Journal of Medicinal Chemistry (m, 2H, CH2), 0.87 (t, 3H, J = 7.3 Hz, CH3). 13C NMR (acetone-d6): δ 160.1, 150.4, 146.4, 144.8, 138.3, 137.0, 135.5, 134.7, 134.6, 131.4, 129.0, 126.9, 123.1, 49.1, 46.9, 37.9, 27.9, 19.0. MS (APSI−) m/z found 393.9; C18H21ClN3O3S (M− − H) requires 394.1. 4-[3-(2-Chloroethyl)ureido]-N-2-tolylbenzenesulfonamide (21). 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, 40%; yellowish solid; mp, 134−135 °C. IR ν: 3074 (NH), 1683 (CO) cm−1. 1H NMR (CDCl3/DMSO-d6): δ 8.97 (s, 2H, 2 × NH), 7.79−7.64 (m, 4H, Ar), 7.38−7.26 (m, 4H, Ar), 6.31 (brs, 1H, NH), 3.87−3.75 (m, 4H, 2 × CH2), 2.24 (s, 3H, CH3). 13C NMR (DMSO-d6): δ 154.7, 144.3, 135.1, 134.1, 132.7, 130.7, 127.9, 126.4, 126.3, 117.0, 44.3, 41.3, 17.7. MS (APSI+) m/z found 368.1; C16H19ClN3O3S (M+ + H) requires 368.1. 4 - [ 3 - ( 2 - C h l o r o e t h y l ) u r e i d o ] - N - ( 2 - e t h y l p h e n y l ) - benzenesulfonamide (22). 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, 10%; white solid; mp, 214−215 °C. IR ν: 3100 (NH), 1682 (CO) cm−1. 1H NMR (CDCl3/DMSO-d6): δ 7.53−7.40 (m, 4H, Ar), 7.13−7.01 (m, 4H, Ar), 3.60−3.49 (m, 4H, 2 × CH2), 2.38 (q, 2H, J = 7.6 Hz, CH2), 0.99 (t, 3H, J = 7.6, CH3). 13C NMR (DMSO-d6): δ 154.7, 144.2, 140.3, 134.4, 132.3, 128.9, 128.0, 126.6, 126.5, 126.1, 117.0, 44.3, 41.2, 23.1, 14.4. MS (APSI+) m/z found 382.1; C17H21ClN3O3S (M+ + H) requires 382.1. 4 - [ 3 - ( 2 - C h l o r o e t h y l ) u r e i d o ] - N - ( 2 - p r o p y l p h e n y l ) - benzenesulfonamide (23). Method B was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (90:10)) and was crystallized with methylene chloride and ﬁltered. Yield, 21%; white solid; mp, 178−180 °C. IR ν: 3376 (NH), 1684 (CO) cm−1. 1H NMR (DMSO-d6): δ 9.36 (s, 1H, NH), 9.15 (s, 1H, NH), 7.64−7.57 (m, 4H, Ar), 7.21− 6.91 (m, 4H, Ar), 6.62 (brs, 1H, NH), 3.73−3.69 (m, 2H, CH2), 3.48−3.46 (m, 2H, CH2), 2.55−2.47 (m, 2H, CH2), 1.44−1.39 (m, 2H, CH2), 0.85 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (DMSO-d6): δ 154.7, 144.2, 138.8, 134.6, 132.4, 129.6, 128.0, 126.4, 126.4, 126.1, 117.0, 44.3, 41.3, 32.3, 22.9, 14.0. MS (APSI−) m/z found 393.9; C18H21ClN3O3S (M− − H) requires 394.1. 2-Tolyl 3-[3-(3-Chloropropyl)ureido]benzenesulfonate (24). Method C in dry MeCN under microwave at 130 °C for 45 min with washing with HCl (1 N) was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (90:10)). Yield, 45%; white solid; mp, 129 °C. IR ν: 3327 (NH), 1626 (CO) cm−1. 1H NMR (DMSO-d6): δ 9.05 (s, 1H, NH), 8.19 (s, 1H, Ar), 7.70−6.67 (m, 1H, Ar), 7.54−7.52 (m, 1H, Ar), 7.37−7.21 (m, 4H, Ar), 6.99−6.97 (m, 1H, Ar), 6.45 (brs, 1H, NH), 3.69−3.67 (m, 2H, CH2), 3.25−3.23 (m, 2H, CH2), 2.06 (s, 3H, CH3), 1.93−1.91 (m, 2H, CH2). 