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M.A. Jun et al. / European Journal of Medicinal Chemistry 43 (2008) 1889e1902
5.2.9. (R)-4-({2-[3-tert-Butoxycarbonylamino-4-(2,4,5-
trifluorophenyl)butyryl]-3,4-dihydro-2H-pyrazole-3-
carbonyl}amino)benzoic acid ethyl ester (8k)
J ¼ 6.0 Hz, 2H), 2.80 (d, J ¼ 8.1 Hz, 2H), 1.36 (s, 9H), 1.30
(t, J ¼ 7.2 Hz, 3H).
Yield: 23%. 1H NMR (CDCl3, 300 MHz) d 8.00 (d,
J ¼ 8.7 Hz, 2H), 7.61 (d, J ¼ 8.7 Hz, 2H), 7.07 (s, 1H),
7.07e7.06 (m, 1H), 6.91e6.87 (m, 1H), 5.15e5.09 (m, 2H),
4.35 (q, J ¼ 7.2 Hz, 1H), 4.40e4.20 (m, 1H), 3.90e3.80 (m,
1H), 3.11e2.89 (m, 4H), 1.38 (t, J ¼ 7.2 Hz, 3H), 1.33 (s, 9H).
5.2.15. (R)-{3-[({2-[3-tert-Butoxycarbonylamino-4-(2,4,5-
trifluorophenyl)butyryl]-3,4-dihydro-2H-pyrazole-3-
carbonyl}amino)methyl]phenoxy}acetic acid ethyl ester (8q)
Yield: 62%. 1H NMR (CDCl3, 300 MHz) d 7.64 (br s, 1H),
7.22 (t, J ¼ 7.8 Hz, 1H), 7.05e6.99 (m, 1H), 6.99 (s,
1H), 6.92e6.87 (m, 1H), 6.88 (d, J ¼ 7.8 Hz, 1H), 6.85
(s, 1H), 6.83 (d, J ¼ 7.8 Hz, 1H), 5.10 (br, 1H), 4.92 (dd,
J ¼ 4.8, 11.2 Hz, 1H), 4.58 (s, 2H), 4.42 (s, 2H), 4.26 (q,
J ¼ 7.2 Hz, 2H), 4.25e4.23 (m, 1H), 3.72e3.62 (m, 1H),
3.10e2.80 (m, 5H), 1.35 (s, 9H), 1.26 (t, J ¼ 7.2 Hz, 3H).
5.2.10. (R)-[3-{5-(Pyridin-2-ylmethyl)carbamoyl-4,5-
dihydropyrazol-1-yl)-3-oxo-1-(2,4,5-trifluorobenzyl)
propyl]carbamic acid tert-butyl ester (8l)
Yield: 40%. 1H NMR (CDCl3, 300 MHz) d 8.51 (d,
J ¼ 4.5 Hz, 1H), 8.07 (br s, 1H), 7.65 (t, J ¼ 7.5 Hz, 1H),
7.26e7.15 (m, 2H), 7.00e6.98 (m, 2H), 6.88e6.85 (m, 1H),
5.65e5.50 (br, 1H), 5.01e4.94 (m, 1H), 4.58 (s, 2H), 4.30e
4.15 (m, 1H), 3.70e3.55 (m, 1H), 3.14e2.77 (m, 5H), 1.35
(s, 9H). LCeMS m/z 520 (MHþ).
5.2.16. (R)-[3-[5-(4-Morpholin-4-ylphenylcarbamoyl)-4,5-
dihydropyrazol-1-yl]-3-oxo-1-(2,4,5-trifluorobenzyl)
propyl]carbamic acid tert-butyl ester (8r)
Yield: 69%. 1H NMR (CDCl3, 300 MHz) d 7.43 (d,
J ¼ 9.0 Hz, 2H), 7.20e7.00 (m, 1H), 7.04 (s, 1H), 6.90e
6.87 (m, 1H), 6.85 (d, J ¼ 9.0 Hz, 2H), 5.08 (dd, J ¼ 4.8,
11.7 Hz, 1H), 4.35e4.20 (m, 1H), 3.87e3.79 (m, 6H),
3.12e3.09 (m, 4H), 2.94e2.88 (m, 4H), 1.30 (s, 9H).
5.2.11. (R)-[3-{5-[(1H-Benzoimidazol-2-ylmethyl)
carbamoyl]-4,5-dihydro-pyrazol-1-yl}-3-oxo-1-(2,4,5-
trifluorobenzyl)propyl]carbamic acid tert-butyl ester (8m)
Yield: 28%. 1H NMR (CDCl3, 300 MHz) d 8.15 (br s, 3H),
7.55e7.53 (m, 2H), 7.24e7.20 (m, 2H), 7.05e6.84 (m, 3H),
5.75e5.55 (m, 1H), 4.76 (s, 2H), 4.57e4.49 (m, 1H), 4.32e
4.28 (m, 1H), 3.10e2.81 (m, 5H), 1.35 (s, 9H). LCeMS m/z
559 (MHþ).
5.2.17. (R)-[3-Oxo-3-[5-(4-sulfamoylphenylcarbamoyl)
-4,5-dihydropyrazol-1-yl]-1-(2,4,5-trifluorobenzyl)
propyl]carbamic acid tert-butyl ester (8s)
1
Yield: 83%. H NMR (CDCl3, 300 MHz) d 9.93 (br, 1H),
8.21 (br s, 3H), 7.11e7.08 (m, 1H), 6.91e9.79 (m, 2H),
6.58e6.51 (m, 4H), 5.50e5.30 (br, 1H), 5.30e5.23 (m, 1H),
4.21e4.10 (m, 1H), 4.09e3.56 (m, 1H), 3.42e3.22 (m, 2H),
2.83e2.81 (m, 1H), 1.80e1.60 (m, 2H), 1.36 (s, 9H).
