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B.-T. Yin et al. / European Journal of Medicinal Chemistry 71 (2014) 148e159
benzaldehyde (1.060 g, 10 mmol). Yield: 53.4%; mp: 135e136 ꢃC; IR
(KBr) : 3110, 3078 (AreH, ]CeH), 2976 (CH2), 1653 (C]O), 1634,
1596, 1503, 1454, 1401, 1242, 1165, 1128, 866, 768, 692 cmꢁ1 1H
NMR (300 MHz, CDCl3) : 8.09 (s, 1H, triazole 5-H), 8.07 (s, 1H,
4.1.16. (Z)-1-(2,4-Di(piperidin-1-yl)phenyl)-3-phenyl-2-(1H-1,2,4-
triazol-1-yl) prop-2-en-1-one (10a)
Compound 10a (0.750 g) was obtained as red syrup according to
the general procedure described for 10aec starting from piperidine
(1.700 g, 20 mmol), compound 7d (2.230 g, 10 mmol) and benzal-
n
;
d
triazole 3-H), 7.56 (s, 1H, C]CH), 7.46e7.28 (m, 4H, chalcone
60,2,4,6-H), 6.88 (d, 2H, J ¼ 9.0 Hz, chalcone 3,5-H), 6.77 (t, 1H,
J ¼ 9.0 Hz, chalcone 30-H), 6.71e6.67 (m, 1H, chalcone 50-H), 2.95 (s,
4H, piperidyl 2,6-H), 1.64 (s, 4H, piperidyl 3,5-H), 1.52 (s, 2H,
dehyde (1.060 g, 10 mmol). Yield: 17.0%; IR (KBr)
H, ]CeH), 2964, 2858 (CH2), 1665 (C]O), 1612, 1573, 1552 (C]C),
1449, 1231, 1201, 1057, 951, 818, 617 cmꢁ1 1H NMR (300 MHz,
CDCl3) : 8.08 (s, 2H, triazole 3,5-H), 7.51 (s, 1H, C]CH), 7.43 (d, 1H,
n: 3125, 3075 (Are
;
piperidyl 4-H) ppm; 13C NMR (75 MHz, CDCl3)
d
: 192.5 (chalcone
d
C]O), 166.8, 163.5 (chalcone 40-C), 154.1, 154.0 (chalcone 20-C),
152.3 (triazole 5-C), 145.1 (triazole 3-C), 140.4 (chalcone 1-C), 132.4
J ¼ 9.2 Hz, chalcone 60-H), 7.33e7.29 (m, 3H, chalcone 2,4,6-H), 6.88
(d, 2H, J ¼ 9.2 Hz, chalcone 3,5-H), 6.56 (d, 1H, J ¼ 6.0 Hz, chalcone
50-H), 6.40 (s, 1H, chalcone 30-H), 3.29e3.27 (m, 4H, 20-piperidyl
2,6-H), 2.94e2.92 (m, 4H, 4΄-piperidyl 2,6-H), 1.69e1.61 (m, 12H,
(chalcone a b-C),
-C), 132.3, 132.2 (chalcone 60-C), 131.3 (chalcone
131.2 (chalcone 4-C), 130.0 (chalcone 2,6-C), 129.1 (chalcone 3,5-C),
127.4,127.3 (chalcone 10-C),109.0,108.7 (chalcone 50-C),105.8,105.5
(chalcone 30-C), 53.8 (piperidyl 2,6-C), 25.9 (piperidyl 3,5-C), 23.8
(piperidyl 4-C) ppm; ESI-MS (m/z): 399 [M þ Na]þ, 377 [M þ H]þ,
274 [M þ H ꢁ F ꢁ piperidyl]þ; HRMS (TOF) calcd for C22H21FN4O
[M þ H]þ, 377.1769; found, 377.1774.
piperidyl 3,4,5-H) ppm; 13C NMR (75 MHz, CDCl3)
d: 192.1 (chal-
cone C]O), 154.9 (chalcone 20-C), 154.3 (chalcone 40-C), 152.1 (tri-
azole 5-C), 145.2 (triazole 3-C), 139.0 (chalcone 60-C), 133.1
(chalcone 1-C), 132.8 (chalcone
a-C), 131.9 (chalcone b-C), 130.5
(chalcone 4-C), 129.8 (chalcone 2,6-C), 128.9 (chalcone 3,5-C), 120.7
(chalcone 10-C), 108.3 (chalcone 50-C), 104.2 (chalcone 30-C), 54.0
(20-piperidyl 2,6-C), 49.1 (40-piperidyl 2,6-C), 26.0 (20-piperidyl 3,5-
C), 25.5 (40-piperidyl 3,5-C), 24.3 (20-piperidyl 4-C), 24.1 (40-piper-
idyl 4-C) ppm; ESI-MS (m/z): 442 [M þ H]þ; HRMS (TOF) calcd for
4.1.14. (Z)-1-(4-Fluoro-2-(morpholin-4-yl)phenyl)-3-phenyl-2-
(1H-1,2,4-triazol-1-yl)prop-2-en-1-one (9b)
Compound 9b (2.090 g) was obtained as yellow solid according
to the general procedure described for 9aec starting from mor-
pholine (1.740 g, 20 mmol), compound 7d (2.230 g, 10 mmol) and
benzaldehyde (1.060 g, 10 mmol). Yield: 55.3%; mp: 123e124 ꢃC; IR
C
27H31N5O [M þ H]þ, 442.2599; found, 442.2601.
