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CH2Cl2À MeOH 97:3 v/v to give the product as a brown oil, yield
0.49 g (56%). TLC (95:5 CH2Cl2/MeOH), Rf=0.72. 1H NMR (CDCl3):
δ 10.75 (s, 1H, NH), 7.78 (s, 1H, imidazole), 7.63 (d, J=7.7 Hz, 2H,
Ar), 7.48 (d, J=7.4 Hz, 1H, indole), 7.35 (d, J=7.7 Hz, 2H, Ar), 7.32 (s,
1H, pyrazole), 7.19 (d, J=7.5 Hz, 1H, indole), 7.16 (t, J=7.7 Hz, 1H,
para-Ar), 7.05 (m, 2H, indole), 6.94 (s, 1H, imidazole), 6.75 (s, 1H,
imidazole), 4.99 (s, 2H, CH2). 13C NMR (CDCl3): δ 144.6 (C, Ar), 139.8
(C, indole), 134.9 (C, pyrazole), 129.5 (2×CH, Ar), 129.0 (CH,
pyrazole), 127.6 (C, indole), 126.8 (CH, imidazole), 122.9 (C, indole),
120.8 (CH, imidazole), 119.3 (CH, imidazole), 119.1 (2×CH, indole),
119.0 (3×CH, Ar), 118.7 (C, indole), 111.0 (2×CH, indole), 104.4 (C,
pyrazole), 41.9 (CH2). [ESI-HRMS] calculated for C21H17ClN5: 374.1172
[M+H]+. Found: 374.1187 [M+H]+.
4-((1H-Imidazol-1-yl)methyl)-3-(4-(tert-butyl)
phenyl)-1-phenyl-1H-pyrazole (10g)
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Prepared from 3-(4-(tert-butyl)phenyl)-4-(chloromethyl)-1-phenyl-
1H-pyrazole (9g) (0.50 g, 1.53 mmol). The product was eluted with
CH2Cl2À MeOH 97.5:2.5 v/v to give the product as a yellow solid,
°
yield 0.31 g (57%). M.p. 116–117 C. TLC (95:5 CH2Cl2/MeOH), Rf=
0.72. H NMR (DMSO-d6): δ 8.52 (s, 1H, pyrazole), 7.87 (d, J=7.8 Hz,
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2H, Ar), 7.68 (s, 1H, imidazole), 7.57 (d, J=8.3 Hz, 2H, Ar), 7.53 (t, J=
7.7 Hz, 2H, Ar), 7.49 (d, J=8.3 Hz, 2H, Ar), 7.34 (t, J=7.3 Hz, 1H,
para-Ar), 7.16 (s, 1H, imidazole), 6.91 (s, 1H, imidazole), 5.30 (s, 2H,
CH2), 1.32 (s, 9H, 3×CH3). 13C NMR (DMSO-d6): δ 151.2 (C, Ar), 150.7
(C, pyrazole), 139.8 (C, Ar), 139.8 (C, Ar), 137.5 (CH, imidazole), 130.1
(2×CH, Ar), 130.0 (CH, imidazole), 129.1 (CH, para-Ar), 127.6 (2×CH,
Ar), 126.9 (CH, pyrazole), 126.0 (2×CH, Ar), 119.7 (CH, imidazole),
118.8 (2×CH, Ar), 117.2 (C, pyrazole), 41.0 (CH2), 34.9 (C(CH3)3), 31.5
(3×CH3). Anal. Calcd for C23H24N4 (356.4694): C, 77.50; H, 6.79; N,
15.71. Found: C, 77.92; H, 7.04; N, 15.88.
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4-(4-((1H-1,2,4-Triazol-1-yl)methyl)-1-phenyl-1H-pyrazol-3-yl)
pyridine (11a)
Prepared
from
4-(4-(chloromethyl)-1-phenyl-1H-pyrazol-3-yl)
pyridine (9a) (0.50 g, 1.82 mmol). The product was eluted with
CH2Cl2À MeOHÀ Et3N 92.5:7.5:1 v/v/v to give the product as a white
4-((1H-Imidazol-1-yl)
methyl)-3-([1,1’-biphenyl]-4-yl)-1-phenyl-1H-pyrazole (10h)
°
solid, yield 0.27 g (48%). M.p. 98–100 C. TLC (9:1 CH2Cl2/MeOH),
Rf=0.69. 1H NMR (DMSO-d6): δ 8.67 (m, 3H, 2×pyridine, 1×triazole),
8.60 (s, 1H, pyrazole), 7.98 (s, 1H, triazole), 7.90 (d, J=7.7 Hz, 2H, Ar),
7.78 (d, J=5.8 Hz, 2H, pyridine), 7.55 (t, J=7.7 Hz, 2H, Ar), 7.38 (t,
J=7.2 Hz, 1H, para-Ar), 5.60 (s, 2H, CH2). 13C NMR (CDCl3): δ 152.1
(CH, triazole), 150.6 (2x CH, pyridine), 148.3 (C, Ar), 140.0 (C, Ar),
139.5 (C, Ar), 131.0 (CH, Ar), 130.2 (2x CH, Ar), 127.5 (CH, Ar), 122.3
(2×CH, Ar), 122.1 (CH, triazole), 119.2 (2x CH, Ar), 117.0 (C, Ar), 43.5
(CH2). [ESI-HRMS] calculated for C17H15N6: 303.1358 [M+H]+. Found:
303.1364 [M+H]+.
