P. C. Chen et al. / Bioorg. Med. Chem. 16 (2008) 4839–4853
4847
(DMSO-d6, 400 MHz) d 1.18–1.26 (2H, m), 1.52 (2H, p,
J = 14.9, 7.4 Hz), 1.84 (2H, p, J = 7.0, 14.3 Hz), 1.93
(2H, t, J = 7.2 Hz), 3.79 (3H, s), 4.36 (2H, t,
J = 6.9 Hz), 6.86–6.89 (1H, m), 7.33 (1H, app. t), 7.39–
7.41 (2H, m), 8.58 (1H, s), 8.67 (1H, s), 10.33 (1H, s);
13C NMR (DMSO-d6, 100 MHz) d 24.5, 25.4, 29.3,
32.0, 49.3, 55.0, 110.1, 113.3, 117.2, 121.2, 129.8,
131.9, 145.9, 159.3, 168.6; HRMS (EI) calcd for
[C16H20N3O3+H]+ 304.1661, found 304.1688.
by flash chromatography (silica, gradient 2:1; 1:1
hexanes/EtOAc) to give 90 mg (22%) of 6o as a pale
yellowish solid. H NMR (CDCl3, 400 MHz) d 1.31–
1
1.39 (2H, m), 1.61–1.69 (2H, m), 1.89–1.95 (2H, m),
2.28 (2H, t, J = 7.2 Hz), 3.62 (3H, s), 4.35 (2H, t,
J = 7.2 Hz), 7.32 (1H, t, J = 8.0 Hz), 7.41 (2H, t,
J = 8.0 Hz), 7.58–7.63 (4H, m), 7.76 (1H, s), 7.87 (2H, d,
J = 8.0 Hz); 13C NMR (CDCl3, 100 MHz) d 24.1, 25.9,
29.9, 33.6, 49.9, 51.4, 119.4, 125.7, 126.6, 127.1, 128.5,
129.4, 140.1, 140.4, 147.0, 173.3; HRMS (FAB, thioglyc-
erol) calcd for [C21H23N3O2+H]+ 350.1868, found
350.1885.
5.1.2.16. Methyl 6-(2-anisolyl)triazolylhexanoate (6l).
Reaction of methyl 6-azidohexanoate 2c (0.2 g,
1.17 mmol) and 2-ethynylanisole 5t (0.232 mg,
1.75 mmol) within 24 h as described for the synthesis
of 3a, followed by flash chromatography (silica, 3:2 hex-
anes/EtOAc) gave 336 mg (95%) of 6l as colorless oil. 1H
NMR (CDCl3, 400 MHz) d 1.41–1.21 (2H, m), 1.47 (2H,
p, J = 15.1, 7.4 Hz), 1.75 (2H, p, J = 14.8, 7.2 Hz), 2.11
(2H, t, J = 7.42 Hz), 3.47 (3H, s), 3.73 (3H, s), 4.18 (2H,
t, J = 7.1 Hz), 6.79 (1H, d, J = 8.3 Hz), 6.89 (1H, t,
J = 7.4 Hz), 7.09–7.13 (1H, m), 8.21 (1H, dd, J = 7.6,
1.5 Hz); 13C NMR (CDCl3, 100 MHz) d 23.8, 25.4,
29.5, 33.1, 49.3, 50.9, 54.8, 110.2, 118.8, 120.1, 122.4,
126.6, 128.1, 142.1, 154.8, 172.8; HRMS (FAB, thioglyc-
erol) calcd for [C16H21N3O3+H]+ 304.1661, found
304.1676.
5.1.2.20. Methyl 6-(3-biphenyl)triazolylhexnaoate
(6p). Reaction of methyl 6-azidohexnoate 2c (0.2 g,
1.16 mmol) and 3-ethynylbiphenyl 5i (0.32 g, 1.79 mmol)
within 24 h as described for the synthesis of 3a, followed
by flash chromatography (silica, gradient 2:1; 1:1
hexanes/EtOAc) gave 300 mg (74%) of 6p as a white
solid. 1H NMR (CDCl3, 400 MHz) d 1.27–1.35 (2H, m),
1.58–1.65 (2H, m), 1.85–1.93 (2H, m), 2.25 (2H, t,
J = 7.6 Hz), 3.60 (3H, s), 4.31 (2H, t, J = 7.2 Hz), 7.32
(1H, t, J = 7.2 Hz), 7.39–7.46 (3H, m), 7.52 (1H, d,
J = 8.0 Hz), 7.62 (2H, d, J = 7.6 Hz), 7.77 (1H, d,
J = 7.6 Hz), 7.82 (1H, s), 8.08 (1H, s); 13C NMR (CDCl3,
100 MHz) d 23.9, 25.7, 29.7, 33.4, 49.7, 51.2, 119.5,
123.9, 124.1, 126.3, 126.7, 127.0, 128.3, 128.8, 130.8,
140.2, 141.2, 147.0, 173.2; HRMS (FAB, thioglycerol)
calcd for [C21H23N3O2+H]+ 350.1868, found 350.1870.
