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5.1.8. N-(4-(4-Fluorophenyl)thiazol-2-yl)-2-(4-(methylsulfonyl)
phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide (9i)
White solid, yield 51.2%; 1H NMR (300 MHz, CDCl3) d 11.19 (br
s, 1H), 7.82 (m, 2H), 7.70 (d, J = 8.4 Hz, 2H), 7.19 (s, 1H), 7.11 (t,
J = 8.7 Hz, 2H), 7.03 (d, J = 8.1 Hz, 2H), 3.80 (d, J = 10.5 Hz, 2H),
3.36 (t, J = 7.2 Hz, 1H), 3.15 (m, 2H), 3.05 (s, 3H), 1.93 (m, 1H),
1.54 (m, 1H), 1.24 (d, J = 12.0 Hz, 2H), 1.05 (m, 3H); 13C NMR
(100 MHz, CDCl3) d 170.2, 164.1, 161.6, 159.1, 148.6, 144.6,
139.7, 130.1, 128.3, 127.9, 127.8, 127.7, 116.2, 116.0, 107.8,
67.51, 67.48, 49.2, 44.4, 40.3, 32.6, 32.4, 32.3; EI-MS m/z 488
(M+). Anal. Calcd for (C24H25FN2O4S2ꢂH2O): C, 56.90; N, 5.53; H,
5.37. Found: C, 56.71; N, 5.25; H, 5.11.
5.1.13. N-(5-Bromo-4-isopropylthiazol-2-yl)-2-(4-(cyclopropyl
sulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
(9n)
Yellow foam, 46.9%; 1H NMR (300 MHz, CDCl3) d 9.75 (br s, 1H),
7.81 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.7 Hz, 2H), 3.91 (dd, J = 11.7,
3.0 Hz, 2H), 3.84 (t, J = 7.8 Hz, 1H), 3.29 (t, J = 10.8 Hz, 2H), 3.13
(m, 1H), 2.56 (m, 1H), 2.19 (m, 1H), 1.71 (m, 1H), 1.59 (d,
J = 11.1 Hz, 2H), 1.37 (m, 5H), 1.14 (d, J = 6.6 Hz, 3H), 1.11 (d,
J = 7.2 Hz, 3H), 1.04 (m, 2H); 13C NMR (CDCl3, 100 MHz) d 169.9,
156.2, 154.4, 144.6, 139.5, 128.8, 128.2, 97.3, 67.6, 49.0, 40.6,
32.8, 32.7, 32.6, 32.5, 28.1, 21.6, 6.13, 6.08; EI-MS m/z 542 (M+).
HRMS Calcd for C23H29BrN2O4S2: 542.0752. Found: 542.0793.
5.1.9. 2-(4-(Cyclopropylsulfonyl)phenyl)-N-(4-(prop-1-en-2-
yl)thiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide (9j)
White solid, 79.6% yield; 1H NMR (300 MHz, CDCl3) d 11.94 (br
s, 1H), 7.70 (m, 2H), 7.12 (m, 2H), 6.88 (s, 1H), 5.77 (s, 1H), 5.16 (s,
1H), 3.86 (d, J = 10.1 Hz, 2H), 3.62 (t, J = 6.3 Hz, 1H), 3.23 (m, 2H),
2.46 (m, 1H), 2.12 (s, 3H), 1.98 (m, 1H), 1.67 (m, 1H), 1.46 (d,
J = 10.5 Hz, 2H), 1.34 (m, 5H), 1.05 (m, 2H); 13C NMR (100 MHz,
CDCl3) d 170.4, 158.4, 150.4, 144.3, 139.8, 136.7, 128.4, 128.2,
114.2, 109.3, 67.61, 67.57, 49.2, 49.1, 40.2, 32.8, 32.7, 32.5, 32.4,
20.3, 6.2, 6.0; ESI-MS m/z 461 (M+). Anal. Calcd for (C23H28N2O4S2):
C, 59.97; N, 6.08; H, 6.13. Found: C, 59.87; N, 6.02; H, 6.21.
