Month 2016
Synthesis and Pharmacological Evaluation of Novel Pyrazolyl Piperidine Derivatives
as Effective Antiplatelet Agents
(2H, m, CH2); 1.97–2.01 (2H, m, CH2); 2.79–2.87 (3H, m,
CH,CH2); 3.18–3.21 (2H, m, CH2); 6.40 (1H, s, pyrazol
proton); 7.33–7.35 (1H, m, ArH, J=8.4Hz,); 7.39–7.43
(1H, d, J=8.4Hz, ArH); 7.73–7.75 (1H, m, ArH). 13C
NMR (100MHz, CDCl3): δ 33.1, 34.7, 46.5, 99.5, 125.6,
127.8, 128.7, 132.4, 149.3, 152.5. IR (KBr, cmÀ1): 3237,
3236, 1646, 1320, 1295, 1079. ESI/MS 296.1 [M]+, 298.2
[M+2]+, 300.1 [M+4]+ calculated for C14H15N3Cl2.
Anal. Calcd. for C14H15N3Cl2: C, 56.77; H, 5.10; N,
14.19; Found: C, 56.63; H, 5.45; N, 14.35.
2.00–2.02 (2H, m, CH2); 2.75–2.90 (3H, m, CH, CH2);
3.21–3.24 (2H, m, CH2); 6.46 (1H, s, pyrazol proton);
7.69–7.71 (2H, m, ArH, J =8.4 Hz,); 7.88–7.90 (2H, d,
J = 8.4 Hz, ArH). 13C NMR (100MHz, DMSO): δ 33.0,
34.2, 46.3, 100.2, 109.7, 119.5, 125.9, 133.1, 138.4,
147.9, 151.4. IR (KBr, cmÀ1): 3355, 3068, 2265, 1364,
1265, 1004, 907. ESI/MS 253.2 [M +1]+ calculated for
C15H16N4. Anal. Calcd. for C15H16N4: C, 71.40; H, 6.39;
N, 22.21; Found: C, 71.17; H, 6.55; N, 22.28.
4-(5-(4-Tolyl)-1H-pyrazol-3-yl)piperidine (3k).
White
1
4-(5-(3-Bromophenyl)-1H-pyrazol-3-yl)piperidine (3g). White
solid, mp 152–156°C; yield 62%; reaction time 20 min.
1H NMR (400 MHz, CDCl3): δ 1.69–1.79 (2H, m,
CH2); 1.99–2.02 (2H, m, CH2); 2.74–2.80 (2H, m,
CH); 2.82–2.88 (1H, m, CH); 3.20–3.23 (2H, d, CH2);
6.39 (1H, s, pyrazol proton); 6.99–7.04 (1H, m, ArH,
J = 8.4 Hz); 7.36–7.40 (1H, m, ArH, J = 8.4 Hz,); 7.45–
7.48 (1H, m, J = 8.4 Hz, ArH); 7.52–7.54 (1H, m,
ArH,). 13CNMR (100 MHz, CDCl3): δ 33.1, 34.4, 46.4,
99.8, 112.3, 112.6, 114.5, 114.7, 121.2, 130.1, 130.2,
130.3, 135.1. IR (KBr, cmÀ1): 3336, 3079, 2996,
2953, 2817, 1360, 1287, 1119. ESI/MS 306.1 [M]+,
308.1 [M + 2]+ calculated for C14H16N3Br. Anal. Calcd.
for C14H16N3Br: C, 54.91; H, 5.27; N, 26.10; Found:
C, 55.00; H, 5.38; N, 13.64.
solid, mp 158–161°C; yield 62%; reaction time 1 h. H
NMR (400 MHz, CDCl3): δ 1.68–1.76 (2H, m, CH2);
1.97–2.00 (2H, m, CH2); 2.38 (3H, s, CH3); 2.69–2.77
(1H, m, CH); 2.79–2.85(2H, m, CH2); 3.18–3.02 (2H, m,
CH2); 6.34 (1H, s, pyrazol proton); 7.20–7.22 (2H, m,
ArH, J= 8.4 Hz,); 7.59–7.61 (2H, d, J = 8.4 Hz, ArH). 13C
NMR (100MHz, CDCl3): δ 21.3, 33.1, 34.8, 46.5, 99.3,
125.5, 129.4, 137.7, 148.9, 152.8. IR (KBr, cmÀ1): 3248,
3068, 1361, 1265, 1004, 907. ESI/MS 242.2 [M+ 1]+
calculated for C15H19N3. Anal. Calcd. for C15H19N3: C,
74.65; H, 7.94; N, 17.41; Found: C, 74.93; H, 7.76; N,
17.31.
3-Chloro-4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine
(3l). White solid, mp 176–179°C; yield 48%; reaction time
1
10 min. H NMR (400MHz, DMSO): δ 1.47–1.57 (2H, m,
4-(5-(4-Fluorophenyl)-1H-pyrazol-3-yl)piperidine (3h).
