C. Sheng et al. / European Journal of Medicinal Chemistry 46 (2011) 5276e5282
5281
J ¼ 13.6 Hz), 2.38 (s, 3H), 2.34 (br, 10H), 1.90 (m, 2H). MS (ESI) m/z:
6.1.14. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(4-chlorophenyl)-1H-
538 (M). Anal. calcd for C27H32F2N8O2: C 60.21, H 5.99, N 20.80,
found: C 60.39, H 5.97, N 20.72.
1,2,4-triazol-5(4H)-one (11i)
1H NMR (500 MHz, CDCl3, TMS):
d 8.14 (s, 1H), 7.78 (s, 1H), 7.65
6.1.8. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-phenyl-1H-1,2,4-
triazol-5(4H)-one (11c)
(s, 1H), 6.79e7.54 (m, 7H), 5.30 (s, 1H), 4.50 (dd, J1 ¼ 5.2 Hz,
J2 ¼ 14.3 Hz, 2H), 3.86 (t, J ¼ 6.9 Hz, 2H), 3.04 (d, J ¼ 13.5 Hz, 1H),
2.64 (d, J ¼ 13.5 Hz, 1H), 2.34 (br, 10H), 1.91 (m, 2H). MS (ESI) m/z:
560 (M þ 1). Anal. calcd for C26H29ClF2N8O2: C 55.86, H 5.23, N
20.04, found: C 55.84, H 5.24, N 20.08.
1H NMR (500 MHz, CDCl3, TMS):
d 8.13 (s, 1H), 7.79 (s, 1H), 7.67
(s, 1H), 6.79e7.54 (m, 8H), 5.30 (s, 1H), 4.50 (d, J ¼ 2.4 Hz, 2H), 3.88
(t, J ¼ 6.9 Hz, 2H), 3.04 (d, J ¼ 13.8 Hz, 1H), 2.64 (d, J ¼ 13.6 Hz, 1H),
2.37 (br, 10H), 1.90 (m, 2H). 13C NMR (500 MHz, CDCl3, TMS):
6.1.15. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(3,4-dichlorophenyl)-
1H-1,2,4-triazol-5(4H)-one (11j)
d
163.63, 161.59, 159.84, 157.87, 151.70, 150.92, 144.53, 133.84,
133.44, 129.54, 129.24, 127.48, 126.08, 111.44, 104.18, 71.95, 62.18,
56.28, 55.09, 54.03, 53.34, 52.91, 43.76, 25.56. MS (ESI) m/z: 525
(M þ 1). Anal. calcd for C26H30F2N8O2: C 59.53, H 5.76, N 21.36,
found: C 59.64, H 5.73, N 21.33.
1H NMR (500 MHz, CDCl3, TMS):
d 8.14 (s, 1H), 7.78 (s, 1H), 7.66
(s, 1H), 6.79e7.75 (m, 6H), 5.30 (s, 1H), 4.50 (dd, J1 ¼ 5.8 Hz,
J2 ¼ 14.3 Hz, 2H), 3.86 (t, J ¼ 6.9 Hz, 2H), 3.04 (d, J ¼ 13.8 Hz, 1H),
2.64 (d, J ¼ 13.6 Hz, 1H), 2.33 (br, 10H), 1.90 (m, 2H). MS (ESI) m/z:
594 (M þ 1). Anal. calcd for C26H28Cl2F2N8O2: C 52.62, H 4.76, N
18.88, found: C 52.46, H 4.77, N 18.93.
6.1.9. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(4-tert-butylphenyl)-
1H-1,2,4-triazol-5(4H)-one (11d)
1H NMR (300 MHz, CDCl3, TMS):
d
8.14 (s, 1H), 7.78 (s, 1H), 7.63
6.1.16. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(4-bromophenyl)-1H-
1,2,4-triazol-5(4H)-one (11k)
(s, 1H), 6.77e7.54 (m, 7H), 5.31 (s, 1H), 4.51 (s, 2H), 3.87 (t,
J ¼ 6.9 Hz, 2H), 3.05 (d, J ¼ 13.5 Hz, 1H), 2.64 (d, J ¼ 13.5 Hz, 1H),
2.38 (br, 10H), 1.91 (m, 2H), 1.34 (s, 9H). MS (ESI) m/z: 581 (M þ 1).
