L. Zhao, W. Yin, Y. Sun et al.
European Journal of Medicinal Chemistry 224 (2021) 113715
NMR (150 MHz, DMSO‑d
6
)
d
163.14 (s), 151.12 (s), 145.33 (s), 143.19
151.58 (s), 145.78 (s), 143.59 (s), 143.51 (s), 142.28 (s), 129.30 (s, 2C),
129.08 (s, 2C), 128.24 (s, 3C), 128.12 (s), 127.84 (s, 2C), 127.05 (s),
126.40 (s), 126.37 (s), 126.35 (s, 2C), 124.75 (q, J ¼ 272.1 Hz), 76.70
(
1
s), 142.13 (s), 138.87 (s), 131.42 (s), 131.16 (s), 129.97 (s), 129.76 (s),
29.62 (s, 2C), 128.60 (s, 2C), 127.99 (s, 2C), 127.67 (s), 127.64 (s),
126.06 (s), 125.87 (s, 2C), 76.18 (s), 75.56 (s), 57.13 (s). HRMS (ESI, m/
(s), 75.96 (s), 57.66 (s). HRMS (ESI, m/z) calcd for C25
H
19
3
F N
4
O,
þ
þ
z) calcd for C24
H
19ClN
4
O, [MþNa] , 437.1140; found 437.1177.
[MþNa] , 471.1403; found 471.1437.
0
0
0
0
4-((1H-1,2,4-triazol-1-yl)methyl)-2-(3 -chloro-[1,1 -biphenyl]-4-
4-((1H-1,2,4-triazol-1-yl)methyl)-2-(2 -fluoro-[1,1 -biphenyl]-4-
yl)-4-(3-fluorophenyl)-4,5-dihydrooxazole (A30).
yl)-4-phenyl-4,5-dihydrooxazole (A25).
1
ꢀ
1
Light white solid; yield: 42.5 %. H NMR (600 MHz, DMSO‑d
6
)
Light white solid; yield: 43.4 %; mp: 100.4e102.1 C. H NMR
(600 MHz, DMSO‑d
d
8.32 (s, 1H), 7.96 (d, J ¼ 8.5 Hz, 2H), 7.90 (s, 1H), 7.84 (d, J ¼ 8.4 Hz,
6
)
d
8.35 (s, 1H), 7.98 (d, J ¼ 8.4 Hz, 2H), 7.90 (s,
2
7
4
1
1
H), 7.81 (t, J ¼ 1.8 Hz, 1H), 7.73e7.71 (m, 1H), 7.55e7.48 (m, 4H),
1H), 7.68 (dd, J ¼ 8.2, 1.2 Hz, 2H), 7.59 (td, J ¼ 7.9, 1.5 Hz, 1H),
.41 (t, J ¼ 7.7 Hz, 2H), 7.33 (t, J ¼ 7.3 Hz, 1H), 5.14 (d, J ¼ 8.9 Hz, 1H),
7.50e7.43 (m, 2H), 7.39e7.33 (m, 4H), 7.16 (td, J ¼ 8.3, 2.1 Hz, 1H),
.74 (d, J ¼ 14.2 Hz, 1H), 4.61 (d, J ¼ 14.1 Hz, 1H), 4.46 (d, J ¼ 8.9 Hz,
5.13 (d, J ¼ 9.1 Hz, 1H), 4.77 (d, J ¼ 14.1 Hz, 1H), 4.64 (d, J ¼ 14.1 Hz,
13
13
H). C NMR (150 MHz, DMSO‑d
43.16 (s), 141.85 (s), 141.19 (s), 133.91 (s), 130.94 (s), 128.76 (s, 2C),
28.63 (s, 2C), 128.07 (s), 127.67 (s), 127.16 (s, 2C), 126.66 (s), 126.25
6
)
d
163.11 (s), 151.12 (s), 145.33 (s),
1H), 4.48 (d, J ¼ 9.1 Hz, 1H). C NMR (150 MHz, DMSO‑d
6
) d 163.45
(s), 162.18 (d, J ¼ 243.4 Hz),159.07 (d, J ¼ 247.0 Hz),151.14 (s),145.92
(d, J ¼ 6.7 Hz), 145.39 (s), 138.61 (s), 130.79 (d, J ¼ 2.4 Hz), 130.63 (d,
J ¼ 8.0 Hz), 130.35 (d, J ¼ 8.3 Hz), 129.11 (d, J ¼ 2.3 Hz, 2C), 128.40 (s,
2C), 127.23 (d, J ¼ 13.0 Hz), 125.91 (s), 125.12 (d, J ¼ 3.5 Hz), 122.02
(s), 116.26 (d, J ¼ 22.3 Hz), 114.49 (d, J ¼ 20.9 Hz), 113.03 (d,
1
(
(
4
s), 125.90 (s, 2C), 125.66 (s), 76.23 (s), 75.48 (s), 57.22 (s). HRMS
þ
ESI, m/z) calcd for
37.1170.