13C NMR (DMSO-d6): δ 160.2, 153.0, 147.0, 140.8, 137.0, 136.2, 135.3, 132.5, 128.5, 127.1, 125.3, 121.3, 48.3, 41.9, 37.8, 21.0. MS (APSI+) m/z found 383.1; C17H20ClN2O4S (M+ + H) requires 383.1. 2 - E t h y l p h e n y l 3 - [ 3 - ( 3 - C h l o r o p r o p y l ) u r e i d o ] - benzenesulfonate (25). Method C in dry MeCN under microwave at 130 °C for 45 min with washing with HCl (1 N) was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (75:25) to hexanes/ethyl acetate (25:75)). Yield, 36%; white solid; mp, 102 °C. IR ν: 3326 (NH), 1633 (CO) cm−1. 1H NMR (DMSO-d6): δ 9.04 (s, 1H, NH), 8.21 (s, 1H, Ar), 7.69−7.67 (m, 1H, Ar), 7.56−7.51 (m, 1H, Ar), 7.40−7.23 (m, 4H, Ar), 6.99−6.67 (m, 1H, Ar), 6.45 (t, 1H, J = 5.6 Hz, NH), 3.71−3.67 (m, 2H, CH2), 3.27−3.20 (m, 2H, CH2), 2.52−2.45 (m, 2H, CH2), 1.94−1.89 (m, 2H, CH2), 1.06 (t, 3H, J = 7.6 Hz, CH3). 13C NMR (DMSO-d6): δ 160.2, 152.5, 147.0, 141.8, 140.8, 135.3, 132.7, 132.5, 128.5, 126.9, 125.2, 121.2, 48.2, 1.9, 37.8, 27.4, 19.3. MS (APSI+) m/z found 397.1; C18H22ClN2O4S (M+ + H) requires 397.1. 2 - P r o p y l p h e n y l 3 - [ 3 - ( 3 - C h l o r o p r o p y l ) u r e i d o ] - benzenesulfonate (26). Method C in dry MeCN under microwave at 130 °C for 45 min with washing with HCl (1 N) was used. The Article crude product was puriﬁed by ﬂash chromatography (silica gel, chloroform to chloroform/ethyl acetate (80:20)). Yield, 55%; white solid; mp, 100 °C. IR ν: 1634 (CO) cm−1. 1H NMR (CDCl3): δ 8.29 (s, 1H, NH), 8.02 (s, 1H, Ar), 7.64−7.61 (m, 1H, Ar), 7.41−7.31 (m, 2H, Ar), 7.18−7.03 (m, 3H, Ar), 6.93−6.91 (m, 1H, Ar), 6.00 (brs, 1H, NH), 3.54 (t, 2H, J = 6.2 Hz, CH2), 3.40−3.36 (m, 2H, CH2), 2.44 (t, 2H, J = 7.7 Hz, CH2), 1.97−1.89 (m, 2H, CH2), 1.55− 1.42 (m, 2H, CH2), 0.86−0.81 (t, 3H, J = 7.3, CH3). 13C NMR (CDCl3): δ 156.1, 148.0, 140.6, 136.5, 135.8, 130.7, 129.9, 127.2, 127.0, 124.5, 121.9, 121.8, 117.9, 42.4, 37.5, 32.5, 31.8, 23.0, 13.9. MS (APSI+) m/z found 411.2; C19H24ClN2O4S (M+ + H) requires 411.1. 4-(tert-Butyldimethylsilyloxy)phenyl 3-[3-(3-Chloropropyl)- ureido]benzenesulfonate (27). Method D was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (95:5)). Yield, 83%; yellowish oil. IR ν: 1662 (CO) cm−1. 1H NMR (CDCl3): δ 8.24 (s, 1H, NH), 8.06 (s, 1H, Ar), 7.57−7.55 (m, 1H, Ar), 7.28−7.21 (m, 2H, Ar), 6.81−6.78 (m, 2H, Ar), 6.69−6.67 (m, 2H, Ar), 6.05 (brs, 1H, NH), 3.59−3.55 (m, 2H, CH2), 3.44−3.40 (m, 2H, CH2), 1.98−1.95 (m, 2H, CH2), 0.93 (s, 9H, 3 × CH3), 0.14 (s, 6H, 2 × CH3). 13C NMR (CDCl3): δ 156.1, 154.6, 143.3, 140.6, 135.4, 129.6, 124.6, 123.2, 122.2, 120.8, 118.0, 42.4, 37.5, 32.6, 25.6, 18.1, −4.5. 