A. K. Mahalingam et al. / Bioorg. Med. Chem. 18 (2010) 4570–4590
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15H). 13C NMR d (CDCl3): 148.5, 142.6, 142.2, 136.8, 135.9, 133.1,
129.9, 128.8, 128.3, 54.6, 51.7, 39.2, 30.5, 29.5, 22.1; Anal. Calcd
for C20H27N5O2S2: C, 55.4; H, 6.3; N, 16.2. Found: C, 55.9; H, 6.4;
N, 15.9.
Pd(PPh3)4 (0.032 g, 0.026 mmol) were mixed under N2. The mix-
ture was heated at 100 °C for 6 h and then diluted with EtOAc
(20 mL), washed with water, brine and dried over MgSO4. The sol-
vent was evaporated and the residue was purified by flash chroma-
tography using pet.ether/acetone (2:1) as an eluent to give 29
(255 mg, 0.550 mmol) in 59% yield. 1H NMR (CDCl3, 270 MHz): d
7.56 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.3 Hz, 2H), 6.73 (s, 1H), 4.39
(s, 2H), 4.16 (s, 1H), 3.27 (m, 2H), 3.17 (m, 2H), 2.82 (s, 3H), 2.66
(d, J = 6.9 Hz, 2H), 1.90 (m, 1H), 0.95 (m, 15H); 13C NMR (CDCl3,
67.5 MHz): d 161.4, 148.2, 142.7, 137.7, 136.2, 133.9, 129.1,
128.8, 128.1, 54.4, 48.1, 44.9, 42.1, 39.1, 31.4, 30.4, 29.3, 22.1; IR
(compression cell): 3302, 3049, 2869, 1700, 1512 cmÀ1, Anal.
Calcd for C23H33N3O3S2: C, 59.6; H, 7.2; N, 9.1. Found: C, 59.7; H,
7.1; N, 9.0.
5.1.24. 3-[4-(2-Oxo-pyrrolidin-1-yl-methyl)-phenyl]-5-iso-
butyl-N-tert-butylthiophene-2-sulfonamide (26)
Compound 24 (200 mg, 0.626 mmol), 3 (106 mg, 0.418 mmol),
toluene (20 mL), ethanol (1.5 mL), NaOH (2.5 mL, 1.0 M, 2.5 mmol)
and Pd(PPh3)4 (15 mg, 13 lmol) was mixed under N2. The mixture
was warmed to reflux for 2 h. The mixture was diluted with EtOAc
(50 mL), washed with water, brine and dried over MgSO4. The sol-
vent was evaporated and the residue was purified by flash chroma-
tography using hexane/acetone (2:1) as eluent to give 26 (157 mg,
0.350 mmol) in 84% yield. 1H NMR (CDCl3, 270 MHz): d 7.60 (d,
J = 8.1 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 6.74 (s, 1H), 4.50 (s, 2H),
3.31 (t, J = 7.3 Hz, 2H), 2.69 (d, J = 7.1 Hz, 2H), 2.50 (t, J = 8.4 Hz,
2H), 2.05 (m, 2H), 1.91 (m, 1H), 0.98 (s, 9H), 0.96 (d, J = 6.9 Hz,
6H); 13C NMR (CDCl3, 67.5 MHz): d 175.2, 148.4, 142.6, 136.8,
134.3, 132.2, 129.4, 128.9, 128.1, 54.5, 46.8, 46.3, 39.1, 30.8, 30.5,
29.4, 22.1, 17.7; IR (compression cell): 3281, 2955, 1686,
1465 cmÀ1; Anal. Calcd for C23H32N2O3S2: C, 61.6; H, 7.2; N, 6.2.
Found: C, 61.7; H, 7.1; N, 6.0.
