Journal of Medicinal Chemistry 23.0, 13.9. MS (APSI+) m/z found 411.2; C19H24ClN2O4S (M+ + H) requires 411.1. 4-(tert-Butyldimethylsilyloxy)phenyl 4-[3-(3-Chloropropyl)- ureido]benzenesulfonate (32). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (90:10)). Yield, 60%; yellowish oil. IR ν: 3303 (NH), 1672 (CO) cm−1. 1H NMR (CDCl3): δ 7.89 (s, 1H, NH), 7.65−7.62 (m, 2H, Ar), 7.52−7.50 (m, 2H, Ar), 6.82−6.79 (m, 2H, Ar), 6.72−6.68 (m, 2H, Ar), 5.78 (brs, 1H, NH), 3.58−3.55 (m, 2H, CH2), 3.41−3.37 (m, 2H, CH2), 1.98− 1.94 (m, 2H, CH2), 0.95−0.91 (s, 9H, 3 × CH3), 0.15 (s, 6H, 2 × CH3). 13C NMR (CDCl3): δ 155.2, 154.7, 145.4, 143.3, 130.0, 126.9, 123.3, 120.8, 117.9, 42.3, 37.5, 32.4, 25.6, 18.1, −4.5. 4 - H y d r o x y p h e n y l 4 - [ 3 - ( 3 - C h l o r o p r o p y l ) u r e i d o ] - benzenesulfonate (33). Method E was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, ethyl acetate to ethyl acetate/methanol (90:10)). Yield, 63%; Yellowish oil. IR ν: 3620− 3375 (OH), 1678 (CO), 1359 (OH). 1H NMR (DMSO-d6): δ 9.67 (s, 1H, OH), 9.17 (s, 1H, NH), 7.64 (s, 4H, Ar), 6.80−6.68 (m, 4H, Ar), 6.54 (t, 1H, J = 5.6, NH), 3.72−3.67 (m, 2H, CH2), 3.28−3.22 (m, 2H, CH2), 1.97−1.88 (m, 2H, CH2). 13C NMR (DMSO-d6): δ 156.2, 154.7, 146.3, 141.4, 129.7, 125.1, 123.1, 117.1, 115.9, 43.0, 36.7, 32.5. MS (APSI+) m/z found 385.1; C16H18ClN2O5S (M+ + H) requires 385.1. 3-[3-(3-Chloropropyl)ureido]-N-2-tolylbenzenesulfonamide (34). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ ethyl acetate (70:30)) and recrystallized with MeOH and ﬁltered. Yield, 40%; yellowish solid; mp, 150 °C. IR ν: 3353 (NH), 1648 (C O) cm−1. 1H NMR (DMSO-d6): δ 9.55 (s, 1H, NH), 8.85 (s, 1H, NH), 7.91 (s, 1H, Ar), 7.58−7.56 (m, 1H, Ar), 7.40−7.35 (m, 1H, Ar), 7.16−7.08 (m, 4H, Ar), 6.70−6.67 (m, 1H, Ar), 6.33 (t, 1H, J = 5.5 Hz, NH), 3.70−3.66 (m, 2H, CH2), 3.25−3.19 (m, 2H, CH2), 2.03 (s, 3H, CH3), 1.95−1.88 (m, 2H, CH2). 13C NMR (DMSO-d6): δ 155.0, 141.2, 134.9, 134.2, 130.7, 129.4, 126.4, 126.3, 121.2, 118.9, 115.3, 113.1, 43.1, 36.6, 32.6, 17.7. MS (APSI+) m/z found 382.1; C17H21ClN3O3S (M+ + H) requires 382.1. 3 - [ 3 - ( 3 - C h l o r o p r o p y l ) u r e i d o ] - N - ( 2 - e t h y l p h e n y l ) - benzenesulfonamide (35). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (40:60) to hexanes/ethyl acetate (10:90)) and recrystallized with methanol and ﬁltered. Yield, 14%; yellowish solid; mp, 125 °C. IR ν: 3316 (NH), 1641 (CO) cm−1. 1H NMR (DMSO-d6): δ 9.05 (s, 1H, NH), 7.97 (s, 1H, Ar), 7.77−7.75 (m, 1H, Ar), 7.53−7.43 (m, 2H, Ar), 7.27−7.22 (m, 3H, Ar), 6.97−6.95 (m, 1H, Ar), 6.42 (t, 1H, J = 5.5, NH), 3.69 (t, 2H, J = 6.4 Hz, CH2), 3.25−3.21 (m, 2H, CH2), 2.26 (q, 2H, J = 7.3 Hz, CH2), 1.96−1.87 (m, 2H, CH2), 0.98 (t, 3H, J = 7.3 Hz, CH3). 