Journal of Medicinal Chemistry 3098 (NH), 1678 (CO) cm−1. 1H NMR (CDCl3/DMSO-d6): δ 9.02 (s, 1H, NH), 8.77 (s, 1H, NH), 7.51−7.44 (m, 4H, Ar), 7.10− 6.88 (m, 4H, Ar), 6.14 (brs, 1H, NH), 3.19−3.11 (m, 2H, CH2), 2.46 (t, 2H, J = 7.9 Hz, CH2), 1.45−1.32 (m, 2H, CH2), 1.08 (t, 3H, J = 7.1 Hz, CH3), 0.82 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (DMSO-d6): δ 154.8, 144.4, 138.5, 134.5, 131.9, 129.3, 127.7, 126.0, 125.9, 125.7, 116.5, 34.0, 33.3, 22.9, 15.2, 13.8. MS (APSI−) m/z found 360.0; C18H22N3O3S (M− − H) requires 360.1. General Procedure for the Synthesis of Compounds 56−73. For method F, the 3-nitrobenzene-1-sulfonyl chloride or 4-nitro- benzene-1-sulfonyl chloride (7.5 mmol) was dissolved in dry methylene chloride (20 mL) under a dry Ar atmosphere. The selected phenol or aniline (7.5 mmol) and trietylamine were then added dropwise to the solution. The reaction mixture was stirred for 24 h at room temperature. The solvent was evaporated and the residue dissolved in ethyl acetate. The solution was washed with 1 N HCl, 1 N NaOH, brine, dried over anhydrous Na2SO4, ﬁltered, and evaporated to dryness. For method G, the 3-nitrobenzene-1-sulfonyl chloride or 4- nitrobenzene-1-sulfonyl chloride (8 mmol) was dissolved in dry acetonitrile (10 mL) under an Ar atmosphere. The relevant aniline (8 mmol) and 4-dimethylaminopyridine were successively added dropwise, and the mixture was stirred for 48 h at room temperature. The solvent was evaporated and the residue dissolved in ethyl acetate. The solution was washed with hydrochloric acid (1 N), brine, dried over Na2SO4, ﬁltered, and evaporated to dryness. 2-Tolyl 4-Nitrobenzenesulfonate (56). Method F was used. Yield, 98%; yellowish solid; mp, 84−85 °C. IR ν: 1533 (NO2), 1191 (SO) cm−1. 1H NMR (CDCl3): δ 8.35 (d, 2H, J = 8.8 Hz, Ar), 8.06 (d, 2H, J = 8.8 Hz, Ar), 7.19−7.10 (m, 3H, Ar), 6.96−6.93 (m, 1H, Ar), 2.09 (s, 3H, CH3). 13C NMR (CDCl3): δ 151.0, 148.0, 141.7, 132.0, 131.4, 129.8, 127.6, 127.3, 124.5, 121.9, 16.3. 3-Tolyl 4-Nitrobenzenesulfonate (57). Method F was used. Yield, 97%; yellowish solid; mp, 94−95 °C. IR ν: 1533 (NO2), 1351 (NO2) cm−1. 1H NMR (CDCl3): δ 8.35 (d, 2H, J = 8.8 Hz, Ar), 8.02 (d, 2H, J = 8.8 Hz, Ar), 7.19−7.06 (m, 2H, Ar), 6.86 (s, 1H, Ar), 6.73−6.70 (m, 1H, Ar), 2.29 (s, 3H, CH3). 13C NMR (CDCl3): δ 151.0, 149.2, 141.1, 140.6, 129.9, 129.6, 128.5, 124.3, 122.7, 118.8, 21.2. 4-Tolyl 4-Nitrobenzenesulfonate (58). Method F was used. Yield, 96%; white solid; mp, 94−95 °C. IR ν: 1520 (NO2), 1199 (S O) cm−1. 1H NMR (CDCl3): δ 8.35 (d, 2H, J = 8.7 Hz, Ar), 8.01 (d, 2H, J = 8.7 Hz, Ar), 7.09 (d, 2H, J = 8.2 Hz, Ar), 6.85 (d, 2H, J = 8.2 Hz, Ar), 2.30 (s, 3H, CH3). 13C NMR (CDCl3) δ: 151.0, 147.1, 141.0, 137.8, 130.5, 129.9, 124.3, 121.8, 20.8. 4-Methoxyphenyl 4-Nitrobenzenesulfonate (59). Method F was used. Yield, 89%; white solid; mp, 150−151 °C. IR ν: 1540 (NO2), 1378 (NO2) cm−1. 