4 - H y d r o x y p h e n y l 3 - [ 3 - ( 3 - C h l o r o p r o p y l ) u r e i d o ] - benzenesulfonate (28). Method E was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, ethyl acetate to ethyl acetate/methanol (90:10)). Yield, 60%; yellowish oil. IR ν: 3450− 3050 (OH), 1666 (CO), 1364 (OH) cm−1. 1H NMR (acetone-d6): δ 8.12−8.11 (m, 1H, Ar), 7.78−7.63 (m, 1H, Ar), 7.44−7.28 (m, 2H, Ar), 6.84−6.68 (m, 4H, Ar), 3.67−3.62 (m, 2H, CH2), 3.38−3.34 (m, 2H, CH2), 2.02−1.94 (m, 2H, CH2). 13C NMR (acetone-d6): δ 157.0, 155.8, 143.1, 142.5, 136.6, 130.3, 124.0, 124.0, 121.7, 117.9, 116.6, 43.3, 37.8, 33.7. MS (APSI+) m/z found 385.1; C16H18ClN2O5S (M+ + H) requires 385.1. 2-Tolyl 4-[3-(3-Chloropropyl)ureido]benzenesulfonate (29). Method C in dry MeCN under microwave at 130 °C for 45 min with washing with HCl (1 N) was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, methylene chloride to methylene chloride/ethyl acetate (90:10)). Yield, 41%; sticky solid. IR ν: 3395 (NH), 1675 (CO) cm−1. 1H NMR (CDCl3): δ 7.90 (s, 1H, NH), 7.70−6.67 (m, 2H, Ar), 7.53−7.50 (m, 2H, Ar), 7.14−6.96 (m, 4H, Ar), 3.58−3.54 (m, 2H, CH2), 3.42−3.38 (m, 2H, CH2), 2.06 (s, 3H, CH3), 2.00−1.92 (m, 2H, CH2). 13C NMR (CDCl3): δ 155.2, 148.1, 145.3, 131.8, 131.5, 129.8, 127.8, 127.3, 127.1, 122.2, 118.0, 42.3, 37.5, 32.3, 16.3. MS (APSI+) m/z found 383.1; C17H20ClN2O4S (M+ + H) requires 383.1. 2 - E t h y l 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 (30). Method A in dry DCM was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (75:25) to hexanes/ethyl acetate (25:75)). Yield, 85%; yellowish sticky solid. IR ν: 3363 (NH), 1664 (NH) cm−1. 1H NMR (CDCl3): δ 8.07 (s, 1H, NH), 7.71−7.68 (m, 2H, Ar), 7.54− 7.51 (m, 2H, Ar), 7.19−7.07 (m, 3H, Ar), 6.98−6.96 (m, 1H, Ar), 5.88 (brs, 1H, NH), 3.56−3.52 (m, 2H, CH2), 3.41−3.36 (m, 2H, CH2), 2.48 (q, 2H, J = 7.6 Hz, CH2), 1.96−1.92 (m, 2H, CH2), 1.08 (t, 3H, J = 7.6 Hz, CH3). 13C NMR (CDCl3): δ 155.4, 147.7, 145.4, 137.2, 130.0, 129.7, 127.8, 127.4, 127.0, 121.9, 118.0, 42.3, 37.5, 32.4, 22.8, 14.1. MS (APSI+) m/z found 397.1; C18H22ClN2O4S (M+ + H) requires 397.1. 2 - P r o p y l 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 (31). Method C in dry MeCN under microwave at 130 °C for 45 min with washing with HCl (1 N) was used. The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (75:25) to hexanes/ethyl acetate (25:75)). Yield, 27%; yellow oil. IR ν: 3352 (NH), 1672 (CO) cm−1. 1H NMR (CDCl3): δ 7.72−7.50 (m, 4H, Ar), 7.16−6.96 (m, 4H, Ar), 3.58−3.54 (m, 2H, CH2), 3.41−3.37 (m, 2H, CH2), 2.43−3.39 (m, 2H, CH2), 1.99−1.94 (m, 2H, CH2), 1.55−1.45 (m, 2H, CH2), 0.86− 0.81 (m, 3H, CH3). 13C NMR (CDCl3): δ 155.1, 147.9, 145.1, 135.7, 130.8, 129.7, 128.1, 127.2, 127.0, 121.9, 118.1, 42.3, 37.6, 32.3, 31.8, 6202 dx.doi.org/10.1021/jm3006492 | J. Med. Chem. 2012, 55, 6194−6208