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LETTER
further purified by flash chromatography over silica gel
(2) (a) Yildiz-Oren, I.; Yalcin, I.; Aki-Sener, E.; Ucarturk, N.
Eur. J. Med. Chem. 2004, 39, 291. (b) Tekiner-Gulbas, B.;
Temiz-Arpaci, O.; Yildiz, I.; Aki-Sener, E.; Yalcin, I.
SAR QSAR Environ Res. 2006, 17, 121. (c) Clark, R. L.;
Pessolano, A. A.; Witzel, B.; Lanza, T.; Shen, T. Y. J. Med.
Chem. 1978, 21, 1158. (d) Boger, D. L.; Miyauchi, H.; Du,
W.; Hardouin, C.; Fecik, R. A.; Cheng, H.; Hwang, I.;
Hedrick, M. P.; Leung, D.; Acevedo, O.; Guimarães, C. R.
W.; Jorgensen, W. L.; Cravatt, B. F. J. Med. Chem. 2005, 48,
1849. (e) Deng, J. Z.; McMasters, D. R.; Rabbat, P. M. A.;
Williams, P. D.; Coburn, C. A.; Yan, Y. W.; Kuo, L. C.;
Lewis, S. D.; Lucas, B. J.; Krueger, J. A.; Strulovici, B.;
Vacca, J. P.; Lylea, T. A.; Burgeya, C. S. Bioorg. Med.
Chem. Lett. 2005, 15, 4411. (f) Walczynński, K.;
Zuiderveld, O. P.; Timmerman, H. Eur. J. Med. Chem. 2005,
15.
column with PE–EtOAc (5:1) to give the pure product 3a.
(9) Selected Spectral Data
Compound 3a: mp 101–102 °C. Rf = 0.55 (EtOAc–PE, 1:2).
IR (KBr): 2913, 1617, 1544 cm–1. 1H NMR (300 MHz,
CDCl3): d = 8.38 (dd, J = 5.1, 1.5 Hz, 1 H), 8.34 (d, J = 1.5
Hz, 1 H), 8.34 (d, J = 2.1 Hz, 1 H), 8.10 (dd, J = 7.8, 1.5 Hz,
1 H), 7.55–7.62 (m, 3 H), 7.36–7.41 (m, 1 H). MS (EI):
m/z = 196 [M]+. Anal. Calcd for C12H8N2O: C, 73.46; H,
4.11; N, 14.28. Found: C, 73.46; H, 4.43; N, 14.18.
Compound 3i: mp 79–81 °C. Rf = 0.38 (EtOAc–PE, 1:2). IR
(KBr): 2924, 1602, 1523 cm–1. 1H NMR (300 MHz, CDCl3):
d = 8.35 (dd, J = 4.2, 1.5 Hz, 1 H), 8.21 (dd, J = 7.8, 1.5 Hz,
1 H), 8.12 (dd, J = 7.8, 1.5 Hz, 1 H), 7.53–7.56 (m, 1 H),
7.32–7.37 (m, 1 H), 7.10–7.16 (m, 2 H), 4.05 (s, 3 H). MS
(EI): m/z = 226 [M]+. Anal. Calcd for C13H10N2O2: C, 69.02;
H, 4.46; N, 12.38. Found: C, 68.67; H, 4.34; N, 12.38.
Compound 3k: mp 172–174 °C. Rf = 0.42 (EtOAc–PE, 1:2).
IR (KBr): 1496, 1620, 1223 cm–1. 1H NMR (300 MHz,
CDCl3): d = 8.34 (dd, J = 4.5, 1.5 Hz, 1 H), 8.05 (dd, J = 7.8,
1.5 Hz, 1 H), 7.54 (s, 2 H), 7.33–7.37 (m, 1 H), 4.04 (s, 9 H).
MS (EI): m/z = 286 [M]+. Anal. Calcd for C15H14N2O4: C,
62.93; H, 4.93; N, 9.79; Found: C, 63.12; H, 4.74; N, 9.78.
Compound 6a: mp 163–164 °C. Rf = 0.38 (EtOAc–PE, 1:2).