Prepared from 3-([1,1’-biphenyl]-4-yl)-4-(chloromethyl)-1-phenyl-1H-
pyrazole (9h)[26] (0.40 g, 1.16 mmol). The product was eluted with
CH2Cl2À MeOH 98:2 v/v to give the product as a yellow solid, yield
°
0.20 g (46%). M.p. 114–115 C. TLC (95:5 CH2Cl2/MeOH), Rf=0.65.
1H NMR (DMSO-d6): δ 8.56 (s, 1H, pyrazole), 7.90 (d, J=7.6 Hz, 2H,
Ar), 7.77 (m, 6H, Ar), 7.71 (s, 1H, imidazole), 7.54 (t, J=7.9 Hz, 2H,
Ar), 7.50 (t, J=7.8 Hz, 2H, Ar), 7.40 (t, J=7.8 Hz, 1H, para-Ar), 7.36 (t,
J=7.7 Hz, 1H, para-Ar), 7.18 (s, 1H, imidazole), 6.91 (s, 1H,
imidazole), 5.37 (s, 2H, CH2). 13C NMR (DMSO-d6): δ 150.3 (C,
pyrazole), 140.3 (C, Ar), 140.0 (C, Ar), 139.7 (C, Ar), 132.0 (2×CH, Ar),
130.2 (2×CH, Ar), 130.1 (CH, imidazole), 129.5 (2×CH, Ar), 129.1
(CH, imidazole), 128.4 (2×CH, Ar), 128.2 (2×CH, Ar), 127.4 (2×CH,
Ar), 127.1 (2×CH, Ar), 127.0 (CH, para-Ar), 119.7 (CH, imidazole),
118.9 (CH, para-Ar), 117.5 (C, pyrazole), 41.0 (CH2). [ESI-HRMS]
calculated for C25H21N4: 377.1766 [M+H]+. Found: 377.1770 [M+
H]+.
3-(4-((1H-1,2,4-Triazol-1-yl)methyl)-1-phenyl-1H-pyrazol-3-yl)
pyridine (11b)
Prepared
from
3-(4-(chloromethyl)-1-phenyl-1H-pyrazol-3-yl)
pyridine (9b) (0.50 g, 1.82 mmol). The product was eluted with
CH2Cl2À MeOHÀ Et3N 92.5:7.5:1 v/v/v to give the product as a yellow
°
solid, yield 0.31 g (55%). M.p. 110–112 C. TLC (9:1 CH2Cl2/MeOH),
Rf=0.68. 1H NMR (DMSO-d6): δ 8.67 (m, 3H, 2×pyridine, 1×triazole),
8.60 (s, 1H, pyrazole), 7.98 (s, 1H, triazole), 7.90 (d, J=7.7 Hz, 2H, Ar),
7.78 (d, J=5.8 Hz, 2H, pyridine), 7.55 (t, J=7.7 Hz, 2H, Ar), 7.38 (t,
J=7.2 Hz, 1H, para-Ar), 5.60 (s, 2H, CH2). 13C NMR (CDCl3): δ 152.1
(CH, triazole), 150.6 (2x CH, pyridine), 148.3 (C, Ar), 140.0 (C, Ar),
139.5 (C, Ar), 131.0 (CH, Ar), 130.2 (2x CH, Ar), 127.5 (CH, Ar), 122.3
(2×CH, Ar), 122.1 (CH, triazole), 119.2 (2x CH, Ar), 117.0 (C, Ar), 43.5
(CH2). [ESI-HRMS] calculated for C17H15N6: 303.1358 [M+H]+. Found:
4-((1H-Imidazol-1-yl)methyl)-3-(benzo[d][1,3]
dioxol-5-yl)-1-phenyl-1H-pyrazole (10i)
Prepared
from
3-(benzo[d][1,3]dioxol-5-yl)-4-(chloromethyl)-1-
phenyl-1H-pyrazole (9i) (0.60 g, 1.92 mmol). The product was
eluted with CH2Cl2À MeOH 98:2 v/v to give the product as a yellow
°
solid, yield 0.32 g (49%). M.p. 62–64 C. TLC (95:5 CH2Cl2/MeOH),
Rf=0.47. 1H NMR (CDCl3): δ 7.72 (s, 1H, pyrazole), 7.65 (d, J=7.9 Hz,
