J. Doiron et al. / European Journal of Medicinal Chemistry 46 (2011) 4010e4024
4017
CH2Cl2), 1H NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm) ¼ 7.72 (d, 4H,
CH2Cl2), yield ¼ 80%. Mp ¼ 66e70 ꢀC, Rf ¼ 0.28 (1% MeOH/CH2Cl2),
J ¼ 8.4 Hz, N^CC(CH)), 7.55 (s, 1H, ]CHN), 7.27e7.24 (m, 6H,
N^CC(CHCH) þ ClC(CH)), 7.12 (s, 1H, PheCHePh), 6.91 (m, 2H,
ClC(CHCH)), 5.20 (s, 2H, CH2eOePh), 13C NMR (101 MHz, CDCl3,
1H NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm) ¼ 7.72 (d, 4H, J ¼ 8.3 Hz,
N^CC(CH)), 7.58e7.53 (m, 5H, HAr þ ]CHN), 7.47e7.42 (m, 2H,
HAr), 7.36e7.32 (m, 1H, HAr), 7.27 (d, 4H, J ¼ 8.3 Hz, N^CC(CHCH)),
7.12 (s, 1H, PheCHePh), 7.08e7.04 (m, 2H, HAr), 5.29 (s, 2H, CH2O),
25 ꢀC),
d
(ppm) ¼ 156.58, 144.57, 141.56, 133.05, 129.49, 128.87,
126.48, 122.90, 117.79, 116.14, 113.47, 67.18, 62.25; HRMS m/z calc.
13C NMR (101 MHz, CDCl3, 25 ꢀC),
d
(ppm) ¼ 157.53, 145.00, 141.62,
for C24H16ClN5O þ (Hþ): 426.1116; found: 426.1111.
140.44, 134.64, 133.04, 128.89, 128.83, 128.26, 126.94, 126.71,
122.86, 117.80, 115.11, 113.44, 67.18, 62.15; HRMS m/z calc. for
C30H21N5O þ (Hþ): 468.1819; found: 468.1813.
4.2.9. 1-(4,40-Dicyanodiphenylmethyl)-4-((4-cyanophenoxy)
methyl)-1H-1,2,3-triazole (10j)
From azide 8 and 4-(prop-2-ynyloxy)benzonitrile. White solid
after silica gel circular chromatography (0e0.4% MeOH/CH2Cl2),
yield ¼ 97%. Mp ¼ 72e75 ꢀC, Rf ¼ 0.32 (2% MeOH/CH2Cl2), 1H NMR
4.2.14. 1-(Diphenylmethyl)- 1H-1,2,3-triazole (11a)
Compound 11a was prepared from azide 9 [32] and acetylene
using the general procedure for the synthesis of 10a. Purification by
chromatography (0e20% AcOEt/Hex) gave 11a as a white solid;
yield ¼ 92%. Mp ¼ 119e120 ꢀC, Rf ¼ 0.27 (40% AcOEt/hexane), 1H
(400 MHz, CDCl3, 25 ꢀC),
d
(ppm) ¼ 7.73 (d, 4H, J ¼ 8.5 Hz,
N^CC(CH)), 7.63e7.59 (m, 3H, HAr þ ]CHN), 7.28 (d, 4H, J ¼ 8.5 Hz,
N^CC(CHCH)), 7.13 (s, 1H, PheCHePh), 7.07 (m, 2H, HAr), 5.27 (s,
2H, CH2eOePh), 13C NMR (101 MHz, CDCl3, 25 ꢀC),
NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm) ¼ 7.75 (s, 1H, ]CHN]), 7.45
(s, 1H, ]CHNePh), 7.40e7.37, (m, 6H, HAr), 7.17 (s, 1H, CHePh),
d
(ppm) ¼ 161.24, 143.68, 141.48, 134.11, 133.08, 128.89, 123.18,
7.14e7.12 (m, 4H, HAr), 13C NMR (101 MHz, CDCl3, 25 ꢀC),
d
(ppm):
118.91, 117.75, 115.46, 113.53, 104.89, 67.26, 62.00; HRMS m/z calc.
for C25H16N6O þ (Hþ): 417.1458; found: 417.1449.
138.19, 133.65, 128.94, 128.59, 128.08, 123.56, 67.94; HRMS m/z calc.
for C15H13N3 þ (Hþ): 236.1182; found: 236.1178.