IR (KBr): 2920, 1670, 1580 cm–1. 1H NMR (300 MHz,
CDCl3): d = 8.56 (s, 1 H), 8.46 (dd, J = 1.5, 7.2 Hz, 2 H),
7.81 (s, 1 H), 7.75–7.65 (m, 3 H), 2.65 (s, 3 H). 13C NMR (75
MHz, CDCl3): d = 165.1, 154.4, 147.3, 132.3, 130.6, 129.0,
128.0, 126.7, 118.5, 18.9. ESI-MS: m/z = 211 [M+ + 1].
Anal. Calcd for C13H10N2O: C, 74.27; H, 4.79; N, 13.33.
Found: C, 74.05; H, 4.77; N, 13.28.
(3) (a) Doise, M.; Dennin, F.; Blondeau, D.; Sliwa, H.
Tetrahedron Lett. 1990, 31, 1155. (b) Doise, M.; Blondeau,
D.; Sliwa, H. Synth. Commun. 1992, 22, 2891.
(c) Myllymäki, M. J.; Koskinen, A. M. P. Tetrahedron Lett.
2007, 48, 2295. (d) Heuser, S.; Keenanb, M.; Weichert,
A. G. Tetrahedron Lett. 2005, 46, 9001. (e) Phoon, C. W.;
Ng, P. Y.; Ting, A. E.; Yeob, S. L.; Sima, M. M. Bioorg.
Med. Chem. Lett. 2001, 11, 1647.
(4) (a) Flouzat, C.; Guillaumet, G. Synthesis 1990, 64.
(b) Walczynński, K.; Zuiderveld, O. P.; Timmerman, H.
Eur. J. Med. Chem. 2005, 40, 15. (c) Garnier, E.;
Blanchard, S.; Rodriguez, I.; Jarry, C.; Léger, J.-M.;
Caubère, P.; Guillaumet, G. Synthesis 2003, 2033.
(5) Altenhoff, G.; Glorius, F. Adv. Synth. Catal. 2004, 346,
1661.
(6) (a) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003,
42, 5400. (b) Kunz, K.; Scholz, U.; Ganzer, D. Synlett 2003,
2428. (c) Finet, J. P.; Fedorov, A. Y.; Combes, S.; Boyer, G.
Curr. Org. Chem. 2002, 6, 597.
(7) Evindar, G.; Batey, R. A. J. Org. Chem. 2006, 71, 1802.
(8) Typical Procedure for the Synthesis and Purification of
3a
Compound 6b: mp 165–167 °C. Rf = 0.35 (EtOAc–PE, 1:2).
IR (KBr): 2918, 1620, 1550 cm–1.1H NMR (300 MHz,
CDCl3): d = 8.57 (s, 1 H), 8.32 (d, J = 8.4 Hz, 2 H), 8.01 (d,
J = 8.3 Hz, 2 H), 7.84 (s, 1 H), 3.95 (s, 1 H), 2.64 (s, 3 H).
ESI-MS: m/z = 241 [M+ + 1]. Anal. Calcd for C13H10N2O: C,
69.99; H, 5.03; N, 11.66. Found: C, 69.78; H, 4.98; N, 11.69.
Compound 6c: mp 193–194 °C. Rf = 0.32 (EtOAc–PE, 1:2).
IR (KBr): 2918, 1610, 1560 cm–1.1H NMR (300 MHz,
CDCl3): d = 8.59 (s, 1 H), 8.16 (d, J = 8.7 Hz, 2 H), 8.04 (d,
J = 8.1 Hz, 2 H), 7.84 (s, 1 H), 2.64 (s, 3 H). 13C NMR (75
Hz, CDCl3): d = 164.3, 154.2, 147.7, 143.3, 138.4, 130.9,
129.3, 126.2, 118.6, 99.5, 18.9. ESI-MS: m/z = 337 [M+ + 1].
Anal. Calcd for C13H9IN2O: C, 46.45; H, 2.70, N, 8.33.
Found: C, 46.53; H, 2.75; N, 8.40.
To a mixture of 2a (2.0 mmol), CuI (0.1 mmol), N,N¢-
dimethylethylenediamine (0.2 mmol), and K2CO3 (4.0
mmol) was added dry toluene (5.0 mL) under a nitrogen
atmosphere. The reaction was refluxed for 12 h and then
allowed to cool to r.t. The crude mixture was added to 10 mL
H2O and then was extracted by CH2Cl2 (2 × 20 mL). The
organic layer was dried over anhyd Na2SO4 and
concentrated in vacuo to give the crude product, which was
Synlett 2009, No. 7, 1172–1174 © Thieme Stuttgart · New York