M.S. Ayoup, M.M. Abu-Serie, H. Abdel-Hamid et al.
European Journal of Medicinal Chemistry 220 (2021) 113475
NMR (500 MHz, DMSO‑d6) dH: 8.90 (dd, J ¼ 4.5 Hz, 1.5 Hz, 2H, Py
-H), 8.10e8.08 (m, 4H, AreH, Py -H), 7.65e7.58 (m, 3H, AreH); 13C
NMR (125 MHz, DMSO‑d6) dC: 173.9, 168.5 (oxadiazole-C), 151.2 (Py
-C), 131.9, 130.3, 129.4, 127.1, 125.7, 121.3 (AreC); EIMS m/z [M]þ
calcd for [C13H9N3O]þ: 223.07, found 223.01 Anal. Calcd for
169.3 (oxadiazole-C), 157.5, 136.2, 135.1, 130.2, 129.4, 129.0, 127.4,
120.2, 117.8, 110.1 (AreC), 31.7 (PhCH2); EIMS m/z [M]þ calcd for
[C15H12N2O2]þ: 252.08, found 252.53; Anal. Calcd for C15H12N2O2:
C, 71.42; H, 4.79; N, 11.10. Found: C, 71.80; H, 4.91; N, 11.29.
C
13H9N3O: C, 69.95; H, 4.06; N, 18.82. Found: C, 70.20; H, 4.42; N,
5.1.2.9. 5-Phenyl-3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazole
(16). Yield 66% (193 mg), as a white solid: m.p ¼ 91e93 ꢃC (lit [129].
m.p ¼ 91e92 ꢃC); IR (KBr) nmax (cmꢂ1): 3550, 3475, 3415, 3065,
2098, 1928, 1807, 1614, 1554, 1451, 1418, 1321, 1171, 1111, 918, 848,
and 722; 1H NMR{19F} (500 MHz, CDCl3) dH: 8.23 (d, J ¼ 10.5 Hz, 2H,
AreH), 8.15 (d, J ¼ 11 Hz, 2H, AreH), 7.70 (d, J ¼ 10.0 Hz, 2H, AreH),
7.58e7.55 (m, 1H, AreH), 7.50 (t, J ¼ 9 Hz, 2H, AreH); 13C NMR{19F}
(125 MHz, CDCl3) dC: 176.2, 168.0 (oxadiazole-C), 132.9, 132.7,
130.3129.1, 128.1, 127.8 (AreC), 125.8 (CF3), 123.9, 122.4 (AreC);
EIMS m/z [M]þ calcd for [C15H9F3N2O]þ: 290.06, found 290.03;
Anal. Calcd for C15H9F3N2O: C, 62.07; H, 3.13; N, 9.65. Found: C,
62.40; H, 3.28; N, 9.53.
18.95.
5.1.2.4. 2-(3-Phenyl-1,2,4-oxadiazol-5-yl)phenol (11). Yield 59%
(141 mg), as a white solid: m.p ¼ 158e159 ꢃC; IR (KBr) nmax (cmꢂ1
)
3471, 3415, 3039, 2963, 2927, 1965, 1808, 1614, 1544, 1459, 1362,
1113, 914, and 740; 1H NMR (500 MHz, DMSO‑d6) dH: 10.57 (s, 1H,
OH exchangeable with D2O), 8.08 (dd, J ¼ 7.5 Hz, 1.5 Hz, 2H,AreH),
7.98 (dd, J ¼ 7.5 Hz, 1.5 Hz, 1H, AreH), 7.60e7.56 (m, 3H, AreH), 7.50
(td, J ¼ 8.5 Hz, 2 Hz, 1H, AreH), 7.10 (d, J ¼ 8.5 Hz, 1H, AreH), 7.01 (t,
J ¼ 7.5 Hz, 1H, AreH); 13C NMR (125 MHz, DMSO‑d6) dC: 175.0, 167.2
(oxadiazole-C), 157.2, 134.8, 131.6, 130.0, 129.2, 127.1, 126.0, 119.7,
117.4, 109.7 (AreC); EIMS m/z [M]þ calcd for [C14H10N2O2]þ: 238.07,
found 238.54; Anal. Calcd for C14H10N2O2: C, 70.58; H, 4.23; N,11.76.
Found: C, 70.37; H, 4.41; N, 11.51.
