J
D. V. Horváth et al.
Paper
Synthesis
IR (ATR): 2122, 2099, 1598, 1576, 1487, 1443, 1384, 1283, 1096, 1038,
962, 891, 820, 748, 691, 644, 594, 532 cm–1
1H NMR (500 MHz, CDCl3): δ = 9.56 (s, 1 H), 8.62 (d, J = 5.7 Hz, 1 H),
7.80 (d, J = 5.7 Hz, 1 H), 7.48–7.45 (m, 1 H), 7.33 (s, 1 H), 7.29 (d, J = 7.9
Hz, 1 H), 7.27–7.24 (m, 2 H), 2.66 (s, 3 H), 2.54 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 150.0, 142.6, 138.3, 136.3, 135.5,
133.3, 133.1, 131.6, 131.3, 131.1, 129.3, 127.9, 124.9, 118.6, 117.5,
18.5, 15.2.
Njardarson, J. T. J. Med. Chem. 2014, 57, 10257. (f) Iranshahy, M.;
Quinn, R. J.; Iranshahi, M. RSC Adv. 2014, 4, 15900.
(g) Chrzanowska, M.; Grajewska, A.; Rozwadowska, M. D. Chem.
Rev. 2016, 116, 12369.
.
(2) (a) Pomeranz, C. Monatsh. Chem. 1893, 14, 116. (b) Fritsch, P.
Ber. Dtsch. Chem. Ges. 1893, 26, 419. (c) Pictet, A.; Spengler, T.
Ber. Dtsch. Chem. Ges. 1911, 44, 2030. (d) Bischler, A.;
Napieralski, B. Ber. Dtsch. Chem. Ges. 1893, 26, 1903. (e) For a
recent diversity-oriented approach, see: Awuah, E.; Capretta, A.
J. Org. Chem. 2010, 75, 5627.
(3) For pioneering work, see: (a) Roesch, K. R.; Larock, R. C. J. Org.
Chem. 1998, 63, 5306. (b) Guimond, N.; Fagnou, K. J. Am. Chem.
Soc. 2009, 131, 12050. (c) Gerfaud, T.; Neuville, L.; Zhu, J. Angew.
Chem. Int. Ed. 2009, 48, 572. (d) Shi, Z.; Koester, D. C.;
Boultadakis-Arapinis, M.; Glorius, F. J. Am. Chem. Soc. 2013, 135,
12204. For recent examples, see: (e) Jiang, H.; Yang, J.; Tang, X.;
Wu, W. J. Org. Chem. 2016, 81, 2053. (f) Chu, H.; Xue, P.; Yu, J.-T.;
Cheng, J. J. Org. Chem. 2016, 81, 8009. (g) Kuai, C.; Wang, L.; Li,
B.; Yang, Z.; Cui, X. Org. Lett. 2017, 19, 2102.
Ellipticine (11)15 and 5,6a-Dimethyl-6aH-pyrido[3,4-a]carbazole (33)
Azide 32 (36 mg, 0.13 mmol) was dissolved in 1,2-dichlorobenzene (2
mL). The mixture was heated in a microwave reactor at 190 °C for 1 h.
Two products formed according to TLC. The mixture was concentrat-
ed under reduced pressure and purified by flash chromatography
(hexane–EtOAc, 1:1, then hexane–EtOAc, 1:4) to give 11 (55%) as a
yellow powder and 33 (45%) as an orange powder.
Ellipticine (11)
(4) (a) Schlosser, M. Angew. Chem. Int. Ed. 2005, 44, 376.
(b) Schlosser, M. Angew. Chem. Int. Ed. 2006, 45, 5432.
(5) Grethe, G. The Chemistry of Heterocyclic Compounds, Isoquino-
lines; John Wiley & Sons: New York, 1981.
(6) Fortner, P. Monatsh. Chem. 1893, 14, 146.
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(9) Walker, M. D.; Andrews, B. I.; Burton, A. J.; Humphreys, L. D.;
Kelly, G.; Schilling, M. B.; Scott, P. W. Org. Process Res. Dev. 2010,
14, 108.
Yield: 18 mg (55%); mp 306–308 °C.
1H NMR (50 MHz, DMSO): δ = 11.36 (s, 1 H), 9.70 (s, 1 H), 8.47–8.31
(m, 2 H), 7.92 (d, J = 5.6 Hz, 1 H), 7.61–7.49 (m, 2 H), 7.26 (t, J = 7.0 Hz,
1 H), 3.27 (s, 3 H), 2.80 (s, 3 H).
13C NMR (125 MHz, DMSO): δ = 149.6, 142.6, 140.51, 140.45, 132.4,
128.0, 127.0, 123.7, 123.4, 123.1, 121.9, 119.1, 115.8, 110.6, 108.0,
14.3, 11.8.
5,6a-Dimethyl-6aH-pyrido[3,4-a]carbazole (33)
(10) Tilstam, U.; Weinmann, H. Org. Process Res. Dev. 2002, 6, 384.
(11) (a) Keilin, B.; Cass, W. E. J. Am. Chem. Soc. 1942, 64, 2442.
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Chem. 2005, 48, 4972.
(12) (a) Tscherniac, J. German Patent 134979, 1901. (b) Einhorn, A.;
Bischkopff, E.; Szelinski, B.; Schupp, G.; Spröngerts, E.; Ladisch,
C.; Mauermayer, T. Liebigs Ann. Chem. 1905, 343, 207.
(13) According to the literature,9 the benzene ring of 5,8-dichloroiso-
quinoline can be oxidized to give the appropriate pyridine-3,4-
dicarboxylic acid.
Yield: 13 mg (45%); mp 117–122 °C.
1H NMR (500 MHz, CDCl3): δ = 9.20 (s, 1 H), 8.72 (d, J = 5.22 Hz, 1 H),
7.71 (d, J = 8.67 Hz, 1 H), 7.44 (d, J = 7.17 Hz, 1 H), 7.38 (t, J = 8.36 Hz, 1
H), 7.27 (t, J = 8.16 Hz, 1 H), 7.21 (d, J = 5.03 Hz, 1 H), 6.55 (br s, 1 H),
2.08 (br s, 3 H), 1.41 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 182.4, 154.6, 153.0, 146.4, 144.5,
141.7, 135.4, 130.2, 128.5, 126.2, 124.2, 121.9, 121.7, 118.6, 57.2, 27.6,
19.0.
(14) (a) Rossini, A. F. C.; Muraca, A. C. A.; Casagrande, G. A.;
Raminelli, C. J. Org. Chem. 2015, 80, 10033. (b) Ku, A. F.; Cuny, G.
D. Org. Lett. 2015, 17, 1134. (c) Chen, J.; Wan, M.; Hua, J.; Sun, Y.;
Lv, Z.; Li, W.; Liu, L. Org. Biomol. Chem. 2015, 13, 11561.
(15) (a) Miller, R. B.; Moock, T. Tetrahedron Lett. 1980, 21, 3319.
(b) Miller, R. B.; Dugar, S.; Epperson, J. R. Heterocycles 1987, 25,
217. (c) Nagao, Y.; Endo, R.; Tokumaru, M.; Arimitsu, K. Hetero-
cycles 2009, 77, 1403. (d) Nagao, Y.; Hirota, K.; Tokumaru, M.;
Kozawa, K. Heterocycles 2007, 73, 593. (e) Liu, C.-Y.; Knochel, P.
J. Org. Chem. 2007, 72, 7106.
Funding Information
We gratefully acknowledge the financial support from the National
Research, Development and Innovation Office (K-116150). We are
also grateful for the financial support from Soneas Research Ltd.
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Supporting Information
Supporting information for this article is available online at
(16) Godard, A.; Rocca, P.; Pomel, V.; Thomas-dit-Dumont, L.; Rovera,
J. C.; Thaburet, J. F.; Marsais, F.; Quéguiner, G. J. Organomet. Chem.
1996, 517, 25.
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(17) (a) Sam, J.; Shafik, R. M.; Aparajithan, K. J. Pharm. Sci. 1970, 59,
59. (b) Wieting, M. J.; Fisher, J. T.; Schafer, G. A.; Visco, D. M.;
Gallucci, C. J.; Mattson, E. A. Eur. J. Org. Chem. 2015, 525.
(18) (a) Cannon, G. J.; Kim, C. J.; Aleem, A. M. J. Heterocycl. Chem.
1972, 731. (b) Tang, H.; Wei, Y.-B.; Zhang, C.; Ning, F.-X.; Qiao,
W.; Huang, S.-L.; Ma, L.; Huang, Z.-S.; Gu, L.-Q. Eur. J. Med.
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References
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J