4.2.10. 1-(4,40-Dicyanodiphenylmethyl)-4-((4-nitrophenoxy)
methyl)-1H-1,2,3-triazole (10k)
4.2.15. 1-(Diphenylmethyl)-4-propyl-1H-1,2,3-triazole (11b)
From azide 9 and 1-pentyne and using the general procedure for
the synthesis of 10ben. White solid after silica gel circular chro-
matography (0e20% AcOEt/Hex), yield ¼ 40%. Mp ¼ 89e90 ꢀC,
Rf ¼ 0.25 (30% AcOEt/Hex), 1H NMR (400 MHz, CDCl3, 25 ꢀC)
From azide 8 and 1-nitro-4-(prop-2-ynyloxy)benzene. White
solid after silica gel circular chromatography (0e0.4% MeOH/
CH2Cl2), yield ¼ 71%. Mp ¼ 72e76 ꢀC, Rf ¼ 0.21 (1% MeOH/CH2Cl2),
1H NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm) ¼ 8.22 (dt, 2H, J ¼ 7.0 Hz,
d (ppm): 7.40e7.34 (m, 6H, HAr), 7.15 (s, 1H, ]CHN), 7.14e7.11 (m,
2.8 Hz, NO2C(CH)), 7.73 (d, 4H, J ¼ 8.5 Hz, N^CC(CH)), 7.63 (s, 1H, ]
4H, HAr), 7.10 (s, 1H, PheCHePh), 2.70 (t, 2H, J ¼ 7.4 Hz,
CHN), 7.29 (d, 4H, 8.5 Hz, N^CC(CHCH)), 7.13 (s, 1H,
J
¼
CH2CH2CH3), 1.69 (sext., 2H, J ¼ 7.4 Hz, CH2CH2CH3), 0.96 (t, 3H,
PheCHePh), 7.08 (dt, 2H, J ¼ 7.0 Hz, 2.8 Hz, NO2C(CHCH)), 5.32 (s,
J ¼ 7.4 Hz, CH3), 13C NMR (101 MHz, CDCl3, 25 ꢀC)
d (ppm): 148.10,
2H, CH2eOePh), 13C NMR (101 MHz, CDCl3, 25 ꢀC),
138.44, 128.87, 128.45, 128.09, 120.66, 67.88, 27.81, 22.70, 13.80.
d
(ppm) ¼ 162.90, 143.48, 142.06, 141.44, 133.09, 128.88, 125.98,
HRMS m/z calc. for C18H19N3 þ (Hþ): 278.1652; found: 278.1645.
123.24, 117.74, 114.77, 113.56, 67.30, 62.33; HRMS m/z calc. for
C24H16N6O3 þ (Hþ): 437.1357; found: 437.1351.
4.2.16. 1-(Diphenylmethyl)-4-hexyl-1H-1,2,3-triazole (11c)
From azide 9 and 1-octyne and using the general procedure for
the synthesis of 10ben. White solid after silica gel circular chro-
matography (0e13% AcOEt/Hex), yield ¼ 68%. Mp ¼ 70e72 ꢀC,
Rf ¼ 0.11 (30% AcOEt/Hex), 1H NMR (400 MHz, CDCl3, 25 ꢀC)
4.2.11. 1-(4,40-Dicyanodiphenylmethyl)-4-((p-tolyloxy)methyl)-1H-
1,2,3-triazole (10l)
From azide 8 and 1-methyl-4-(prop-2-ynyloxy)benzene. White
solid after silica gel circular chromatography (0e0.4% MeOH/
CH2Cl2), yield ¼ 77%. Mp ¼ 55e64 ꢀC, Rf ¼ 0.47 (2% MeOH/CH2Cl2),
d
(ppm): 7.40e7.35 (m, 6H, HAr), 7.162e7.109 (m, 5H, HAr þ ]CHN),
7.10 (s, 1H, PheCHePh), 2.71 (t, 2H, J ¼ 7.7 Hz, CH2CH2(CH2)3CH3),
1.66 (quint., 2H, J ¼ 7.7 Hz, CH2CH2(CH2)3CH3), 1.39e1.27 (m, 6H,
CH2CH2(CH2)3CH3), 0.88 (m, 3H, CH3), 13C NMR (101 MHz, CDCl3,
1H NMR (400 MHz, CDCl3, 25 ꢀC),
N^CC(CH)), 7.56 (s, 1H, ]CHN), 7.26 (d, 4H,
d
(ppm) ¼ 7.71 (d, 4H, J ¼ 8.4 Hz,
8.4 Hz,
J
¼
N^CC(CHCH)), 7.12e7.09 (m, 3H, HAr þ PheCHePh), 6.87 (m, 2H,
25 ꢀC
d (ppm): 148.35, 138.45, 128.86, 128.44, 128.09, 120.56, 67.87,
HAr), 5.20 (s, 2H, CH2eOePh), 2.31 (s, 3H, CH3), 13C NMR (101 MHz,
31.51, 29.39, 28.92, 25.83, 22.54, 14.03. HRMS m/z calc. for
CDCl3, 25 ꢀC),
d
(ppm) ¼ 155.90, 145.23, 141.68, 133.02, 130.86,
C21H25N3 þ (Hþ): 320.2121; found 320.2116.