1H NMR (DMSO-d6): δ 8.47 (d, 2H, J = 8.7 Hz, Ar), 8.14 (d, 2H, J = 8.7 Hz, Ar), 7.02−6.91 (m, 4H, Ar), 3.74 (s, 3H, CH3). 13C NMR (DMSO-d6): δ 158.3, 151.1, 142.1, 139.6, 130.1, 125.0, 123.2, 115.1, 55.6. 4-(Dimethylamino)phenyl 4-Nitrobenzenesulfonate (60). Method F was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (90:10) to hexanes/ ethyl acetate (70:30)). Yield, 41%; orange solid; mp, 129−130 °C. IR ν: 1513 (NO2), 1187 (SO) cm−1. 1H NMR (DMSO-d6): δ 8.47− 8.44 (m, 2H, Ar), 8.14−8.11 (m, 2H, Ar), 6.86−6.83 (m, 2H, Ar), 6.64−6.61 (m, 2H, Ar), 2.87 (s, 6H, 2 × CH3). 13C NMR (DMSO- d6): δ 149.4, 139.0, 130.1, 124.9, 122.4, 112.5, 40.1. 4-(tert-Butyldimethylsilyloxy)phenyl 4-Nitrobenzenesulfo- nate (61). Method F was used. Yield, 96%; yellowish solid; mp, 94−95 °C. IR ν: 1495 (NO2), 1377 (NO2) cm−1. 1H NMR (CDCl3): δ 8.33 (d, 2H, J = 8.7 Hz, Ar), 7.98 (d, 2H, J = 8.7 Hz, Ar), 6.84−6.70 (m, 4H, Ar), 0.92 (s, 9H, 3 × CH3), 0.15 (s, 6H, 2 × CH3). 13C NMR (CDCl3): δ 154.9, 151.0, 143.1, 140.9, 130.0, 124.3, 123.1, 121.0, 25.6, 18.1, −4.5. 2-Tolyl 3-Nitrobenzenesulfonate (62). Method F was used. Yield, 91%; white solid; mp, 63−64 °C. IR ν: 1533 (NO2), 1351 (NO2) cm−1. 1H NMR (CDCl3): δ 8.70 (s, 1H, Ar), 8.53 (d, 1H, J = 8.0 Hz, Ar), 8.20 (d, 1H, J = 7.7 Hz, Ar), 7.83−7.77 (m, 1H, Ar), Article 7.21−7.14 (m, 3H, Ar), 6.98 (d, 1H, J = 7.3 Hz, Ar), 2.12 (s, 3H, CH3). 13C NMR (CDCl3): δ 148.2, 148.0, 138.1, 133.8, 132.0, 131.3, 130.9, 128.7, 127.7, 127.3, 123.5, 122.0, 16.3. 2-Ethylphenyl 3-Nitrobenzenesulfonate (63). Method F was used. Yield, 78%; colorless oil. IR ν: 1533 (NO2), 1381 (NO2) cm−1. 1H NMR (CDCl3): δ 8.75 (s, 1H, Ar), 8.54 (d, 1H, J = 7.7 Hz, Ar), 8.23 (d, 1H, J = 7.7 Hz, Ar), 8.21−7.80 (m, 1H, Ar), 7.24−7.13 (m, 3H, Ar), 7.02−7.00 (m, 1H, Ar), 2.52 (q, 2H, J = 7.6 Hz, CH2), 1.13 (t, 3H, J = 7.6 Hz, CH3). 13C NMR (CDCl3): δ 148.3, 147.5, 138.3, 137.0, 133.7, 130.7,130.2, 128.6, 127.8, 127.2, 123.6, 121.8, 22.8, 14.04. 2-Propylphenyl 3-Nitrobenzenesulfonate (64). Method F was used. Yield, 80%; yellowish oil. IR ν: 1533 (NO2), 1381 (NO2) cm−1. 1H NMR (CDCl3): δ 8.75 (s, 1H, Ar), 8.55 (d, 1H, J = 7.9 Hz, Ar), 8.23 (d, 1H, J = 7.9 Hz, Ar), 7.82−7.77 (m, 1H, Ar), 7.23−7.15 (m, 3H, Ar), 7.05−7.03 (m, 1H, Ar), 2.44 (t, 2H, J = 7.8 Hz, CH2), 1.58− 1.47 (m, 2H, CH2), 0.87 (t, 3H, J = 7.4 Hz, CH3). 13C NMR (CDCl3): δ 148.3, 147.7, 138.4, 135.5, 133.7, 130.9, 130.7, 128.6, 127.6, 127.3, 123.6, 121.8, 31.9, 23.0, 13.9. 4-(tert-Butyldimethylsilyloxy)phenyl 3-Nitrobenzenesulfo- nate (65). Method F was used. Yield, 95%; yellowish oil. IR ν: 1542 (NO2), 1377 (NO2) cm−1. 1H NMR (CDCl3): δ 8.65 (s, 1H, Ar), 8.52−8.50 (m, 1H, Ar), 8.14−8.12 (m, 1H, Ar), 7.78−7.73 (m, 1H, Ar), 6.86−6.83 (m, 2H, Ar), 6.75−6.72 (m, 2H, Ar), 0.95 (s, 9H, 3 × CH3), 0.17 (s, 6H, 2 × CH3). 