-((1H-1,2,4-triazol-1-yl)methyl)-2-(4 -chloro-[1,1 -biphenyl]-4-
yl)-4-phenyl-4,5-dihydrooxazole (A26).
Light white solid; yield: 50.7 %; mp: 156.1e156.8 C. 1H NMR
600 MHz, DMSO‑d
8.32 (s, 1H), 7.95 (d, J ¼ 8.5 Hz, 2H), 7.89 (s,
C
24
H
19ClN
4
O, [MþNa] , 437.1140; found
0
0
4
J ¼ 22.8 Hz), 75.95 (s), 75.43 (s), 56.90 (s). HRMS (ESI, m/z) calcd for
þ
C
24
H
18
F
2
N
4
O, [MþNa] , 439.1341; found 439.1387.
ꢀ
0
0
4-((1H-1,2,4-triazol-1-yl)methyl)-2-(3 -fluoro-[1,1 -biphenyl]-4-
yl)-4-(3-fluorophenyl)-4,5-dihydrooxazole (A31).
Light white solid; yield: 46.5 %; mp: 128.6e130.4 C. H NMR
(600 MHz, DMSO‑d
(
1
6
) d
ꢀ
1
H), 7.80 (d, J ¼ 8.5 Hz, 2H), 7.77 (d, J ¼ 8.6 Hz, 2H), 7.56 (d,
J ¼ 8.6 Hz, 2H), 7.53e7.51 (m, 2H), 7.40 (t, J ¼ 7.7 Hz, 2H), 7.32 (t,
J ¼ 7.3 Hz, 1H), 5.14 (d, J ¼ 8.9 Hz, 1H), 4.74 (d, J ¼ 14.2 Hz, 1H), 4.61
6
)
d
8.34 (s, 1H), 7.96 (d, J ¼ 8.5 Hz, 2H), 7.89 (s,
1H), 7.84 (d, J ¼ 8.5 Hz, 2H), 7.62e7.59 (m, 2H), 7.57e7.53 (m, 1H),
7.44 (td, J ¼ 8.0, 6.2 Hz, 1H), 7.39e7.34 (m, 2H), 7.28e7.24 (m, 1H),
7.18e7.14 (m, 1H), 5.13 (d, J ¼ 9.0 Hz, 1H), 4.77 (d, J ¼ 14.2 Hz, 1H),
13
(
d, J ¼ 14.1 Hz, 1H), 4.46 (d, J ¼ 8.9 Hz, 1H). C NMR (150 MHz,
DMSO‑d
38.30 (s), 133.63 (s), 129.52 (s, 2C), 129.24 (s, 2C), 129.16 (s, 2C),
29.07 (s, 2C), 128.11 (s), 127.36 (s, 2C), 126.43 (s), 126.35 (s, 2C),
6
) d 163.58 (s), 151.57 (s), 145.77 (s), 143.63 (s), 142.55 (s),
13
1
1
4.63 (d, J ¼ 14.1 Hz, 1H), 4.48 (d, J ¼ 9.0 Hz, 1H). C NMR (150 MHz,
DMSO‑d
6
)
d
163.43 (s),163.25 (d, J ¼ 80.8 Hz),161.64 (d, J ¼ 80.7 Hz),
7
6.67 (s), 75.92 (s), 57.68 (s). HRMS (ESI, m/z) calcd for C24
H19ClN
4
O,
151.13 (s), 145.91 (d, J ¼ 6.8 Hz), 145.37 (s), 142.08 (s), 141.43 (d,
J ¼ 7.8 Hz),131.05 (d, J ¼ 8.8 Hz),130.63 (d, J ¼ 8.5 Hz),128.77 (s, 2C),
127.11 (s, 2C), 126.07 (s), 123.01 (d, J ¼ 2.1 Hz), 122.03 (d, J ¼ 2.1 Hz),
114.98 (d, J ¼ 21.3 Hz), 114.48 (d, J ¼ 20.8 Hz), 113.67 (d, J ¼ 22.5 Hz),
þ
[MþNa] , 437.1140; found 437.1182.
4
'-(4-((1H-1,2,4-triazol-1-yl)methyl)-4-phenyl-4,5-
0
dihydrooxazol-2-yl)-[1,1 -biphenyl]-4-carbonitrile (A27).
Light white solid; yield: 38.3 %; mp: 157.1e159.1 C. 1H NMR
ꢀ
113.03 (d, J ¼ 22.4 Hz), 75.96 (s), 75.39 (s), 56.93 (s). HRMS (ESI, m/z)
þ
(
600 MHz, DMSO‑d
6
)
d
8.32 (s, 1H), 8.00e7.94 (m, 6H), 7.90e7.86
calcd for C24
H
18
F
2
N
4
O, [MþNa] , 439.1341; found 439.1371.
0
(
m, 3H), 7.53 (dd, J ¼ 8.2, 1.1 Hz, 2H), 7.40 (t, J ¼ 7.7 Hz, 2H), 7.33 (t,
4-((1H-1,2,4-triazol-1-yl)methyl)-4-(3-chlorophenyl)-2-(2 -flu-
0
J ¼ 7.3 Hz, 1H), 5.15 (d, J ¼ 8.9 Hz, 1H), 4.74 (d, J ¼ 14.2 Hz, 1H), 4.61
oro-[1,1 -biphenyl]-4-yl)-4,5-dihydrooxazole (A32).
13
ꢀ
1
(
d, J ¼ 14.2 Hz, 1H), 4.47 (d, J ¼ 8.9 Hz, 1H). C NMR (150 MHz,
DMSO‑d 161.39 (s), 149.50 (s), 143.71 (s), 141.88 (s), 141.51 (s),
39.87 (s), 131.37 (s, 2C), 127.22 (s, 2C), 127.00 (s, 2C), 126.23 (s, 2C),
26.05 (s), 125.82 (s, 2C), 125.20 (s), 124.27 (s, 2C), 117.14 (s), 109.16
Light white solid; yield: 54.3 %; mp: 102.7e103.6 C. H NMR
(600 MHz, DMSO‑d
6
)
d
6
)
d
8.36 (s, 1H), 7.98 (d, J ¼ 8.3 Hz, 2H), 7.90 (s,
1
1
1H), 7.71e7.66 (m, 2H), 7.62e7.57 (m, 2H), 7.50e7.46 (m, 2H), 7.43
(t, J ¼ 7.7 Hz, 1H), 7.41e7.38 (m, 1H), 7.35 (dd, J ¼ 15.5, 7.9 Hz, 2H),
(
C
s), 74.63 (s), 73.90 (s), 55.58 (s). HRMS (ESI, m/z) calcd for
5.14 (d, J ¼ 9.1 Hz, 1H), 4.77 (d, J ¼ 14.2 Hz, 1H), 4.64 (d, J ¼ 14.1 Hz,
þ
13
25
H
19
N
5
O, [MþNa] , 428.1482; found 428.1527.
1H), 4.48 (d, J ¼ 9.1 Hz, 1H). C NMR (150 MHz, DMSO‑d
6
) d 163.96
4-((1H-1,2,4-triazol-1-yl)methyl)-4-phenyl-2-(4'-(tri-
(s), 159.55 (d, J ¼ 246.7 Hz), 151.61 (s), 145.97 (s), 145.87 (s), 139.10
(s), 133.77 (s), 131.25 (d, J ¼ 2.8 Hz), 130.97 (s), 130.81 (d, J ¼ 8.3 Hz),
129.58 (d, J ¼ 2.8 Hz, 2C), 128.88 (s, 2C), 128.13 (s), 127.71 (d,
J ¼ 13.0 Hz), 126.43 (s), 126.38 (s), 125.58 (d, J ¼ 3.5 Hz), 125.18 (s),
0
fluoromethoxy)-[1,1 -biphenyl]-4-yl)-4,5-dihydrooxazole (A28).
Light white solid; yield: 41.5 %; mp: 117.1e118.7 C. 1H NMR
ꢀ
(
1
1
600 MHz, DMSO‑d
H), 7.87 (d, J ¼ 8.8 Hz, 2H), 7.81 (d, J ¼ 8.5 Hz, 2H), 7.52 (dd, J ¼ 8.3,
.1 Hz, 2H), 7.50 (d, J ¼ 8.1 Hz, 2H), 7.40 (t, J ¼ 7.7 Hz, 2H), 7.33 (t,
J ¼ 7.3 Hz, 1H), 5.14 (d, J ¼ 8.9 Hz, 1H), 4.74 (d, J ¼ 14.2 Hz, 1H), 4.61
6
)
d
8.32 (s, 1H), 7.96 (d, J ¼ 8.5 Hz, 2H), 7.90 (s,
116.72 (d, J ¼ 22.6 Hz), 76.41 (s), 75.87 (s), 57.41 (s). HRMS (ESI, m/z)
þ
calcd for C24
H
18ClFN
4
O, [MþNa] , 455.1045; found 455.1079.
