Journal of Medicinal Chemistry
ARTICLE
3,4,5-Trimethoxyphenyl-4-(2-oxoimidazolidin-1-yl)benzene-
sulfonate (45). Method B: flash chromatography (methylene chloride
to methylene chloride/ethyl acetate 7:3). Yield: 31%. Mp: 191ꢀ192 ꢀC.
Ar), 4.55 (s, 1H, NH), 4.06ꢀ4.00 (m, 2H, CH2), 3.65ꢀ3.59 (m, 2H,
CH2), 1.29 (s, 3H, CH3). 13C NMR (acetone-d6): δ 159.1, 146.9, 146.0,
141.4, 130.1, 124.6, 124.5, 120.9, 120.7, 116.9, 114.8, 45.3, 37.4, 17.4.
HRMS (ESþ) m/z found 348.1060; C16H17N3O4S (Mþ þ H) requires
348.1018.
4-Ethylphenyl-4-(2-oxoimidazolidin-1-yl)benzenesulfonate
(52). Method B: flash chromatography (ethyl acetate to ethyl acetate/
methanol 95:5). Yield: 79%. White solid. Mp: 155ꢀ157 ꢀC. IR ν: 3230,
1715 cmꢀ1. 1H NMR (DMSO-d6): δ 7.83ꢀ7.74 (m, 4H, Ar), 7.42 (s,
1H, NH), 7.21 (d, 2H, J = 8.4 Hz, Ar), 6.92 (d, 2H, J = 8.4 Hz, Ar),
3.95ꢀ3.90 (m, 2H, CH2), 3.49ꢀ3.43 (m, 2H, CH2), 2.58 (q, 2H, J = 7.5
Hz, CH2), 1.15 (t, 3H, J = 7.5 Hz, CH3). 13C NMR (DMSO-d6):
δ 158.2, 147.2, 146.1, 142.9, 129.4, 129.2, 125.4, 121.9, 116.3, 44.2, 36.3,
27.5, 15.4. HRMS (ESþ) m/z found 347.0906; C17H18N2O4S (Mþ þ
H) requires 347.1066.
4-Propylphenyl-4-(2-oxoimidazolidin-1-yl)benzenesulfo-
nate (53). Method B: flash chromatography (ethyl acetate to ethyl
acetate/methanol 95:5). Yield: 78%. White solid. Mp: 198ꢀ200 ꢀC. IR
ν: 3208, 2955, 1712 cmꢀ1. 1H NMR(DMSO-d6 and CDCl3):δ7.68ꢀ7.60
(m, 4H, Ar), 7.02 (s, 1H, Ar or NH), 6.99 (s, 1H, Ar or NH), 6.79ꢀ6.76
(m, 3H, Ar), 3.91ꢀ3.86 (m, 2H, CH2), 3.54ꢀ3.49 (m, 2H, CH2), 2.47
(t, 2H, J = 7.6 Hz, CH2), 1.59ꢀ1.47 (m, 2H, CH2), 0.84 (t, 3H, J = 7.3
Hz, CH3). 13C NMR (DMSO-d6 and CDCl3): δ 158.3, 147.1, 145.4,
141.2, 129.0, 129.0, 126.3, 121.5, 116.0, 44.2, 36.8, 36.5, 23.8, 13.3.
HRMS (ESþ) m/z found 361.0652; C18H20N2O4S (Mþ þ H) requires
361.1222.
4-sec-Butylphenyl-4-(2-oxoimidazolidin-1-yl)benzenesul-
fonate (54). Method B: flash chromatography (methylene chloride to
methylene chloride/ethyl acetate 8:2). Yield: 74%. White solid. Mp:
179ꢀ180 ꢀC. IR ν: 3245, 1711 cmꢀ1. 1H NMR (acetone-d6): δ 7.90ꢀ
7.73 (m, 4H, Ar), 7.19 (d, 2H, J = 8.6 Hz, Ar), 6.95 (d, 2H, J = 8.6 Hz,
Ar), 6.40 (brs, 1H, NH), 4.06ꢀ4.01 (m, 2H, CH2), 3.65ꢀ3.60 (m, 2H,
CH2), 2.65ꢀ2.58 (m, 1H, CH), 1.58ꢀ1.23 (m, 2H, CH2), 1.18 (d, 3H,
J = 6.9 Hz, CH3), 0.77 (t, 3H, J = 7.4 Hz, CH3). 13C NMR (acetone-d6):
δ 159.0, 147.6, 146.6, 145.3, 129.7, 128.1, 127.9, 122.1, 116.6, 44.9,
41.1, 37.1, 31.1, 21.7, 12.1. HRMS (ESþ) m/z found 375.0776;
C19H22N2O4S (Mþ þ H) requires 375.1379.
