X. Pan et al. / European Journal of Medicinal Chemistry 163 (2019) 1e9
7
4.1.7. 2-methoxy-5-(4-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl) methyl)
4.1.12. 3-(4-((4-(2-fluorophenyl)-1H-1,2,3-triazol-1-yl) methyl)
phenyl)pyridine (BD5)
phenyl)pyridine (BD10)
Mp. ¼158e160 ꢀC. MS (EI) [M]þ: m/z ¼ 356. 1H NMR (400 MHz,
Mp. ¼115e117 ꢀC. MS (EI) [M]þ: m/z ¼ 344. 1H NMR (400 MHz,
DMSO‑d6)
d
8.65 (s, 1H), 8.49 (s, 1H), 8.01 (dd, J ¼ 8.7, 2.6 Hz, 1H),
DMSO‑d6) d 8.89 (s, 1H), 8.63e8.54 (m, 2H), 8.17e8.11 (m, 1H), 8.07
7.69 (d, J ¼ 8.2 Hz, 3H), 7.65 (d, J ¼ 7.8 Hz, 1H), 7.48e7.43 (m, 2H),
7.33 (t, J ¼ 7.6 Hz, 1H), 7.15 (d, J ¼ 7.7 Hz, 1H), 6.92 (d, J ¼ 8.6 Hz, 1H),
5.69 (s, 2H), 3.89 (s, 3H), 2.35 (s, 3H).13C NMR (101 MHz, DMSO‑d6)
(d, J ¼ 8.1 Hz, 1H), 7.76 (d, J ¼ 8.3 Hz, 2H), 7.49 (dd, J ¼ 13.1, 5.9 Hz,
3H), 7.43e7.29 (m, 3H), 5.76 (s, 2H). 13C NMR (101 MHz, DMSO‑d6)
d
149.15, 148.16, 140.40, 137.42, 136.45, 135.49, 134.63, 130.25,
d
163.68, 147.31, 145.26, 138.56, 138.07, 137.39, 135.62, 131.08,
130.16, 129.24, 127.82, 125.46, 124.61, 124.49, 124.37, 116.62, 116.41,
53.00.
129.32, 129.24, 129.21, 129.06, 127.25, 126.24, 122.83, 122.01, 111.15,
53.80, 53.20, 21.55.
4.1.13. 3-(4-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)phenyl)
pyridine (BD11)
4.1.8. 2-methoxy-5-(4-((4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-
triazol-1-yl)methyl)phenyl) pyridinþe (BD6)
Mp. ¼162e164 ꢀC. MS (EI) [M]þ: m/z ¼ 312. 1H NMR (400 MHz,
Mp. ¼163e165 ꢀC. MS (EI) [M] : m/z ¼ 410. 1H NMR (400 MHz,
DMSO‑d6)
d
8.90 (s, 1H), 8.70 (s, 1H), 8.58 (s, 1H), 8.08 (d, J ¼ 8.1 Hz,
DMSO‑d6)
d
8.87 (s, 1H), 8.49 (d, J ¼ 2.2 Hz, 1H), 8.09 (d, J ¼ 8.1 Hz,
1H), 7.92e7.86 (m, 2H), 7.77 (d, J ¼ 8.2 Hz, 2H), 7.52e7.42 (m, 5H),
2H), 8.01 (dd, J ¼ 8.6, 2.6 Hz, 1H), 7.82 (d, J ¼ 8.3 Hz, 2H), 7.70 (d,
7.34 (t, J ¼ 7.4 Hz, 1H).13C NMR (101 MHz, DMSO‑d6)
d 149.17, 148.18,
J ¼ 8.2 Hz, 2H), 7.47 (d, J ¼ 8.2 Hz, 2H), 6.92 (d, J ¼ 8.6 Hz, 1H), 5.73
147.23, 137.45, 136.46, 135.51, 134.65, 131.15, 129.42, 129.22, 128.43,
127.86, 125.68, 124.40, 122.15, 53.17.
(s, 2H), 3.89 (s, 3H). 13C NMR (101 MHz, DMSO‑d6)
d 163.68, 145.84,
145.27, 138.06, 137.47, 135.40, 135.13, 129.27, 129.21, 127.27, 126.44,
126.40, 126.21, 123.38, 111.15, 53.79, 53.34.