130.04, 128.90, 122.82, 117.84, 114.67, 113.37, 67.12, 62.19, 20.50;
HRMS m/z calc. for C15H19N5O þ (Hþ): 416.1662; found: 406.1659.
4.2.17. 1-(Diphenylmethyl)-4-heptyl-1H-1,2,3-triazole (11d)
From azide 9 and 1-nonyne and using the general procedure
for the synthesis of 10ben. White solid after silica gel circular
4.2.12. 1-(4,40-Dicyanodiphenylmethyl)-4-((4-methoxyphenoxy)
methyl)-1H-1,2,3-triazole (10m)
chromatography
(0e15%
AcOEt/Hex),
yield
¼
66%.
From azide
8
and 1-methoxy-4-(prop-2-ynyloxy)benzene.
Mp ¼ 70e71 ꢀC, Rf ¼ 0.29 (30% AcOEt/Hex). 1H NMR (400 MHz,
White solid after silica gel circular chromatography (0e0.4% MeOH/
CDCl3, 25 ꢀC)
d (ppm): 7.40e7.34 (m, 6H, HAr), 7.16e7.11 (m, 5H,
CH2Cl2), yield ¼ 70%. Mp ¼ 55e63 ꢀC, 1H NMR (400 MHz, CDCl3,
HAr þ ]CHN), 7.10 (s, 1H, PheCHePh), 2.71 (t, 2H, J ¼ 7.6 Hz,
CH2CH2(CH2)4CH3), 1.66 (quit., 2H, J ¼ 7.6 Hz, CH2CH2(CH2)4
CH3), 1.36e1.27 (m, 8H, CH2CH2(CH2)4CH3), 0.88 (m, 3H, CH3).
25 ꢀC),
CHN), 7.26 (d, 4H,
d
(ppm) ¼ 7.72 (d, 4H, J ¼ 8.4 Hz, N^CC(CH)), 7.53 (s, 1H, ]
J
¼
8.4 Hz, N^CC(CHCH)), 7.11 (s, 1H,
PheCHePh), 6.92e6.89 (m, 2H, HAr), 6.87e6.83 (m, 2H, HAr), 5.19 (s,
13C NMR (101 MHz, CDCl3, 25 ꢀC)
d
(ppm): 148.35, 138.46,
2H, CH2eOePh), 3.79 (s, 3H, OCH3), 13C NMR (101 MHz, CDCl3,
128.86, 128.44, 128.09, 120.56, 67.88, 31.74, 29.43, 29.22, 28.97,
25.82, 22.59, 14.08. HRMS m/z calc. for C22H27N3
334.2278; found: 334.2270.
25 ꢀC),
d
(ppm) ¼ 154.41, 152.06, 145.26, 141.64, 133.03, 128.88,
þ
(Hþ):
122.75, 117.81, 115.97, 114.70, 113.43, 67.13, 62.82, 55.70; HRMS m/z
calc. for C25H19N5O2 þ (Hþ): 422.1612; found: 422.1603.
4.2.18. 1-(Diphenylmethyl)-4-decyl-1H-1,2,3-triazole (11e)
4.2.13. 1-(4,40-Dicyanodiphenylmethyl)-4-((4-phenylphenoxy)
methyl)-1H-1,2,3-triazole (10n)
From azide 8 and 1-phenyl-4-(prop-2-ynyloxy)benzene. White
solid after silica gel circular chromatography (0e0.25% MeOH/
From azide 9 and 1-dodecyne and using the general procedure
for the synthesis of 10ben. White solid after silica gel circular
chromatography (0e25% AcOEt/Hex), yield ¼ 88%. Mp ¼ 83e84 ꢀC,
Rf ¼ 0.52 (30% AcOEt/Hex). 1H NMR (400 MHz, CDCl3, 25 ꢀC)