Journal of Medicinal Chemistry 4-(tert-Butyldimethylsilyloxy)phenyl 3-(3-Ethylureido)- benzenesulfonate (43). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (75:25)). Yield, 48%; yellowish oil. IR ν: 3370 (NH), 1659 (CO) cm−1. 1H NMR (CDCl3): δ 7.98 (s, 1H, NH), 7.83 (s, 1H, Ar), 7.79−7.76 (m, 1H, Ar), 7.30−7.26 (m, 2H, Ar), 6.82−6.79 (m, 2H, Ar), 6.68−6.65 (m, 2H, Ar), 5.60 (brs, 1H, NH), 3.29−3.22 (m, 2H, CH2), 1.13−1.08 (m, 2H, CH2), 0.93 (s, 9H, 3 × CH3), 0.13 (s, 6H, 2 × CH3). 13C NMR (DMSO-d6): δ 155.8, 154.6, 143.4, 140.7, 135.4, 129.7, 124.5, 123.2, 122.0, 120.7, 117.9, 35.1, 25.6, 18.1, 15.2, −4.5. 4-Hydroxyphenyl 3-(3-Ethylureido)benzenesulfonate (44). Method E was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, ethyl acetate to ethyl acetate/methanol (90:10)). Yield, 50%; white sticky solid. IR ν: 1649 (CO) cm−1. 1H NMR (DMSO-d6): δ 9.67 (s, 1H, OH), 8.95 (s, 1H, NH), 8.09 (s, 1H, Ar), 7.66−7.26 (m, 3H, Ar), 6.82−6.68 (m, 4H, Ar), 6.27 (t, 1H, J = 5.1 Hz, NH), 3.14−3.09 (m, 2H, CH2), 1.06 (t, 3H, J = 7.0 Hz, CH3). 13C NMR (DMSO-d6): δ 156.3, 154.8, 141.8, 141.3, 134.9, 129.9, 123.0, 123.0, 120.2, 116.2, 116.0, 34.1, 15.3. MS (APSI+) m/z found 337.1; C15H17N2O5S (M+ + H) requires 337.1. 2-Tolyl 4-(3-Ethylureido)benzenesulfonate (45). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ ethyl acetate 90:10)). Yield, 70%; white solid; mp, 137−138 °C. IR ν: 3363 (NH), 1663 (CO) cm−1. 1H NMR (CDCl3): δ 8.08 (s, 1H, NH), 7.66−7.63 (m, 2H, Ar), 7.55−7.52 (m, 2H, Ar), 7.11−7.06 (m, 3H, Ar), 6.96−6.93 (m, 1H, Ar), 5.69 (brs, 1H, NH), 3.27−3.19 (m, 2H, CH2), 2.05 (s, 3H, CH3), 1.09 (t, 3H, J = 7.1 Hz, CH3). 13C NMR (CDCl3): δ 155.5, 148.2, 145.8, 131.7, 131.5, 129.7, 127.4, 127.2, 126.9, 122.2, 117.8, 34.9, 16.3, 15.2. MS (APSI+) m/z found 335.1; C16H19N2O4S (M+ + H) requires 335.1. 2-Ethylphenyl 4-(3-Ethylureido)benzenesulfonate (46). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (65:35) to hexanes/ethyl acetate (55:45)). Yield, 83%; orange solid; mp, 123 °C. IR ν: 3389 (NH), 1671 (CO) cm−1. 1H NMR (CDCl3): δ 8.19 (s, 1H, NH), 7.72−769 (m, 2H, Ar), 7.56−7.52 (m, 2H, Ar), 7.18−7.07 (m, 3H, Ar), 6.99−6.96 (m, 1H, Ar), 5.81 (brs, 1H, NH), 3.28−3.22 (m, 2H, CH2), 2.49 (q, 2H, J = 7.5 Hz, CH2), 1.12−1.05 (m, 6H, 2 × CH3). 13C NMR (CDCl3): δ 155.5, 147.7, 145.6, 137.2, 130.0, 129.7, 127.4, 126.9, 121.9, 117.9, 102.6, 35.0, 22.8, 15.2, 14.0. MS (APSI+) m/z found 349.1; C17H21N2O4S (M+ + H) requires 349.1. 2-Propylphenyl 4-(3-Ethylureido)benzenesulfonate (47). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (65:35) to hexanes/ethyl acetate (55:45)). Yield, 73%; yellowish solid; mp, 108 °C. IR ν: 3383 (NH), 1666 (CO) cm−1. 