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´
´
´
S.; Galgoczya, K.; Horvatha, C.; Farkasa, S.; Domany, G.
6.32 (d, J = 3.5 Hz, 1H), 6.34 (s, 1H), 6.44 (dd, J = 8.5,
2.6 Hz, 1H), 6.52 (dd, J = 13.2, 2.6 Hz, 1H), 7.06 (t,
J = 9.1 Hz, 1H), 7.54 (d, J = 3.5 Hz, 1H); compound 11
(300 MHz, DMSO-d6): d = À0.11 (s, 9H), 0.82 (t,
J = 8.1 Hz, 2H), 3.50 (t, J = 8.1 Hz, 2H), 6.33 (d, J =
3.6 Hz, 1H), 6.36 (s, 1H), 6.86 (m, 1H), 6.95 (t, 1H,
J = 7.8), 7.05 (m, 2H), 7.55 (d, J = 3.6 Hz, 1H); com-
pound 12 (300 MHz, DMSO-d6): d = À0.09 (s, 9H), 0.81
(t, J = 8.2 Hz, 2H), 3.51 (t, J = 8.2 Hz, 2H), 6.35
(d, J = 3.5 Hz, 1H), 6.37 (s, 1H), 7.27 (s, 2H), 7.55
(d, J = 3.5 Hz, 1H); compound 13 (300 MHz, DMSO-d6):
d = À0.10 (s, 9H), 0.81 (t, J = 8.1 Hz, 2H), 3.51 (t, J =
8.1 Hz, 2H), 6.34 (d, J = 3.6 Hz, 1H), 6.37 (s, 1H), 6.97
(d, J = 8 Hz, 2H), 7.57 (d, J = 3.6 Hz, 1H), 7.62 (d, J =
8 Hz, 2H).
Bioorg. Med. Chem. Lett. 2004, 14, 3953–3956.
7. Kuehler, T. C.; Swanson, M.; Shcherbuchin, V.; Larsson,
H.; Mellgard, B.; Sjoestroem, J. E. J. Med. Chem. 1998,
41, 1777–1788.
8. Benoit, S.; Gingras, S. U.S. Provisional Patent 60/367,401,
2003.
´
9. Thutewohl, M.; Schirok, H.; Bennabi, S.; Figueroa-Perez,
S. Synthesis 2006, 629–632.
10. (a) Banks, R. E.; Burgess, J. E.; Cheng, W. M.; Haszel-
dine, R. N. J. Chem. Soc. 1965, 575–581; (b) Chambers, R.
D.; Drakesmith, F. G.; Musgrave, W. K. R. J. Chem.
Soc. 1965, 5045–5048; (c) Aksenov, V. V.; Vlasov, V. M.;
Yakobson, G. G. J. Fluorine Chem. 1982, 20, 439–458;
(d) Mittelbach, M. Synthesis 1988, 479–480; (e) Laev, S.
S.; Shteingarts, V. D. J. Fluorine Chem. 1999, 96, 175–185;
(f) Miller, A. D.; Krasnov, V. I.; Peters, D.; Platonov, V.
E.; Miethchen, R. Tetrahedron Lett. 2000, 41, 3817–
3819.
11. L’Heureux, A.; Thibault, C.; Ruel, R. Tetrahedron Lett.
2004, 45, 2317–2319.
12. Minakata, S.; Komatsu, M.; Oshiro, Y. Synthesis 1992,
661–663.
13. Antonini, I.; Claudi, F.; Cristalli, G.; Franchetti, P.;
Grifantini, M.; Martelli, S. J. Med. Chem. 1982, 25, 1258–
1261.
15. Methyl 2-(4-nitro-2-fluorophenyl)acetate (908 mg, 4.26
mmol) was dissolved in DMF (10 mL) and sodium
hydride (60% in mineral oil, 170 mg, 4.26 mmol) was
added. The mixture was stirred at rt for 30 min. Com-
pound 5b (698 mg, 2.13 mmol) in DMF (5 mL) was then
added and the reaction was heated to 70 °C and further
stirred for 2 h. After being cooled, the solution was poured
into ice water and the suspension was extracted with ethyl
acetate. The organic extracts were combined and washed
with brine. After removal of the solvent, the residue was
purified by column chromatography. 1H NMR (400 MHz,
DMSO-d6): d = À0.12 (s, 9H), 0.80 (t, J = 8.1 Hz, 2H),
3.52 (t, J = 8.1 Hz, 2H), 3.74 (s, 3H), 5.57 (s, 2H), 6.02
(s, 1H), 6.60 (d, J = 3.6 Hz, 1H), 7.15 (s, 1H), 7.57 (t, J =
8.1 Hz, 1H), 7.72 (d, J = 3.6 Hz, 1H), 8.05 (dd, J = 8.5,
2.2 Hz, 1H), 8.17 (dd, J = 10.0, 2.2 Hz, 1H).
14. In a typical experiment, 5a or 5b and the corresponding
phenol (1.5 equiv) were dissolved in DMSO, 2 equiv of
K2CO3 was then added and the suspension was stirred at
100 °C until the starting azaindole was consumed. After
being cooled, the reaction was poured into ice water and
the product was extracted with ethyl acetate. The organic
extracts were combined and washed with brine. After
removal of the solvent, the residues were purified by
16. 1H NMR: compound 9 (DMSO-d6, 300 MHz): d = 5.40
(s, 2H), 6.23 (dd, J = 3.5, 1.8 Hz, 1H), 6.29 (dd, J = 5.3,
0.8 Hz, 1H), 6.43 (ddd, J = 8.7, 2.4, 1.7 Hz, 1H), 6.52
(dd, J = 13.5, 2.4 Hz, 1H), 7.01 (t, J = 9.0 Hz, 1H), 7.32
(dd, J = 3.3, 2.6 Hz, 1H), 8.03 (d, J = 5.3 Hz, 1H), 11.65
(s, 1H).
column chromatography. 1H NMR: compound
6
(300 MHz, DMSO-d6): d = À0.09 (s, 9H), 0.82 (t,
J = 8.2 Hz, 2H), 3.51 (t, J = 8.2 Hz, 2H), 5.53 (s, 2H),