Y. J. Rao, and A. Srinivas
Vol 000
REFERENCES AND NOTES
7.3–7.45(m, 6H, aromatic), 7.80(d, J = 8.2 Hz, 1H, aromatic),
8.28 (s, 1H, triazole), 8.5(d, 1H, J = 1.5 Hz, H-3). ESI-MS: m/z
363 [M + H]+. Anal. Calcd for C20H18N4O3 C, 66.29; H, 4.97;
N, 17.94. Found C, 66.13; H, 4.75; N, 17.80.
[1] Carlsen, L.; Do¨pp, D.; Do¨pp, H.; Duus, F.; Hartmann, H.;
Lang-Fugmann, S.; Schulze, B.; Smalley, R. K.; Wakefield, B. J.
In Houben-Weyl Methods in Organic Chemistry; Schaumann, E., Ed.;
Georg Thieme Verlag: Stuttgart, Germany, 1992; Vol. E8a, pp 45–204;
(b) Sperry, J.; Wright, D. Curr Opin Drug Discovery Dev 2005, 8, 723.
[2] Rowley, M.; Broughton, H. B.; Collins, I.; Baker, R.; Emms, F.;
Marwood, R.; Patel, S.; Ragan, C. I. J Med Chem 1996, 39, 1943.
[3] Frolund, B.; Jorgensen, A. T.; Tagmose, L.; Stensbol, T. B.;
Vestergaard, H. T.; Engblom, C.; Kristiansen, U.; Sanchez, C.; Krogsgaard-
Larsen, P.; Liljefors, T. J Med Chem 2002, 45, 2454.
2-[4-(4-[2-(5-Isoxazolyl)-5-methoxyphenoxy]methyl-1H-1,2,3-
triazol-1-yl)butyl]-1,3-isoindolinedione (6f).
85% yield, mp
1
130–132ꢀC; H nmr: d1.45(m, 2H), 1.85(m, 2H), 3.8 (t, N–CH2,
ptholoyl), 3.6 (s, 3H, OCH3), 4.4 (t, N–CH2, triazole), 5.3 (s, 2H,
OCH2), 6.6 (d, 1H, J = 1.5 Hz, H-4), 6.7 (m, 1H, aromatic),
7.65–7.85 (m, 6H, aromatic), 8.3 (s, 1H, triazole), 8.5 (d, 1H,
J = 1.5 Hz, H-3). ESI-MS: m/z 473 [M + H]+. Anal. Calcd for
C25H23N5O5 C, 63.42; H, 4.86; N, 14.79. Found C, 63.28; H,
4.72; N, 14.72.
[4] Daidone, G.; Raffa, D.; Maggio, B.; Plescia, F.; Cutuli, V. M. C.;
Mangano, N. G.; Caruso, A. Arch Pharm Pharm Med Chem 1999,
332, 50.
2-(4-[2-(5-Isoxazolyl)-5-methoxyphenoxy]methyl-1H-1,2,3-
[5] Tomita, K.; Takahi, Y.; Ishizuka, R.; Kamamura, S.;
Nakagawa, M.; Ando, M.; Nakanishi, T.; Nakamura, T.; Udaira, H. Ann
Sankyo Res Lab 1973, 1, 25. Chem Abstr 1974, 80, 120808.
[6] (a) Talley, J. J Prog Med Chem 1999, 13, 201; (b) Talley, J. J.;
Brown, D. L.; Carter, J. S.; Graneto, M. J.; Koboldt, C. M.; Masferrer, J. L.;
Perkins, W. E.; Rogers, R. S.; Shaffer, A. F.; Zhang, Y. Y.; Zweifel, B. S.;
Seibert, K. J Med Chem 2000, 43, 775.
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Bartolini, A.; Kal Piaz, V. J Med Chem 2003, 46, 1055.