1H NMR (CDCl3): δ 8.08 (s, 1H, NH), 7.72−7.69 (m, 2H, Ar), 7.55−7.52 (m, 2H, Ar), 7.16− 7.06 (m, 3H, Ar), 6.99−6.97 (m, 1H, Ar), 5.67 (brs, 1H, NH), 3.26− 3.22 (m, 2H, CH2), 2.42 (t, 2H, J = 7.7 Hz, CH2), 1.55−1.43 (m, 2H, CH2), 1.10 (t, 3H, J = 7.2 Hz, CH3), 0.83 (t, 3H, J = 7.3 Hz, CH3). 13C NMR (CDCl3): δ 155.3, 147.9, 145.5, 135.7, 130.7, 129.7, 127.8, 127.2, 127.0, 122.0, 117.8, 35.1, 31.8, 23.0, 15.2, 13.9. MS (APSI+) m/ z found 363.1; C18H23N2O4S (M+ + H) requires 363.1. 4-(tert-Butyldimethylsilyloxy)phenyl 4-(3-Ethylureido)- benzenesulfonate (48). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (75:25)). Yield, 53%; yellowish oil. IR ν: 3357 (NH), 1665 (CO) cm−1. 1H NMR (CDCl3): δ 7.93 (s, 1H, NH), 7.66−7.60 (m, 2H, Ar), 7.49−7.42 (m, 2H, Ar), 7.86−7.78 (m, 2H, Ar), 6.72−6.66 (m, 2H, Ar), 5.50 (brs, 1H, NH), 3.28−3.20 (m, 2H, CH2), 1.15−1.05 (m, 3H, CH3), 0.92 (s, 9H, 3 × CH3), 0.14 (s, 6H, 2 × CH3). 13C NMR (CDCl3): δ 155.1, 154.6, 145.5, 143.4, 131.0, 129.9, 123.3, 120.7, 117.7, 35.7, 25.6, 18.1, 15.2, −4.5. 4-Hydroxyphenyl 4-(3-Ethylureido)benzenesulfonate (49). Method E was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, ethyl acetate to ethyl acetate/methanol (90:10)). Yield, 66%; white oil. IR ν: 3450−3075 (OH), 1666 (C O), 1357 (OH) cm−1. 1H NMR (acetone-d6): δ 8.48 (s, 1H, NH), Article 7.73−7.63 (m, 4H, Ar), 6.84−6.75 (m, 4H, Ar), 6.02 (brs, 1H, NH), 3.27−3.21 (m, 2H, CH2), 1.12 (t, 3H, J = 7.1 Hz, CH3), 3.08 (brs, 1H, OH). 13C NMR (acetone-d6): δ 156.9, 155.2, 147.3, 143.2, 130.5, 127.2, 124.1, 117.9, 116.5, 35.2, 15.5. MS (APSI+) m/z found 337.1; C15H17N2O5S (M+ + H) requires 337.1. 3-(3-Ethylureido)-N-2-tolylbenzenesulfonamide (50). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (50:50) to ethyl acetate) and was recrystallized with MeOH and ﬁltered. Yield, 15%; white solid; mp, 199−200 °C. IR ν: 3333 (NH), 1685 (CO) cm−1. 1H NMR (CDCl3/DMSO-d6): δ 9.55 (s, 1H, NH), 8.81 (s, 1H, NH), 7.90 (s, 1H, Ar), 7.59−7.57 (m, 1H, Ar), 7.40−7.35 (m, 1H, Ar), 7.16−7.08 (m, 4H, Ar), 7.00−6.97 (m, 1H, Ar), 6.17 (brs, 1H, NH), 3.16−3.07 (m, 2H, CH2), 2.03 (s, 3H, CH3), 1.06 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (DMSO-d6): δ 154.9, 141.3, 141.2, 135.0, 134.2, 130.7, 129.4, 126.4, 126.4, 126.3, 121.1, 118.8, 115.2, 34.0, 17.7, 15.4. MS (APSI+) m/z found 334.2; C16H20N3O3S (M+ + H) requires 334.1. N-(2-Ethylphenyl)-3-(3-ethylureido)benzenesulfonamide (51). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (40:60) to hexanes/ethyl acetate (80:20)) and was recrystallized with MeOH and ﬁltered. Yield, 4%; yellowish solid; mp, 229−230 °C. IR ν: 3312 (NH), 1643 (CO) cm−1. 