5.1.14. 2-(4-(Cyclopropylsulfonyl)phenyl)-N-(5-iodo-4-isopro-
pylhiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide (9o)
Yellow solid, 62% yield; 1H NMR (300 MHz, CDCl3) d 9.55 (s, 1H),
7.82 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 7.8 Hz, 2H), 3.91 (dd, J = 12.0,
2.7 Hz, 2H), 3.82 (t, J = 7.2 Hz, 1H), 3.29 (t, J = 11.4 Hz, 2H), 3.08
(m, 1H), 2.56 (m, 1H), 2.19 (m, 1H), 1.68 (m, 1H), 1.59 (d,
J = 11.4 Hz, 2H), 1.38 (m, 5H), 1.11 (m, 6H), 1.04 (m, 2H); 13C
NMR (CDCl3, 100 MHz) d 169.9, 160.9, 159.4, 144.5, 139.7, 128.7,
128.2, 67.6, 62.0, 49.1, 40.6, 32.9, 32.8, 32.7, 32.6, 30.2, 21.8, 6.1;
EI-MS m/z 588 (M+). Anal. Calcd for (C23H29IN2O4S2): C, 46.94; N,
4.76; H, 4.97. Found: C, 46.77; N, 4.58; H, 4.94.
5.1.15. N-(6-Fluorobenzo[d]thiazol-2-yl)-2-(4-(methylsulfonyl)
phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide (9p)
White solid, yield 36.0%; 1H NMR (300 MHz, CDCl3) d 7.85 (d,
J = 8.1 Hz, 2H), 7.66 (m, 1H), 7.53 (m, 1H), 7.38 (d, J = 8.4 Hz, 2H),
7.18 (m, 1H), 3.90 (d, J = 11.1 Hz, 2H), 3.80 (t, J = 7.5 Hz, 2H), 3.26
(t, J = 11.1 Hz, 2H), 3.09 (s, 3H), 2.17 (m, 1H), 1.77 (m, 1H), 1.54
(d, J = 11.7 Hz, 2H), 1.31 (m, 3H); 13C NMR (100 MHz, CDCl3) d
170.7, 160.9, 158.5, 157.9, 144.5, 144.4, 139.8, 133.0, 128.8,
128.1, 121.5, 115.0, 114.9, 109.1, 109.0, 67.56, 67.52, 49.4, 44.4,
40.3, 32.8, 32.5; EI-MS m/z 462 (M+). Anal. Calcd for
(C22H23FN2O4S2): C, 57.12; N, 6.06; H, 5.01. Found: C, 57.02; N,
5.66; H, 5.30.
5.1.10. (R)-2-(4-(Cyclopropylsulfonyl)phenyl)-N-(4-isopropyl
thiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide (R-9k)
White foam, yield 61.2%, 95% ee; 1H NMR (300 MHz, CDCl3) d
9.77 (br s, 1H), 7.82 (d, J = 7.8 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H),
6.51 (s, 1H), 3.88 (d, J = 11.4 Hz, 2H), 3.80 (t, J = 7.5 Hz, 1H), 3.26
(t, J = 11.1 Hz, 2H), 2.88 (m, 1H), 2.53 (m, 1H), 2.17 (m, 1H), 1.72
(m, 1H), 1.57 (d, J = 11.4 Hz, 2H), 1.33 (m, 5H), 1.20 (d, J = 6.9 Hz,
6H), 1.02 (m, 2H); 13C NMR (100 MHz, CDCl3) d 169.8, 157.8,
157.0, 144.7, 139.5, 128.6, 128.1, 105.8, 67.5, 49.1, 40.4, 32.74,
32.68, 32.5, 32.4, 30.6, 22.1, 22.0, 6.0, 5.9; EI-MS m/z 462 (M+).
Anal. Calcd for (C23H30N2O4S2): C, 59.71; N, 6.06; H, 6.54. Found:
C, 59.58; N, 5.77; H, 6.66.
5.1.16. 2-(4-(Cyclopropylsulfonyl)phenyl)-3-(tetrahydro-2H-
pyran-4-yl)-N-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)
propanamide (9q)
5.1.11. N-(4,5-Dimethylthiazol-2-yl)-2-(4-(methylsulfonyl)
phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide (9l)
Viscous white solid, yield 30.0%; 1H NMR (300 MHz, CDCl3) d 7.86
(d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 3.90 (m, 3H), 3.26 (t,
J = 11.4 Hz, 2H), 2.29 (s, 3H), 2.21 (s, 3H), 2.16 (m, 1H), 1.79 (m,
1H), 1.58 (t, J = 11.4 Hz, 2H), 1.29 (m, 3H); 13C NMR (100 MHz,
CDCl3+CD3OD) d 170.7, 155.8, 144.6, 139.4, 137.6, 128.9, 127.8,
120.5, 67.5, 48.7, 46.8, 44.1, 40.1, 32.6, 32.4, 32.3, 12.7, 10.5; EI-MS
m/z 422 (M+). This compound was converted to its HBr salt for anal-
ysis. Anal. Calcd for (C20H26N2O4S2ꢂ1.5HBrꢂ1.5H2O): C, 42.07; N,
4.91; H, 5.38. Found: C, 42.37; N, 4.80; H, 5.55.
White foam, yield 78.6%; 1H NMR (300 MHz, CDCl3) d 7.79 (d,
J = 8.1 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 3.87 (d, J = 11.4 Hz, 2H),
3.74 (t, J = 7.5 Hz, 1H), 3.24 (t, J = 11.4 Hz, 2H), 2.68 (s, 2H),
2.60 (s, 2H), 2.48 (m, 1H), 2.13 (m, 1H), 1.83 (m, 4H), 1.73 (m,
1H), 1.54 (t, J = 10.2 Hz, 2H), 1.32 (m, 5H), 1.04 (m, 2H); 13C
NMR (100 MHz, CDCl3)
d 169.7, 155.7, 144.5, 143.6, 139.8,
128.6, 128.1, 123.3, 67.6, 49.2, 40.1, 32.8, 32.5, 32.4, 26.2, 23.1,
22.8, 22.7, 6.1, 6.0; EI-MS m/z 474 (M+). Anal. Calcd for
(C24H30N2O4S2): C, 60.73; N, 5.90; H, 6.37. Found: C, 60.37; N,
5.68; H, 6.36.
5.1.12. N-(5-Isopropyl-4-methylthiazol-2-yl)-2-(4-(methyl
sulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
(9m)
5.1.17. 2-(4-(Cyclopropylsulfonyl)phenyl)-N-(5,6-dihydro-4H-
cyclopenta[d]thiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)
propanamide (9r).
White solid, yield 42.0% (purified by preparative TLC with
EtOAc/1%MeOH/0.5%HOAc as the eluent); 1H NMR (300 MHz,
CDCl3) d 7.82 (dd, J = 8.4, 2.1 Hz, 2H), 7.38 (dd, J = 8.4, 2.7 Hz, 2H),
3.89 (d, J = 8.4 Hz, 2H), 3.69 (t, J = 7.5 Hz, 2H), 3.25 (t, J = 11.1 Hz,
2H), 3.15 (m, 1H), 3.06 (s, 3H), 2.22 (s, 3H), 2.15 (m, 1H), 1.71
(m, 1H), 1.54 (t, J = 10.2 Hz, 2H), 1.31 (m, 9H); 13C NMR
(100 MHz, CDCl3) d 169.5, 154.1, 144.9, 139.7, 139.4, 134.5,
128.7, 128.0, 67.6, 49.4, 44.4, 40.3, 32.8, 32.6, 27.0, 24.7, 14.7; EI-
MS m/z 450 (M+). Anal. Calcd for (C22H30N2O4S2ꢂ0.6HOAc): C,
57.26; N, 5.76; H, 6.71. Found: C, 57.53; N, 5.39; H, 7.00.
White foam, yield 36.9%; 1H NMR (300 MHz, CDCl3) d 7.79 (d,
J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 3.87 (d, J = 11.7 Hz, 2H),
3.77 (t, J = 7.5 Hz, 1H), 3.23 (t, J = 11.7 Hz, 2H), 2.89 (m, 2H), 2.74
(m, 2H), 2.46 (m, 3H), 2.15 (m, 1H), 1.73 (m, 1H), 1.54 (t,
J = 11.4 Hz, 2H), 1.31 (m, 5H), 1.03 (m, 2H); 13C NMR (100 MHz,
CDCl3) d 169.8, 161.5, 154.6, 144.4, 139.8, 129.1, 128.5, 128.2,
67.6, 49.2, 40.2, 32.8, 32.6, 27.6, 27.3, 26.6, 6.1, 6.0; EI-MS m/z
460 (M+). Anal. Calcd for (C23H28N2O4S2): C, 59.97; N, 6.08; H,
6.13. Found: C, 59.67; N, 6.90; H, 6.38.