13C NMR (acetone-d6/CDCl3): δ 156.2, 147.4, 141.9, 140.0, 132.1, 131.1, 130.1, 129.9, 126.9, 124.9, 122.5, 118.8, 117.4, 43.2, 37.8, 33.7, 24.2, 14.3. MS (APSI−) m/z found 393.9; C18H21ClN3O3S (M− − H) requires 394.1. 3 - [ 3 - ( 3 - C h l o r o p r o p y l ) u r e i d o ] - N - ( 2 - p r o p y l p h e n y l ) - benzenesulfonamide (36). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (80:20)) and recrystallized with MeOH and ﬁltered. Yield, 6%; yellowish solid; mp, 112 °C. IR ν: 3319 (NH), 1642 (CO). 1H NMR (DMSO-d6): δ 9.55 (s, 1H, NH), 8.85 (s, 1H, NH), 7.93 (s, 1H, Ar), 7.58−756 (m, 1H, Ar), 7.41−7.36 (m, 1H, Ar), 7.20−7.05 (m, 4H, Ar), 6.93−6.91 (m, 1H, Ar), 6.33 (brs, 1H, NH), 3.70−3.66 (m, 2H, CH2), 3.25−3.19 (m, 2H, CH2), 2.48− 2.43 (m, 2H, CH2), 1.94−1.86 (m, 2H, CH2), 1.41−1.28 (m, 2H, CH2), 0.81 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (DMSO-d6): δ 155.0, 141.2, 139.0, 138.8, 134.4, 129.6, 129.4, 126.6, 126.5, 126.2, 121.1, 119.0, 115.3, 43.1, 36.7, 32.6, 32.3, 22.9, 14.0. MS (ESI−) m/z found 408.1; C19H23ClN3O3S (M− − H) requires 408.1. 4-[3-(3-Chloropropyl)ureido]-N-2-tolylbenzenesulfonamide (37). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (80:20)) and was recrystallized with MeOH and ﬁltered. Yield, 20%; white solid; mp, 204−205 °C. IR: Article 3079 (NH), 1678 (CO) cm−1. 1H NMR (DMSO-d6): δ 9.35 (s, 1H, NH), 8.95 (s, 1H, NH), 7.56−7.49 (m, 4H, Ar), 7.13−7.00 (m, 4H, Ar), 6.45 (brs, 1H, NH), 3.70−3.66 (m, 2H, CH2), 3.27−3.21 (m, 2H, CH2), 2.02 (s, 3H, CH3), 1.93−1.89 (m, 2H, CH2). 13C NMR (DMSO-d6): δ 154.8, 144.5, 135.1, 134.0, 132.1, 130.7, 127.9, 126.4, 126.3, 126.2, 116.9, 43.0, 36.6, 32.5, 17.7. MS (ESI−) m/z found 380.1; C17H19ClN3O3S (M− − H) requires 380.1. 4 - [ 3 - ( 3 - C h l o r o p r o p y l ) u r e i d o ] - N - ( 2 - e t h y l p h e n y l ) - benzenesulfonamide (38). 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)) and was recrystallized with MeOH and ﬁltered. Yield, 13%; white solid; mp, 192 °C. IR ν: 3076 (NH), 1679 (CO) cm−1. 1H NMR (CDCl3/DMSO-d6): δ 7.54−7.41 (m, 4H, Ar), 7.18−7.03 (m, 4H, Ar), 3.58 (t, 2H, J = 6.3 Hz, CH2), 3.36−3.31 (m, 2H, CH2), 2.38 (q, 2H, J = 7.5 Hz, CH2), 1.99−1.91 (m, 2H, CH2), 1.01 (t, 3H, J = 7.5 Hz, CH3). 13C NMR (DMSO-d6): δ 155.5, 145.6, 140.4, 135.5, 133.3, 129.7, 129.0, 127.2, 126.9, 126.8, 117.8, 43.2, 37.8, 33.7, 24.1, 14.7. MS (ESI−) m/z found 394.1; C18H21ClN3O3S (M− − H) requires 394.1. 4 - [ 3 - ( 3 - C h l o r o p r o p y l ) u r e i d o ] - N - ( 2 - p r o p y l p h e n y l ) - benzenesulfonamide (39). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (95:15)) and was recrystallized with MeOH and ﬁltered. Yield, 11%; white solid; mp, 219−220 °C. IR ν: 3277 (NH), 1657 (CO) cm−1. 