4050 Journal of Medicinal Chemistry, 2009, Vol. 52, No. 13
Valdez et al.
MHz, CDCl3) δ 8.09 (s, 1H), 7.93 (s, 1H), 7.77 (d, J ) 15.7, 1H),
7.70 (d, J ) 7.9, 1H), 7.50 (d, J ) 7.74, 1H), 7.15 (t, J ) 7.8, 1H),
6.87 (d, J ) 15.7, 1H), 4.07 (s, 3H); 13C NMR (150 MHz, CDCl3)
δ 149.2, 139.1, 138.4, 137.8, 137.4, 135.7, 134.1, 130.6, 127.0,
124.5, 94.8, 32.8; HRMS (ESI+) calcd for C12H11IN3O2 [M + H]+
355.9891, found 355.9902. Anal. (C12H10IN3O2): C, 40.58; H, 2.84;
N, 11.83. Found: C, 41.07; H, 2.91; N, 11.12.
32.8, 15.2; HRMS (ESI+) calcd for C17H22N3O4 [M + H]+
332.1605, found 332.1608. Anal. (C17H21N3O4) C, H, N.
2-[(E)-2-Biphenyl-2-ylvinyl]-1-methyl-5-nitro-1H-imidazole (24).
Dimetridazole (1.0 g, 7.1 mmol) was reacted with biphenyl-2-
carbaldehyde (1.67 g, 9.23 mmol, 1.3 equiv) in the presence of
NaOEt (966 mg, 14.2 mmol, 2.0 equiv). The mixture was purified
by column chromatography (CH2Cl2 f 5% CH3OH/CH2Cl2) to give
24 as a yellow solid (455 mg, 21%). 1H NMR (400 MHz, DMSO-
d6) δ 8.13-8.12 (m, 1H), 8.08 (s, 1H), 7.70 (d, J ) 15.6, 1H),
7.51 -7.43 (m, 5H), 7.39-7.32 (m, 4H), 4.02 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 149.7, 141.7, 139.8, 138.9, 135.9, 134.0,
132.9, 130.3, 129.5, 129.2, 128.3, 127.7, 127.4, 126.5, 113.7, 32.7;
HRMS (ESI+) calcd for C18H16N3O2 [M + H]+ 306.1237, found
306.1225. Anal. (C18H15N3O2) C, H, N.
2-[(E)-2-(3-Fluorophenyl)vinyl]-1-methyl-5-nitro-1H-imida-
zole (19). Dimetridazole (1.0 g, 7.1 mmol) was reacted with
3-fluorobenzaldehyde (1.1 g, 8.5 mmol, 1.2 equiv) in the presence
of NaOEt (1.2 g, 17.7 mmol, 2.5 equiv). The mixture was purified
by column chromatography (50% CH2Cl2/hexanes f 100% CH2Cl2)
1
to give 19 as a bright-yellow solid (0.23 g, 13%). H NMR (500
MHz, CDCl3) δ 8.10 (s, 1H), 7.86 (d, J ) 15.7, 1H), 7.40-7.37
(m, 1H), 7.35-7.34 (m, 1H), 7.29 (dt, J ) 10, 2.2, 1H), 7.09 (tdd,
J ) 8.1, 2.6, 1.0, 1H), 6.90 (d, J ) 15.7, 1H), 4.08 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 163.1 (d, J ) 245.2), 149.2, 139.1,
138.3 (d, J ) 2.9), 137.5 (d, J ) 7.3), 134.1, 130.5 (d, J ) 8.1),
123.6 (d, J ) 2.9), 116.6 (d, J ) 21.5), 113.5 (d, J ) 21.8), 112.5,
32.8; HRMS (ESI+) calcd for C12H11FN3O2 [M + H]+ 248.0830,
found 248.0820. Anal. (C12H10FN3O2) C, H, N.
1-Methyl-2-[(E)-2-(1-naphthyl)vinyl]-5-nitro-1H-imidazole (25).
Dimetridazole (1.0 g, 7.1 mmol) was reacted with 1-naphthaldehyde
(1.25 mL, 9.23 mmol, 1.3 equiv) in the presence of NaOEt (966
mg, 14.2 mmol, 2.0 equiv). The mixture was purified by column
chromatography (CH2Cl2 f 10% CH3OH/CH2Cl2) to give 25 as a
1
yellow solid (554 mg, 28%). H NMR (400 MHz, DMSO-d6) δ
8.59 (d, J ) 15.6, 1H), 8.26 (d, J ) 8.4, 1H), 8.25 (s, 1H), 8.16 (d,
J ) 8.0, 1H), 8.01-7.99 (m, 2H), 7.66-7.59 (m, 3H), 7.49 (d, J
) 15.6, 1H), 4.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.7,
134.1, 133.7, 133.3, 132.0, 130.6, 129.7, 128.7, 127.0, 126.1, 125.8,
125.6, 124.6, 128.8, 115.5, 32.8; HRMS (ESI+) calcd for
2-[(E)-2-(3-Methoxyphenyl)vinyl]-1-methyl-5-nitro-1H-imida-
zole (20). Dimetridazole (1.0 g, 7.1 mmol) was reacted with
3-methoxybenzaldehyde (1.13 mL, 9.23 mmol, 1.3 equiv) in the
presence of NaOEt (966 mg, 14.2 mmol, 2.0 equiv). The mixture
was purified by column chromatography (CH2Cl2 f 5% CH3OH/
C16H14N3O2 [M
(C16H13N3O2) C, H, N.