0
0
4-((1H-1,2,4-triazol-1-yl)methyl)-2-(2 -fluoro-[1,1 -biphenyl]-4-
yl)-4-(4-fluorophenyl)-4,5-dihydrooxazole (A33).
13
(
d, J ¼ 14.2 Hz, 1H), 4.46 (d, J ¼ 8.9 Hz, 1H). C NMR (150 MHz,
DMSO‑d 163.10 (s), 151.10 (s), 148.35 (s), 145.31 (s), 143.16 (s),
41.96 (s), 138.35 (s), 128.89 (s, 2C), 128.76 (s, 2C), 128.59 (s, 2C),
27.64 (s), 127.09 (s, 2C), 126.05 (s), 125.88 (s, 2C), 121.57 (s, 2C),
ꢀ
1
6
)
d
Light white solid; yield: 35.1 %; mp: 122.5e1124.4 C. H NMR
(600 MHz, DMSO‑d
1
1
6
)
d
8.34 (s, 1H), 7.98 (d, J ¼ 8.3 Hz, 2H), 7.90 (s,
1H), 7.68 (d, J ¼ 7.1 Hz, 2H), 7.59 (td, J ¼ 7.9, 1.3 Hz, 1H), 7.56 (dd,
J ¼ 8.7, 5.5 Hz, 2H), 7.48 (ddd, J ¼ 9.3, 7.2, 1.5 Hz, 1H), 7.35 (dd,
J ¼ 15.8, 8.3 Hz, 2H), 7.22 (t, J ¼ 8.8 Hz, 2H), 5.13 (d, J ¼ 9.0 Hz, 1H),
4.74 (d, J ¼ 14.1 Hz, 1H), 4.61 (d, J ¼ 14.1 Hz, 1H), 4.46 (d, J ¼ 9.0 Hz,
1
20.10 (dd, J ¼ 513.1, 256.6 Hz), 76.19 (s), 75.47 (s), 57.19 (s). HRMS
þ
(
ESI, m/z) calcd for C25
H
19
F
3
N
4
O
2
, [MþNa] , 487.1352; found
4
87.1380.
13
4
-((1H-1,2,4-triazol-1-yl)methyl)-4-phenyl-2-(4'-(tri-
6
1H). C NMR (150 MHz, DMSO‑d ) d d 163.25 (s), 161.49 (d,
0
fluoromethyl)-[1,1 -biphenyl]-4-yl)-4,5-dihydrooxazole (A29).
J ¼ 243.5 Hz), 159.07 (d, J ¼ 246.5 Hz), 151.11 (s), 145.33 (s), 139.30
(s), 138.56 (s), 130.78 (d, J ¼ 2.9 Hz), 130.33 (d, J ¼ 8.2 Hz), 129.09 (d,
J ¼ 2.7 Hz, 2C), 128.37 (s, 2C), 128.04 (d, J ¼ 8.4 Hz, 2C), 127.23 (d,
J ¼ 12.7 Hz), 125.97 (s), 125.11 (d, J ¼ 3.3 Hz), 116.25 (d, J ¼ 22.3 Hz),
Light white solid; yield: 54.2 %; mp: 116.8e119.0 C. 1H NMR
ꢀ
(
600 MHz, DMSO‑d
6
)
d
8.38 (s, 1H), 8.05 (d, J ¼ 8.5 Hz, 2H), 8.02 (d,
J ¼ 8.2 Hz, 2H), 7.95 (s, 1H), 7.92 (dd, J ¼ 8.1, 5.9 Hz, 4H), 7.59 (dd,
J ¼ 8.2,1.1 Hz, 2H), 7.46 (t, J ¼ 7.7 Hz, 2H), 7.38 (t, J ¼ 7.3 Hz,1H), 5.20
115.30 (d, J ¼ 21.2 Hz, 2C), 75.78 (s), 75.57 (s), 57.12 (s). HRMS (ESI,
þ
(
4
d, J ¼ 8.9 Hz, 1H), 4.80 (d, J ¼ 14.2 Hz, 1H), 4.67 (d, J ¼ 14.2 Hz, 1H),
m/z) calcd for C24
H
18
F
2
N
4
O, [MþNa] , 439.1341; found 439.1382.
13
.52 (d, J ¼ 8.9 Hz, 1H). C NMR (150 MHz, DMSO‑d
6
)
d
163.52 (s),
Retention time: 24.79 min, 98.70 % purity.
18