1H NMR (DMSO-d6): δ 9.11 (s, 1H, NH), 7.80−7.60 (m, 4H, Ar), 7.44−7.08 (m, 4H, Ar), 6.54−6.48 (m, 2H, 2 × NH), 3.51−3.47 (m, 2H, CH2), 3.26−3.22 (m, 2H, CH2), 1.95−1.90 (m, 2H, CH2), 1.78−1.73 (m, 2H, CH2), 1.61−1.59 (m, 2H, CH2), 0.91 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (DMSO-d6): δ 154.8, 152.7, 145.4, 142.9, 134.1, 130.9, 130.5, 129.9, 129.6, 127.1, 116.6, 43.0, 37.8, 36.7, 32.6, 22.5, 14.1. MS (APSI−) m/z found 408.0; C19H23ClN3O3S (M− − H) requires 408.1. 2-Tolyl 3-(3-Ethylureido)benzenesulfonate (40). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride/ethyl acetate (92:8) to methylene chloride/ethyl acetate (88:12)). Yield, 80%; yellowish sticky solid. IR ν: 3317 (NH), 1655 (CO) cm−1. 1H NMR (CDCl3): δ 8.27 (s, 1H, NH), 8.00 (s, 1H, Ar), 7.63−7.61 (m, 1H, Ar), 7.35−7.27 (m, 2H, Ar), 7.09−7.03 (m, 3H, Ar), 6.93−6.90 (m, 1H, Ar), 5.89 (brs, 1H, NH), 3.26−3.19 (m, 2H, CH2), 2.07 (s, 3H, CH3), 1.07 (t, 3H, J = 7.1 Hz, CH3). 13C NMR (CDCl3): δ 156.1, 148.2, 140.8, 136.4, 131.7, 131.5, 129.8, 127.2, 127.0, 124.4, 122.1, 121.6, 117.9, 35.0, 16.3, 15.1. MS (APSI+) m/z found 335.1; C16H19N2O4S (M+ + H) requires 335.1. 2-Ethylphenyl 3-(3-Ethylureido)benzenesulfonate (41). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride/ethyl acetate (92:8) to methylene chloride/ethyl acetate (88:12)). Yield, 78%; white solid; mp, 76−78 °C. IR ν: 3297 (NH), 1655 (CO) cm−1. 1H NMR (CDCl3): δ 8.27 (s, 1H, NH), 7.99 (s, 1H, Ar), 7.66−7.63 (m, 1H, Ar), 7.39−7.32 (m, 2H, Ar), 7.17−7.01 (m, 3H, Ar), 6.94−9.91 (m, 1H, Ar), 5.88 (brs, 1H, NH), 3.25−3.19 (m, 2H, CH2), 2.51 (q, 2H, J = 7.5, CH2), 1.14−1.04 (m, 6H, 2 × CH3). 13C NMR (CDCl3): δ 156.0, 147.8, 140.8, 137.2, 136.5, 129.9, 129.8, 127.3, 126.9, 124.3, 121.9, 121.5, 117.9, 35.0, 22.8, 15.1, 14.0. MS (APSI+) m/z found 349.1; C17H21N2O4S (M+ + H) requires 349.1. 2-Propylphenyl 3-(3-Ethylureido)benzenesulfonate (42). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride/ethyl acetate (92:8) to methylene chloride/ethyl acetate (88:12)). Yield, 99%; sticky solid. IR ν: 3343 (NH), 1655 (CO) cm−1. 1H NMR (CDCl3): δ 8.28 (s, 1H, NH), 8.03 (s, 1H, Ar), 7.62−7.60 (m, 1H, Ar), 7.41−7.29 (m, 2H, Ar), 7.16−7.02 (m, 3H, Ar), 6.95−6.92 (m, 1H, Ar), 5.90 (brs, 1H, NH), 3.25−3.18 (m, 2H, CH2), 2.44 (t, 2H, J = 7.7 Hz, CH2), 1.52−1.44 (m, 2H, CH2), 1.06 (t, 3H, J = 7.1 Hz, CH3), 0.82 (t, 3H, J = 7.3 Hz, CH3). 13C NMR (CDCl3): δ 156.1, 148.0, 140.8, 136.6, 135.8, 130.7, 129.8, 127.1, 127.0, 124.4, 121.9, 121.5, 117.9, 35.0, 31.8, 23.0, 15.1, 13.8. MS (APSI+) m/z found 363.1; C18H23N2O4S (M+ + H) requires 363.1. 6203 dx.doi.org/10.1021/jm3006492 | J. Med. Chem. 2012, 55, 6194−6208