Anal. calcd for C30H38F2N8O2: C 62.05, H 6.60, N 19.30, found:
C 61.92, H 6.61, N 19.37.
1H NMR (500 MHz, CDCl3, TMS):
d 8.14 (s, 1H), 7.78 (s, 1H), 7.65
(s, 1H), 6.78e7.60 (m, 7H), 5.30 (s, 1H), 4.50 (dd, J1 ¼ 5.0 Hz,
J2 ¼ 15.0 Hz, 2H), 3.86 (t, J ¼ 7.0 Hz, 2H), 3.05 (d, J ¼ 13.4 Hz, 1H),
2.65 (d, J ¼ 13.6 Hz, 1H), 2.36 (br, 10H), 1.91 (m, 2H). MS (ESI) m/z:
604 (M þ 1). Anal. calcd for C26H29BrF2N8O2: C 51.75, H 4.84, N
18.57, found: C 51.72, H 4.85, N 18.59.
6.1.10. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(2,4-dimethylphenyl)-
1H-1,2,4-triazol-5(4H)-one (11e)
1H NMR (500 MHz, CDCl3, TMS):
d
8.13 (s, 1H), 7.78 (s, 1H), 7.39
6.1.17. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(2-fluorophenyl)-
1H-1,2,4-triazol-5(4H)-one (11l)
(s, 1H), 6.78e7.56 (m, 6H), 5.30 (s, 1H), 4.51 (d, J ¼ 2.3 Hz, 2H), 3.86
(t, J ¼ 7.0 Hz, 2H), 3.06 (d, J ¼ 13.4 Hz, 1H), 2.66 (d, J ¼ 13.5 Hz, 1H),
2.46 (br, 10H), 2.35 (s, 3H), 2.26 (s, 3H), 1.94 (m, 2H). MS (ESI) m/z:
552 (M). Anal. calcd for C28H34F2N8O2: C 60.86, H 6.20, N 20.28,
found: C 60.62, H 6.19, N 20.34.
1H NMR (500 MHz, CDCl3, TMS):
d 8.14 (s, 1H), 7.77 (s, 1H), 7.63
(s, 1H), 6.78e7.67 (m, 7H), 5.30 (s, 1H), 4.50 (dd, J1 ¼ 2.0 Hz,
J2 ¼ 14.4 Hz, 2H), 3.86 (t, J ¼ 7.0 Hz, 2H), 3.05 (d, J ¼ 13.6 Hz, 1H),
2.64 (d, J ¼ 13.6 Hz, 1H), 2.36 (br, 10H), 1.92 (m, 2H). Anal. calcd for
C26H29F3N8O2: C 57.56, H 5.39, N 20.65, found: C 57.68, H 5.37, N
20.61.
6.1.11. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(3,4-dimethylphenyl)-
1H-1,2,4-triazol-5(4H)-one (11f)
1H NMR (500 MHz, CDCl3, TMS):
d
8.14 (s, 1H), 7.78 (s,1H), 7.60
6.1.18. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(4-fluorophenyl)-1H-
1,2,4-triazol-5(4H)-one (11m)
(s, 1H), 6.78e7.56 (m, 6H), 5.30 (s, 1H), 4.50 (dd, J1 ¼ 3.0 Hz,
J2 ¼ 14.3 Hz, 2H), 3.86 (t, J ¼ 7.0 Hz, 2H), 3.04 (d, J ¼ 13.6 Hz, 1H),
2.64 (d, J ¼ 13.6 Hz, 1H), 2.37 (br, 10H), 2.30 (s, 3H), 2.28 (s, 3H), 1.91
(m, 2H). MS (ESI) m/z: 552 (M). Anal. calcd for C28H34F2N8O2:
C 60.86, H 6.20, N 20.28, found: C 60.73, H 6.22, N 20.30.
