A. Maity et al. / Tetrahedron Letters 52 (2011) 3033–3037
3037
A.; Paira, P.; Saha, P.; Naskar, S.; Paira, R.; Banerjee, S.; Sahu, N. P.; Mondal, N.
B.; Luger, P.; Weber, M. Tetrahedron 2009, 65, 6941–6949.
17. Begouin, A.; Hesse, S.; Queiroz, M. J. R. P.; Kirsch, G. Synthesis 2006, 2794–
2798.
tional simplicity that make it an attractive and useful process for
the synthesis of newer heteroaromatics of biological importance.
18. Pellón, R. F.; Docampo, M. L.; Kunakbaeva, Z.; Gómez, V.; Castro, H. V. Synth.
Commun. 2006, 36, 481–485.
Acknowledgments
19. Palacios, M. L. D.; Comdom, R. F. P. Synth. Commun. 2003, 33, 1777–
1781.
20. Hesse, S.; Kirsch, G. Synthesis 2007, 1571–1575.
21. General reaction procedure for the synthesis of linear and angular fused
quinazolinones:
We are thankful to the Director, IICB for laboratory facilities,
and the Council of Scientific and Industrial Research (CSIR) for fel-
lowships to S.M., R.P., A.H., S.N., K.B.S., P.S. and DBT for fellowships
to A.M. We are also thankful to Dr. B. Achari, Emeritus Scientist,
CSIR, for his valuable suggestions.
One mmol each of the 2-aminopyridine [or 2-aminoisoquinoline] (3a–e or 14)
derivatives and 1- bromo-2-bromomethyl benzene [or 1-bromo-2-
bromomethyl-naphthalene] (4a–b or 9) derivatives were dissolved in dry
DMF and heated at 85 °C for almost 6 h in a 100 ml RB flask. Then 1.5 equiv of
Cs2CO3, 10 mol % of CuI and 20 mol % L-proline were added to the solution and
Supplementary data
heated with constant stirring for 6 h at 80–85 °C. After completion of the
reaction (monitored by TLC), the contents were cooled to room temperature.
Then water was added to the mixture, the content was transferred to a
separating funnel and extracted with ethyl acetate. The organic layer was
washed thoroughly with water until free from alkali, dried over anhydrous
Supplementary data associated with this article can be found, in
sodium sulfate, and evaporated to dryness in
a rotary evaporator under
reduced pressure. The residue was chromatographed over silica gel (60–
120 mesh), eluting with a mixture of hexane and ethyl acetate in different
ratios.
(a) Spectral data of compound 8a: Yellowish product; Rf = 0.59 (20% EtOAc–Pet
ether); mp: 210–212 °C; 1H NMR (300 MHz, CDCl3) d 6.88 (m, 1H), 7.50 (m,
3H), 7.83 (m, 2H), 8.46 (d, 1H, J = 8.1 Hz), 8.89 (d, 1H, J = 7.2 Hz); 13C NMR
(75 MHz, CDCl3) d 112.4 (CH), 116.2 (C), 125.1 (CH), 126.2 (CH), 126.6 (CH),
126.8 (CH), 127.2 (CH), 134.0 (CH), 135.0 (CH), 147.6 (C), 148.4 (C), 158.9 (CO);
MS [ESI] m/z: 197 [M+H]+; HRMS (ESI) m/z: calcd for C12H8N2ONa: [M+Na]+;
219.0529 found; 219.0521.
(b) Spectral data of compound 13a: Yellowish product; Rf = 0.97 (20% EtOAc–Pet
ether); mp: 198–199 °C (lit20 mp 195 °C); 1H NMR (600 MHz, CDCl3) d 7.01 (m,
1H), 7.63 (m, 1H), 7.71(d, 1H, J = 7.2 Hz), 7.74 (m, 2H), 7.78 (d, 1H, J = 9.0 Hz),
7.92 (d, 1H, J = 7.8 Hz), 8.32 (d, 1H, J = 8.4 Hz), 9.04 (d, 1H, J = 7.2 Hz), 9.20 (d,
1H, J = 7.8 Hz); 13C NMR (150 MHz, CDCl3) d 112.1 (C), 113.5 (CH), 122.4 (CH),
125.4 (CH), 125.7 (CH), 126.8 (CH), 126.9 (2 Â CH), 127.9 (CH), 129.7 (CH),
129.8 (C), 134.2 (CH), 136.4 (C), 147.6 (C), 148.0 (C), 158.6 (CO); MS [ESI] m/
z:247 [M+H]+, 269 [M+Na]+; HRMS (ESI) m/z: calcd for C16H11N2O: [M+H]+
247.0866; found; 247.0861.
References and notes
1. (a) Comprehensive Natural Products Chemistry; Barton, D. S., Nakanishi, K., Meth-
Cohn, O., Eds.; Pergamon: London, 1999; Vols. 1–8.; (b) Advances in Heterocyclic
Chemistry; Katritzky, A. R., Ed.; Academic: New York, NY, 1962–2004; Vols. 1–
86.; (c) Advances in Drug Research; Testa, B., Mayer, U.A., Eds.; Academic: New
York, NY, 1966–1996; Vols.1–30.
2. (a) Johne, S.; Groger, D. Pharmazie 1970, 25, 22; (b) Coppola, G. M. Synthesis
1980, 505; (c) Johne, S. Prog. Drug Res. 1982, 26, 259; (d) Johne, S. Prog. Chem.
Org. Nat. Prod. 1984, 46, 159; (e) Michael, J. P. Nat. Prod. Rep. 2000, 17, 603; (f)
Witt, A.; Bergman, J. Curr. Org. Chem. 2003, 7, 659.
3. Chu, J. H. Sci. Rec. (China) 1951, 4, 279; Chem. Abstr. 1952, 46, 11589b.
4. Li, H. T.; Hung, H. I. Yao Hsueh Pao 1966, 13, 265; Chem. Abstr. 1966, 65, 3922c.
5. Schwender, C. F.; Sunday, B. R.; Herzig, D. J. J. Med. Chem. 1979, 22, 114–116.
6. Wolfe, J. F.; Rathman, T. L.; Sleevi, M. C.; Campbell, J. A.; Greenwood, T. D. J. Med.
Chem. 1990, 33, 161–166.
7. Buyuktimkin, S. Pharmazie 1986, 40, 393–395.
8. Yen, M. H.; Sheu, J.-R.; Peng, I.-H.; Lee, Y.-M.; Chern, J.-W. J. Pharm. Pharmacol.
1996, 48, 90–95.
(c) Spectral data of compound 22: Whitish product; Rf = 0.58 (20% EtOAc–Pet
ether); mp: 293–294 °C, 1H NMR (300 MHz, CDCl3) d 7.14 (d, 1H, J = 7.8 Hz),
7.71 (m, 3H), 7.80 (d, 2H, J = 8.7 Hz), 7.91 (m, 2H), 8.32 (d, 1H, J = 8.7 Hz), 8.77
(d, 1H, J = 7.8 Hz), 9.31 (m, 2H); 13C NMR (75 MHz, CDCl3) d 113.6 (C), 113.8
(CH), 121.9 (CH), 122.4 (CH), 125.4 (CH), 126.0 (CH), 126.4 (CH), 126.7 (CH),
127.2 (CH), 127.6 (C), 127.8 (CH), 128.4 (CH), 129.4 (CH), 130.0 (C) 132.1 (CH),
132.9 (C), 136.3 (C), 145.9 (C), 146.3 (C), 159.1 (CO); MS [ESI] m/z:297 [M+H]+,
319 [M+Na]+, HRMS (ESI) m/z: calcd for C20H12N2ONa: [M+Na]+ 319.0842;
found: 319.0888.
9. Jiang, J. B.; Hesson, D. P.; Dusak, B. A.; Dexter, D. L.; Kang, G. J.; Hamel, E. J. J.
Med. Chem. 1990, 33, 1721–1728.
10. Mhaske, S. B.; Argade, N. P. Tetrahedron 2004, 60, 3417–3420.
11. (a) Manhas, M. S.; Amin, S. G.; Rao, V. V. Synthesis 1977, 309–310; (b) Chern, J.-
W.; Chen, H.-T.; Lai, N.-Y.; Wu, K.-R.; Chern, Y.-C. Chem. Pharm. Bull. 1998, 46,
928–933.
12. Kshirsgar, U. A.; Argade, N. P. Tetrahedron 2009, 65, 5244–5250.
13. Chavan, S. P.; Sivappa, R. Tetrahedron Lett. 2004, 45, 997–999.
14. Ababsa, G. B.; Ely, S. C. S.; Hesse, S.; Nassar, E.; Chevallier, F.; Nguyen, T. T.;
Derdour, A.; Mongin, F. J. Org. Chem. 2010, 75, 839–847.
15. (a) Snider, B. B.; Zeng, H. Org. Lett. 2000, 2, 4103; (b) Wang, H.; Ganesan, A. J.
Org. Chem. 2000, 65, 1022; (c) He, F.; Foxman, B. M.; Snider, B. B. J. Am. Chem.
Soc. 1998, 120, 6417.
(d) Spectral data of compound 6a: 1H NMR (600 MHz, DMSO-d6) d 3.34 (s, 2H,
CH2), 5.71 (m, 1H), 6.22 (s, 1H), 6.38 (d, 1H, J = 9.0 Hz), 6.82 (m, 1H), 6.87 (dd,
1H, J = 1.2, 7.8 Hz), 7.22 (m, 2H), 7.33 (m, 1H), 7.64 (dd, 1H, J = 1.2, 7.8 Hz, NH);
13C NMR (150 MHz, DMSO-d6) d 52.2 (CH2), 101.7 (CH), 120.9 (CH), 122.3 (C),
127.6 (CH), 127.8 (CH), 128.8 (CH), 132.5 (CH), 133.7 (CH), 136.4 (C), 138.3
(CH), 158.3 (C).
16. (a) Paira, P.; Hazra, A.; Sahu, K. B.; Banerjee, S.; Mondal, N. B.; Sahu, N. P.;
Weber, M.; Lugar, P. Tetrahedron 2008, 64, 4026–4036; (b) Sahu, K. B.; Hazra,