256
Y. Liu et al. / European Journal of Medicinal Chemistry 78 (2014) 248e258
74% for 2 steps). [
a
]
25D: 2.6 ( c 0.55, CHCl3). 1H NMR (400 MHz, CDCl3):
(m, 2H), 3.71 (brs, 1H), 3.64e3.35 (m, 9H), 2.92e2.75 (m, 4H) ppm.
13C NMR (100 MHz, CDCl3):
157.9, 156.6, 144.9, 140.9, 139.3, 137.3,
129.9,129.8,129.7, 129.4,128.8,127.1, 127.0, 123.8, 122.1, 119.3,118.9,
74.9, 74.8, 71.2, 70.6, 69.6, 53.4, 39.5, 29.7 ppm. MS (ESI, m/z): 580
(Mþ þ 1), 602 (Mþ þ 23), HRMS (ESI): C35H37N3O5 calculated
[M þ H]þ 580.2806, found 580.2810.
d
7.80 (s, 1H), 7.56e7.54 (m, 4H), 7.51 (d, J ¼ 8.1 Hz, 2H), 7.41 (dd,
d
J ¼ 7.6 Hz, 2H), 7.34e7.27 (m, 3H), 6.92 (d, J ¼ 9.0 Hz, 2H), 4.16 (m,
1H), 4.07 (m, 1H), 3.85 (t, J ¼ 4.8 Hz, 4H), 3.69e3.40 (m, 9H), 3.23
(m, 1H), 3.16 (t, J ¼ 4.8 Hz, 4H), 3.03e2.89 (m, 2H), 2.87e2.78 (m,
2H) ppm. 13C NMR (100 MHz, CDCl3):
d 151.3, 144.9, 140.9, 139.3,
137.3, 129.8, 129.6, 128.8, 127.1, 127.0, 121.6, 120.4, 115.7, 74.9, 74.8,
71.3, 70.6, 69.6, 66.7, 48.8, 39.4, 29.7 ppm. MS (ESI, m/z): 559
(Mþ þ 1). HRMS (ESI): C32H38N4O5 calculated [M þ H]þ 559.2915,
found 559.2913.
5.1.30. 4-((4-((S)-3-(2-((S)-3-(biphenyl-4-yl)-2-hydroxypropoxy)
ethoxy)-2-hydroxypropyl)-1H-1,2,3-triazol-1-yl)methyl)
benzonitrile (12)
The procedure was the same as described above for the syn-
thesis of 2; the compound 12 was obtained as white solid (83.4 mg,
5.1.26. 6-(4-((S)-3-(2-((S)-3-(biphenyl-4-yl)-2-hydroxypropoxy)
ethoxy)-2-hydroxypropyl)-1H-1,2,3-triazol-1-yl)-2H-benzo[b] [1,4]
oxazin-3(4H)-one (8)
81% for 2 steps). [a]
25D: 5.9 (c 0.64, CHCl3). 1H NMR (400 MHz, CDCl3):
d
7.60 (d, J ¼ 8.2 Hz, 2H), 7.56 (d, J ¼ 7.3 Hz, 2H), 7.51 (d, J ¼ 8.1 Hz,
The procedure was the same as described above for the syn-
thesis of 2; the compound 8 was obtained as white solid (42.4 mg,
2H), 7.44e7.40 (m, 3H), 7.34e7.26 (m, 5H), 5.48 (s, 2H), 4.07 (m, 2H),
3.68e3.38 (m, 9H), 3.10 (brs, 1H), 2.95e2.79 (m, 4H) ppm. 13C NMR
56% for 2 steps). [
a
]
25D: 6.0 ( c 0.27, CHCl3). 1H NMR (400 MHz, CDCl3):
(100 MHz, CDCl3): d 145.3, 140.9, 140.0, 139.4, 137.2, 132.8, 129.8,
d
7.96 (s, 1H), 7.56e7.54 (m, 3H), 7.51 (d, J ¼ 8.1 Hz, 2H), 7.42 (dd,
128.8, 128.3, 127.2, 127.1, 126.9, 122.4, 118.1, 112.7, 74.8, 74.7, 71.2,
70.6, 69.5, 53.2, 39.4, 29.6 ppm. MS (ESI, m/z): 513 (Mþ þ 1), 535
(Mþ þ 23), HRMS (ESI): C30H32N4O4 calculated [M þ H]þ 513.2496,
found 513.2494.
