T. Takahashi et al. / Bioorg. Med. Chem. 14 (2006) 7501–7511
7511
6. Zarjevski, N.; Cusin, I.; Vettor, R.; Rohner-Jeanrenaud,
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manner similar to that described for 3f, and purified by
flash chromatography on silica gel with 65% EtOAc in
hexanes to afford 64 mg (78%) of 5g as a white solid:
mp 152–155 ꢁC; H NMR (CDCl3) d 7.95 (1H, br s),
7.75 (1H, br s), 7.48 (1H, dd, J = 7.8, 1.2 Hz), 7.36
(1H, d, J = 7.4 Hz), 7.23–7.03 (4H, m), 6.64 (1H, br s),
3.62 (4H, br s), 3.04 (3H, s), 2.78 (4H, t, J = 4.7 Hz),
2.39 (3H, s); HRMS (ESI+) m/z [M+H]+ 455.1866
(C22H27N6O3S requires: 455.1865). Analytical HPLC
99.2% pure, tR = 3.6 min.
1
11. Blomqvist, A. G.; Herzog, H. Trends Neurosci. 1997, 20,
294.
12. Gerald, C.; Walker, M. W.; Criscione, L.; Gustafson, E.
L.; Batzl-Hartmann, C.; Smith, K. E.; Vaysse, P.; Durkin,
M. M.; Laz, T. M.; Linemeyer, D. L.; Schaffhauser, A. O.;
Whitebread, S.; Hofbauer, K. G.; Taber, R. I.; Branch-
chek, T. A.; Weinshank, R. L. Nature 1996, 382, 168.
5.2.51.
N-[3-(3-Methylphenyl)-1H-pyrazol-5-yl]-4-{2-
[(methylsulfonyl)amino]phenyl}piperazine-1-carboxamide
(5h). The title compound was prepared from 7i (31 mg,
0.18 mol) and 13a (59 mg, 0.18 mmol) in a manner sim-
ilar to that described for 3f, and purified by flash chro-
matography on silica gel with 65% EtOAc in hexanes
to afford 22 mg (27%) of 5h as a white solid: mp 146–
´
13. (a) Galiano, S.; Erviti, O.; Perez, S.; Moreno, A.;
Juanenea, L.; Aldana, I.; Monge, A. Bioorg. Med. Chem.
Lett. 2004, 14, 597; (b) Juanenea, L.; Galiano, S.; Erviti,
´
O.; Moreno, A.; Perez, S.; Aldana, I.; Monge, A. Bioorg.
Med. Chem. 2004, 12, 4717.
1
148 ꢁC; H NMR (CDCl3) d 7.74 (1H, br s), 7.50 (1H,
d, J = 7.8 Hz), 7.45 (1H, d, J = 8.8 Hz), 7.40 (1H, d,
J = 8.0 Hz), 7.27 (1H, m), 7.23–7.14 (3H, m), 7.07 (1H,
t, J = 7.6 Hz), 6.73 (1H, br s), 3.64 (4H, br s), 3.08
(3H, s), 2.84 (4H, t, J = 4.7 Hz), 2.36 (3H, s); HRMS
(ESI+) m/z [M+H]+ 455.1867 (C22H27N6O3S requires:
455.1865). Analytical HPLC 99.2% pure, tR = 3.8 min.
14. Rueeger, H.; Gerspacher, M.; Buehlmayer, P.; Rigollier,
P.; Yamaguchi, Y.; Schmidlin, T.; Whitebread, S.; Nuess-
lein-Hildesheim, B.; Nick, H.; Cricione, L. Bioorg. Med.
Chem. Lett. 2004, 14, 2451.
15. Aquino, C. J.; Ramanjulu, J. M.; Heyer, D.; Daniels, A.
J.; Palazzo, F.; Dezube, M. Bioorg. Med. Chem. 2004, 12,
2691.
16. Hammond, M.; Elliott, R. L.; Gillaspy, M. L.; Hager, D.
C.; Hank, R. F.; LaFlamme, J. A.; Oliver, R. M.; DaSilva-
Jardine, P. A.; Stevenson, R. W.; Mack, C. M.; Cassella, J.
V. Bioorg. Med. Chem. Lett. 2003, 13, 1989.
17. (a) Islam, I.; Dhanoa, D.; Finn, J.; Du, P.; Walker, M. W.;
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2002, 12, 1771.
18. Tabuchi, S.; Itani, H.; Sakata, Y.; Oohashi, H.; Satoh, Y.
Bioorg. Med. Chem. Lett. 2002, 12, 1171.
19. Satoh, Y.; Hatori, C.; Ito, H. Bioorg. Med. Chem. Lett.
2002, 12, 1009.
20. Itani, H.; Ito, H.; Sakata, Y.; Hatakeyama, Y.; Oohashi,
H.; Satoh, Y. Bioorg. Med. Chem. Lett. 2002, 12, 757.
21. Itani, H.; Ito, H.; Sakata, Y.; Hatakeyama, Y.; Oohashi,
H.; Satoh, Y. Bioorg. Med. Chem. Lett. 2002, 12, 799.
22. Sato, N.; Takahashi, T.; Shibata, T.; Haga, Y.; Sakuraba,
A.; Hirose, M.; Sato, M.; Nonoshita, K.; Koike, Y.;
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5.2.52.
N-[3-(4-Methylphenyl)-1H-pyrazol-5-yl]-4-{2-
[(methylsulfonyl)amino]phenyl}piperazine-1-carboxamide
(5i). The title compound was prepared from 7j (31 mg,
0.18 mol) and 13a (59 mg, 0.18 mmol) in a manner sim-
ilar to that described for 3f, and purified by flash chro-
matography on silica gel with 65% EtOAc in hexanes
to afford 53 mg (65%) of 5i as a white solid: mp 182–
1
184 ꢁC; H NMR (CDCl3) d 7.74 (1H, s), 7.48 (3H, t,
J = 8.0 Hz), 7.17 (2H, t, J = 6.8 Hz), 7.11–7.03 (2H,
m), 6.72 (1H, s), 3.60 (4H, br s), 3.06 (3H, s), 2.78
(4H, br s), 2.34 (3H, s); HRMS (ESI+) m/z [M+H]+
455.1857 (C22H27N6O3S requires: 455.1865). Analytical
HPLC 99.2% pure, tR = 3.7 min.
Acknowledgment
We thank Mr. Hirokazu Ohsawa (Analytical chemistry,
Tsukuba research institute, Banyu Pharmaceutical Co.,
Ltd.) for analytical support.
24. Elliott, J. M.; Broughton, H.; Cascieri, M. A.; Chicchi, G.;
Huscroft, I. T.; Kurtz, M.; MacLeod, A. M.; Sadowski, S.;
Stevenson, G. I. Bioorg. Med. Chem. Lett. 1998, 8, 1851.
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27. Kanatani, A.; Ishihara, A.; Iwaasa, H.; Nakamura, K.;
Okamoto, O.; Hidaka, M.; Ito, J.; Fukuroda, T.; MacNeil,
D. J.; Van der Ploeg, L. H. T.; Ishii, Y.; Okabe, T.;
Fukami, T.; Ihara, M. Biochem. Biophys. Res. Commun.
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