5.1.2.10. 5-(Pyridin-2-yl)-3-(4-(trifluoromethyl)phenyl)-1,2,4-
oxadiazole (17). Yield 55% (160 mg), as
a
white solid:
m.p ¼ 109e111 ꢃC; 1H NMR (500 MHz, DMSO‑d6) dH: 8.85 (dd, J ¼
4.5 Hz, 1.5 Hz, 1H, Py -H), 8.34 (d, J ¼ 8 Hz, 1H, Py -H), 8.32 (dd, J ¼
8 Hz, 2 Hz, 2H, AreH), 8.13 (td, J ¼ 7.5 Hz, 1.5 Hz, 1H, Py -H), 7.99 (d,
J ¼ 9 Hz, 2H, AreH), 7.74 (m, 1H, Py-H); 13C NMR (125 MHz,
DMSO‑d6) dC: 174.8, 167.4 (oxadiazole-C), 150.6, 142.5, 138.2, 131.6
(q, 2JCF ¼ 32.1 Hz, C-CF3), 129.9,128.0,127.7,126.37,126.34 (AreC, Py
5.1.2.5. 3-Benzyl-5-phenyl-1,2,4-oxadiazole
(12). Yield
70%
(164 mg), as a white solid: m.p ¼ 82e83 ꢃC (lit [131]. m.p ¼
82e84 ꢃC); IR (KBr) nmax (cmꢂ1) 3432, 3061, 3030, 2963, 2930, 2251,
1967, 1821, 1771, 1609, 1557, 1509, 1484, 1361, 1272, 1104, 997, 833,
725; 1H NMR (500 MHz, CDCl3) dH: 8.01 (d, J ¼ 10 Hz, 2H, AreH),
7.44e7.17 (m, 8H, AreH), 4.06 (s, 2H, PhCH2); 13C NMR (125 MHz,
DMSO‑d6) dC: 175.0, 169.9 (oxadiazole-C), 135.7, 133.2, 129.5, 128.9,
128.5, 127.7, 126.9, 123.3, (AreC), 31.4 (PhCH2); EIMS m/z [M]þ calcd
for [C15H12N2O]þ: 236.09, found 236.42; Anal. Calcd for C15H12N2O:
C, 76.25; H, 5.12; N, 11.86. Found: C, 76.51; H, 5.37; N, 11.62.
1
-C), 124.6 (q, JCF ¼ 271 Hz, CF3); EIMS m/z [M]þ calcd for
[C14H8F3N3O]þ: 291.06, found 291.22; Anal. Calcd for C14H8F3N3O:
C, 57.74; H, 2.77; N, 14.43. Found: C, 57.41; H, 2.91; N, 14.27.
5.1.2.11. 5-(Pyridin-4-yl)-3-(4-(trifluoromethyl)phenyl)-1,2,4-
oxadiazole (18). Yield 59% (174 mg), as
a
white solid:
5.1.2.6. 3-Benzyl-5-(pyridin-2-yl)-1,2,4-oxadiazole (13). Yield 58%
(138 mg), as a white solid: m.p ¼ 74e76 ꢃC; IR (KBr) nmax (cmꢂ1):
3549, 3475, 3415, 3026, 2928, 2246, 1963, 1887, 1802, 1615, 1572,
1443, 1363, 1308, 1285, 1073, and 734; 1H NMR (500 MHz,
DMSO‑d6) dH: 8.76 (d, J ¼ 4.0 Hz,1H, Py -H), 8.16 (d, J ¼ 7.5 Hz,1H, Py
-H), 8.02 (td, J ¼ 7.5 Hz, 2.0 Hz, 1H, Py -H), 7.65 (t, 1H, J ¼ 7.0 Hz, Py
-H), 7.33e7.29 (m, 4H, AreH),7.24e7.21 (m, 1H, AreH),4.17 (s, 2H,
PhCH2); 13C NMR (125 MHz, DMSO‑d6) dC: 174.1, 170.1 (oxadiazole-
C), 150.5, 142.7, 138.0, 135.6 (Py -C),128.9, 128.6, 127.4, 126.9, 124.3
(AreC, Py -C),31.4 (PhCH2); EIMS m/z [M]þ calcd for [C14H11N3O]þ:
237.09, found 237.28; Anal. Calcd for C14H11N3O: C, 70.87; H, 4.67;
N, 17.71. Found: C, 70.91; H, 4.76; N, 17.88.
m.p ¼ 119e120 ꢃC; IR (KBr) nmax (cmꢂ1): 3381, 3057, 2101, 1936,
1807, 1654, 1577, 1322, 1142, 1542, 1417, 1059, 1018, 848, and 766; 1H
NMR (500 MHz, DMSO‑d6) dH: 8.89 (dd, J ¼ 5 Hz, 2 Hz, 2H, Py -H),
8.28 (d, J ¼ 6.5 Hz 2H, AreH), 8.08 (dd, J ¼ 4.5 Hz, 1.5 Hz, 2H, Py -H)
7.96 (d, J ¼ 8 Hz 2H, AreH); 13C NMR (125 MHz, DMSO‑d6) dC: 174.4,
2
167.6 (oxadiazole-C), 151.3 (Py -C), 131.8 (q, JCF ¼ 32.2 Hz, C-CF3)
1
130.2, 129.6, 128.1, 126.44, 126.41,124.9 (AreC, Py -C), (q, JCF
¼
271 Hz, CF3), 121.4 (AreC); EIMS m/z [M]þ calcd for [C14H8F3N3O]þ:
291.06, found 291.47; Anal. Calcd for C14H8F3N3O: C, 57.74; H, 2.77;
N, 14.43. Found: C, 57.38; H, 2.93; N, 14.22.