4.1.17. (Z)-1-(2,4-Di(morpholin-4-yl)phenyl)-3-phenyl-2-(1H-
1,2,4-triazol-1-yl)prop-2-en-1-one (10b)
Compound 10b (0.851 g) was obtained as red syrup according to
the general procedure described for 10aec starting from morpholine
(1.740 g, 20 mmol), compound 7d (2.230 g, 10 mmol) and benzalde-
(KBr)
1640, 1601 (C]C), 1573, 1498, 1299, 1109, 987, 881, 774, 617 cmꢁ1
1H NMR (300 MHz, CDCl3)
: 8.11 (s, 1H, triazole 5-H), 8.06 (s, 1H,
n: 3130, 3060 (AreH, ]CeH), 2970, 2855 (CH2), 1655 (C]O),
;
d
triazole 3-H), 7.49 (s, 1H, C]CH), 7.48e7.30 (m, 4H, chalcone
60,2,4,6-H), 6.88e6.86 (m, 3H, chalcone 3,5,30-H), 6.74e6.69 (m, 1H,
chalcone 50-H), 3.75 (t, 4H, J ¼ 4.2 Hz, morpholinyl OCH2), 2.99 (t,
hyde (1.060 g,10 mmol). Yield: 19.1%; IR (KBr)
2840 (CH2), 1632 (C]O), 1506, 1400, 1131, 1109, 617 cmꢁ1; 1H NMR
(300 MHz, CDCl3) : 8.10 (s,1H, triazole 5-H), 8.05 (s,1H, triazole 3-H),
n: 3116 (AreH, ]CeH),
4H, J ¼ 4.5 Hz, morpholinyl NCH2) ppm; 13C NMR (75 MHz, CDCl3)
d
:
d
7.49 (s, 1H, C]CH), 7.46 (s, 1H, chalcone 60-H), 7.35e7.28 (m, 3H,
chalcone 2,4,6-H), 6.88 (d, 2H, J ¼ 9.2 Hz, chalcone 3,5-H), 6.63e6.60
(m, 1H, chalcone 50-H), 6.42 (s, 1H, chalcone 30-H), 3.87 (t, 4H,
J ¼ 4.5 Hz, 20-morpholinyl OCH2), 3.75 (t, 4H, J ¼ 4.5 Hz, 40-morpho-
linyl OCH2), 3.28 (t, 4H, J ¼ 4.5 Hz, 20-morpholinyl NCH2), 3.00 (t, 4H,
192.4 (chalcone C]O), 166.8, 163.6 (chalcone 40-C), 153.1, 153.0
(chalcone 20-C), 152.5 (triazole 5-C), 145.1 (triazole 3-C), 141.0
(chalcone 1-C), 132.6 (chalcone
131.4 (chalcone -C), 131.1 (chalcone 4-C), 130.0 (chalcone 2,6-C),
a
-C), 132.4, 132.3 (chalcone 60-C),
b
129.2 (chalcone 3,5-C), 127.2, 127.1 (chalcone 10-C), 109.9, 109.6
(chalcone 50-C), 105.9, 105.5 (chalcone 30-C), 66.6 (morpholinyl
OCH2), 52.5 (morpholinyl NCH2) ppm; ESI-MS (m/z): 379 [M þ H]þ,
274 [M þ H ꢁ F ꢁ morpholinyl]þ; HRMS-TOF: m/z [M þ H]þ calcd
for C21H19FN4O2: 379.1504, found: 379.1501.
J ¼ 4.5 Hz, 4΄-morpholinyl NCH2) ppm; 13C NMR (75 MHz, CDCl3)
d:
191.8 (chalcone C]O), 169.2 (chalcone 20-C), 154.6 (chalcone 40-C),
153.1 (triazole 5-C), 152.3 (chalcone 60-C), 145.2 (triazole 3-C), 139.7
(chalcone 1-C), 132.9 (chalcone
a-C), 131.5 (chalcone b-C), 130.9
(chalcone 4-C), 129.9 (chalcone 2,6-C), 129.1 (chalcone 3,5-C), 121.4
(chalcone 10-C), 108.5 (chalcone 50-C), 103.5 (chalcone 30-C), 66.8 (20-
morpholinyl OCH2), 66.6 (40-morpholinyl OCH2), 47.9 (20-morpho-
linyl NCH2), 46.6 (40-morpholinyl NCH2) ppm; ESI-MS (m/z): 468
[Mþ Na]þ, 446[Mþ H]þ;HRMS(TOF) calcd forC25H27N5O3 [Mþ H]þ,
446.5144; found, 446.5141.
