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5.3.1.5. N-(4-azidophenyl)methanesulfonamide (G5). Yellow oil;
Yield: 72%; MS [M+H]+ m/z: 213.
(s, 3H). 13C NMR (150 MHz, DMSO-d6) d 161.47, 159.78, 143.01,
139.47, 134.53(2C), 133.04, 131.73, 121.95(2C), 119.91(3C),
119.86(3C), 117.26, 117.12(2C), 112.74, 53.87, 46.41.
5.3.1.6. 1-azido-2-fluorobenzene (G6). Yellow oil; Yield: 68%; MS
[M+H]+ m/z: 138.
5.3.2.6. Preparation of 2-(2-fluorophenyl)-5-((1-(2-fluorophenyl)-1H-
1,2,3-triazol-4-yl)methyl)-5H-imidazo[4,5-c]pyridine
(compound
5.3.1.7. 1-azido-3,5-bis(trifluoromethyl)benzene (G7). Yellow oil;
Yield: 65%; MS [M+H]+ m/z: 256.
6). White solid; Yield: 55%; Mp: 152–153 °C; Purity: 99.6%; MS
[M+H]+ m/z: 389. 1H NMR (400 MHz, DMSO-d6) d 9.34 (s, 1H),
8.84 (s, 1H), 8.43 (d, J = 6.3 Hz, 1H), 8.31 (t, J = 7.0 Hz, 1H), 7.93
(d, J = 6.5 Hz, 1H), 7.86 (t, J = 7.3 Hz, 1H), 7.66–7.53 (m, 3H), 7.44
(t, J = 7.2 Hz, 1H), 7.40–7.33 (m, 2H), 5.98 (s, 2H).
5.3.1.8. 1-(4-azidobenzyl)pyrimidin-2(1H)-one (G8). Yellow oil;
Yield: 72%; MS [M+H]+ m/z: 228.
5.3.1.9. 1-(4-azidobenzyl)pyridin-2(1H)-one (G9). Yellow oil; Yield:
72%; MS [M+H]+ m/z: 227.
5.3.2.7. Preparation of 5-((1-(3,5-bis(trifluoromethyl)phenyl)-1H-
1,2,3-triazol-4-yl)methyl)-2-(2-fl
uorophenyl)-5H-imidazo[4,5-
c]pyridine (compound 7). White solid; Yield: 59%; Mp: 159–161 °C;
Purity: 99.7%; MS [M+H]+ m/z: 507. 1H NMR (400 MHz, DMSO-d6)
d 9.41 (s, 1H), 9.24 (s, 1H), 8.60 (s, 2H), 8.44 (s, 1H), 8.35 (s, 1H),
8.28 (s, 1H), 8.08–7.89 (m, 1H), 7.58–7.52 (m, 1H), 7.37 (s, 2H),
6.03 (s, 2H).
5.3.2. General procedure for preparation of target compounds
(compound 1–9)
Intermediate G (0.8 mmol) was solubilized in ethanol (2 mL),
then intermediate F (0.2 g, 0.8 mmol), CuI (0.01 g, 0.5 mmol) and
DIPEA (0.1 g, 0.8 mmol) were added, the mixture was stirred at rt
for 12 h. After that, filtered, and the filtrate was concentrated
under reduced pressure to yield the title compounds (compound
1–9) as white solid.
5.3.2.8. Preparation of 1-(4-(4-((2-(2-fluorophenyl)-5H-imidazo[4,
5-c]pyridin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)benzyl)pyrimidin-2
(1H)-one (compound 8). White solid; Yield: 54%; Mp: 173–175 °C;
Purity: 94.5%; MS [M+H]+ m/z: 479. 1H NMR (400 MHz, DMSO-
d6) d 9.82 (s, 1H), 8.96 (s, 1H), 8.87 (d, J = 7.1 Hz, 1H), 8.61–8.57
(m, 1H), 8.45–8.41 (m, 1H), 8.33–8.25 (m, 2H), 7.86 (d, J = 8.5 Hz,
2H), 7.79–7.72 (m, 1H), 7.60–7.49 (m, 4H), 6.53–6.49 (m, 1H),
6.15 (s, 2H), 5.13 (s, 2H).
5.3.2.1. Preparation of 2-(2-fluorophenyl)-5-((1-phenyl-1H-1,2,3-tri-
azol-4-yl)methyl)-5H-imidazo [4,5-c]pyridine (compound 1). White
solid; Yield: 56%; Mp: 157–159 °C; Purity: 96.5%; MS [M+H]+
m/z: 371. 1H NMR (400 MHz, DMSO-d6) d 9.26 (s, 1H), 8.96
(s, 1H), 8.28 (s, 2H), 7.89 (d, J = 7.9 Hz, 2H),7.55 (m, 5H), 7.32
(s, 2H), 5.91 (s, 2H).
5.3.2.9. Preparation of 1-(4-(4-((2-(2-fluorophenyl)-5H-imidazo[4,
5-c]pyridin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)benzyl)pyridin-2(1H)-
one (compound 9). White solid; Yield: 55%; Mp: 167–169 °C; Pur-
ity: 97.0%; MS [M+H]+ m/z: 478. 1H NMR (400 MHz, DMSO-d6) d
9.21 (s, 1H), 8.91 (s, 1H), 8.31 (t, J = 7.7 Hz, 2H), 7.85 (d, J = 8.4
Hz, 4H), 7.49 (d, J = 8.4 Hz, 3H), 7.44 (m, 1H), 7.31 (t, J = 7.6 Hz,
2H), 6.43 (d, J = 9.1 Hz, 1H), 6.27 (t, J = 6.7 Hz, 1H), 5.92 (s, 2H),
5.16 (s, 2H).
5.3.2.2. Preparation of 2-(2-fluorophenyl)-5-((1-(4-fluorophenyl)-1H-
1,2,3-triazol-4-yl)methyl)-5H-imidazo[4,5-c]pyridine
(compound
2). White solid; Yield: 58%; Mp: 155–157 °C; Purity: 97.3%; MS
[M+H]+ m/z: 389. 1H NMR (400 MHz, DMSO-d6) d 9.21 (s, 1H),
8.93 (s, 1H), 8.33 (s, 1H), 8.28 (s, 1H), 7.96–7.90 (m, 2H), 7.86 (s,
1H), 7.52–7.40 (m, 3H), 7.32 (s, 2H), 5.92 (s, 2H). 13C NMR (150
MHz, DMSO-d6) d 162.98(2C), 161.35(2C), 143.55, 133.37, 133.35,
131.41(2C), 123.49(2C), 123.10(3C), 117.21(3C), 117.06(3C), 53.21.
5.4. Preparation of target compounds of seriesⅡ (compound 10–14)
5.3.2.3. Preparation of 2-(2-fluorophenyl)-5-((1-(4-methoxyphenyl)-
1H-1,2,3-triazol-4-yl)methyl)-5H-imidazo[4,5-c]pyridine (compound
3). White solid; Yield: 54%; Mp: 158–160 °C; Purity: 99.1%; MS
[M+H]+ m/z: 401. 1H NMR (400 MHz, DMSO-d6) d 9.18 (s, 1H),
8.85 (s, 1H), 8.32 (s, 1H), 8.25 (d, J = 6.4 Hz, 1H), 7.83 (s, 1H), 7.79
(d, J = 9.0 Hz, 2H), 7.48 (t, J = 7.7 Hz, 1H), 7.30 (t, J = 7.5 Hz, 2H),
7.13 (d, J = 9.1 Hz, 2H), 5.89 (s, 2H), 3.82 (s, 3H). 13C NMR (150
MHz, DMSO-d6) d 168.27, 161.67, 159.99, 159.81, 143.33, 132.06
(2C), 131.50, 131.24(2C), 130.19, 123.43(2C), 122.34(2C), 117.05,
116.91, 115.22(2C), 113.08, 55.90, 53.25.
5.4.1. Preparation of 2-(chloromethyl)imidazo[1,2-a]pyrimidine (a1)
A
mixture of pyrimidin-2-amine (6.0 g, 64.0 mmol), 1,3-
dichloroacetone (8.1 g, 64.0 mmol) and dimethyl ether (30 mL)
was stirred at rt for 2 h. After that, The resulting precipitate was fil-
tered, added to ethanol (50 mL) and the mixture was refluxed for 2
h . The solvent was removed under reduced pressure, water (30
mL) was added and the mixture was adjusted to pH 8–9 with sat-
urated sodium carbonate solution. The resulting precipitate was
filtered, washed with water and dried under reduced pressure to
yield the title compound as a white solid (7.0 g, 65%). MS [M+H]+
m/z: 168.
5.3.2.4. Preparation of 2-(2-fluorophenyl)-5-((1-(3-methoxyphenyl)-
1H-1,2,3-triazol-4-yl)methyl)- 7. 5H-imidazo[4,5-c]pyridine (com-
pound 4). White solid; Yield: 54%; Mp: 156–157 °C; Purity:
98.6%; MS [M+H]+ m/z: 401. 1H NMR (400 MHz, DMSO-d6) d 9.32
(s, 1H), 8.98 (s, 1H), 8.40 (d, J = 6.5 Hz, 1H), 8.31 (t, J = 7.4 Hz,
1H), 7.92 (d, J = 6.5 Hz, 1H), 7.58–7.42 (m, 4H), 7.40–7.32 (m,
2H), 7.08 (d, J = 8.8 Hz, 1H), 5.97 (s, 2H), 3.84 (s, 3H).
5.4.2. Preparation of 2-(chloromethyl)-5,7-dimethylimidazo[1,2-a]
pyrimidine (b2)
5.4.2.1. Preparation of 4,6-dimethylpyrimidin-2-amine(a2). A mix-
ture of guanidine nitrate (3.0 g, 25.0 mmol), 2,4-pentandione
(3.7 g, 37.0 mmol), K2CO3 (3.4 g, 25.0 mmol) and distilled water
(15 mL) was stirred at 80 °C for 7 h. After that, the mixture was
cooled to rt and the resulting precipitate was filtered, washed with
water and dried under reduced pressure to yield the title com-
pound as a white solid (2.6 g, 96%). MS [M+H]+ m/z: 123.
5.3.2.5. Preparation of N-(4-(4-((2-(2-fluorophenyl)-5H-imidazo[4,5-
c]pyridin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)methanesulfon-
amide (compound 5). White solid; Yield: 57%; Mp: 164–166 °C;
Purity: 96.0%; MS [M+H]+ m/z: 464. 1H NMR (400 MHz, DMSO-
d6) d 10.12 (s, 1H), 9.43 (s, 1H), 8.89 (s, 1H), 8.51 (d, J = 6.4 Hz,
1H), 8.32 (t, J = 7.7 Hz, 1H), 8.00 (d, J = 6.6 Hz, 1H), 7.83 (d, J = 8.9
Hz, 2H), 7.63–7.56 (m, 1H), 7.44–7.36 (m, 4H), 6.01 (s, 2H), 3.07
5.4.2.2. Preparation of 2-(chloromethyl)-5,7-dimethylimidazo[1,2-a]
pyrimidine (b2). 1,3-dichloroacetone (5.6 g, 41.0 mmol) and inter-
mediate a2 (5.0 g, 41.0 mmol) were solubilized in dimethyl ether
(30 mL), the mixture was stirred at 45 °C for 10 h . The resulting