13C NMR (CDCl3): δ 155.0, 148.2, 143.0, 137.4, 133.9, 130.6, 128.6, 123.8, 123.1, 121.0, 25.6, 18.2, −4.5. 2-Ethylphenyl 4-Nitrobenzenesulfonate (66). Method F was used. Yield, 90%; white solid; mp, 82 °C. IR ν: 1530 (NO2), 1376 (NO2) cm −1. 1H NMR (CDCl3): δ 8.39 (d, 2H, J = 8.7 Hz, Ar), 8.10 (d, 2H, J = 8.7 Hz, Ar), 7.25−7.12 (m, 3H, Ar), 7.00−6.97 (m, 1H, Ar), 2.50 (q, 2H, J = 7.5 Hz, CH2), 1.12 (t, 3H, J = 7.5 Hz, CH3). 13C NMR (CDCl3): δ 150.9, 147.6, 141.8, 137.0, 130.2, 129.7, 127.8, 127.2, 124.4, 121.7, 22.9, 14.04. 2-Propylphenyl 4-Nitrobenzenesulfonate (67). Method F was used. Yield, 85%; yellowish solid; mp, 58 °C. IR ν: 1525 (NO2), 1375 (NO2) cm−1. 1H NMR (CDCl3): δ 8.40 (d, 2H, J = 8.8 Hz, Ar), 8.10 (d, 2H, J = 8.8 Hz, Ar), 7.23−7.13 (m, 3H, Ar), 7.02−6.99 (m, 1H, Ar), 2.42 (t, 2H, J = 7.7 Hz, CH2), 1.59−1.46 (m, 2H, CH2), 0.87 (t, 3H, J = 7.4 Hz, CH3). 13C NMR (CDCl3): δ 150.9, 147.8, 141.9, 135.6, 131.0, 129.7, 127.6, 127.2, 124.4, 121.8, 31.9, 23.0, 13.9. 3-Nitro-N-2-tolylbenzenesulfonamide (68). Method G was used. Yield, 94%; white solid; mp, 156 °C. IR ν: 1529 (NO2), 1354 (NO2) cm−1. 1H NMR (DMSO-d6): δ 10.03 (s, 1H, NH), 8.51−8.44 (m, 2H, Ar), 8.09−8.06 (m, 1H, Ar), 7.91−7.86 (m, 1H, Ar), 7.20− 6.91 (m, 4H, Ar), 2.06 (s, 3H, CH3). 13C NMR (DMSO-d6): δ 147.8, 142.1, 134.7, 134.2, 132.6, 131.4, 131.0, 127.4, 127.0, 126.8, 126.6, 121.4, 17.7. N-(2-Ethylphenyl)-3-nitrobenzenesulfonamide (69). Method F was used. The crude product was puriﬁed by recrystallized with MeOH and ﬁltered. Yield, 56%; white solid; mp, 159−160 °C. IR ν: 1532 (NO2), 1352 (NO2) cm−1. 1H NMR (CDCl3): δ 8.74 (s, 1H, Ar), 8.59−8.56 (m, 1H, Ar), 8.37−8.34 (m, 1H, Ar), 7.87−7.82 (m, 1H, Ar), 7.53−7.42 (m, 2H, Ar), 7.24−7.18 (m, 1H, Ar), 6.87−6.85 (m, 1H, Ar), 2.28 (q, 2H, J = 7.5 Hz, CH2), 1.09 (t, 3H, J = 7.5 Hz, CH3). 13C NMR (CDCl3): δ 148.2, 145.6, 140.9, 134.5, 131.6, 131.5, 131.4, 130.6, 130.1, 128.8, 126.9, 124.3, 23.6, 14.0. 3-Nitro-N-(2-propylphenyl)benzenesulfonamide (70). Meth- od G was used. Yield, 55%; yellowish solid; mp, 64−65 °C. IR ν: 1529 (NO2), 1350 (NO2) cm−1. 1H NMR (CDCl3): δ 8.60−8.55 (m, 1H, Ar), 8.40−8.34 (m, 1H, Ar), 8.05−8.02 (m, 1H, Ar), 7.69−7.63 (m, 1H, Ar), 7.16−7.07 (m, 4H, Ar), 2.34 (t, 2H, J = 7.7 Hz, CH2), 1.43− 1.33 (m, 2H, CH2), 0.81 (t, 3H, J = 7.3 Hz, CH3). 13C NMR (CDCl3): δ 148.2, 141.7, 136.4, 134.6, 132.8, 130.4, 130.2, 127.4, 127.2, 127.1, 124.9, 122.5, 32.7, 23.2, 13.8. 4-Nitro-N-2-tolylbenzenesulfonamide (71). Method G was used. Yield, 86%; orange solid; mp, 158 °C. IR ν: 1528 (NO2), 1343 (NO2) cm−1. 1H NMR (CDCl3/MeOD): δ 7.93−7.90 (m, 2H, Ar), 7.52−7.49 (m, 2H, Ar), 6.74−6.62 (m, 4H, Ar), 1.65 (s, 3H, CH3). 13C NMR (DMSO-d6): δ 149.7, 146.1, 134.6, 134.1, 131.0, 128.2, 127.0, 126.8, 126.6, 124.6, 17.7. 6205 dx.doi.org/10.1021/jm3006492 | J. Med. Chem. 2012, 55, 6194−6208