 124.6,
125.0 (2C), 127.4, 127.7 (2C), 128.6, 133.8, 136.6, 138.2, 138.6,
140.6, 141.5, 153.6, 166.8; MS (ESIꢁ) m/z 487 [MꢁH]ꢁ; Anal. Calcd
for C24H25ClN2O5S: C, 58.95; H, 5.15; Cl, 7.25; N, 5.73; S, 6.56.
Found: C, 58.92; H, 5.16; Cl, 7.27; N, 5.75; S, 6.54.
3.2.4. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(4-methylphenyl)methyl]phenoxyl}acetamide (7d)
Yield 92.1%; mp 190.4–191.7 °C; 1H NMR (DMSO-d6) d (ppm):
2.23 (s, 3H, CH3), 2.25 (s, 3H, CH3), 4.73–4.85 (m, 2H, CH2),
5.93(d, 1H, J = 4.4 Hz, OH), 6.09 (d, 1H, J = 4.4 Hz, CH),7.31 (s, 2H,
NH2), 7.00–7.73 (m, 10H, PhH), 9.59 (s, 1H, NH); 13C NMR
(DMSO-d6) d: 17.8, 20.9, 67.6, 67.9, 114.0, 123.8, 124.4, 125.1,
126.4, 126.6, 127.4, 127.7, 128.5 (2C), 131.8, 135.9, 136.4 (2C),
138.8, 140.6, 141.4, 153.0, 166.6; MS (ESIꢁ) m/z 473 [MꢁH]ꢁ; Anal.
Calcd for C23H23ClN2O5S: C, 58.16; H, 4.88; Cl, 7.46; N, 5.90; S, 6.75.
Found: C, 58.15; H, 4.90; Cl, 7.48; N, 5.93; S, 6.74.
3.2.10. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(2,4-dimethylhenyl)methyl]phenoxyl}acetamide (7j)
Yield 89.9%; mp 185.4–186.3 °C; 1H NMR (DMSO-d6) d (ppm):
2.21 (s, 6H, 2CH3), 2.25 (s, 3H, CH3), 4.72–4.85 (m, 2H, CH2), 5.78
(s, 1H, OH), 6.32 (s, 1H, CH), 7.27 (s, 2H, NH2), 6.92–7.70 (m, 9H,
PhH), 9.45 (s, 1H, NH); 13C NMR (DMSO-d6) d: 17.8, 18.8, 20.6,
65.2, 67.7, 114.0, 123.8, 124.5, 125.1, 126.2, 126.6, 127.3, 127.7
(2C), 130.8, 132.0, 135.1, 135.5, 135.9, 138.6, 138.7, 140.6, 153.6,
166.7; MS (ESIꢁ) m/z 487 [MꢁH]ꢁ; Anal. Calcd for C24H25ClN2O5S:
C, 58.95; H, 5.15; Cl, 7.25; N, 5.73; S, 6.56. Found: C, 58.92; H, 5.17;
Cl, 7.23; N, 5.70; S, 6.57.
3.2.5. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(2-chlorphenyl)methyl]phenoxyl}acetamide (7e)
Yield 88.4%; mp 173.7–174.8 °C; 1H NMR (DMSO-d6) d (ppm):
2.25 (s, 3H, CH3), 4.75–4.89 (m, 2H, CH2), 6.16 (s, 1H, OH), 6.41
(s, 1H, CH), 7.38 (s, 2H, NH2), 7.08–7.75 (m, 10H, PhH), 9.53 (s,
1H, NH); 13C NMR (DMSO-d6) d: 18.2, 66.1, 68.4, 114.9, 124.3,
124.8, 125.6, 127.6, 127.8, 128.2, 128.7, 129.2, 129.4, 129.7,
132.2, 134.4, 134.7, 139.0, 141.0, 141.2, 154.4, 166.2; MS (ESIꢁ)
m/z 493 [MꢁH]ꢁ; Anal. Calcd for C22H20Cl2N2O5S: C, 53.34; H,
4.07; Cl, 14.31; N, 5.65; S, 6.47. Found: C, 53.32; H, 4.05; C,
14.32; N, 5.63; S, 6.49.
3.2.11. ( )-N-[4-(Aminosulfonyl)-2-methylphenyl]-2-{4-chloro-
2-[hydroxyl(2,5-dimethylphenyl)methyl]phenoxyl}acetamide
(7k)
Yield 92.2%; mp 190.4–191.9 °C; 1H NMR (DMSO-d6) d (ppm):
2.22 (s, 9H, 3CH3), 4.72–4.85 (m, 2H, CH2), 5.79 (d, 1H, J = 4.8 Hz,