E. Yamuna et al. / Tetrahedron Letters 53 (2012) 1514–1517
1517
19. Hinschberger, A.; Butt, S.; Lelong, V.; Boulouard, M.; Dumuis, A.; Dauphin, F.;
Burau, R.; Pfeifffer, B.; Renard, P.; Rault, S. J. Med. Chem. 2003, 46, 138.
20. Michael, J. Nat. Prod. Rep. 1997, 14, 605.
21. Microwaves in Organic Synthesis; Loupy, A., Ed.; Wiley-VCH Verlag Gmbh & Co.
KGaA: Weinheim, 2002.
cam.ac.uk) other supplementary data associated with this article
22. Hayes, B. L. Microwave Synthesis: Chemistry at the Speed of Light; CEM
Publishing: Matthews, USA, 2002.
References and notes
23. Yamuna, E.; Zeller, M.; Rajendra Prasad, K. J. Tetrahedron Lett. 2011, 52, 6805.
24. General procedure for the synthesis of 12-ethyl-12H-benzo[g]carbazol[3,2-
b][1,8]naphthyridine (4)
1. Knölker, H.-J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303.
2. Knölker, H.-J. Curr. Org. Synth. 2004, 1, 309.
3. Agarwal, S.; Cammerer, S.; Filali, W.; Frohner, W.; Knoll, J.; Krahl, M. P.; Reddy,
K. R.; Knölker, H.-J. Curr. Org. Chem. 2005, 9, 1601.
4. Stiborova, M.; Bieler, C. A.; Wiessler, M.; Frei, E. Biochem. Pharmacol. 2001, 62,
1675.
5. Auclair, C. Arch. Biochem. Biophys. 1987, 259, 1.
6. Kuramato, Y.; Ohshita, Y.; Yoshida, J.; Yazaki, A.; Shiro, M.; Koike, T. J. Med.
Chem. 2003, 46, 1905.
7. O’Connor, S. P.; Robl, J.; Ahmad, S.; Bisaha, S.; Murugesan, N.; Ngu, K.; Shi, Y.;
Stein, P. D.; Soundararajan, N.; Natalie, K. J., Jr.; Kolla, L. R.; Sausker, J.; Quinlan,
S. L.; Fan, J.; Petsch, D.; Guo, Z. WO Patent 051386, June 09, 2005 (CA 2005, 143,
43869).
Method A:
A
mixture of 3-amino-9-ethylcarbazole (1, 1 mmol) and 2-chloro-3-
formylquinolines (2, 1 mmol) was stirred with DMF and heated at 80 °C for
8 h. After the completion of the reaction, the mixture was poured into crushed
ice and filtered. Then, the precipitated product was filtered and washed with
water, dried and recrystallized using ethanol affording 3. This was heated at
180–190 °C. First the solid melted to a red orange oil and at 210–220 °C a
vigorous exothermic reaction began with liberation of a white sublimate. The
reaction almost subsided within 5 min. It was then kept at 250 °C for another
15 min, and then cooled to room temperature. The crude product obtained was
purified by column chromatography over silica gel using petroleum ether:
8. (a) Hartner, F. W.; Hsaio, Y.; Eng, K. K.; Rivera, N. R.; Palucki, M.; Tan, L.; Yasuda,
N.; Hughes, D. L.; Weissman, S.; Zewge, D.; King, T.; Tschaen, D.; Volante, R. P. J.
Org. Chem. 2004, 69, 8723; (b) Yasuda, N.; Hsiao, Y.; Jensen, M. S.; Rivera, N. R.;
Yang, C.; Wells, K. M.; Yau, J.; Palucki, M.; Tan, L.; Dormer, P. G.; Volante, R. P.;
Hughes, D. L.; Reider, P. J. J. Org. Chem. 2004, 69, 1959; (c) Hutchinson, J. H.;
Halczenko, W.; Brashear, K. M.; Breslin, M. J.; Coleman, P. J.; Duong, L. T.;
Fernandez-Metzler, C.; Gentile, M. A.; Fisher, J. E.; Hartman, G. D.; Huff, J. R.;
Kimmel, D. B.; Leu, C. T.; Meissner, R. S.; Merkle, K.; Nagy, R.; Pennypacker, B.;
Perkins, J. J.; Prueksaritanont, T.; Rodan, G. A.; Varga, S. L.; Wesolowski, G. A.;
Zartman, A. E.; Rodan, S. B.; Duggan, M. E. J. Med. Chem. 2003, 46, 4790.
9. Olepu, S.; Suryadevara, P. K.; Rivas, K.; Yokoyama, K.; Verlinde, C. L. M. J.;
Chakrabarti, D.; Voorhis, W. C.; Gelb, M. H. Bioorg. Med. Chem. Lett. 2008, 18,
494.
ethyl acetate (93:7) as an eluant to get
benzo[g]carbazol[3,2-b][1,8]naphthyridines (4).
Method B:
a red solid 12-ethyl-12H-
A
mixture of 3-amino-9-ethylcarbazole (1, 1 mmol), 2-chloro-3-
formylquinolines (2, 1 mmol) and p-TsOH (20 mol %) was heated at 90 °C for
10 min. under microwave irradiation (Biotage microwave oven, 90 °C). The
crude product obtained was purified by column chromatography over silica gel
using petroleum ether: ethyl acetate (93:7) as an eluant to get a red solid 12-
ethyl-12H-benzo[g]carbazol[3,2-b][1,8]naphthyridines (4).