1
IR ν: 3201, 1706 cmꢀ1. H NMR (DMSO-d6): δ 7.86ꢀ7.80 (m, 4H,
Ar), 7.42 (s, 1H, NH), 6.31 (s, 2H, Ar), 3.95ꢀ3.90 (m, 2H, CH2), 3.65
(s, 6H, 2 ꢁ CH3), 3.63 (s, 3H, CH3), 3.49ꢀ3.44 (m, 2H, CH2). 13C
NMR (DMSO-d6): δ 158.2, 153.1, 146.2, 145.1, 136.3, 129.6, 125.2,
116.4, 100.0, 60.1, 56.1, 44.3, 36.2. HRMS (ESþ) m/z found 409.1068;
C18H20N2O7S (Mþ þ H) requires 409.1070.
3,5-Dichlorophenyl-4-(2-oxoimidazolidin-1-yl)benzenesul-
fonate (46). Method B: flash chromatography (ethyl acetate to ethyl
acetate/methanol 95:5). Yield: 64%. White solid. Mp: 179ꢀ181 ꢀC. IR
ν: 3236, 1709 cmꢀ1. 1H NMR (DMSO-d6): δ 7.87ꢀ7.80 (m, 4H, Ar),
7.66 (m, 1H, Ar), 7.46 (s, 1H, NH), 7.21ꢀ7.20 (m, 2H, Ar), 3.97ꢀ3.91
(m, 2H, CH2), 3.49ꢀ3.44 (m, 2H, CH2). 13C NMR (DMSO-d6):
δ 158.2, 149.7, 146.6, 134.7, 129.6, 127.6, 124.3, 121.7, 116.4, 44.2, 36.3.
HRMS (ESþ) m/z found 386.9956; C15H12Cl2N2O4S (Mþ þ H)
requires 386.9973.
3,4-Difluorophenyl-4-(2-oxoimidazolidin-1-yl)benzenesul-
fonate (47). Method B: flash chromatography (ethyl acetate to ethyl
acetate/methanol 95:5). Yield: 78%. White solid. Mp: 182ꢀ184 ꢀC. IR
ν: 3230, 2918, 1716 cmꢀ1 1H NMR (DMSO-d6 and CDCl3): δ
.
7.77ꢀ7.51 (m, 5H, Ar and NH), 7.27ꢀ7.18 (m, 1H, Ar), 7.03ꢀ6.96
(m, 1H, Ar), 6.77ꢀ6.72 (m, 1H, Ar), 3.93ꢀ3.83 (m, 2H, CH2),
3.51ꢀ3.43 (m, 2H, CH2). 13C NMR (DMSO-d6 and CDCl3): δ 158.8,
158.1, 146.2, 141.6, 138.9, 129.2, 126.2, 124.8, 118.8, 118.8, 118.7, 118.7,
117.7, 117.5, 116.2, 115.8, 112.4, 112.1, 44.5, 44.2, 36.6, 36.4. HRMS
(ESþ) m/z found 354.9966; C15H12F2N2O4S (Mþ þ H) requires
355.0564.
3,5-Difluorophenyl-4-(2-oxoimidazolidin-1-yl)benzenesul-
fonate (48). Method B: flash chromatography (ethyl acetate to ethyl
acetate/methanol 95:5). Yield: 90%. White solid. Mp: 172ꢀ174 ꢀC. IR
ν: 3225, 1716 cmꢀ1. 1H NMR (DMSO-d6 and CDCl3): δ 7.75ꢀ7.66
(m, 4H, Ar), 7.07 (s, 1H, NH), 6.81ꢀ6.74 (m, 1H, Ar), 6.59ꢀ6.55 (m,
2H, Ar), 3.93ꢀ3.87 (m, 2H, CH2), 3.54ꢀ3.48 (m, 2H, CH2). 13C NMR
(DMSO-d6 and CDCl3): δ 164.0, 163.8, 160.7, 160.5, 158.2, 150.2,
146.1, 129.1, 125.0, 116.1, 106.4, 106.3, 106.1, 106.0, 103.0, 102.7, 102.3,
44.2, 36.4. HRMS (ESþ) m/z found 355.0141; C15H12F2N2O4S (Mþ
þ H) requires 355.0564.
4-Ethoxyphenyl-4-(2-oxoimidazolidin-1-yl)benzenesulfo-
nate (55). Method B: flash chromatography (ethyl acetate to ethyl
acetate/methanol 95:5). Yield: 76%. White solid. Mp: 185ꢀ187 ꢀC. IR
ν: 3236, 2908, 1710 cmꢀ1. 1H NMR (DMSO-d6 and CDCl3): δ 7.70ꢀ
7.58 (m, 4H, Ar), 7.01 (s, 1H, NH), 6.79ꢀ6.75 (m, 2H, Ar), 6.72ꢀ6.68
(m, 2H, Ar), 3.95ꢀ3.86 (m, 4H, 2 ꢁ CH2), 3.53ꢀ3.48 (m, 2H, CH2),
1.32 (t, 3H, J = 7.0 Hz, CH3). 13C NMR (DMSO-d6 and CDCl3):
δ 158.3, 157.1, 145.6, 142.4, 129.0, 125.9, 122.9, 115.9, 114.6, 63.3, 44.2,
36.5, 14.4. HRMS (ESþ) m/z found 363.0692; C17H18N2O5S (Mþ þ
H) requires 363.1015.
4-Propoxyphenyl-4-(2-oxoimidazolidin-1-yl)benzenesul-
fonate (56). Method B: flash chromatography (methylene chloride to
methylene chloride/ethyl acetate 8:2). Yield: 56%. White solid. Mp:
156ꢀ157 ꢀC. IR ν: 3226, 1711 cmꢀ1. 1H NMR (CDCl3): δ 7.74ꢀ7.65
(m, 4H, Ar), 6.87ꢀ6.83 (m, 2H, Ar), 6.76ꢀ6.72 (m, 2H, Ar), 5.73 (s,
1H, NH), 3.98ꢀ3.93 (m, 2H, CH2), 3.84 (t, 2H, J = 6.5 Hz, CH2),
3.66ꢀ3.60 (m, 2H, CH2), 1.80ꢀ1.71 (m, 2H, CH2), 1.00 (t, 3H, J = 7.4
Hz, CH3). 13C NMR (CDCl3): δ 158.9, 157.8, 145.3, 142.9, 129.7,
127.6, 123.3, 116.6, 115.0, 69.9, 44.9, 37.1, 22.5, 10.5. HRMS (ESþ) m/z
found 377.0320; C18H20N2O5S (Mþ þ H) requires 377.1171.
4-Butoxyphenyl-4-(2-oxoimidazolidin-1-yl)benzenesulfo-
nate (57). Method B: flash chromatography (methylene chloride to
methylene chloride/ethyl acetate 8:2). Yield: 58%. White solid. Mp:
151ꢀ152 ꢀC. IR ν: 3218, 1696 cmꢀ1. 1H NMR (CDCl3): δ 7.67ꢀ7.59
(m, 4H, Ar), 6.80ꢀ6.76 (m, 2H, Ar), 6.70ꢀ6.66 (m, 2H, Ar), 3.92ꢀ3.80
(m, 4H, 2 ꢁ CH2), 3.57ꢀ3.52 (m, 2H, CH2), 3.10 (s, 1H, NH),
1.70ꢀ1.61 (m, 2H, CH2), 1.45ꢀ1.35 (m, 2H, CH2), 0.88 (t, 3H,
3,4,5-Trifluorophenyl-4-(2-oxoimidazolidin-1-yl)benzene-
sulfonate (49). Method B: flash chromatography (ethyl acetate to
ethyl acetate/methanol 95:5). Yield: 99%. White solid. Mp: 178ꢀ180 ꢀC.
IR ν: 3238, 2914, 1714 cmꢀ1. 1H NMR (DMSO-d6 and CDCl3): δ 7.78ꢀ
7.67 (m, 4H, Ar), 7.24 (s, 1H, NH), 6.84ꢀ6.77 (m, 2H, Ar), 3.94ꢀ3.89
(m, 2H, CH2), 3.53ꢀ3.48 (m, 2H, CH2). 13C NMR (DMSO-d6 and
CDCl3): δ 158.1, 152.0, 151.9, 151.9, 151.8, 148.7, 148.6, 148.5, 148.5,
146.4, 143.8, 143.8, 143.7, 140.3, 140.1, 139.9, 136.8, 129.2, 124.5, 116.2,
108.0, 107.9, 107.8, 107.7, 44.2, 36.4. HRMS (ESþ) m/z found
372.9821; C15H11F3N2O4S (Mþ þ H) requires 373.0470.
3-Methyl-4-nitrophenyl-4-(2-oxoimidazolidin-1-yl)benzene-
sulfonate (50). Method B: flash chromatography (methylene chloride
to methylene chloride/ethyl acetate 8:2). Yield: 65%. White solid. Mp:
215ꢀ216 ꢀC. IR ν: 3225, 1713 cmꢀ1. 1H NMR (DMSO-d6): δ 8.03 (d,
1H, J = 8.9 Hz, Ar), 7.85ꢀ7.81 (m, 4H, Ar), 7.45 (s, 1H, NH),
7.32ꢀ7.31 (m, 1H, Ar), 7.10ꢀ7.07 (m, 1H, Ar), 3.95ꢀ3.90 (m, 2H,
CH2), 3.48ꢀ3.43 (m, 2H, CH2), 2.49 (s, 3H, CH3). 13C NMR (DMSO-
d6): δ 158.2, 151.5, 147.3, 146.5, 135.7, 129.5, 126.7, 126.0, 124.7, 120.6,
116.5, 44.2, 36.3, 19.5. HRMS (ESþ) m/z found 378.0916; C16H15N3O6S
(Mþ þ H) requires 378.0760.
4-Amino-3-methylphenyl-4-(2-oxoimidazolidin-1-yl)ben-
zenesulfonate (51). Method C: flash chromatography (methylene
chloride to methylene chloride/methanol 9:1). Yield: 31%. yellow solid.
1
Mp: 160ꢀ162 ꢀC. IR ν: 3228, 1709 cmꢀ1. H NMR (acetone-d6):
δ 7.87ꢀ7.70 (m, 4H, Ar), 6.75ꢀ6.69 (m, 1H, Ar), 6.57ꢀ6.37 (m, 2H,
4575
dx.doi.org/10.1021/jm200488a |J. Med. Chem. 2011, 54, 4559–4580