5.1.28. 3-[4-(3-Methyl-2,5-dioxo-imidazolidin-1-yl-methyl)-
phenyl]-5-iso-butyl-N-tert-butyl-thiophene-2-sulfonamide (30)
Compound 24 (0.147 g, 0.459 mmol), 7 (0.10 g, 0.35 mmol), CsF
(0.139 g, 0.918 mmol) and DME (5 mL), Pd(PPh3)4 (0.012 g,
0.01 mmol) were mixed under N2. The mixture was heated at
100 °C for 2 h and then diluted with EtOAc (15 mL), washed with
water, brine and dried over MgSO4. The solvent was evaporated
and the residue was purified by flash chromatography using pe-
t.ether/acetone as an eluent to give 30 (129 mg, 0.270 mmol) in
76% yield. 1H NMR (CDCl3, 270 MHz): d 7.54 (d, J = 8.6 Hz, 2H),
7.44 (d, J = 8.6 Hz, 2H), 6.71 (s, 1H), 4.68 (s, 2H), 4.08 (s, 1H), 3.88
(s, 2H), 3.00 (s, 3H), 2.66 (d, J = 6.6 Hz, 2H), 1.90 (m, 1H), 0.96 (s,
9H), 0.93 (d, J = 6.6 Hz, 6H); 13C NMR (CDCl3, 67.5 MHz): d 169.3,
156.4, 148.3, 142.6, 136.3, 134.5, 129.2, 128.8, 128.5, 54.4, 51.7,
42.1, 39.1, 30.4, 29.6, 29.4, 22.1; IR (compression cell): 3272,
2981, 1756, 1712, 1442, 1142 cmÀ1; Anal. Calcd for C23H31N3O4S2:
C, 57.8; H, 6.5; N, 8.8. Found: C, 57.9; H, 6.4; N, 9.0.
5.1.25. 3-[4-(6-Oxo-6H-pyrimidin-1-ylmethyl)-phenyl]-5-iso-
butyl-N-tert-butylthiophene-2-sulfonamide (27)
Compound 24 (200 mg, 0.646 mmol), 4 (111 mg, 0.418 mmol),
Pd(PPh3)4 (15 mg, 0.013 mmol), NaOH (2.5 mL, 1 M, 2.5 mmol), tol-
uene (20 mL) and ethanol (1.5 mL) was mixed under N2. The mix-
ture was warmed to reflux for 2 h. The mixture was diluted with
EtOAc (150 mL), washed with water, brine and dried over MgSO4.
The solvent was evaporated and the residue was purified by flash
chromatography using hexane/EtOAc (5:1) as eluent to give 27
(73.1 mg, 0.159 mmol) in 31% yield. 1H NMR (CDCl3, 270 MHz): d
8.55 (s, 1H), 7.90 (m, 1H), 7.60 (d, J = 8.3 Hz, 2H), 7.43 (d,
J = 8.1 Hz, 2H), 6.72 (s, 1H), 6.51 (d, J = 6.6 Hz, 1H), 5.19 (s, 2H),
2.67 (d, J = 7.1 Hz, 2H), 1.91 (m, 2H), 0.98 (s, 9H), 0.96 (d,
J = 6.6 Hz, 6H); 13C NMR (CDCl3, 67.5 MHz): d 160.0, 151.5, 150.8,
148.6, 142.3, 136.7, 135.4, 134.7, 129.8, 129.4, 128.8, 128.4,
116.2, 54.6, 50.0, 39.1, 30.5, 29.5, 22.1; IR (compression cell):
3134, 2959, 2870, 1685 cmÀ1; Anal. Calcd for C23H29N3O3S2: C,
60.1; H, 6.4; N, 9.1. Found: C, 60.0; H, 6.4; N, 8.7.