1H NMR (500 MHz, CDCl3, TMS):
d 8.13 (s, 1H), 7.78 (s, 1H), 7.62
(s, 1H), 6.78e7.55 (m, 7H), 5.30 (s, 1H), 4.50 (dd, J1 ¼ 3.8 Hz,
J2 ¼ 14.6 Hz, 2H), 3.86 (t, J ¼ 6.7 Hz, 2H), 3.04 (d, J ¼ 13.6 Hz, 1H),
2.65 (d, J ¼ 13.6 Hz, 1H), 2.36 (br, 10H), 1.92 (m, 2H). Anal. calcd for
C26H29F3N8O2: C 57.56, H 5.39, N 20.65, found: C 57.64, H 5.36, N
20.62.
6.1.12. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(3,5-dimethylphenyl)-
1H-1,2,4-triazol-5(4H)-one (11g)
1H NMR (500 MHz, CDCl3, TMS):
d
8.12 (s, 1H), 7.78 (s, 1H), 7.62
6.1.19. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(4-iodophenyl)-
1H-1,2,4-triazol-5(4H)-one (11n)
(s, 1H), 6.77e7.55 (m, 6H), 4.52 (dd, J1 ¼ 3.0 Hz, J2 ¼ 14.3 Hz, 2H),
3.87 (t, J ¼ 6.85 Hz, 2H), 3.05 (d, J ¼ 13.4 Hz,1H), 2.65 (d, J ¼ 13.5 Hz,
1H), 2.39 (br, 10H), 2.35 (s, 6H, CH3), 1.95 (m, 2H). MS (ESI) m/z: 552
(M). Anal. calcd for C28H34F2N8O2: C 60.86, H 6.20, N 20.28, found:
C 60.68, H 6.21, N 20.32.
1H NMR (500 MHz, CDCl3, TMS):
d 8.10 (s, 1H), 7.81 (s, 1H), 7.80
(s, 1H), 6.79e7.80 (m, 7H), 5.30 (s, 1H), 4.50 (s, 2H), 3.89 (t,
J ¼ 6.7 Hz, 2H), 3.08 (d, J ¼ 13.6 Hz, 1H), 2.71 (d, J ¼ 13.8 Hz, 1H),
2.55 (br, 10H), 2.23 (m, 2H). MS (ESI) m/z: 651 (M þ 1). Anal. calcd
for C26H29F2IN8O2: C 48.01, H 4.49, N 17.23, found: C 48.10, H 4.47, N
17.18.
6.1.13. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(3-chlorophenyl)-
1H-1,2,4-triazol-5(4H)-one (11h)
1H NMR (500 MHz, CDCl3, TMS):
d
8.14 (s, 1H), 7.78 (s, 1H), 7.66
6.1.20. 1-(3-(4-(2-(2,4-Difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl) piperazin-1-yl)propyl)-4-(4-ethoxyphenyl)-
1H-1,2,4-triazol-5(4H)-one (11o)
(s, 1H), 6.79e7.62 (m, 7H), 5.30 (s, 1H), 4.50 (d, J ¼ 3.69 Hz, 2H), 3.87
(t, J ¼ 7.0 Hz, 2H), 3.04 (d, J ¼ 13.5 Hz, 1H), 2.64 (d, J ¼ 13.6 Hz, 1H),
2.34 (br, 10H), 1.91 (m, 2H). Anal. calcd for C26H29ClF2N8O2: C 55.86,
H 5.23, N 20.04, found: C 55.92, H 5.21, N 20.00.
1H NMR (500 MHz, CDCl3, TMS):
d
8.13 (s, 1H), 7.78 (s, 1H), 7.58
(s, 1H), 6.78e7.75 (m, 7H), 5.30 (s, 1H), 4.50 (dd, J1 ¼ 2.1 Hz,