CH2); 1.84–1.87 (2H, m, CH2); 2.54–2.60 (2H, m, CH2);
2.74–2.80 (1H, m, CH); 2.98–3.01 (2H, m, CH2); 6.72 (1H,
s, pyrazol proton); 7.84–7.85 (1H, d, ArH, J= 6Hz,); 8.49–
8.50 (1H, d, J= 6.4Hz, ArH); 8.65 (1H, s, ArH); 13.1 (1H,
b, NH, piperidine). 13C NMR (100 MHz, CDCl3): δ 33.0,
34.2, 46.3, 100.2, 119.8, 141.2, 141.6, 147.0, 147.5, 150.4.
IR (KBr, cmÀ1): 3339, 3068, 1364, 1265, 1004, 907.
ESI/MS 263.0 [M]+, 265.1 [M+ 2]+ calculated for
C13H15ClN4. Anal. Calcd. for C13H15ClN4: C, 59.43; H,
5.75; N, 21.32; Found: C, 59.19; H, 5.97; N, 21.19.
White solid, mp 181–184°C; yield 67%; reaction time
1
15min. H NMR (400 MHz, CDCl3): δ 1.68–1.79 (2H,
m, CH2); 1.99–2.02 (2H, m, CH2); 2.73–2.81 (2H, m,
CH); 2.82–2.89 (1H, m, CH); 3.20–3.23 (2H, m, CH2);
6.34 (1H, s, pyrazol proton); 7.07–7.12 (2H, m, ArH);
7.70–7.73 (2H, m, ArH). 13C NMR (100 MHz, CDCl3): δ
33.0, 34.5, 46.4, 99.41, 115.5, 115.7, 127.2, 127.3,
151.7, 161.3, 163.7. IR (KBr, cmÀ1): 3246, 2950, 2830,
1363, 1264, 1095, 1006. ESI/MS 246.2 [M + 1]+
calculated for C14H16N3F. Anal. Calcd. for C14H16N3F:
C, 68.55; H, 6.57; N, 17.13; Found: C, 68.79; H, 6.73;
N, 17.25.
4-(5-(3-Nitrophenyl)-1H-pyrazol-3-yl)piperidine (3m). Yellow
solid, mp 158–161°C; yield 65%; reaction time 1h and
1
45min. H NMR (400MHz, CDCl3): δ 1.75–1.82 (2H, m,
4-(5-(3-Fluoro-4-methoxyphenyl)-1H-pyrazol-3-yl)piperidine
CH2); 1.99–2.03 (2H, m, CH2); 2.73–2.77 (2H, m, CH2);
2.79–2.80 (1H, m, CH); 3.20–3.23 (2H, m, CH2); 6.43
(1H, s, pyrazol proton); 7.59–7.55 (1H, m, ArH); 8.01–
8.10 (1H, d, J=8.4Hz, ArH); 8.22–8.24 (1H, m, ArH,
J=8.4Hz,); 8.56–8.61 (1H, m, ArH, J=8.4Hz). 13C NMR
(100MHz, DMSO): δ 33.1, 34.7, 46.5, 99.5, 125.6, 127.8,
128.7, 132.4, 149.3, 152.5. IR (KBr, cmÀ1): 3326, 3002,
2267, 1531, 2217, 1348. ESI/MS 273.0 [M+1]+ calculated
for C14H16N4O2. Anal. Calcd. for C14H16N4O2: C, 61.75;
H, 5.92; N, 20.58; Found: C, 61.59; H, 6.04; N, 20.51.
4-(5-(2-Nitrophenyl)-1H-pyrazol-3-yl)piperidine (3n). Yellow
solid, mp 140–142°C; yield 67%; reaction time 3h. 1H NMR
(400 MHz, CDCl3): δ 1.74–1.80 (2H, m, CH2); 2.00–2.03
(2H, m, CH2); 2.74–2.78 (2H, m, CH2); 2.80–2.83 (1H, m,
CH); 3.20–3.23 (2H, m, CH2); 6.48 (1H, s, pyrazol proton);
7.60–7.68 (1H, m, ArH); 7.89–7.92 (1H, m, ArH, ) 8.00–8.20
(3i). White solid, mp 142–144°C; yield 74%; reaction time
1
45min. H NMR (400MHz, CDCl3): δ 1.69–1.77 (2H, m,
CH2); 1.96–2.00 (2H, m, CH2); 2.71–2.75 (2H, m, CH2);
2.77–2.85 (1H, m, CH); 3.18–3.21 (2H, m, CH2); 3.92
(3H, S, OCH3); 6.30 (1H, s, pyrazol proton); 6.96–7.00
(1H, t, ArH, J=8.8, 8.4Hz,); 7.45–7.50 (2H, m, ArH). 13C
NMR (100MHz, CDCl3): δ 32.9, 34.5, 46.5, 56.3, 99.3,
105.4, 113.4, 113.6, 121.3, 121.4, 147.3, 151.2, 153.7. IR
(KBr, cmÀ1): 3335, 2945, 2842, 1364, 1270. ESI/MS
276.1 [M+1]+ calculated for C15H18N3FO. Anal. Calcd.
for C15H18N3FO: C, 65.44; H, 6.59; N, 15.26; Found: C,
65.57; H, 6.51; N, 15.42.
4-(3-(Piperidin-4-yl)-1H-pyrazol-5-yl)benzonitrile (3j). White
1
solid, mp 168–170°C; yield 76%; reaction time 40 min. H
NMR (400 MHz, CDCl3): δ 1.71–1.79 (2H, m, CH2);
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet