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methanol 90:10) compound 15 was obtained as a white solid
(90 mg, 94%). Rf (dichloromethane/methanol 90:10): 0.35;
m.p. 198 °C; IR (KBr, cm–1) m 3312, 1607, 1512, 1291, 1248,
1184, 1051, 828; 1H NMR (DMSO-d6, 250 MHz): d 3.74 (t,
4H, J = 5.2 Hz), 4.05 (t, 4H, J = 5.0 Hz), 7.08 (d, 4H,
J = 8.7 Hz), 7.77 (d, 4H, J = 8.7 Hz), 8.19 (t, 1H, J = 2.2 Hz),
8.78 (d, 2H, J = 2.0 Hz); 13C NMR (DMSO-d6, 62.5 MHz): d
59.5 (2 × CH2), 69.8 (2 × CH2), 115.2 (4 × CH), 127.1
(2 × Cq), 128.8 (4 × CH), 135.7 (CH), 137.3 (2 × Cq), 140.2
(2 × CH), 159.7 (2 × Cq); MS (IS): 352 (M + 1)+;Anal. Calc.
for C21H21NO4: C, 71.78; H, 6.02; N, 3.99. Found: C, 71.97;
H, 5.91; N, 4.14.
Cs2CO3 (310 mg, 0.95 mmol), flash chromatography
(dichloromethane/methanol/triethylamine 80:20:0.01); com-
pound 19 was obtained as a white solid (77 mg, 50%). Rf
(dichloromethane/methanol/triethylamine 80:20:0.01) 0.29;
m.p. 184 °C; IR (KBr, cm–1) m 2952, 2817, 2769, 1606, 1475,
1283, 1254, 1225, 1032, 819; 1H NMR (CDCl3, 250 MHz): d
2.36 (s, 12H), 2.76 (t, 4H, J = 5.7 Hz), 4.12 (t, 4H, J = 7.4 Hz),
7.03 (d, 4H, J = 7.6 Hz), 7.54 (d, 2H, J = 8.5 Hz), 7.70 (d,
1H, J = 8.2 Hz), 7.85 (dd, 1H, J = 2.2, 8.2 Hz), 7.97 (d, 2H,
J = 8.8 Hz), 8.84 (s, 1H); 13C NMR (CDCl3, 62.5 MHz): d
46.0 (4 × CH3), 58.4 (2 × CH2), 66.2 (2 × CH2), 114.9
(2 × CH), 115.3 (2 × CH), 119.6 (CH), 128.0 (2 × CH), 128.1
(2 × CH), 130.3 (Cq), 131.9 (Cq), 133.9 (Cq), 134.6 (CH),
147.6 (CH), 155.3 (Cq), 159.0 (Cq), 159.8 (Cq); MS (IS):
406 (M + 1)+;Anal. Calc. for C25H31N3O2: C, 74.04; H, 7.70;
N, 10.36. Found: C, 74.27; H, 7.60; N, 10.42.
4.1.17. 2,5-Bis-(4-methoxyphenyl)-pyridine (17) [11,16]
Following general procedure A. 2,5-Dibromopyridine 16
(4.22 mmol) and 4-methoxyphenyl boronic acid
3
(10.97 mmol), toluene (86 ml), ethanol (52 ml) and aqueous
saturated NaHCO3 solution (34 ml). Flash chromatography
(ether petroleum/ethyl acetate 7:3); compound 17 was
obtained as a yellow solid (1.13 g, 92%). Rf (petroleum
ether/ethyl acetate 7:3): 0.32; m.p. 210 °C; IR (KBr, cm–1) m
4.1.20. 2,5-Bis-[4-(3-dimethylamino-propoxy)-phenyl]-
pyridine (20)
Following general procedure C. Compound 18 (100 mg,
0.38 mmol), Cs2CO3 (273 mg, 0.84 mmol), 3-chloropropyl-
dimethylamine hydrochloride (133 mg, 0.84 mmol), Cs2CO3
(310 mg, 0.95 mmol), flash chromatography (dichloro-
methane/methanol/triethylamine 80:20:0.01); compound 20
was obtained as a white solid (107 mg, 65%). Rf (dichloro-
methane/methanol/triethylamine 80:20:0.01): 0.26; m.p.
174 °C; IR (KBr, cm–1) m 2946, 2764, 2362, 1607, 1468, 1251,
1222, 1057, 818; 1H NMR (CDCl3, 250 MHz): d 1.99 (q, 4H,
J = 6.6 Hz), 2.27 (s, 12H), 2.48 (t, 4H, J = 7.2 Hz), 4.07 (td,
4H, J = 3.1, 6.3 Hz), 7.00 (d, 4H, J = 8.8 Hz), 7.53 (d, 2H,
J = 8.5 Hz), 7.68 (d, 1H, J = 8.2 Hz), 7.84 (dd, 1H, J = 2.2,
8.2 Hz), 7.96 (d, 2H, J = 8.5 Hz), 8.84 (d, 1H, J = 2.2 Hz);
13C NMR (CDCl3, 62.5 MHz): d 27.6 (2 × CH2), 45.6
(4 × CH3), 56.4 (CH2), 56.5 (CH2), 66.4 (CH2), 66.4 (CH2),
114.8 (2 × CH), 115.2 (2 × CH), 119.6 (CH), 128.0 (2 × CH),
128.1 (2 × CH), 130.1 (Cq), 131.7 (Cq), 133.9 (Cq), 134.6
(CH), 147.6 (CH), 155.3 (Cq), 159.2 (Cq), 159.9 (Cq); MS
(IS): 434 (M + 1)+;Anal. Calc. for C27H35N3O2: C, 74.79; H,
8.14; N, 9.69. Found: C, 75.11; H, 8.24; N, 9.50.