J ¼ 7.6 Hz, 2H), 7.34e7.27 (m, 4H), 7.22 (dd, J ¼ 8.7, 2.4 Hz, 1H), 7.02
(d, J ¼ 8.6 Hz, 1H), 4.62 (s, 2H), 4.15 (m, 1H), 4.06 (m, 1H), 3.71e3.42
(m, 9H), 3.06e2.91 (m, 2H), 2.87e2.77 (m, 2H) ppm. 13C NMR
(125 MHz, CDCl3):
d 165.2, 145.0, 143.4, 140.6, 139.1, 136.9, 131.7,
129.5, 128.5, 127.6, 126.9, 126.7, 120.6, 117.1, 114.8, 108.5, 74.6, 71.0,
70.3, 69.1, 66.9, 39.2, 29.4 ppm. MS (ESI, m/z): 545 (Mþ þ 1). HRMS
(ESI): C30H32N4O6 calculated [M þ H]þ 545.2395, found 545.2393.
5.1.31. (S)-1-(biphenyl-4-yl)-3-(2-((S)-2-hydroxy-3-(1-
(naphthalen-2-ylmethyl)-1H-1,2,3-triazol-4-yl)propoxy)ethoxy)
propan-2-ol (13)
The procedure was the same as described above for the syn-
thesis of 2; the compound 13 was obtained as white solid (89.2 mg,
5.1.27. (S)-1-(1-(1H-indol-5-yl)-1H-1,2,3-triazol-4-yl)-3-(2-((S)-3-
(biphenyl-4-yl)-2-hydroxypropoxy)ethoxy)propan-2-ol (9)
75% for 2 steps). [a]
25D: 3.0 (c 0.74, CHCl3). 1H NMR (400 MHz, CDCl3):
The procedure was the same as described above for the syn-
thesis of 2; the compound 9 was obtained as pale yellow solid
d
7.79e7.77 (m, 2H), 7.67 (s, 1H), 7.54 (d, J ¼ 7.2 Hz, 2H), 7.50e7.48
(m, 3H), 7.42e7.35 (m, 5H), 7.33e7.24 (m, 4H), 5.56 (s, 2H), 4.06 (m,
1H), 4.03 (m, 1H), 3.61 (m, 1H), 3.60e3.47 (m, 6H), 3.43e3.33 (m,
2H), 3.22 (brs, 1H), 2.87e2.75 (m, 4H) ppm. 13C NMR (125 MHz,
(32.0 mg, 59% for 2 steps). [
CDCl3): 8.87 (s, 1H), 7.84 (s, 1H), 7.78 (s, 1H), 7.54e7.52 (m, 2H),
a]
25D: 4.9 ( c 0.51, CHCl3). 1H NMR (400 MHz,
d
7.48 (d, J ¼ 8.0 Hz, 2H), 7.43e7.38 (m, 4H), 7.32e7.25 (m, 4H), 6.56
(m, 1H), 4.20 (m, 1H), 4.09 (m, 1H), 3.71e3.40 (m, 9H), 3.15 (brs, 1H),
3.03e2.91 (m, 2H), 2.87e2.77 (m, 2H) ppm. 13C NMR (125 MHz,
CDCl3): d 145.0, 140.9, 139.2, 137.3, 133.2, 133.1, 132.2, 129.8, 129.0,
128.9,128.8,127.9,127.8,127.3,127.1,127.0,126.7,126.6,125.3,122.3,
74.8, 74.7, 71.2, 70.5, 69.5, 54.2, 39.4, 29.7 ppm. MS (ESI, m/z): 538
(Mþ þ 1). HRMS (ESI): C33H35N3O4 calculated [M þ H]þ 538.2700,
found 538.2700.
CDCl3):
d 144.6, 140.9, 139.3, 137.1, 135.5, 130.4, 129.7, 128.7, 128.0,
127.1, 126.9, 126.4, 121.2, 115.5, 113.1, 111.9, 103.2, 74.8, 74.7, 71.3,
70.6, 69.7, 39.4, 29.6 ppm. MS (ESI, m/z): 513 (Mþ þ 1), 535
(Mþ þ 23), HRMS (ESI): C30H32N4O4 calculated [M þ H]þ 513.2496,
found 513.2495.
5.1.32. (S)-1-(1-(biphenyl-3-ylmethyl)-1H-1,2,3-triazol-4-yl)-3-(2-
((S)-3-(biphenyl-4-yl)-2-hydroxypropoxy)ethoxy)propan-2-ol (14)
The procedure was the same as described above for the syn-
thesis of 2; the compound 14 was obtained as white solid (82.1 mg,
5.1.28. 6-(4-((S)-3-(2-((S)-3-(biphenyl-4-yl)-2-hydroxypropoxy)
ethoxy)-2-hydroxypropyl)-1H-1,2,3-triazol-1-yl)benzo[d]thiazol-
2(3H)-one (10)
77% for 3 steps). [a]
25D: 6.1 (c 0.59, CHCl3). 1H NMR (400 MHz, CDCl3):
d
7.56e7.48 (m, 7H), 7.44e7.38 (m, 7H), 7.33 (dd, J ¼ 7.9 Hz, 2H),
The procedure was the same as described above for the syn-
thesis of 2; the compound 10 was obtained as pale yellow solid
7.27e7.24 (m, 2H), 7.18 (d, J ¼ 7.6 Hz, 1H), 5.48 (s, 2H), 4.08 (m, 1H),
4.04 (m, 1H), 3.62e3.35 (m, 9H), 3.19 (brs, 1H), 2.92e2.75 (m, 4H)
(47.2 mg, 49% for 2 steps). [
CDCl3):
(d, J ¼ 8.1 Hz, 2H), 7.40e7.36 (m, 3H), 7.31e7.25 (m, 4H), 7.07 (d,
J ¼ 8.6 Hz, 1H), 4.20 (m, 1H), 4.11 (m, 1H), 3.73e3.44 (m, 9H), 3.03e
2.89 (m, 2H), 2.87e2.77 (m, 2H) ppm. 13C NMR (125 MHz, CDCl3):
a
]
25D: 3.9 ( c 0.47, CHCl3). 1H NMR (400 MHz,
ppm. 13C NMR (100 MHz, CDCl3):
d 145.0, 142.2, 141.0, 140.3, 139.3,
d
7.78 (s, 1H), 7.59 (d, J ¼ 1.8 Hz, 1H), 7.52e7.50 (m, 2H), 7.46
137.3, 135.4, 129.8, 129.5, 128.9, 128.7, 127.7, 127.4, 127.1, 127.0, 126.8,
122.2, 74.8, 74.7, 71.2, 70.6, 69.6, 54.0, 39.5, 29.7 ppm. MS (ESI, m/z):
564 (Mþ þ 1), 586 (Mþ þ 23), HRMS (ESI): C35H37N3O4 calculated
[M þ H]þ 564.2857, found 564.2857.
d
171.2, 145.3, 140.7, 139.2, 137.1, 135.5, 132.5, 129.7, 128.7, 127.1,
126.9, 125.4, 120.6, 118.7, 114.7, 112.1, 74.8, 71.3, 70.6, 69.5, 39.4,
29.6 ppm. MS (ESI, m/z): 547 (Mþ þ 1). HRMS (ESI): C29H30N4O5S
calculated [M þ H]þ 547.2010, found 547.2009.
5.1.33. (S)-1-(biphenyl-4-yl)-3-(2-((S)-2-hydroxy-3-(1-(4-
(trifluoromethyl)benzyl)-1H-1,2,3-triazol-4-yl)propoxy)ethoxy)
propan-2-ol (15)
The procedure was the same as described above for the syn-
thesis of 2; the compound 15 was obtained as pale yellow solid
5.1.29. (S)-1-(biphenyl-4-yl)-3-(2-((S)-2-hydroxy-3-(1-(4-
phenoxybenzyl)-1H-1,2,3-triazol-4-yl)propoxy)ethoxy)propan-2-ol
(11)
(88.6 mg, 80% for 3 steps). [
CDCl3):
a]
25D: 6.9 (c 0.45, CHCl3). 1H NMR (400 MHz,
7.59e7.54 (m, 5H), 7.51 (d, J ¼ 7.4 Hz, 2H), 7.42 (dd,
d
The procedure was the same as described above for the syn-
thesis of 2; the compound 11 was obtained as white solid (82.1 mg,
J ¼ 7.4 Hz, 2H), 7.34e7.27 (m, 5H), 4.07 (br, 1H), 3.93 (br, 1H), 3.63e
3.40 (m, 8H), 3.45e3.40 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3):
79% for 3 steps). [
a
]
25D: 3.9 (c 0.56, CHCl3). 1H NMR (400 MHz, CDCl3):
d 140.8, 139.3, 138.4, 137.1, 129.7, 128.7, 128.3, 127.1, 126.9, 126.0,
d
7.55 (d, J ¼ 7.3 Hz, 2H), 7.50 (d, J ¼ 8.1 Hz, 2H), 7.40 (dd, J ¼ 7.6 Hz,
125.1, 123.1, 74.7, 74.6, 71.2, 70.6, 70.5, 69.3, 53.7, 39.4, 29.4 ppm. MS
(ESI, m/z): 556 (Mþ þ 1). HRMS (ESI): C30H32F3N3O4 calculated
[M þ H]þ 556.2418, found 556.2419.
2H), 7.36e7.25 (m, 6H), 7.18 (d, J ¼ 8.5 Hz, 2H), 7.10 (dd, J ¼ 7.4 Hz,
1H), 6.98 (d, J ¼ 7.8 Hz, 2H), 6.93 (d, J ¼ 8.5 Hz, 2H), 5.37 (s, 2H), 4.07