[8] Li, W. T.; Hwang, D. R.; Chen, C. P.; Shen, C. W.; Huang, C. L.;
Chen, T. W.; Lin, C. H.; Chang, Y. L.; Chang, Y. Y.; Lo, Y. K.; Tseng, H. Y.;
Lin, C. C.; Song, J. S.; Chen, H. C.; Chen, S. J.; Wu, S. H.; Chen, C. T. J Med
Chem 2003, 46, 1706.
triazol-1-yl)-1-morpholino-1-ethanone (6g).
85% yield, mp
105–108ꢀC; 1H nmr : d 3.4–3.7(m, 8H, morpholine protons),
3.8 (s, 3H, OCH3), 5.28 (s, 2H, OCH2), 5.50 (s, 2H, OCH2), 6.6
(d, 1H, J = 1.5 Hz, H-4), 6.7 (m, 1H, aromatic), 7.0 (m, 1H,
aromatic), 7.8 (d, 1H, J = 8.2 Hz aromatic), 8.2 (s, 1H, triazole),
8.5 (d, 1H, J = 1.5 Hz, H-3). ESI-MS: m/z 384 [M + H]+. Anal.
Calcd for C19H21N5O5: C, 57.14; H, 5.26; N, 17.54. Found:
C,57.06; H, 5.14; N, 17.40.
4-2-[(1-Butyl-1H-1,2,3-triazol-4-yl)methoxy]-4-metho-
xyphenylisoxazole (6h). 88% yield, mp 116–120ꢀC; 1H nmr:d
0.8 (t, 3H), 1.2(m, 2H), 1.8 (t, 2H), 4.3(t, 2H), 3.7(s, 3H, OCH3), 5.4
(s, 2H, OCH2), 6.5 (d, J = 1.5 Hz, 1H, H-4), 6.8(m, 1H, aromatic),
7.0 (m, 1H, aromatic), 7.7(d, J = 8.2 Hz, 1H, aromatic) 8.1(s, 1H,
triazole), 8.4(d, J = 1.5 Hz, 1H, H-3); ESI-MS: m/z 328 [M+ H]+.
Anal. Calcd for C17H19N4O3 C, 62.38; H, 5.81; N, 17.12. Found
C, 62.22; H, 5.65; N, 16.98.
5-2-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-5-chloro-4-
methoxyphenylisoxazole (6i). 81% yield, mp 138–140ꢀC; 1H
nmr : d 3.9 (s, 3H, OCH3), 5.4(s, 2H, benzylic), 5.60 (s, 2H, OCH2),
6.6 (d, 1H, J = 1.5Hz, H-4), 7.2–7.5 (m, 8H, aromatic), 7.8 (d,
1H, J = 8.0 Hz, aromatic), 8.3(s, 1H, triazole), 8.6 (d, 1H,
J = 1.5 Hz, H-3). ESI-MS: m/z 397 [M + H]+. Anal. Calcd for
C20H17N4O7Cl: C,52.11; H, 3.69; N, 12.16. Found: C, 51.97; H,
3.52; N, 12.04.
2-[4-(4-[4-Chloro-2-(5-isoxazolyl)-5-methoxyphenoxy]methyl-
1H-1,2,3-triazol-1-yl)butyl]-1,3-isoindolinedione (6j). 78% yield,
mp 145–148ꢀC; 1H nmr: d 1.5(m, 2H), 1.85(m, 2H), 3.4–3.7(m, 8H,
morpholine protons), 3.6(t, 2H, N–CH2, pthaloyl), 3.9 (s, 3H, OCH3),
4.4 (t, 2H, N–CH2, triazole), 5.4 (s, 2H, OCH2), 6.6 (d, 1H,
J= 1.5 Hz, H-4), 7.2 (s, 1H, aromatic), 7.6–7.9 (m, 7H, aromatic),
8.3 (s, 1H, triazole), 8.5 (d, 1H, J= 1.5 Hz, H-3). ESI-MS: m/z 508
[M + H]+. Anal. Calcd for C25H22N5O5Cl: C, 59.11; H, 4.33; N,
13.79. Found: C, 58.95; H, 4.05; N, 13.62.
[9] Kashima, C. Heterocycles 1979, 12, 1343.
[10] (a) Kochetkov, N. K. Izv akad nauk SSSR, Ser Khim 1954, 47;
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Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega, K. C.; Hester, J. B.;
Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford, C. W.; Zurenko, G. E.;
Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. J Med Chem 2000,
43, 953e970; (b) Alvarez, R.; Velazquez, S.; San-Felix, A.; Aquaro, S.;
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Castro, H. C.; Souza, S. L.; de Souza, T. M.; Rodrigues, D. Q.;
Souza, A. M.; Abreu, P. A.; Passamani, F.; Rodrigues, C. R.; Ferreira, V. F.
Eur J Med Chem 2009, 44, 373e383; (b) Hou, D. R.; Alam, S.; Kuan, T. C.;
Ramanathan, M.; Lin, T. P.; Hung, M. S. Bioorg Med Chem Lett 2009,
19, 1022e1025; (c) Shu, H.; Izenwasser, S.; Wade, D.; Stevens, E. D.;
Trudell, M. L. Bioorg Med Chem Lett 2009, 19, 891e893.
[13] (a) Bakunov, S. A.; Bakunova, S. M.; Wenzler, T.; Ghebru, M.;
Werbovetz, K. A.; Brun, R.; Tidwell, R. R. J Med Chem 2010, 53, 254e272;
(b) Banday, A. H.; Shameem, S. A.; Gupta, B. D.; Sampath Kumar, H. M.
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[14] (a) Abbe, G. L. Chem Rev 1969, 69, 345e363; (b)
Lwowski, W. In 1,3-Dipolar Cycloaddition Chemistry, Padwa, A.
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[15] Rostovtsev, H. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew Chem Int Ed Engl 2002, 41, 2596e2599.
[16] Torne, C. W.; Christensen, C.; Meldal, M. J Org Chem 2002,
67, 3057e3064.
2-(4-[4-Chloro-2-(5-isoxazolyl)-5-methoxyphenoxy]methyl-1H-
1,2,3-triazol-1-yl)-1-morpholino-1-ethanone (6k). 80% yield, mp
1
137–139ꢀC; H nmr: d 3.4–3.6(m, 8H, morpholine protons), 3.9
[17] (a) Srinivas, H.; Sudhir, K. J Org Chem 2006, 71, 364e367.
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Scheel, A.; Voit, B.; Pyun, J.; Frechet, J. M. J.; Sharpless, K. B.; Fokin,
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IB51080, 2008.
(s, 3H, OCH3), 5.4–5.6 (2s, 4H, OCH2, COCH2), 6.65 (d, 1H,
J= 1.5 Hz, H-4), 7.2 (s, 1H, aromatic), 7.8 (s, 1H, aromatic), 8.2 (s,
1H, triazole), 8.6 (d, 1H, J= 1.5 Hz, H-3). ESI-MS: m/z 434
[M + H]+. Anal. Calcd for C19H20N5O5Cl: C, 52.59; H,4.61; N,
16.14. Found: C, 52.45; H,4.48; N, 16.02.
5-2-[(1-Butyl-1H-1,2,3-triazol-4-yl)methoxy]-5-chloro-4-
methoxyphenylisoxazole (6l). 80% yield, mp 120–123ꢀC; 1H nmr
: d 0.8 (t, 3H), 1.2(m, 2H), 1.8 (t, 2H), 4.0 (s, 3H, OCH3), 4.4 (t, 2H),
5.4 (s, 2H, OCH2), 6.6 (d, 1H, J= 1.5 Hz, H-4), 7.2 (s, 1H, aromatic),
7.8 (s, 1H, aromatic), 8.3(s, 1H, triazole), 8.6 (d, 1H, J= 1.5 Hz, H-3).
ESI-MS: m/z 262 [M + H]+. Anal. Calcd for C17H18N4O3Cl: C,
56.43; H, 4.97; N, 15.49. Found C, 56.26; H, 4.83; N, 15.32.
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11, 4136.
[24] Gamill, R. B. Synthesis 1979, 901.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet