3002
R. Murugan et al. / Tetrahedron 67 (2011) 2998e3002
7. (a) Rathna Durga, R. S. M.; Jayashankaran, J.; Ramesh, R.; Raghunathan, R. Tet-
575 cmꢁ1
;
dH (300 MHz, DMSO-d6) 7.98 (1H, s, pyrazole C]CH),
rahedron Lett. 2006, 47, 7571e7574; (b) Jayashankaran, J.; Rathna Durga, R. S.
M.; Raghunathan, R. Tetrahedron Lett. 2006, 47, 2265e2270; (c) Pimerova, E. V.;
Voronina, E. V. J. Pharm. Chem. 2001, 35, 18e21.
8. Gandhale, D. N.; Patil, A. S.; Awate, B. G.; Naik, L. M. Pesticides 1982, 16, 27e28.
9. Takagi, K.; Tanaka, M.; Murakami, Y.; Morita, H.; Aotsuka, T. Eur. J. Med. Chem.-
Chim. Ther. 1986, 21, 65e69.
7.78 (1H, d, J 15.0 Hz, Ph), 7.63 (2H, d, J 5.8 Hz, Ph), 7.52e7.40 (4H, m,
Ph), 7.39e7.28 (2H, m, Ph), 4.25e4.01 (4H, m, CO2CH2Me), 2.58 (6H,
s, Me), 1.01 (6H, t, J 7.1 Hz, CO2CH2Me); dC (75 MHz, CDCl3) 167.5,
149.2, 147.0, 144.0, 139.7, 132.8, 131.8, 129.6, 129.1, 128.4, 127.8,
126.5, 126.1, 123.8, 118.7, 102.7, 50.8, 29.7, 19.3.
10. Bauer, V. J.; Dalalian, H. P.; Fanshawe, S. R.; Safir, S. R.; Tocus, E. C.; Benedict, A. J.
Med. Chem. 1968, 11, 981e984.
11. Genin, M. J.; Biles, C.; Keiser, B. J.; Poppe, S. M.; Swaney, S. M.; Tarpley, W. G.;
Yagi, Y.; Romero, D. L. J. Med. Chem. 2000, 43, 1034e1040.
12. Baraldi, P. G.; Garuti, L.; Leoni, A.; Cacciari, B.; Budriesi, R.; Chiarini, A. Drug Des.
4.2.8. 2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(3-(4-chloro phenyl)-
1-phenyl-pyrazol-4-yl)pyridine (2h). Yield (179 mg, 90%) as a white
solid; [found: C, 65.68; H, 4.61; N, 8.87. C26H22ClN3O4 requires C,
65.62; H, 4.66; N, 8.83; mp 144e145 ꢀC; nmax (neat) 2950, 2924,
2851, 1730, 1598, 1579, 1558, 1498, 1435, 1402, 1371, 1336, 1278,
1229,1104,1064,1036, 958, 862, 833, 753, 730, 686 cmꢁ1; m/z 476.2
[M]; dH (300 MHz, CDCl3) 7.92 (1H, s, pyrazole C]CH), 7.75 (2H, d, J
7.8 Hz, Ph), 7.47e7.44 (4H, m, Ph), 7.29e7.27 (3H, m, Ph), 3.51 (6H, s,
CO2Me), 2.59 (6H, s, Me); dC (75 MHz, CDCl3) 167.8, 155.8, 149.5,
139.3, 137.8, 134.0, 130.7, 129.5, 129.4, 128.6, 128.5, 127.7, 126.8,
118.8, 115.5, 52.2, 23.1.
Discovery 1993, 10, 319e329.
13. Bretschneider, T.; Franken, E.M.; Goergens, U.; Fuesslein, M.; Hense, A.; Kluth, J.;
Schwarz, H. G.; Koehler, A.; Malsam, O.; Voerste, A. PCT Int. Appl. 2010, WO
2010006713 A2 20100121.
14. Stanley, J. M.; Zhu, X.; Yang, X.; Holliday, B. J. Inorg. Chem. 2010, 49, 2035e2037.
15. (a) Boker, R. H.; Guengerich, F. P. J. Med. Chem. 1986, 29, 1596e1603; (b)
Goldman, S.; Stoltefuss, J. Angew. Chem., Int. Ed. Engl. 1991, 30, 1559e1578.
16. Na: (a) Liao, X.; Lin, W.; Lu, J.; Wanga, C. Tetrahedron Lett. 2010, 51, 3859e3861
K: (b) Eynde, J. V.; Orazio, R. D.; Van Haverbeke, Y. Tetrahedron 1994, 50,
2479e2484 Fe: (c) Liu, D.; Gui, J.; Wang, C.; Lu, F.; Yang, Y.; Sun, Z. Synth.
Commun. 2010, 40, 1004e1008; (d) Heravi, M. M.; Behbahani, F. K.; Oskooie, H.
A.; Shoar, R. H. Tetrahedron Lett. 2005, 46, 2775e2777; (e) Lu, J.; Bai, Y.; Wang,
Z.; Yang, B.; Li, W. Synth. Commun. 2001, 31, 2625e2630 Mn: (f) Moghadam, M.;
Nasr-Esfahani, M.; Tangestaninejad, S.; Mirkhani, V. Bioorg. Med. Chem. Lett.
2006, 16, 2026e2030; (g) Vanden Eynde, J.-J.; Delfosse, F.; Mayence, A.; Van
Haverbeke, Y. Tetrahedron 1995, 51, 6511e6516; (h) Varma, R. S.; Kumar, D.
Tetrahedron Lett. 1999, 40, 21e24 Cr: (i) Vanden Eynde, J.-J.; Mayence, A.;
Maquestiau, A. Tetrahedron 1992, 48, 463e468; (j) Sausins, A.; Duburs, G.
Heterocycles 1988, 27, 291e314; (k) Love, B.; Snader, K. M. J. Org. Chem. 1965, 30,
1914e1916 Pt: (l) Zhang, D.; Wu, L. Z.; Zhou, L.; Han, X.; Yang, Q. Z.; Zhang, L. P.;
Tung, C. H. J. Am. Chem. Soc. 2004, 126, 3440e3441 Pd/C; (m) Nakamichi, N.;
Kawashita, Y.; Hayashi, M. Org. Lett. 2002, 4, 3955e3957 Ce: (n) Pfister, J. R.
Synthesis 1990, 689e690 Bi: (o) Sabir, H.; Mashraqui, M.; Karnik, A. Synthesis
1998, 713e714; (p) Adibi, H.; Hajipour, A. R. Bioorg. Med. Chem. Lett. 2007, 17,
1008e1012 Co: (q) Anniyappan, M.; Muralidharan, D.; Perumal, P. T. Tetrahe-
dron 2002, 58, 5069e5073; (r) Hashemi, M. M.; Ahmadibeni, Y.; Ghafuri, H.
Monatsh. Chem. 2003, 134, 107e110; (s) Wang, B.; Hu, Y.; Hu, H. Synth. Commun.
1999, 29, 4193e4195 Ni: (t) Shaikh, A. C.; Chen, C. Bioorg. Med. Chem. Lett. 2010,
20, 3664e3668 V: (u) Filipan-Litvic, M.; Litvic, M.; Vinkovic, V. Tetrahedron
2008, 64, 10912e10918; (v) Su, J.; Zhang, C.; Lin, D.; Duan, Y.; Fu, X.; Mu, R.
Synth. Commun. 2010, 40, 595e600 Zr: (w) Sabitha, G.; Reddy, G. S. K. K.; Reddy,
C. S.; Fatima, N.; Yadav, J. S. Synthesis 2003, 1267e1271 Sb: (x) Filipan-Litvic, M.;
Litvic, M.; Cepanec, I.; Vinkovic, V. ARKIVOC 2008, 11, 96e103 Ru/O2: (y) Sabir,
H.; Mashraqui, M.; Karnik, A. Tetrahedron Lett. 1998, 39, 4895e4898.
17. Filipan-Litvic, M.; Litvic, M.; Vinkovic, V. Tetrahedron 2008, 64, 5649e5656.
18. Peng, L.-J.; Wang, J.-T.; Lu, Z.; Liu, Z.-Q.; Wu, L.-M. Tetrahedron Lett. 2008, 49,
1586e1588.
4.2.9. 2,6-Dimethyl-3,5-diethoxycarbonyl-4-(3-(4-chloro phenyl)-1-
phenyl-pyrazol-4-yl)pyridine (2i). Yield (185 mg, 93%) as a white
solid; mp 101e102 ꢀC; [found: C, 66.67; H, 5.25; N, 8.27.