5.1.29. 3-[4-(3,4,4-Trimethyl-2,5-dioxo-imidazolidin-1-yl-
methyl)-phenyl]-5-iso-butyl-tert-butyl-thiophene-2-
sulfonamide (31)
Compound 24 (0.16 g, 0.50 mmol), 8 (0.12 g, 0.39 mmol), CsF
(0.152 g, 1.00 mmol) and DME (5 mL), Pd(PPh3)4 (0.017 g,
0.015 mmol) were mixed under N2. The mixture was heated at
100 °C for 3 h and then diluted with EtOAc (15 mL), washed with
water, brine and dried over MgSO4. The solvent was evaporated
and the residue was purified by flash chromatography using pe-
t.ether/acetone as an eluent to give 31 (132 mg, 0.261 mmol) in
68% yield. 1H NMR (CDCl3, 270 MHz): d 7.53 (d, J = 8.3 Hz, 2H),
7.39 (d, J = 8.3 Hz, 2H), 6.70 (s, 1H), 4.66 (s, 2H), 4.03 (s, 1H), 2.86
(s, 3H), 2.64 (d, J = 6.6 Hz, 2H), 1.88 (m, 1H), 1.34 (s, 6H), 0.94 (d,
J = 6.9 Hz, 6H), 0.91 (s, 9H); 13C NMR (CDCl3, 67.5 MHz): d 176.3,
155.1, 148.3, 142.5, 136.6, 134.4, 129.2, 128.7, 128.2, 61.2, 54.4,
41.8, 39.1, 30.4, 29.4, 24.4, 22.1, 22.0; IR (compression cell):
5.1.26. 3-(4-Pyrazole-1-ylmethyl-phenyl)-5-iso-butyl-N-tert-
butylthiophene-2-sulfonamide (28)
Compound 24 (438 mg, 1.370 mmol), 5 (250 mg, 1.054 mmol),
toluene (10 mL), ethanol (3 mL), NaOH (4.2 mL, 1.0 M) and
Pd(PPh3)4 (37 mg, 0.031 mmol) was mixed under N2. The mixture
was warmed to reflux for 2 h at 100 °C. The mixture was diluted
with H2O (50 mL), extracted with EtOAc (3 Â 50 mL), washed with
water and brine, and dried over MgSO4. The solvent was removed
and the residue was separated by flash c.c. with petroleum ether/
acetone (3:1) as an eluent to give 28 (251 mg, 0.581 mmol) in
55% yield. 1H NMR d (CDCl3): 7.53 (m, 3H), 7.40 (m, 1H), 7.25 (m,
2H), 6.70 (s, 1H), 6.27 (t, J = 2.3 Hz, 1H), 5.34 (s, 2H), 4.11 (s, 1H),
2.63 (m, 2H), 1.88 (m, 1H), 0.93 (m, 15H); 13C NMR d (CDCl3):
148.3, 142.5, 139.6, 137.0, 134.6, 129.4, 129.2, 128.7, 127.6,
106.1, 55.4, 54.4, 39.1, 30.4, 29.4, 22.1; IR (compression cell):
3313, 3095, 2957, 2868, 1731, 1613, 1514, 1466 cmÀ1. Anal.
Calcd for C22H29N3O2S2: C, 61.2; H, 6.8; N, 9.7. Found: C, 61.1.4;
H, 6.8; N, 9.7.
3317, 2973, 1765, 1708, 1442, 1136 cmÀ1
. Anal. Calcd for
C25H35N3O4S2: C, 59.4; H, 7.0; N, 8.3. Found: C, 59.6; H, 8.4; N, 8.4.
5.1.30. 3-[4-(4-Methyl-imidazole-1-ylmethyl)-phenyl]-5-iso-
butyl-N-tert-butylthiophene-2-sulfonamide (32)
Compound 24 (401 mg, 0.628 mmol), 9 (210 mg, 0.836 mmol),
toluene (20 mL), ethanol (3 mL), NaOH (5 mL, 1.0 M) and Pd(PPh3)4
(30 mg, 0.026 mmol) was mixed under N2. The mixture was
warmed to reflux for 2 h at 100 °C. The reaction mixture was di-
luted with EtOAc (50 mL), washed with water and brine, and dried
over MgSO4. The solvent was removed and the residue was purified
on LC/MS to give 32 (211 mg, 0.473 mmol) in 57% yield. 1H NMR d
(10%CD3OD in CDCl3): 7.68 (s, 1H), 7.62 (d, J = 8.2 Hz, 2H), 7.29 (d,
J = 8.1 Hz, 2H), 6.76 (s, 1H), 6.70 (s, 1H), 5.14 (s, 2H), 2.70 (d,
J = 6.4 Hz, 2H), 2.21 (s, 3H), 1.92 (m, 1H), 1.01 (s, 9H), 0.97 (d,
J = 6.7 Hz, 6H); 13C NMR d (CDCl3): 148.6, 142.8, 137.4, 136.6,
136.0, 135.2, 129.9, 129.2, 127.7, 116.3, 54.3, 50.9, 39.3, 30.7,
5.1.27. 3-[4-(3-Methyl-2-oxoimidazolidin-1-yl-methyl)-
phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (29)
Compound 24 (0.444 g, 1.39 mmol), 6 (0.25 g, 0.93 mmol), tolu-
ene (3.5 mL), ethanol (1 mL) and NaOH (1.0 M, 1.5 mL, 3.70 mmol),