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E. A. Muravyova et al.
PAPER
4,6-Bis(4-methoxyphenyl)-1¢,3¢-dimethyl-3-phenyl-1H-1,4,6,7-
tetrahydro-2¢H-spiro[pyrazolo[3,4-b]pyridine-5,5¢-pyrimi-
dine]-2¢,4¢,6¢(1¢H,3¢H)-trione (6f)
(3) See, for example: (a) Kappe, C. O. Angew. Chem. Int. Ed.
2004, 43, 6250. (b) Hayes, B. L. Aldrichimica Acta 2004,
37, 266. (c) Roberts, B. A.; Strauss, C. R. Acc. Chem. Res.
2005, 38, 653. (d) De La Hoz, A.; Diaz-Ortiz, A.; Moreno,
A. Chem. Soc. Rev. 2005, 34, 164. (e) Kappe C. O., Stadler
A.; Microwaves in Organic and Medicinal Chemistry;
Wiley-VCH: Weinheim, 2005.
(4) See, for example: (a) Bonrath, W.; Paz Schmidt, R. In
Advances in Organic Synthesis; Atta-ur-Rahman, Ed.;
Bentham Science: Amsterdam, 2005, Chap. 3, 81–117.
(b) Mason, T. J.; Luche, J.-L. In Chemistry Under Extreme
or Non-Classical Conditions; van Eldick, R.; Hubbard, C.
D., Eds.; John Wiley: Chichester, 1997. (c) Cravotto, G.;
Cintas, P. J. Chem. Soc. Rev. 2006, 35, 180. (d) Mason, T.
J. Chem. Soc. Rev. 1997, 26, 443. (e) Muravyova, E. A.;
Desenko, S. M.; Musatov, V. I.; Knyazeva, I. V.; Shishkina,
S. V.; Shishkin, O. V.; Chebanov, V. A. J. Comb. Chem.
2007, 9, 798.
(5) (a) Huang, Z.; Ma, Q.; Bobbitt, J. M. J. Org. Chem. 1993, 58,
4837. (b) Vicente, J.; Chicote, M. T.; Guerrero, R.;
de Arellano, M. C. R. Chem. Commun. 1999, 1541.
(c) Alajarin, R.; Avarez-Buila, J.; Vaquero, J. J.; Sunkel, C.;
Fau, J.; Statkov, P.; Sanz, J. Tetrahedron: Asymmetry 1993,
4, 617. (d) Bossert, F.; Vater, W. Med. Res. Rev. 1989, 9,
291. (e) Triggle, D. J.; Langs, D. A.; Janis, R. A. Med. Res.
Rev. 1989, 9, 123. (f) Tsuda, Y.; Mishina, T.; Obata, M.;
Araki, K.; Inui, J.; Nakamura, T. WO 8,504,172, 1985.
(g) Tsuda, Y.; Mishina, T.; Obata, M.; Araki, K.; Inui, J.;
Nakamura, T. JP 61,227,584, 1986. (h) Tsuda, Y.; Mishina,
T.; Obata, M.; Araki, K.; Inui, J.; Nakamura, T. EP
0,217,142, 1987. (i) Atwal, K. S.; Vaccaro, W.; Lloyd, J.;
Finlay, H.; Yan, L.; Bhandaru, R. S. US 2007,099,899,
2007. (j) Atwal, K. S.; Moreland, S. Bioorg. Med. Chem.
Lett. 1991, 1, 291.
(6) (a) Sanghvi, Y. S.; Larson, S. B.; Wills, R. C.; Robins, R. K.;
Revankar, G. R. J. Med. Chem. 1989, 32, 945. (b) Bell, M.
R.; Ackerman, J. H. US 4,920,128, 1990. (c) Farghaly, A.
M.; Habib, N. S.; Hazzaa, A. B.; El-Sayed, O. A. J. Pharm.
Sci. 1989, 3, 90. (d) Ganjee, A.; Adair, O. O.; Queener, S. F.
J. Med. Chem. 2003, 46, 5074. (e) Rosowsky, A.; Chen, H.;
Fu, H.; Queener, S. F. Bioorg. Med. Chem. 2003, 11, 59.
(f) Dishington, A. P.; Johnson, P. D.; Kettle, J. G.
Tetrahedron Lett. 2004, 45, 3733.
Yellow solid; mp 156–157 °C.
1H NMR (200 MHz, DMSO-d6): d = 2.67 (s, 3 H, NCH3), 2.83 (s, 3
H, NCH3), 3.49 (s, 3 H, OCH3), 3.69 (s, 3 H, OCH3), 4.81 (d, J = 7.3
Hz, 1 H, 6-CH), 5.28 (s, 1 H, 4-CH), 6.02 (d, J = 7.3 Hz, 1 H, 7-
NH), 6.40–7.10 (m, 13 Harom), 12.07 (s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): d = 170.6, 164.6, 162.5, 159.6,
158.2, 149.6, 129.8, 128.6, 128.5, 128.2, 127.6, 127.1, 126.8, 113.7,
113.0, 99.6, 65.8, 60.6, 55.1, 54.8, 46.4, 35.7, 30.7, 28.1, 27.3.
MS (EI, 70 eV): m/z (%) = 551 (30.8) [M+], 277 (100), 273 (70.6),
274 (62.2).
Anal. Calcd For C31H29N5O5: C, 67.50; H, 5.30; N, 12.70. Found:
C, 67.47; H, 5.33; N, 12.67.
4-(4-Ethylphenyl)-6-(4-methoxyphenyl)-3-methyl-1H-1,4,6,7-
tetrahydro-2¢H-spiro[pyrazolo[3,4-b]pyridine-5,5¢-pyrimi-
dine]-2¢,4¢,6¢(1¢H,3¢H)-trione (6g)
Yellow solid; mp 219–220 °C.
