3140
Y. Jiang et al. / European Journal of Medicinal Chemistry 46 (2011) 3135e3141
m, eCH2CH2CH3), 0.99e1.04 (3H, t, eCH2CH2CH3); IR (KBr): 3324,
163.60, 161.12, 160.49, 157.47, 152.14, 150.56, 144.98, 138.28, 135.00,
129.94, 128.77, 124.14, 122.04, 119.52, 110.96, 103.86, 74.46, 54.93,
51.76, 36.43, 31.21, 28.67, 28.51, 25.09, 22.10, 13.95. HRMS (m/z):
calcd. for C27H31F2N7O3: 540.2529; found: 540.2543.
3200, 3128, 3059, 2978, 2940, 2881, 2822, 1703, 1679, 1604, 1537,
1419, 1274, 1139; 13C NMR
d (ppm): 171.57, 163.70, 161.23, 160.59,
157.56, 152.14, 150.66, 144.94, 138.30, 135.08, 129.91, 128.86, 124.19,
122.01, 119.57, 110.87, 103.82, 74.45, 54.91, 51.73, 36.44, 31.20, 28.67.
HRMS (m/z): calcd. for C23H23F2N7O3: 484.1830; found: 484.1826.
6.3.9. 2-cyano-N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-
1,2,4-triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
acetamide (6h)
6.3.5. N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
pentanamide (6d)
Mp: 176.4w178.9 ꢀC; 1HNMR
d (ppm): 10.45 (1H, s, NH), 8.35
(1H, s, triazoleeH), 8.30 (1H, s, triazoleeH), 6.17e7.71 (8H, m,
AreH), 4.60e4.81 (2H, dd, J ¼ 14.5 Hz, triazoleeCH2e), 4.20 (2H, s,
eCH2etriazolone), 3.31 (2H, s, eCH2e); IR (KBr): 3528, 3285, 3139,
3076, 2970, 1682, 1614, 1561, 1518, 1419, 1270, 1139, 966; 13C NMR
Mp: 208.9w210.1 ꢀC; 1HNMR
d (ppm): 10.11 (1H, s, NH), 8.17
(1H, s, triazole-H), 7.89 (1H, s, triazole-H), 6.77e7.65 (8H, m, AreH),
4.72 (2H, m, triazoleeCH2e), 4.17e4.64 (2H, dd, J ¼ 15.3 Hz,
eCH2etriazolone), 2.36e2.41 (2H, t, eCH2CH2CH2CH3), 1.70e1.73
(2H, m, eCH2CH2CH2CH3), 1.41e1.43 (2H, m, eCH2CH2CH2CH3),
0.94e0.99 (3H, t, eCH2CH2CH2CH3); IR (KBr): 3412, 3325, 3200,
3127, 3055, 2957, 2931, 2871, 1701, 1615, 1519, 1417, 1273, 1137; 13C
d
(ppm): 171.63, 163.84, 161.12, 160.69, 157.45, 152.01, 150.45,
144.77, 138.43, 135.25, 129.77, 128.74, 125.64, 124.27, 122.05, 119.68,
110.77, 103.73, 74.57, 54.84, 51.67, 26.27. HRMS (m/z): calcd. for
C22H18F2N8O3: 481.1470; found: 481.1339.
NMR
d (ppm): 171.52, 163.65, 161.17, 160.54, 157.51, 152.19, 150.62,
144.97, 138.33, 135.02, 129.96, 128.80, 124.15, 122.06, 119.54, 110.99,
103.87, 74.48, 54.95, 51.78, 36.46, 31.23, 28.67, 28.51. HRMS (m/z):
calcd. for C24H25F2N7O3: 498.2060; found: 498.2080.
6.3.10. N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
cyclopropanecarboxamide (6i)
Mp: 183.7w185.5 ꢀC; 1HNMR
d (ppm): 10.35 (1H, s, NH), 8.33
6.3.6. N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
hexanamide (6e)
(1H, s, triazoleeH), 8.30 (1H, s, triazoleeH), 6.18e7.71 (8H, m,
AreH), 4.60e4.81 (2H, dd, J ¼ 14.4 Hz, triazoleeCH2e), 4.19 (2H, s,
eCH2etriazolone), 1.75e1.79 (2H, t, eCH2e), 0.79e0.81 (4H, d,
eCH2eCH2e); IR (KBr): 3324, 3200, 3128, 3059, 2978, 2940, 2881,
Mp: 195.8w196.5 ꢀC; 1HNMR
d (ppm): 10.20 (1H, s, NH), 8.45
(1H, s, triazoleeH), 7.85 (1H, s, triazoleeH), 6.79e7.65 (8H, m,
AreH), 4.79 (2H, s, triazoleeCH2e), 4.22e4.59 (2H, dd, J ¼ 14.4 Hz,
eCH2etriazolone), 2.36e2.41 (2H, t, eCH2CH2CH2CH2CH3),
1.70e1.73 (2H, m, eCH2CH2CH2CH2CH3), 1.38e1.42 (4H, m,
eCH2CH2CH2CH2CH3) 0.94e0.99 (3H, t, eCH2CH2CH2CH2CH3); IR
(KBr): 3318, 3195, 3129, 3060, 2959, 2931, 2871, 1708, 1617, 1518,
2822, 1703, 1679, 1604, 1537, 1419, 1274, 1139; 13C NMR
d (ppm):
171.51, 163.64, 161.19, 160.57, 157.52, 152.18, 150.63, 144.99, 138.35,
135.04, 129.98, 128.81, 124.16, 122.08, 119.55, 110.97, 103.86, 74.47,
54.96, 51.77, 36.45, 31.24, 31.26. HRMS (m/z): calcd. for
C23H21F2N7O3: 482.1566; found: 482.1589.