+
H]+ 280.1080, found 280.1085. Anal.
1
CH2Cl2) to give 20 as a yellow solid (588 mg, 32%). H NMR
(400 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.70 (d, J ) 16.0, 1H), 7.35
(d, J ) 16.0, 1H), 7.34 (br s, 1H), 7.29 (d, J ) 5.2, 1H), 6.93-6.90
(m, 1H), 3.99 (s, 3H), 3.77 (s, 3H); 13C NMR (100 MHz, DMSO-
d6) δ 159.6, 149.7, 139.0, 137.9, 136.8, 134.1, 129.8, 120.5, 115.3,
113.3, 112.4, 55.2, 32.8; HRMS (ESI+) calcd for C13H14N3O3 [M
+ H]+ 260.1030, found 260.1029. Anal. (C13H13N3O3) C, H, N.
1-Methyl-5-nitro-2-{(E)-2-[4-(trifluoromethoxy)phenyl]vinyl}-
1H-imidazole (21). Dimetridazole (1.0 g, 7.1 mmol) was reacted
with 4-(trifluoromethoxy)benzaldehyde (1.33 mL, 9.23 mmol, 1.3
equiv) in the presence of NaOEt (966 mg, 14.2 mmol, 2.0 equiv).
The mixture was purified by column chromatography (CH2Cl2 f
10% CH3OH/CH2Cl2) to give 21 as a yellow solid (311 mg, 14%).
1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.88 (d, J ) 8.8,
2H), 7.73 (d, J ) 15.6, 1H), 7.38 (d, J ) 15.6, 2H), 7.36 (d, J )
8.8, 1H), 3.98 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 149.3,
148.6, 148.5, 148.6, 148.6, 142.0, 139.1, 136.1, 134.8, 134.0, 129.5,
128.0, 121.2, 120.6, 118.7, 114.3, 32.8; HRMS (ESI+) calcd for
C13H11F3N3O3 [M + H]+ 314.0747, found 314.0752. Anal.
(C13H10F3N3O3): C, 49.85; H, 3.22; N, 13.42. Found: C, 49.92; H,
3.60; N, 13.88.
1-Methyl-2-[(E)-2-(2-naphthyl)vinyl]-5-nitro-1H-imidazole (26).
Dimetridazole (1.0 g, 7.1 mmol) was reacted with 2-naphthaldehyde
(1.44 g, 9.23 mmol, 1.3 equiv) in the presence of NaOEt (966 g,
14.2 mmol, 2.0 equiv). The mixture was purified by column
chromatography (CH2Cl2 f 10% CH3OH/CH2Cl2) to give 26 as a
1
yellow solid (385 mg, 19%). H NMR (400 MHz, DMSO-d6) δ
8.22 (s, 1H), 8.21 (br s, 1H), 8.07 (dd, J ) 8.8, 1.6, 1H), 7.98-7.92
(m, 4H), 7.56-7.52 (m, 3H), 4.08 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 149.8, 137.8, 134.2, 133.3, 133.1, 133.0, 128.6, 128.3,
128.2, 127.6, 126.9, 126.8, 126.6, 123.9, 113.5, 32.8; HRMS (ESI+)
calcd for C16H14N3O2 [M + H]+ 280.1080, found 280.1081. Anal.
(C16H13N3O2): C, 68.81; H, 4.69; N, 15.05. Found: C, 68.21; H,
4.78; N, 14.95.
2-[(E)-2-(3a,7a-Dihydro-1,3-benzodioxol-5-yl)vinyl]-1-methyl-
5-nitro-1H-imidazole (27). Dimetridazole (1.0 g, 7.1 mmol) was
reacted with piperonal (1.39 g, 9.23 mmol, 1.3 equiv) in the
presence of NaOEt (966 mg, 14.2 mmol, 2.0 equiv). The mixture
was purified by column chromatography (CH2Cl2 f 10% CH3OH/
1
CH2Cl2) to give 27 as a yellow solid (600 mg, 31%). H NMR
(400 MHz, DMSO-d6) δ 8.17 (s, 1H), 7.70 (d, J ) 15.6, 1H), 7.57
(d, J ) 1.6, 1H), 7.25 (d, J ) 15.6, 1H), 7.21 (dd, J ) 8.0, 1.6z,
1H), 6.96 (d, J ) 8.0, 1H), 6.09 (s, 2H), 4.01 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 150.1, 148.4, 148.0, 137.9, 134.3, 130.0,
124.0, 111.0, 108.4, 106.0, 101.4, 89.3, 32.7; HRMS (ESI+) calcd
for C13H12N3O4 [M + H]+ 274.0822, found 274.0823. Anal.