1
3051, 1607, 1521, 1279, 1251, 1179, 1028, 819; H NMR
(CDCl3, 250 MHz): d 3.87 (s, 3H), 3.88 (s, 3H), 7.02 (dd, 4H,
J = 8.9, 2.4 Hz), 7.56 (d, 2H, J = 8.7 Hz), 7.71 (d, 1H,
J = 8.2 Hz), 7.87 (dd, 1H, J = 8.4, 2.4 Hz), 7.99 (d, 2H,
J = 8.9 Hz), 8.85 (d, 1H, J = 2.0 Hz); 13C NMR (CDCl3,
62.5 MHz): d 55.5 (2 × CH3), 114.3 (2 × CH), 114.7 (2 × CH),
119.7 (2 × CH), 128.1 (CH), 128.2 (CH), 130.3 (Cq), 131.9
(CH), 134.0 (CH), 134.7 (CH), 147.7 (2 × Cq), 155.4 (Cq),
159.8 (Cq), 160.6 (Cq); MS (IS): 292 (M + 1)+; Anal. Calc.
for C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C, 78.66;
H, 5.74; N, 4.69.
4.1.18. 2,5-Bis-(4-hydroxyphenyl)-pyridine (18) [11,14]
Following general procedure B. Compound 17 (950 mg,
3.26 mmol), CH2Cl2 (20 ml), BBr3 (32.6 ml, 1 M in CH2Cl2,
32.6 mmol), 3 h, flash chromatography (dichloromethane/
methanol 96:4); compound 18 was obtained as a yellow solid
(817 mg, 95%). Rf (dichloromethane/methanol 96:4): 0.43;
m.p. 155 °C; IR (KBr, cm–1) m 3112, 1611, 1597, 1509, 1459,
1
1265, 1186, 823, 504; H NMR (DMSO-d6, 250 MHz): d
4.1.21. 2,5-Bis-[4-(2-benzyloxy-ethoxy)-phenyl]-pyridine
(21)
6.95 (d, 2H, J = 8.5 Hz), 7.02 (d, 2H, J = 8.5 Hz), 7.75 (d,
2H, J = 8.7 Hz), 7.96 (d, 2H, J = 8.5 Hz), 8.28 (d, 1H,
J = 8.7 Hz), 8.68 (dd, 1H, J = 2.2, 8.7 Hz), 8.89 (d, 1H,
J = 2.0 Hz); 13C NMR (DMSO-d6, 62.5 MHz): d 116.2
(2 × CH), 116.3 (2 × CH), 122.1 (Cq), 23.8 (CH), 124.3 (Cq),
128.5 (2 × CH), 129.7 (2 × CH), 135.4 (Cq), 139.1 (CH),
141.2 (CH), 149.6 (Cq), 158.9 (Cq), 160.8 (Cq); MS (IS):
264 (M + 1)+; Anal. Calc. for C17H13NO2: C, 77.55; H, 4.98;
N, 5.32. Found: C, 77.78; H, 4.83; N, 5.46.
Following general procedure D. Compound 18 (523 mg,
1.99 mmol), Cs2CO3 (1.42 g, 4.37 mmol), 2-bromo-
ethoxymethylbenzene (1.03 g, 4.77 mmol), flash chromatog-
raphy (dichloromethane/ether petroleum 9:1); compound 21
was obtained as a brown solid (646 mg, 61%). Rf
(dichloromethane/ether petroleum 8:2): 0.49; m.p. 147 °C;
IR (KBr, cm–1) m 2869, 1605, 1473, 1248, 1120, 1035, 823,
739; 1H NMR (CDCl3, 250 MHz): d 3.86 (t, 4H, J = 4.7 Hz),
4.22 (t, 4H, J = 5.4 Hz), 4.66 (s, 4H), 7.04 (dd, 4H, J = 2.3,
J = 8.8 Hz), 7.29–7.38 (m, 10H), 7.55 (d, 2H, J = 8.8 Hz),
7.71 (d, 1H J = 8.3 Hz), 7.87 (dd, 1H, J = 2.3, J = 8.3 Hz),
7.98 (d, 2H, J = 8.6 Hz), 8.85 (d, 1H, J = 2.3 Hz); 13C NMR
(CDCl3, 62.5 MHz): d 67.7 (2 × CH2), 68.6 (2 × CH2), 73.6
(2 × CH2), 115.0 (2 × CH), 115.4 (2 × CH), 119.7 (CH), 127.9
4.1.19. 2,5-Bis-[4-(2-dimethylamino-ethoxy)-phenyl]-pyri-
din-3-yl}-phenoxy)-ethyl]-dimethyl amine (19)
Following general procedure C. Compound 18 (100 mg,
0.38 mmol), Cs2CO3 (273 mg, 0.84 mmol), 2-chloro-
ethyldimethylamine hydrochloride (121 mg, 0.84 mmol),