1418, 1273, 1135; 13C NMR
d
(ppm): 171.50, 163.63, 161.15, 160.52,
6.3.11. N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
cyclohexanecarboxamide (6j)
157.50, 152.17, 150.59, 144.99, 138.31, 135.01, 129.97, 128.79, 124.16,
122.05, 119.53, 110.97, 103.89, 74.47, 54.94, 51.79, 36.48, 31.20,
28.69, 28.50, 25. 10. HRMS (m/z): calcd. for C25H27F2N7O3:
512.2261; found: 512.2241.
Mp: 181.2w183.3 ꢀC; 1HNMR
d (ppm): 10.33 (1H, s, NH), 8.32
(1H, s, triazoleeH), 8.30 (1H, s, triazoleeH), 6.20e7.76 (8H, m,
AreH), 4.60e4.81 (2H, dd, J ¼ 14.4 Hz, triazoleeCH2e), 4.20(2H, s,
eCH2etriazolone), 2.38e2.39 (1H, m, CH), 1.91e1.95 (4H, m,
2 ꢂ CH2); 1.43e1.49 (6H, m, 3 ꢂ CH2); IR (KBr): 3320, 3125, 3066,
6.3.7. N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
heptanamide (6f)
2931, 2853, 1707, 1618, 1518, 1417, 1250, 963; 13C NMR
d (ppm):
Mp: 176.5w177.1 ꢀC; 1HNMR
d
(ppm): 10.02 (1H, s, NH), 8.32 (1H, s,
171.44, 163.60, 161.13, 160.50, 157.47, 152.14, 150.58, 144.97, 138.30,
135.07, 129.98, 128.70, 124.14, 122.03, 119.53, 110.95, 103.80, 74.44,
54.91, 51.77, 36.40, 31.25, 28.69, 28.54, 25.09, 22.10. HRMS (m/z):
calcd. for C26H27F2N7O3: 522.2071; found: 522.2077.
triazoleeH), 8.30 (1H, s, triazoleeH), 6.18e7.71 (8H, m, AreH),
4.60e4.81 (2H, m, triazoleeCH2e), 4.19 (2H, dd, J ¼ 14.7 Hz,
eCH2etriazolone), 2.27e2.32 (2H, t, eCH2CH2CH2CH2CH2CH3),
1.55e1.57 (2H, m, eCH2CH2CH2CH2CH3), 1.26e1.31 (6H, m,
eCH2CH2CH2CH2CH2CH3), 0.83e0.87 (3H,t,eCH2CH2CH2CH2CH2CH3);
IR (KBr): 3322, 3197, 3135, 3066, 2955, 2930, 2858, 1699, 1677, 1613,
6.3.12. N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
nicotinamide (6k)
1521, 1420, 1275, 1142; 13C NMR
d (ppm): 171.46, 163.61, 161.14, 160.52,
157.49, 152.15, 150.59, 144.99, 138.31, 135.03, 129.93, 128.75, 124.16,
122.06, 119.54, 110.97, 103.88, 74.45, 54.92, 51.79, 36.41, 31.23, 28.68,
28.53, 25.07, 22.12. HRMS (m/z): calcd. for C26H29F2N7O3: 526.2192;
found: 526.2217.
Mp: 173.6e175.9 ꢀC; 1HNMR
d (ppm): 10.83 (1H, s, NH), 8.76
(1H, s, triazoleeH), 8.74 (1H, s, triazoleeH), 6.88e8.39 (12H, m,
AreH), 4.62e4.82 (2H, dd, J ¼ 14.4 Hz, triazoleeCH2e), 4.61 (2H, s,
eCH2etriazolone); IR (KBr): 3409, 3198, 3073, 1706, 1696, 1553,
1405,1384,1270,1136, 967; 13C NMR
d (ppm): 171.44,164.07,161.57,
6.3.8. N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
octanamide (6g)
160.20, 157.32, 151.14, 150.58, 148.97, 143.54, 135.30, 133.07, 131.24,
129.31, 128.70, 125.14, 122.03, 121.81, 121.74, 121.65, 119.53, 110.97,
103.82, 74.46, 54.90, 51.79. HRMS (m/z): calcd. for C25H20F2N8O3:
519.1626; found: 519.1683.
Mp: 187.7w188.5 ꢀC; 1HNMR
d (ppm): 10.02 (1H, s, NH), 8.33 (1H,
s, triazole-H), 8.31 (1H, s, triazole-H), 6.18e7.71 (8H, m, AreH),
4.60e4.81 (2H, dd, J ¼ 14.7 Hz, triazoleeCH2e), 4.19 (2H, s,
eCH2etriazolone), 2.27e2.32 (2H, t, eCH2CH2CH2CH2CH2CH2CH3),
1.55e1.57 (2H, m, eCH2CH2CH2CH2CH2CH3),1.25e1.27 (8H, m, eCH2
CH2CH2CH2CH2CH2CH3) 0.83e0.87 (3H, t, eCH2CH2CH2CH2
CH2CH2CH3); IR (KBr): 3321, 3197, 3134, 3065, 2954, 2928, 2856,
6.3.13. N-(4-(1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-
triazol-1-yl)propyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)phenyl)
picolinamide (6l)
d (ppm): 10.85 (1H, s, NH), 8.78
(1H, s, triazoleeH), 8.73 (1H, s, triazoleeH), 6.88e8.32 (12H, m,
AreH), 4.64e4.83 (2H, dd, J ¼ 14.4 Hz, triazoleeCH2e), 4.63 (2H, s,
Mp: 171.3e173.7 ꢀC; 1HNMR
1699, 1677, 1613, 1523, 1420, 1275, 1142; 13C NMR
d (ppm): 171.47,