5.1.2.17. Methyl 6-(2,6-dimethoxyphenyl)triazolylhex-
anoate (6m). Reaction of methyl 6-azidohexnoate 2c
(0.15 g, 0.88 mmol) and 2-ethynyl-1,3-dimethoxyben-
zene 5j (0.16 g, 0.99 mmol) within 24 h as described for
the synthesis of 3a, followed by flash chromatography
(silica, gradient 2:1; 1:1; 1:2; hexanes/EtOAc) gave
114 mg (39%) of 6m as a white solid. 1H NMR (CDCl3,
400 MHz) d 1.38–1.46 (2H, m), 1.66–1.73 (2H, m), 1.95–
2.02 (2H, m), 2.33 (2H, t, J = 7.2 Hz), 3.66 (3H, s), 3.80
(6H, s), 4.40 (2H, t, J = 7.2 Hz), 6.65 (2H, d, J = 8.4 Hz),
7.29 (1H, t, J = 9.2 Hz), 7.68 (1H, s); 13C NMR (CDCl3,
100 MHz) d 24.1, 25.8, 29.8, 33.5, 49.6, 51.2, 55.7, 103.8,
108.4, 123.7, 129.2, 139.3, 157.8, 173.2; HRMS (FAB,
thioglycerol) calcd for [C17H23N3O4+H]+ 334.1766,
found 334.1776.
5.1.2.21. Methyl 7-(3-biphenyl)triazolylheptanaoate
(6q). Reaction of methyl 7-azidoheptanoate 2d
(0.184 g, 1.03 mmol) and 3-ethynylbiphenyl 5i (185 mg,
1.03 mmol) within 24 h as described for the synthesis
of 3a, followed by flash chromatography (silica, 3:2 hex-
anes/EtOAc) gave 201 mg (54%) of 6q as colorless oil.
1H NMR (CDCl3, 400 MHz) d 1.32–1.35 (4H, m), 1.59
(2H, p, J = 14.72, 7.36), 1.91 (2H, m), 2.26 (2H, t,
J = 7.4 Hz), 3.62 (3H, s), 4.35 (2H, t, J = 7.1 Hz),
7.31–7.35 (1H, m), 7.39–7.44 (2H, m), 7.46 (1H, dd,
J = 7.6, 0.4 Hz), 7.51–7.54 (1H, m), 7.60–7.63 (2H, m),
7.73–7.78 (1H, m), 7.79 (1H, s), 8.05–8.06 (1H, m); 13C
NMR (CDCl3, 100 MHz) d 24.6, 26.1, 28.4, 30.1, 33.8,
50.2, 51.4, 119.4, 124.2, 124.3, 126.9, 127.2, 128.5,
129.0, 129.3, 130.9, 140.5, 141.5, 147.3, 173.6; HRMS
(EI) calcd for [C22H25N3O2+H]+ 364.2025, found
364.2045.
5.1.2.18. Methyl 6-(2-thiopyl)triazolylhexnoate (6n).
Reaction of methyl 6-azidohexnoate 2c (0.2 g,
1.16 mmol) and 2-ethynylthiophene 5e (0.1 mL,
1.02 mmol) within 24 h as described for the synthesis
of 3a, followed by flash chromatography (silica, gradient
2:1; 1:1 hexanes/EtOAc) gave 209 mg (74%) of 6n as a
5.1.2.22. Methyl 6-(2-biphenyl)triazolylhexanoate (6r).
Reaction of methyl 6-azidohexnoate 2c (0.16 g,
0.93 mmol) and 2-ethynylbiphenyl 5g (0.11 g, 0.62 mmol)
within 24 h as described for the synthesis of 3a, fol-
lowed by flash chromatography (silica, gradient 2:1; 1:1
hexanes/EtOAc) gave 161 mg (75%) of 6r as a white
solid. 1H NMR (CDCl3, 400 MHz) d 1.09–1.17 (2H, m),
1.49–1.57 (2H, m), 1.61–1.69 (2H, m), 2.21 (2H, t,
J = 7.6 Hz), 3.59 (3H, s), 4.09 (2H, t, J = 6.8 Hz), 6.35
(1H, s), 7.16–7.18 (2H, m), 7.24–7.34 (5H, m), 7.39
(2H, t, J = 7.2 Hz); 13C NMR (CDCl3, 100 MHz) d
24.0, 25.6, 29.6, 33.4, 49.5, 51.3, 121.8, 126.9, 127.4,
127.5, 128.0, 128.2, 128.8, 128.9, 129.7, 139.8, 141.3,
145.8, 173.2; HRMS (FAB, thioglycerol) calc for
[C21H23N3O2+H]+ 350.1868, found 350.1877.
1
white solid. H NMR (CDCl3, 400 MHz) d 1.24–1.31
(2H, m), 1.54–1.62 (2H, m), 1.81–1.89 (2H, m), 2.22
(2H, t, J = 7.2 Hz), 3.57 (3H, s), 4.28 (3H, t,
J = 5.4 Hz), 7.29 (1H, dd, J = 4.8, 2.8 Hz), 7.38 (1H,
dd, J = 4.8, 1.2 Hz), 7.59 (1H, dd, J = 3.2, 1.2 Hz),
7.63 (1H, s); 13C NMR (CDCl3, 100 MHz) d 24.0,
25.7, 29.8, 33.5, 49.8, 51.3, 119.1, 120.5, 125.4, 125.9,
131.6, 143.4, 173.2; HRMS (FAB, thioglycerol) calcd
for [C13H17N3O2S+H]+ 280.1244, found 280.1223.
5.1.2.19. Methyl 6-(4-biphenyl)triazolylhexnoate (6o).
Reaction of methyl 6-azidohexanoate 2c (0.2 g,
1.17 mmol) and 4-ethynylbiphenyl 5h (0.317 g, 1.75 mmol)
within 24 h as described for the synthesis of 3a, followed