1H NMR (200 MHz, DMSO-d6): d = 1.11 (t, J = 7.6 Hz, 3 H, CH3),
1.51 (s, 3 H, CH3), 2.56 (q, J = 7.6 Hz, 2 H, CH2), 3.70 (s, 3 H,
OCH3), 4.66 (d, J = 7.3 Hz, 1 H, 6-CH), 4.80 (s, 1 H, 4-CH), 5.78
(d, J = 7.3 Hz, 1 H, 7-NH), 6.79–7.15 (m, 8 Harom), 9.95 (s, 1 H,
NH), 10.85 (s, 1 H, NH), 11.06 (s, 1 H, NH).
MS (EI, 70 eV): m/z (%) = 459 (31) [M+], 457 (55), 332 (39.5), 215
(52).
Anal. Calcd For C25H25N5O4: C, 65.35; H, 5.48; N, 15.24. Found:
C, 65.37; H, 5.51; N, 15.23.
6-(4-Methoxyphenyl)-1¢,3,3¢-trimethyl-4-[4-(methylsulfan-
yl)phenyl]-1-phenyl-1,4,6,7-tetrahydro-2¢H-spiro[pyrazolo[3,4-
b]pyridine-5,5¢-pyrimidine]-2¢,4¢,6¢(1¢H,3¢H)-trione (6h)
Colorless solid; mp 252–253 °C.
1H NMR (200 MHz, DMSO-d6): d = 1.59 (s, 3 H, CH3), 2.41 (s, 3
H, SCH3), 2.77 (s, 3 H, NCH3), 2.84 (s, 3 H, NCH3), 3.69 (s, 3 H,
OCH3), 4.76 (d, J = 7.3 Hz, 1 H, 6-CH), 4.95 (s, 1 H, 4-CH), 6.24
(d, J = 7.3 Hz, 1 H, 7-NH), 6.80–7.80 (m, 13 Harom).
13C NMR (100 MHz, DMSO-d6): d = 170.2, 164.9, 159.6, 158.9,
149.6, 145.5, 144.2, 139.6, 138.0, 133.0, 132.8, 132.2, 132.0, 129.0,
128.7, 128.1, 125.6, 125.5, 121.1, 113.8, 101.9, 66.5, 58.6, 55.0,
46.6, 28.2, 27.5, 14.2, 13.9.
(7) Tseng, C. P. US 4,838,925, 1989.
(8) (a) Hahn, W. E.; Muszynski, M. Chem. Stosow. 1986, 30,
421. (b) Muszynski, M.; Hahn, W. E. PL 130681, 1984;
Chem. Abstr. 1986, 104, 159328a.
MS (EI, 70 eV): m/z (%) = 581 (93) [M+], 565 (37.8), 290 (100),
426 (54.9), 306 (40.1).
(9) (a) Chebanov, V. A.; Desenko, S. M. Curr. Org. Chem.
2006, 10, 297. (b) Chebanov, V. A.; Sakhno, Ya. I.;
Desenko, S. M.; Chernenko, V. N.; Musatov, V. I.;
Shishkina, S. V.; Shishkin, O. V.; Kappe, C. O. Tetrahedron
2007, 63, 1229. (c) Quiroga, J.; Insuasty, B.; Hormaza, A.;
Saitz, C.; Jullian, C. J. Heterocycl. Chem. 1998, 35, 575.
(d) Drizin, I.; Holladay, M. W.; Yi, L.; Zhang, G. Q.;
Gopalakrishnan, S.; Gopalakrishnan, M.; Whiteaker, K. L.;
Buckner, S. A.; Sullivan, J. P.; Carroll, W. A. Bioorg. Med.
Chem. Lett. 2002, 12, 1481. (e) Chebanov, V. A.; Saraev, V.
E.; Desenko, S. M.; Chernenko, V. N.; Shishkina, S. V.;
Shishkin, O. V.; Kobzar, K. M.; Kappe, C. O. Org. Lett.
2007, 9, 1691. (f) Gladkov, E. S.; Chebanov, V. A.;
Desenko, S. M.; Shishkin, O. V.; Shishkina, S. V.; Dallinger,
D.; Kappe, C. O. Heterocycles 2007, 63, 469.
Anal. Calcd For C32H31N5O4S: C, 66.07; H, 5.37; N, 12.04. Found:
C, 66.03; H, 5.33; N, 12.03.
References
(1) (a) Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39,
3168. (b) Wender, P. A.; Handy, S. T.; Wright, D. L. Chem.
Ind. (London) 1997, 765.
(2) Multicomponent Reactions; Zhu, J.; Bienayme, H., Eds.;
Wiley-VCH: Weinheim, 2005. (a) Bagley, M. C.; Lubinu,
M. C. Top. Heterocycl. Chem. 2006, 1, 31. (b) Simon, C.;
Constantieux, T.; Rodriguez, J. Eur. J. Org. Chem. 2004,
4957. (c) Orru, R. V. A.; de Greef, M. Synthesis 2003, 1471.
(d) Dömling, A. Chem. Rev. 2006, 106, 17.
(g) Chebanov, V. A.; Sakhno, Y. I.; Desenko, S. M.;
Shishkina, S. V.; Musatov, V. I.; Shishkin, O. V.; Knyazeva,
I. V. Synthesis 2005, 2597. (h) Chebanov, V. A.; Saraev, V.
E.; Desenko, S. M.; Chernenko, V. N.; Knyazeva, I. V.;
(e) Groenendaal, B.; Ruijter, E.; Orru, R. V. A. Chem.
Commun. 2008, 5474.
Synthesis 2009, No. 8, 1375–1385 © Thieme Stuttgart · New York