N-((2-Chloro-6-methylquinolin-3-yl)methylene)-9-ethyl-9H-carbazol-3-
amine (3a): Yellow solid (0.373 g, 94%) mp 203 °C; IR (KBr) 3425, 2973, 1686,
1588, 1051 cmꢁ1 1H NMR (500 MHz, CDCl3): d (ppm) 1.47 (t, 3H, J = 7.2 Hz, N-
;
CH2CH3), 2.56 (s, 3H, 6-CH3), 4.40 (q, 2H, J = 7.2 Hz, N-CH2CH3), 7.26 (d t, 1H,
Jo = 7.6 Hz, Jm = 2.00 Hz, 6-H), 7.43 (d, 1H, J = 8.4 Hz, 8-H), 7.46 (d, 1H, J = 8.2 Hz,
1-H), 7.50 (d t, 1H, J = 7.8 Hz, 7-H), 7.58 (d d, 1H, J = 7.8 Hz, 2-H), 7.61 (d d, 1H,
Jo = 8.2 Hz, Jm = 2.0 Hz, 70-H), 7.72 (s, 1H, 50-H), 7.94 (d, 1H, J = 8.4 Hz, 80-H),
8.13 (d, 1H, J = 2.0 Hz, 4-H), 8.15 (d, 1H, J = 7.6 Hz, 5-H), 9.00 (s, 1H, 40-H), 9.15
(s, 1H, CH@N); 13C NMR (125 MHz, CDCl3): d (ppm) 13.9, 21.7, 37. 8, 108. 8,
108.9, 113.4, 119.2, 120.0, 120.7, 123.0, 123.6, 126.1, 127.4, 127.5, 127.9, 128.0,
128.2, 128.4, 133.9, 135.9, 136.5, 143.1, 146.9, 149.5, 152.8; MS: m/z (%) 397
(M+, 100); Anal. Calcd for: C25H20ClN3: C, 75.46; H, 5.07; N, 10.56%. Found: C,
75.48; H, 5.09; N, 10.58%.
10. Bera, S.; Pandey, K. K.; Vora, A. C.; Grandgenett, D. P. J. Mol. Biol. 2011, 410,
831.
11. (a) Roma, G.; Grossi, G.; Braccio, M. D.; Piras, D.; Ballabeni, V.; Tognolini, M.;
Bertoni, S.; Barocelli, E. Eur. J. Med. Chem. 2008, 43, 1665; (b) Roma, G.;
Braccio, M. D.; Grossi, G.; Mattioli, F.; Ghia, M. Eur. J. Med. Chem. 2000, 1021,
35; (c) Atanasova, M.; Ilieva, S.; Galabov, B. Eur. J. Med. Chem. 2007, 42,
1184.
12. (a) Litvinov, V. P. Russ. Chem. Rev. 2004, 73, 637; (b) Schramm, O. G.; Oeser, T.;
Müller, T. J. J. J. Org. Chem. 2006, 71, 3494; (c) Zong, R.; Zhou, H.; Thummel, R. P.
J. Org. Chem. 2008, 73, 4334; (d) Litvinov, V. P. Advances in the Chemistry of
Naphthyridines. In Advanced Heterocyclic Chemistry; Elsevier, San Diego,
2006; Vol. 91, p 189.; (e) Lahue, B. R.; Lo, S.-M.; Wan, Z.-K.; Woo, G. H. C.;
Snyder, J. K. J. Org. Chem. 2004, 69, 7171.
13. Noravyan, A. S.; Paronikyan, E. G.; Vartanyan, S. A. Khim-Farm. Zh. 1985, 19,
790. Chem. Abstr. 1985, 104, 186324.
14. Litvinov, V. P.; Roman, S. V.; Dyachenko, V. D. Usp. Khim. 2000, 69, 218 [Engl.
Transl. Russ., 2000, 69, 201].
15. Chrzastek, L.; Sliwa, W. Australian J. Chem. 1994, 47, 2129.
16. Barbara, B.; Teresa, Z. ARKIVOC 2001, 6, 77.
17. Roseman, K.; Gould, M.; Linfield, M.; Edwards, B. J. Med. Chem. 1970, 13,
230.
12-Ethyl-2-methyl-12H-benzo[g]carbazol[3,2-b][1,8]naphthyridine (4a): Red
solid (0.296 g, 82%); mp 197 °C; Yield: IR (KBr) 3408, 2923, 1630, 1486 cmꢁ1
;
1H NMR (500 MHz, CDCl3): d (ppm) 1.50 (t, 3H, J = 7.2 Hz, N12-CH2CH3), 2.55 (s,
3H, 2-CH3), 4.44 (q, 2H, N12-CH2CH3, J = 7.2 Hz), 7.41 (d, 1H, J = 8.0 Hz, 3-H),
7.50 (s, 1H, 1-H), 7.56 (d, 1H, J = 8.0 Hz, 4-H), 7.65 (d d, 1H, Jo = 8.8 Hz,
Jm = 1.6 Hz, 11-H), 7.78 (s, 1H, 13-H), 7.85 (t, 2H, 9- & 10-H), 7.99 (s, 1H, 7-H),
8.17 (d, 1H, J = 8.0 Hz, 8-H), 9.17 (s, 1H, 15-H), 9.29 (s, 1H, 14-H); 13C NMR
(125 MHz, CDCl3): d (ppm) 13.70 (N12CH2CH3), 18.2, 37.8, 105.5, 106.1, 108.8,
115.7, 118.9, 119.3, 121.4, 121.9, 123.7, 124.4, 126.4, 127.9, 128.5, 129.2, 129.9,
132.6, 134.5, 134.5, 136.3, 139.2, 142.9, 148.6; MS: m/z (%) 361 (M+, 100); Anal.
Calcd for: C25H19N3: C, 83.08; H, 5.30; N, 11.63%. Found: C, 83.02; H, 5.35; N,
11.64%.
18. Gorlitzer, K.; Bode, M.; Jones, P. G.; Jomaa, H.; Wiesner, J. Pharmazie 2007, 62,
15.