1H NMR (DMSO-d6): δ 8.97 (s, 1H, NH), 7.96 (s, 1H, NH), 7.78−7.76 (m, 1H, Ar), 7.53−7.24 (m, 6H, Ar), 6.97−6.95 (m, 1H, Ar), 6.23 (brs, 1H, NH), 3.18−3.11 (m, 2H, CH2), 2.28−2.24 (m, 2H, CH2), 1.22−0.95 (m, 6H, 2 × CH3). 13C NMR (DMSO-d6): δ 154.8, 145.7, 141.6, 139.0, 132.1, 131.6, 130.6, 129.7, 129.2, 126.5, 123.0, 120.2, 116.7, 34.1, 22.8, 15.4, 13.8. MS (APSI−) m/z found 346.0; C17H20N3O3S (M− − H) requires 346.1. 3-(3-Ethylureido)-N-(2-propylphenyl)benzenesulfonamide (52). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ ethyl acetate (75:25)) and was recrystallized with MeOH and ﬁltered. Yield, 11%; yellowish solid; mp, 147 °C. IR ν: 3288 (NH), 1649 (C O) cm−1. 1H NMR (DMSO-d6): δ 9.54 (s, 1H, NH), 8.81 (s, 1H, NH), 7.93 (s, 1H, Ar), 7.60−7.57 (m, 1H, Ar), 7.41−6.91 (m, 6H, Ar), 3.17−3.10 (m, 2H, CH2), 2.47 (m, 2H, J = 7.8 Hz, CH2), 1.41−1.32 (m, 2H, CH2), 1.06 (t, 3H, J = 7.1 Hz, CH3), 0.82 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (DMSO-d6): δ 154.8, 141.3, 141.2, 138.8, 134.4, 129.6, 129.3, 126.6, 126.5, 126.1, 121.0, 118.8, 115.3, 34.0, 32.3, 22.9, 15.4, 14.0. MS (APSI+) m/z found 362.2; C18H24N3O3S (M+ + H) requires 362.2. 4-(3-Ethylureido)-N-2-tolylbenzenesulfonamide (53). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ ethyl acetate (75:25)) and was recrystallized with MeOH and ﬁltered. Yield, 15%; white solid; mp, 246−247 °C. IR ν: 3051 (NH), 1679 (CO) cm−1. 1H NMR (CDCl3/DMSO-d6): δ 7.46−7.22 (m, 4H, Ar), 7.12−6.91 (m, 4H, Ar), 3.15 (q, 2H, J = 7.2 Hz, CH2), 1.92 (s, 3H, CH3), 1.04 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (DMSO-d6): δ 154.7, 144.6, 135.1, 134.0, 131.9, 130.7, 127.8, 126.4, 126.3, 126.2, 116.8, 34.0, 17.7, 15.3. MS (APSI−) m/z found 331.9; C16H18N3O3S (M− − H) requires 332.1. N-(2-Ethylphenyl)-4-(3-ethylureido)benzenesulfonamide (54). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (75:25)) and was recrystallized with MeOH and ﬁltered. Yield, 53%; white solid; mp, 223−224 °C. IR ν: 3107 (NH), 1683 (CO) cm−1. 1H NMR (DMSO-d6): δ 9.35 (s, 1H, NH), 8.91 (s, 1H, NH), 7.55−7.49 (m, 4H, Ar), 7.21−7.05 (m, 4H, Ar), 6.89 (t, 1H, J = 5.4 Hz, NH), 3.17−3.08 (m, 2H, CH2), 2.55−2.48 (m, 2H, CH2), 1.22−1.05 (m, 6H, 3 × CH3). 13C NMR (DMSO-d6): δ 154.5, 144.5, 140.2, 134.4, 131.9, 128.9, 127.9, 126.5, 126.4, 126.1, 116.8, 34.0, 23.1, 15.3, 14.4. MS (APSI+) m/z found 346.0; C17H20N3O3S (M+ + H) requires 346.1. 4-(3-Ethylureido)-N-(2-propylphenyl)benzenesulfonamide (55). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (75:25)) and was recrystallized with MeOH and ﬁltered. Yield, 21%; yellowish solid; mp, 203 °C. IR ν: 6204 dx.doi.org/10.1021/jm3006492 | J. Med. Chem. 2012, 55, 6194−6208