(C13H11N3O4) C, H, N.
1-Methyl-5-nitro-2-[(E)-2-(2,3,4-trimethoxyphenyl)vinyl]-1H-
imidazole (22). Dimetridazole (1.0 g, 7.1 mmol) was reacted with
2,3,4-trimethoxybenzaldehyde (1.67 g, 8.52 mmol, 1.2 equiv) in
the presence of NaOEt (1.2 g, 17.8 mmol, 2.5 equiv). The mixture
was purified by column chromatography (CH2Cl2 f 10% CH3OH/
1
CH2Cl2) to give 22 as a yellow solid (362 mg, 16%). H NMR
(400 MHz, CDCl3) δ 8.06 (s, 1H), 7.94 (d, J ) 16.0, 1H), 7.23 (d,
J ) 8.8, 1H), 6.96 (d, J ) 16.0, 1H), 6.68 (d, J ) 8.8, 1H), 4.00
(s, 3H), 3.93 (s, 3H), 3.88 (s, 3H), 3.87 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 155.1, 152.9, 150.7, 142.4, 138.7, 135.2, 134.4,
123.4, 122.2, 110.6, 107.5, 61.1, 60.8, 56.0, 32.6; HRMS (ESI+)
calcd for C15H18N3O5 [M + H]+ 320.1241, found 320.1240. Anal.
(C15H17N3O5) C, H, N.
1-Methyl-2-[(E)-2-(1-methyl-1H-imidazol-2-yl)vinyl]-5-nitro-
1H-imidazole (28). Dimetridazole (1.06 g, 7.5 mmol) was reacted
with 1-methyl-1H-imidazole-2-carbaldehyde (1.0 g, 9.1 mmol, 1.2
equiv) in the presence of NaOEt (1.27 g, 18.8 mmol, 2.5 equiv).
The mixture was purified by column chromatography (CH2Cl2 f
10% CH3OH/CH2Cl2) to give 28 as a yellow solid (1.36 g, 77%).
1H NMR (400 MHz, DMSO-d6) δ 8.20 (s, 1H), 7.64 (d, J ) 15.2,
1H), 7.33 (d, J ) 15.2, 1H), 7.31 (s, 1H), 7.07 (s, 1H), 3.99 (s,
3H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.3, 143.4,
134.1, 129.2, 124.0, 123.0, 113.6, 32.7, 32.4; HRMS (ESI+) calcd
for C10H12N5O2 [M + H]+ 234.0985, found 234.0986. Anal.
(C10H11N5O2) C, H, N.
2-[(E)-2-(2-Furyl)vinyl]-1-methyl-5-nitro-1H-imidazole (29).
Dimetridazole (1.0 g, 7.1 mmol) was reacted with furan-2-
carbaldehyde (0.65 mL, 7.81 mmol, 1.1 equiv) in the presence of
NaOEt (1.2 g, 17.8 mmol, 2.5 equiv). The mixture was purified by
column chromatography (CH2Cl2 f 10% CH3OH/CH2Cl2) to give
29 as a yellow solid (825 mg, 53%). 1H NMR (400 MHz, DMSO-
2-{(E)-2-[4-(Diethoxymethyl)phenyl]vinyl}-1-methyl-5-nitro-
1H-imidazole (23). Dimetridazole (20 g, 142 mmol) was reacted
with 4-(diethoxymethyl)benzaldehyde (34.5 mL, 170 mmol, 1.2
equiv) in the presence of NaOEt (24 g, 354 mmol, 2.5 equiv). The
mixture was purified by column chromatography (CH2Cl2 f 10%
1
CH3OH/CH2Cl2) to give 23 as a yellow solid (5.67 g, 24%). H
NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.87 (d, J ) 16.0, 1H),
7.56 (d, J ) 8.0, 2H), 7.51 (d, J ) 8.0, 2H), 6.89 (d, J ) 16.0,
1H), 5.52 (s, 1H), 4.05 (s, 3H), 3.65-3.53 (m, 4H, 2 × OCH2CH3),
1.25 (t, J ) 7.2, 6H, 2 × OCH2CH3); 13C NMR (100 MHz, CDCl3)
δ 149.8, 140.9, 139.4, 135.2, 134.2, 127.3, 111.3, 101.0, 89.8, 61.1,