2H, Ar), 7.50 (s, 1H, imidazole), 7.39 (t, J=7.6 Hz, 2H, Ar), 7.24 (t, J=
7.4 Hz, 1H, para-Ar), 7.09 (s, 1H, imidazole), 7.06 (s, 1H, benzo[d][1,3]
dioxole), 6.94 (d, J=1.6 Hz, 1H, benzo[d][1,3]dioxole), 6.89 (s, 1H,
imidazole), 6.82 (d, J=8.0 Hz, 1H, benzo[d][1,3]dioxole), 5.93 (s, 2H,
benzo[d][1,3]dioxole), 5.10 (s, 2H, CH2). 13C NMR (CDCl3): δ 151.0 (C,
pyrazole), 148.1 (C, benzo[d][1,3]dioxole), 147.9 (C, benzo[d][1,3]
dioxole), 139.5 (C, Ar), 137.0 (CH, imidazole), 129.7 (CH, imidazole),
129.5 (2×CH, Ar), 127.6 (CH, para-Ar), 126.7 (CH, pyrazole), 121.5
(CH, benzo[d][1,3]dioxole), 118.8 (2×CH, Ar), 118.6 (CH, imidazole),
108.5 (CH, benzo[d][1,3]dioxole), 108.3 (CH, benzo[d][1,3]dioxole),
101.3 (CH2, benzo[d][1,3]dioxole), 41.9 (CH2). [ESI-HRMS] calculated
for C20H17N4O2: 345.1352 [M+H]+. Found: 345.1366 [M+H]+.
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303.1364 [M+H]+. H NMR (CDCl3): δ 8.96 (s, 1H, pyrazole), 8.68 (s,
1H, triazole), 8.08 (s, 1H, pyridine), 8.05 (s, 1H, triazole), 8.02 (m, 2H,
pyridine), 7.75 (d, J=7.6 Hz, 2H, Ar), 7.51 (t, J=7.4 Hz, 2H, Ar), 7.43
(t, J=6.2 Hz, 1H, pyridine), 7.37 (t, J=7.4 Hz, 1H, para-Ar), 5.48 (s,
2H, CH2). 13C NMR (CDCl3): δ 152.5 (CH, triazole), 149.4 (CH, pyridine),
148.5 (CH, pyridine), 148.4 (C, Ar), 139.4 (C, pyrazole), 135.5 (CH,
pyridine), 129.6 (2×CH, Ar), 128.8 (CH, triazole), 128.5 (C, pyrazole),
127.3 (CH, para-Ar), 123.8 (CH, pyridine), 119.2 (2×CH, Ar), 119.1
(CH, pyrazole), 115.0 (C, pyridine), 44.2 (CH2). [ESI-HRMS] calculated
for C17H15N6: 303.1353 [M+H]+. Found: 303.1352 [M+H]+.
3-((1H-Imidazol-1-yl)
methyl)-1-(4-methoxyphenyl)-5-methyl-1H-pyrazole (23)
Prepared from 3-(chloromethyl)-1-(4-methoxyphenyl)-5-methyl-1H-
pyrazole (21) (1 g, 4.22 mmol). The product was eluted with
CH2Cl2À MeOH 97.5:2.5 v/v to give the product as a brown oil, yield
0.65 g (58%). TLC (9:1 CH2Cl2/MeOH), Rf=0.47. 1H NMR (CDCl3):
δ 7.43 (s, 1H, imidazole), 7.16 (d, J=8.9 Hz, 2H, Ar), 7.08 (s, 1H,
3-(4-((1H-Imidazol-1-yl)
methyl)-1-phenyl-1H-pyrazol-3-yl)-2-chloro-1H-indole (10j)
Prepared from 2-chloro-3-(4-(chloromethyl)-1-phenyl-1H-pyrazol-3-
yl)-1H-indole (9j) (0.80 g, 2.33 mmol). The product was eluted with
ChemistryOpen 2019, 8, 995–1011
1008
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA