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HETEROCYCLES, Vol. 78, No. 1, 2009
(17.3 g, 0.1 mol) in CHCl3 (40 mL) at 0 °C for 1.5 h. After further stirred for 4 h, the reaction mixture
was washed sequently with 10% aqueous sodium sulfite, saturated aqueous sodium bicarbonate solution
and water. After removal of the chloroform in vacuo, the crude product was crystallized from EtOAc to
give the pure product 14 (238 g, 65%) as a white solid, mp 175-176 °C. 1H NMR δ 1.28-2.15 (m, 14H),
2.94 (t, 2H, J = 7.4 Hz), 4.14 (t, 2H, J = 5.8 Hz), 4.04-4.20 (m, 1H), 7.10 (d, 1H, J = 2.6 Hz), 7.25 (dd,
1H, J1 = 8.6 Hz, J2 = 6.3 Hz), 7.34 (dd, 1H, J1 = 9.3 Hz, J1 = 2.6 Hz), 7.62 (d, 1H, J = 8.6 Hz), 8.38 (d, 1H,
13
J = 6.3 Hz), 8.65 (d, 1H, J = 9.3 Hz). C NMR (DMSO-d6): δ 21.80, 23.17, 24.59, 27.79, 32.45, 56.06,
67.61, 107.32, 120.61, 122.34, 122.38, 124.06, 131.86, 133.29, 136.38, 154.08, 158.06. ESI m/z 368.3
(M+ + H). Anal. Calcd for C20H25N5O2: C, 65.37; H, 6.86; N, 19.06. Found: C, 65.37; H, 6.89; N, 19.10.
6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-1-hydroxyquinolin-2-one (15)
Lead tetraacetate (15.0 g, wet with acetic acid) and calcium carbonate (0.8 g) were added portionwise to a
solution of quinoline N-oxide 14 (5.5 g, 1.7 mmol) in benzene (150 mL) at 0 °C for 10 min. The mixture
was heated at reflux for 6 h. After cooling, the reaction mixture was filtered to remove inorganic salts.
The filtrate was concentrated in vacuo to dryness. 3% Dilute HCl (50 mL) was added to the residue, and
the mixture heated to 80 °C for 2 h, resulting in the formation of a brown solid. After filtration, the crude
product was recrystallized from EtOAc/CHCl3 to yield 15 (4.1 g, 72%) as a white solid, mp 135-137 °C.
1H NMR (CDCl3): δ 1.22-2.15 (m, 14H), 2.94 (t, 2H, J = 7.5 Hz), 4.08 (t, 2H, J = 6.0 Hz), 4.13 (m, 1H),
6.84 (d, 1H, J = 9.3 Hz), 7.04 (d, 1H, J = 2.7 Hz), 7.34 (dd, 1H, J1 = 9.3 Hz, J2 = 2.7 Hz), 7.68 (d, 1H, J =
13
9.6 Hz), 7.76 (d, 1H, J = 9.6 Hz). C NMR (CDCl3): δ 22.93, 23.82, 24.70, 25.22, 28.36, 32.81, 57.53,
67.56, 109.37, 114.71, 119.52, 120.60, 121.17, 131.49, 136.90, 154.61, 156.94. ESI m/z 384.3 (M+ + H).
Anal. Calcd for C20H25N5O3: C, 62.65; H, 6.57; N, 18.26. Found: C, 62.62; H, 6.61; N, 18.31.
1,6-Bis[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-1H-quinolin-2-one (7)
A mixture of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-1-hydroxyquinolin-2-one 15 (4 g 10.4 mmol),
5-(4-chlorobutyl)-1-cyclohexyl- 1H-tetrazole 4 (2.8 g, 11.5 mmol) and potassium carbonate (2.9 g, 20.8
mmol) in DMF (25 mL) was stirred at 80 °C under nitrogen for 7 h. The reaction mixture was cooled to
25 °C and diluted with water (200 mL), resulting in the formation of a brown precipitate. The precipitate
was isolated by filtration, washed with H2O (3×50 mL), and recrystallized from EtOAc to give 7 (4.6 g,
1
75%) as a white solid, mp 98-99 °C. H NMR (CDCl3): δ 1.20-2.23 (m, 28H), 2.93 (t, 2H, J = 7.5 Hz),
3.11 (t, 2H, J = 7.5 Hz), 4.06 (t, 2H, J = 6.0 Hz), 4.13 (m, 1H), 4.29 (t, 2H, J = 6.0 Hz), 4.34 (m, 1H),
6.73 (d, 1H, J = 9.3 Hz), 7.01 (d, 1H, J = 2.7 Hz), 7.19 (dd, 1H, J1 = 9.3 Hz, J2 = 2.7 Hz), 7.47 (d, 1H, J =
9.6 Hz), 7.60 (d, 1H, J = 9.6 Hz). 13C NMR (DMSO-d6): δ 21.67, 21.83, 24.59, 26.69, 27.94, 32.46, 32.51,
55.98, 56.06, 67.48, 74.03, 111.15, 112.91, 120.39, 122.66, 132.57, 138.23, 154.09, 156.32. ESI m/z