4.1.15. (Z)-1-(4-Fluoro-2-(pyrrolidin-1-yl)phenyl)-3-phenyl-2-(1H-
1,2,4-triazol-1-yl) prop-2-en-1-one (9c)
Compound 9c (0.830 g) was obtained as yellow solid according
to the general procedure described for 9aec starting from pyrro-
lidine (1.420 g, 20 mmol), compound 7d (2.230 g, 10 mmol) and
benzaldehyde (1.060 g, 10 mmol). Yield: 23.1%; mp: 150e152 ꢃC; IR
4.1.18. (Z)-1-(2,4-Di(pyrrolidin-1-yl)phenyl)-3-phenyl-2-(1H-1,2,4-
triazol-1-yl)prop -2-en-1-one (10c)
Compound 10c (0.530 g) was obtained as red syrup according to
the general procedure described for 10aec starting from pyrroli-
dine (1.420 g, 20 mmol), compound 7d (2.230 g, 10 mmol) and
(KBr)
1592 (C]C), 1502, 1399, 1109, 856, 752, 638 cmꢁ1
(300 MHz, CDCl3) : 8.17 (s, 1H, triazole 5-H), 8.16 (s, 1H, triazole 3-
n
: 3114, 3040 (AreH, ]CeH), 2929, 2852 (CH2), 1663 (C]O),
;
1H NMR
d
H), 7.64 (s, 1H, C]CH), 7.50e7.45 (m, 1H, chalcone 60-H), 7.37e7.28
(m, 3H, chalcone 2,4,6-H), 6.89 (d, 2H, J ¼ 6.0 Hz, chalcone 3,5-H),
6.50e6.40 (m, 2H, chalcone 30,50-H), 3.21 (t, 4H, J ¼ 6.3 Hz, pyrro-
lidyl 2,5-H), 1.98 (t, 4H, J ¼ 6.3 Hz, pyrrolidyl 3,4-H) ppm; 13C NMR
benzaldehyde (1.060 g,10 mmol). Yield: 13.1%; IR (KBr)
H, ]CeH), 2964, 2868 (CH2), 1668 (C]O), 1600, 1501 (C]C), 1448,
1397, 1132, 1110, 797, 696, 638 cmꢁ1; 1H NMR (300 MHz, CDCl3)
n: 3103 (Are
d
:
(75 MHz, CDCl3) d
: 180.7 (chalcone C]O), 167.0, 163.7 (chalcone 40-
8.20 (s, 1H, triazole 5-H), 8.14 (s, 1H, triazole 3-H), 7.56 (s, 1H, C]
CH), 7.54 (s,1H, chalcone 60-H), 7.32e7.28 (m, 3H, chalcone 2,4,6-H),
6.90 (d, 2H, J ¼ 6.0 Hz, chalcone 3,5-H), 6.02e5.99 (m, 1H, chalcone
50-H), 5.80 (d, 1H, J ¼ 3.0 Hz, chalcone 30-H), 3.35 (t, 4H, J ¼ 7.5 Hz,
20-pyrrolidyl 2,5-H), 3.25 (t, 4H, J ¼ 6.0 Hz, 4΄-pyrrolidyl 2,5-H),
C), 152.5 (triazole 5-C), 150.0, 149.8 (chalcone 20-C), 145.1 (triazole
3-C), 141.6 (chalcone 1-C), 133.5 (chalcone -C), 133.2, 133.1 (chal-
cone 60-C), 131.3 (chalcone
-C), 131.1 (chalcone 4-C), 130.2 (chal-
a
b
cone 2,6-C), 129.0 (chalcone 3,5-C), 118.3 (chalcone 10-C), 102.8,
102.5 (chalcone 50-C), 100.7, 100.4 (chalcone 30-C), 51.2 (pyrrolidyl
2,5-C), 25.9 (pyrrolidyl 3,6-C) ppm; ESI-MS (m/z): 363 [M þ H]þ,
274 [M þ H ꢁ F ꢁ pyrrolidyl]þ; HRMS (TOF) calcd for C21H19FN4O
[M þ H]þ, 362.1509; found, 362.1505.
2.02e1.95 (m, 8H, pyrroly 3,4-H) ppm; 13C NMR (75 MHz, CDCl3)
d:
187.7 (chalcone C]O), 152.2 (chalcone 20-C), 151.1 (chalcone 40-C),
150.8 (triazole 5-C), 145.1 (triazole 3-C), 137.9 (chalcone 60-C), 134.4
(chalcone 1-C), 134.2 (chalcone
a-C), 131.9 (chalcone b-C), 130.3