5.2.12. (R)-[3-[5-(4-Amino-benzylcarbamoyl)-4,5-
dihydropyrazol-1-yl]-3-oxo-1-(2,4,5-trifluorobenzyl)
propyl]carbamic acid tert-butyl ester (8n)
Yield: 58%. 1H NMR (CDCl3, 300 MHz) d 7.48 (br s, 1H),
7.05 (d, J ¼ 8.4 Hz, 2H), 6.99 (s, 1H), 6.99e6.85 (m, 2H),
6.61 (d, J ¼ 8.4 Hz, 2H), 5.30 (br s, 1H), 4.89 (dd, J ¼ 4.8,
11.7 Hz, 1H), 4.31 (d, J ¼ 5.7 Hz, 2H), 4.29e4.23 (m, 1H),
3.71e3.70 (m, 1H), 3.63e3.61 (br, 2H), 3.03 (dd, J ¼ 11.7,
18.9 Hz, 1H), 2.91e2.78 (m, 4H), 1.37 (s, 9H).
5.2.18. (R)-4-({2-[3-tert-Butoxycarbonylamino-4-(2,4,5-
trifluorophenyl)butyryl]-3,4-dihydro-2H-pyrazole-3-
carbonyl}amino)benzenesulfonic acid (8t)
Yield: 100%. 1H NMR (CDCl3, 300 MHz) d 7.13e7.07 (m,
1H), 6.90e6.82 (m, 3H), 6.55 (s, 1H), 6.54 (d, J ¼ 5.1 Hz,
2H), 5.30e5.23 (m, 1H), 4.21e4.05 (m, 2H), 3.43e3.05 (m,
2H), 2.88e2.60 (m, 2H), 1.80e1.60 (m, 1H), 1.37 (s, 9H).
5.2.13. (R)-[3-Oxo-3-[5-(4-sulfamoyl-benzylcarbamoyl)-4,5-
dihydropyrazol-1-yl]-1-(2,4,5-trifluorobenzyl)propyl]
carbamic acid tert-butyl ester (8o)
5.2.19. (R)-{4-[{2-[3-tert-Butoxycarbonylamino-4-(2,4,5-
trifluorophenyl)butyryl]3,4-dihydro-2H-pyrazole-3-
1
Yield: 42%. H NMR (CDCl3, 300 MHz) d 7.93 (br, 1H),
7.84 (d, J ¼ 8.1 Hz, 2H), 7.67 (br s, 1H), 7.39 (d,
J ¼ 8.1 Hz, 2H), 7.10e6.99 (m, 1H), 7.01 (s, 1H), 6.93e
6.85 (m, 1H), 5.10e5.08 (br, 1H), 4.97e4.87 (m, 1H), 4.49
(s, 2H), 4.40e4.21 (m, 2H), 3.65e3.49 (m, 1H), 2.89e2.83
(m, 1H), 1.35 (s, 9H).
carbonyl}amino]phenoxy}acetic acid ethyl ester (8u)
Yield: 76%. 1H NMR (CDCl3, 300 MHz) d 7.45 (d,
J ¼ 9.0 Hz, 2H), 7.20e7.05 (m, 1H), 7.04 (s, 1H), 6.92e
6.84 (m, 1H), 6.86 (d, J ¼ 9.0 Hz, 2H), 5.07 (dd, J ¼ 4.8,
11.7 Hz, 1H), 4.58 (s, 2H), 4.30e4.22 (m, 1H), 4.26 (q,
J ¼ 7.2 Hz, 2H), 3.90e3.80 (m, 1H), 3.11e2.89 (m, 5H),
1.33 (s, 9H), 1.26 (t, J ¼ 7.2 Hz, 3H).
5.2.14. (R)-{4-[({2-[3-tert-Butoxycarbonylamino-4-(2,4,
5-trifluorophenyl)butyryl]-3,4-dihydro-2H-pyrazole-3-
carbonyl}amino)methyl]phenoxy}acetic acid ethyl ester (8p)
Yield: 33%. 1H NMR (CDCl3, 300 MHz) d 7.61 (br s, 1H),
7.19 (d, J ¼ 8.7 Hz, 2H), 7.05e6.98 (m, 1H), 6.99 (s, 1H),
6.92e6.88 (m, 1H), 6.84 (d, J ¼ 8.7 Hz, 2H), 5.18 (br,
1H), 4.90 (dd, J ¼ 4.8, 11.7 Hz, 1H), 4.57 (s, 2H), 4.37 (s,
2H), 4.26 (q, J ¼ 7.2 Hz, 2H), 4.27e4.22 (m, 1H), 3.70e
3.64 (m, 1H), 3.03 (dd, J ¼ 11.7, 20.1 Hz, 1H), 2.89 (d,
5.2.20. (R)-{3-[{2-[3-tert-Butoxycarbonylamino-4-(2,4,5-
trifluorophenyl)butyryl]3,4-dihydro-2H-pyrazole-3-
carbonyl}amino]phenoxy}acetic acid ethyl ester (8v)
1
Yield: 77%. H NMR (CDCl3, 300 MHz) d 9.63 (s, 1H),
7.34 (s, 1H), 7.21 (t, J ¼ 8.1 Hz, 1H), 7.05e7.03 (m, 3H),
6.88 (d, J ¼ 8.1 Hz, 1H), 6.67 (d, J ¼ 8.1 Hz, 1H), 5.20e
5.00 (br s, 1H), 5.08 (dd, J ¼ 4.8, 11.7 Hz, 1H), 4.60