4.1.14. 3-(4-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl) phenyl)
pyridine (BD12)
4.1.9. 3-(1-(4-(6-methoxypyridin-3-yl)benzyl)-1H-1,2,3-triazol-4-
yl)aniline (BD7)
Mp. ¼162e164 ꢀC. MS (EI) [M]þ: m/z ¼ 326. 1H NMR (400 MHz,
DMSO‑d6)
d
8.90 (d, J ¼ 2.1 Hz, 1H), 8.66e8.63 (m, 1H), 8.59 (d,
Mp. ¼156e158 ꢀC. MS (EI) [M]þ: m/z ¼ 357. 1H NMR (400 MHz,
J ¼ 4.7 Hz, 1H), 8.08 (d, J ¼ 8.1 Hz, 1H), 7.76 (t, J ¼ 7.7 Hz, 4H), 7.49 (d,
DMSO‑d6)
d
8.49 (d, J ¼ 2.4 Hz, 1H), 8.02 (dd, J ¼ 8.7, 2.6 Hz, 1H), 7.70
J ¼ 8.3 Hz, 3H), 7.26 (d, J ¼ 8.0 Hz, 2H), 5.71 (s, 2H), 2.33 (s, 3H).13
C
(d, J ¼ 8.2 Hz, 1H), 7.46 (d, J ¼ 8.2 Hz, 2H), 7.15e7.05 (m, 2H),
6.98e6.89 (m, 2H), 6.54 (d, J ¼ 7.9 Hz, 1H), 5.68 (s, 2H), 5.19 (s, 2H),
NMR (101 MHz, DMSO‑d6) d 149.18, 148.19, 147.29, 137.72, 137.44,
136.49, 135.52, 134.65, 129.97, 129.23, 128.39, 127.85, 125.62, 124.41,
121.71, 53.14, 21.34.
3.90 (s, 3H).13C NMR (101 MHz, DMSO‑d6)
d 163.66, 149.57, 147.88,
145.25, 138.06, 137.35, 135.73, 131.61, 129.86, 129.25, 129.17, 127.22,
121.62, 114.11, 113.51, 111.13, 110.94, 53.79, 53.10.
4.1.15. 3-(4-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl) phenyl)
pyridine (BD13)
4.1.10. N-(4-(1-(4-(6-methoxypyridin-3-yl)benzyl)-1H-1,2,3-
triazol-4yl)phenyl) cyclopropanecar boxamide (BD8)
Mp. ¼165e167 ꢀC. MS (EI) [M]þ: m/z ¼ 326. 1H NMR (400 MHz,
DMSO‑d6)
d
8.81 (d, J ¼ 1.9 Hz, 1H), 7.61 (s, 2H), 7.57 (d, J ¼ 7.8 Hz,
3-(1-(4-(6-methoxypyridin-3-yl)benzyl)-1H-1,2,3-triazol-4-yl)
aniline (BD7) (0.20 g, 0.56 mmol) was dissolved in anhydrous
CH2Cl2 (10 mL), and the mixture was stirred on the ice-bath for
10 min. Triethanolamine (0.14 mL, 1.01 mmol) diluted with CH2Cl2
(2 mL) was then added into the mixture. Stirring was continued for
30 min, a solution of cyclopropanecarbonyl chloride (0.11 mL,
1.12 mmol) in anhydrous CH2Cl2 was added dropwise to the above
mixture. Then, the ice bath was removed, and the mixture was
reacted at room temperature overnight. The reaction solution was
diluted with water (10 mL), and extracted with CH2Cl2 (30 mL ꢁ 3).
The combined organic layer was washed with water (20 mL ꢁ 2)
and brine, and dried over Na2SO4. After filtration and concentration
in vacuo, the residues was purified by silica gel flash chromatog-
raphy (PE/AcOEt ¼ 15:1) to afford (BD8) as white solid (0.19 g, 80%).
Mp. ¼ 218e220 ꢀC. MS (EI) [M]þ: m/z ¼ 424. 1H NMR (400 MHz,
1H), 7.45e7.38 (m, 1H), 7.25 (t, J ¼ 7.6 Hz, 1H). 13C NMR (101 MHz,
DMSO‑d6)
d 149.18, 148.19, 147.32, 138.56, 137.46, 136.46, 135.52,
134.66, 131.07, 129.32, 129.26, 129.08, 127.86, 126.25, 124.41, 122.83,
122.08, 53.16, 21.55.
4.1.16. 3-(4-((4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)
methyl)phenyl)pyridine (BD14)
Mp. ¼173e175 ꢀC. MS (EI) [M]þ: m/z ¼ 380. 1H NMR (400 MHz,
DMSO‑d6)
d
8.90 (d, J ¼ 2.0 Hz, 2H), 8.58 (d, J ¼ 6.0 Hz, 1H), 8.09 (t,
J ¼ 8.1 Hz, 3H), 7.80 (dd, J ¼ 18.0, 8.3 Hz, 4H), 7.54e7.47 (m, 3H), 5.76
(s, 2H). 13C NMR (101 MHz, DMSO‑d6)
d
149.19, 148.19, 145.86,
137.54, 136.23, 135.49, 135.12, 134.65, 129.32, 127.88, 126.43, 126.39,
126.21, 126.11, 124.39, 123.44, 53.30.
4.1.17. 3-(4-((4-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)
methyl)phenyl)Pyridine (BD15)
DMSO‑d6)
d
8.51 (d, J ¼ 2.6 Hz, 1H), 8.19 (s, 1H), 8.04 (d, J ¼ 8.5 Hz,
1H), 7.71 (d, J ¼ 7.9 Hz, 2H), 7.58 (d, J ¼ 7.7 Hz, 1H), 7.47 (t, J ¼ 4.4 Hz,
3H), 7.37 (s,1H), 6.94 (d, J ¼ 8.5 Hz,1H), 5.71 (s,1H), 3.91 (s,1H),1.81
(s, 1H), 0.83 (d, J ¼ 8.0 Hz, 4H). 13C NMR (101 MHz, DMSO‑d6)
Mp. ¼110e112 ꢀC. MS (EI) [M]þ: m/z ¼ 380. 1H NMR (400 MHz,
DMSO‑d6)
d 8.90 (s, 2H), 8.64e8.56 (m, 1H), 8.21 (s, 2H), 8.08 (d,
J ¼ 8.0 Hz, 1H), 7.78 (d, J ¼ 8.2 Hz, 2H), 7.71 (d, J ¼ 5.1 Hz, 2H),
d
172.27, 163.67, 147.16, 145.27, 140.41, 138.08, 137.40, 135.63, 131.59,
7.54e7.45 (m, 3H), 5.75 (s, 2H). 13C NMR (101 MHz, DMSO‑d6)
129.84, 129.25, 127.25, 122.09, 120.45, 118.96, 116.09, 111.15, 53.81,
53.20, 15.07, 7.74.
d 149.20, 148.18, 145.86, 137.54, 136.22, 135.49, 134.66, 132.22,
130.65, 129.46, 129.34, 127.89, 124.93, 124.89, 124.41, 123.15, 122.04,
122.01, 53.32.
4.1.11. 3-(4-((4-(3-chlorophenyl)-1H-1,2,3-triazol-1-yl) methyl)
phenyl)pyridine (BD9)
4.1.18. 3-(1-(4-(pyridin-3-yl)benzyl)-1H-1,2,3-triazol-4-yl) aniline
(BD16)
Mp. ¼140e142 ꢀC. MS (EI) [M]þ: m/z ¼ 346. 1H NMR (400 MHz,
DMSO‑d6)
d
8.90 (d, J ¼ 1.9 Hz, 1H), 8.81 (s, 1H), 8.59 (dd, J ¼ 4.8,
Mp. ¼189e191 ꢀC. MS (EI) [M]þ: m/z ¼ 327. 1H NMR (400 MHz,
1.5 Hz, 1H), 8.08 (d, J ¼ 8.0 Hz, 1H), 7.94 (s, 1H), 7.86 (d, J ¼ 7.8 Hz,
1H), 7.78 (d, J ¼ 8.3 Hz, 2H), 7.54e7.47 (m, 4H), 7.40 (dd, J ¼ 7.6,
DMSO‑d6)
d
8.90 (s, 1H), 8.59 (s, 1H), 8.52 (s, 1H), 8.08 (d, J ¼ 8.1 Hz,
1H), 7.76 (d, J ¼ 8.2 Hz, 2H), 7.49 (t, J ¼ 7.0 Hz, 3H), 7.14e7.03 (m,
1.5 Hz, 1H), 5.74 (s, 2H).13C NMR (101 MHz, DMSO‑d6)
d 149.16,
2H), 6.94 (d, J ¼ 7.6 Hz, 1H), 6.52 (d, J ¼ 9.3 Hz, 1H), 5.69 (s, 2H), 5.18
148.16, 145.86, 137.49, 136.22, 135.46, 134.63, 134.18, 133.22, 131.36,
129.28, 128.17, 127.85, 125.26, 124.38, 124.16, 122.89, 53.25.
(s, 2H). 13C NMR (101 MHz, DMSO‑d6)
d 149.57, 149.17, 148.18,
147.89, 137.41, 136.57, 135.53, 134.65, 131.60, 129.87, 129.22, 127.84,