5.1.2.12. 2-(3-(4-(Trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)
phenol (19). Yield 61% (185 mg), as
a
white solid:
5.1.2.7. 3-Benzyl-5-(pyridin-4-yl)-1,2,4-oxadiazole (14). Yield 65%
(152 mg), as a white solid: m.p ¼ 86e88 ꢃC; IR (KBr) nmax
(cmꢂ1):3415, 3039, 2963, 2927, 1965, 1808, 1614, 1544, 1459, 1362,
1113, 914, and 740; 1H NMR (500 MHz, DMSO‑d6) dH: 8.84 (dd, J ¼
5.0 Hz, 2 Hz, 2H, Py -H), 7.98 (dd, J ¼ 5.0 Hz, 2 Hz, 2H, Py -H),
7.35e7.33 (m, 4H, AreH), 7.25e7.24 (m, 1H, AreH), 4.21 (s, 2H,
PhCH2); 13C NMR (125 MHz, DMSO‑d6) dC: 173.5, 170.3 (oxadiazole-
C), 151.1 (Py -C), 135.5, 130.3, 128.9, 128.6, 128.0, 127.0, 121.2 (AreC,
Py -C),31.3 (PhCH2); EIMS m/z [M]þ calcd for [C14H11N3O]þ: 237.09,
found 237.90; Anal. Calcd for C14H11N3O: C, 70.87; H, 4.67; N, 17.71.
Found: C, 70.48; H, 4.88; N, 17.52.
m.p ¼ 162e163 ꢃC; IR (KBr) nmax (cmꢂ1): 3415, 3196, 1930, 2863,
1810, 1628, 1419, 1369, 1322, 1548, 1485, 1064, and 754; 1H NMR
{
19F} (400 MHz, DMSO‑d6) dH: 10.70 (s, 1H, OH exchangeable with
D2O), 8.32 ((d, J ¼ 10 Hz, 2H, AreH),8.03 (d, J ¼ 8 Hz, 1H, AreH) 7.98
(d, J ¼ 10.5 Hz, 2H, AreH), 7.56 (t, J ¼ 10.5 Hz, 1H, AreH), 7.15 (d, J ¼
10.5 Hz, 1H, AreH), 7.06 (t, J ¼ 9.5 Hz, 1H, AreH; 13C NMR{19F}
(100 MHz, DMSO‑d6) dC: 176.0, 166.8 (oxadiazole-C), 157.7, 135.4,
132.2, 131.7, 130.7, 130.5, 128.5 (AreC), 126.7 (CF3), 120.2, 117.9,
110.22 (AreC); EIMS m/z [M]þ calcd for [C15H9F3N2O2]þ: 306.06,
found 306.85; Anal. Calcd for C15H9F3N2O2: C, 58.83; H, 2.96; N,
9.15. Found: C, 58.61; H, 3.14; N, 9.29.
5.1.2.8. 2-(3-Benzyl-1,2,4-oxadiazol-5-yl)phenol (15). Yield 60%
(142 mg), as a white solid: m.p ¼ 90e91 ꢃC; IR (KBr) nmax (cmꢂ1):
3415, 3174, 3030, 2929, 2861, 1960, 1809, 1660, 1627, 1590, 1551,
5.1.2.13. 5-Methyl-3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazole
(20). Yield 72% (164 mg), as a White solid: m.p ¼ 88e90 ꢃC (lit [81].
m.p. 89e90 ꢃC); 1H NMR{19F} (400 MHz, CDCl3) dH: 8.12 (d, J ¼
10 Hz, 2H, AreH), 7.67 (d, J ¼ 10 Hz, 2H, AreH), 2.60 (s, 3H, CH3); 13C
NMR{19F} (100 MHz, CDCl3) dC: 177.0, 167.6 (oxadiazole-C), 133.1,
130.3, 127.7 (AreC), 125.9 (CF3), 122.5 (AreC), 12.2 (CH3); EIMS m/z
[M]þ calcd for [C10H7F3N2O]þ: 228.05, found 228.59; Anal. Calcd for
1479, 1319, 1243, 1028, and 704; 1H NMR (500 MHz, DMSO‑d6) dH
:
10.57 (s, 1H, OH exchangeable with D2O), 7.90 (dd, J ¼ 10.0 Hz,
1.5 Hz, 1H, AreH), 7.51 (td, J ¼ 10.5 Hz, 2.0 Hz, 1H, AreH), 7.36e7.26
(m, 5H, AreH), 7.10 (d, J ¼ 10.5 Hz, 1H, AreH), 7.01 (t, J ¼ 9.5 Hz, 1H,
AreH), 4.19 (s, 2H, PhCH2); 13C NMR (125 MHz, DMSO‑d6) dC: 174.9,
C
10H7F3N2O: C, 52.64; H, 3.09; N, 12.28. Found: C, 52.90; H, 3.31; N,
15