C28H26ClN3O4 requires C, 66.73; H, 5.20; N, 8.34%]; m/z 504.2 (M);
nmax (neat) 2982, 2899, 2361, 1716, 1559, 1502, 1441, 1413, 1379,
1339, 1296, 1238, 1205, 1091, 1039, 1007, 956, 863, 831, 754, 730,
691 cmꢁ1
; dH (300 MHz, DMSO-d6) 8.63 (1H, s, pyrazole C]CH),
7.90 (2H, d, J 7.9 Hz, Ph), 7.52 (2H, t, J 7.9 Hz, Ph), 7.44e7.41 (4H, m,
Ph), 7.35 (1H, t, J 7.2 Hz, Ph), 3.97e3.87 (4H, m, CO2CH2Me), 2.49
(6H, s, Me), 0.80 (6H, t, J 7.0 Hz, CO2CH2Me); dC (75 MHz, DMSO-d6)
166.9, 155.6, 148.9, 139.4, 138.1, 133.3, 131.3, 130.1, 129.0, 128.9,
128.0, 127.2, 118.6, 115.8, 61.6, 23.1, 13.6.
Acknowledgements
The authors gratefully acknowledge the funding support of the
Ministry of Education (MOE) Singapore, under the project grant
number 265-000-318-112.
19. Ko, K. Y.; Kim, J. Y. Tetrahedron Lett. 1999, 40, 3207e3208.
20. Fang, X.; Liu, Y. C.; Li, C. J. Org. Chem. 2007, 72, 8608e8610.
21. Yadav, J. S.; Reddy, B. V. S.; Basak, A. K.; Baishya, G.; Narsaiah, A. V. Synthesis
2006, 451e454.
Supplementary data
22. Itoh, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.; Ohsawa, A. J. Org. Chem. 1997, 62,
3582e3585.
23. Balogh, M.; Hermecz, I.; Meszaros, Z.; Laszlo, P. Helv. Chim. Acta 1984, 67,
2270e2272.
Supplementary data associated with this article can be found in
24. Mao, Y. Z.; Jin, M. Z.; Liu, Z. L.; Wu, L. M. Org. Lett. 2000, 2, 741e742.
25. Zolfigol, M. A.; Choghamarani, A. G.; Shahamirian, M.; Safaiee, M.; Baltork, I. M.;
Mallakpour, S.; Alibeik, M. A. Tetrahedron Lett. 2005, 46, 5581e5584.
26. Pragst, F.; Kaltofen, B.; Volke, J.; Kuthan, J. J. Electroanal. Chem.1981,119, 301e314.
27. Jin, M. Z.; Yang, L.; Wu, L. M.; Liu, Y. C.; Liu, Z. L. Chem. Commun. 1998,
2451e2452.
References and notes
1. (a) Dunnill, P. M.; Fowden, L. Phytochemistry 1965, 4, 935e937; (b) Noe, F. F.;
Fowden, L. Biochem. J. 1960, 77, 543e546; (c) Ursic, U.; Bevk, D.; Pirc, S.; Pezdirc,
L.; Stanovnik, B.; Svete, J. Synthesis 2006, 14, 2376e2384.
28. Berson, J. A.; Brown, E. J. Am. Chem. Soc. 1955, 77, 447e450.
29. (a) Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis 1994, 639e666;
(b) Michalak, K.; Michalak, M.; Wicha, J. Tetrahedron Lett. 2010, 51, 4344e4346;
(c) Shing, T. K. M.; Cheng, H. M. J. Org. Chem. 2007, 72, 6610e6613; (d) Gorini, L.;
Caneschi, A.; Menichetti, S. Synlett 2006, 948e950; (e) Campestrini, S.; Carraro,
M.; Franco, L.; Ciriminna, R.; Pagliaro, M. Tetrahedron Lett. 2008, 49, 419e423.
30. Debache, A.; Ghalem, W.; Boulcina, R.; Belfaitah, A.; Rhouati, S.; Carboni, B.
Tetrahedron Lett. 2009, 50, 5248e5250.
2. Vinge, E.; Bjorkman, S. B. Acta Pharmacol. Toxicol. 1986, 59, 165e172.
3. Kameyama, T.; Ukai, M.; Nabeshima, T. Chem. Pharm. Bull. 1978, 26, 3265e3270.
4. Takabatake, E.; Kodama, R.; Tanaka, Y.; Dohmori, R.; Tachizawa, H.; Naito, T.
Chem. Pharm. Bull. 1970, 18, 1900e1907.
5. McQuay, H. J.; Moore, R. A. NSAIDS and coxibs: clinical use In Wall and Melzack’s
Textbook of Pain; McMahon, S., Koltzenburg, M., Eds.; Churchill Livingstone:
Edinburgh, 2005; pp 471e480.
6. Bragt, P. C.; Bansberg, J. I.; Bonta, I. L. Inflammation 1980, 4, 289e299.