Chemistry of Heterocyclic Compounds 2015, 51(8), 723–733
14.0. Mass spectrum, m/z (Irel, %): 276 [M(81Br)+H]+ (98), 276
J = 4.8, H-7); 8.26 (1H, d, J = 7.6, H-4'); 8.77 (1H, s, H-2').
13C NMR spectrum (DMSO-d6 + NaH + D2O), δ, ppm: 171.1;
159.5; 157.8; 141.6; 140.5; 136.5; 133.5; 130.4; 128.4; 128.3;
128.2; 123.2; 116.1. Mass spectrum, m/z (Irel, %): 240 [M+H]+
(100). Found, %: C 64.40; H 3.78; N 17.28. C13H9N3O2.
Calculated (with 1.9% H2O), %: C 64.06; H 3.92; N 17.24.
3-(3H-Imidazo[4,5-c]pyridin-2-yl)benzoic acid (14).
Yield 0.172 g (72%). Mp >370°C (EtOH). 1H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 7.60 (1H, br. d,
J = 4.0, H-7); 7.71 (1H, t, J = 7.2, H-5'); 8.09 (1H, d, J = 7.6,
H-6'); 8.31 (1H, d, J = 6.0, H-6); 8.46 (1H, d, J = 8.0, H-4');
8.82 (1H, s, H-2'); 8.96 (1H, s, H-4). Mass spectrum, m/z
(Irel, %): 240 [M+H]+ (100). Found, %: C 61.65; H 4.14;
N 16.58. C13H9N3O2. Calculated (with 5.3% H2O), %: C 61.77;
H 4.19; N 16.63.
[M(79Br)+H]+ (100). Found, %: C 39.17; H 4.37; N 15.32.
C9H12BrN3O2.Calculated, %: C 39.43; H 4.41; N 15.33.
5-Bromo-N2-(n-butyl)pyridine-2,3-diamine (6). The mixture
of compound 5 (0.6 g, 2.19 mmol) in 25% HCl (15 ml) and
EtOH (10 ml) was stirred vigorously. Zinc dust (1.5 g,
23 mmol) was added to this mixture in several portions at
room temperature. After the addition of zinc dust was
completed, the mixture was heated on a water bath at 97°C
for 1 h. Reaction mixture was cooled and made alkaline
with 10% NaOH solution, then extracted with EtOAc. The
extract was washed with water, dried over anhydrous
Na2SO4, and evaporated. Residue was purified by column
chromatography (eluent n-hexane–AcOEt, 1:3). Yield 0.26 g
1
(49%). Dark-purple powder. H NMR spectrum (CDCl3),
δ, ppm (J, Hz): 0.87 (3H, t, J = 7.2, CH3); 1.31–1.39 (2H,
m, CH2CH3); 1.50–1.58 (2H, m, CH2CH2CH3); 3.20 (2H,
br. s, NH2); 3.30 (2H, t, J = 7.6, NHCH2); 4.04 (1H, br. s,
NH); 6.86 (1H, d, J = 2.4, H-6); 7.68 (1H, d, J = 2.4, H-4).
13C NMR spectrum (CDCl3), δ, ppm: 149.4; 139.2; 129.7;
124.0; 107.4; 41.9; 32.0; 20.5; 14.2. Mass spectrum, m/z
(Irel, %): 246 [M(81Br)+H]+ (98), 244 [M(79Br)+H]+ (100).
Synthesis of compounds 11–26 (General method). An
aromatic aldehyde (6.0 mmol) was dissolved in EtOH (20 ml),
and sodium metabisulfite (0.64 g, 3.37 mmol) in H2O
(3 ml) was added in portions. The reaction mixture was
stirred vigorously and more EtOH was added. The mixture
was kept in a refrigerator for several hours. The precipitate
was filtered and dried. The mixture of the obtained sodium
aryl(hydroxy)methanesulfonate (1.0 mmol) and pyridine-
diamine 4, 6–10 (1.0 mmol) in DMF (1–2 ml) was heated
at 110°C for 4 h. The reaction mixture was cooled, poured
into water, and the crude product was filtered off if it was
solid, or, alternatively, it was extracted with chloroform, dried
over anhydrous Na2SO4, evaporated, then crystallized from
appropriate solvent, unless stated otherwise.
4-(3H-Imidazo[4,5-b]pyridin-2-yl)benzoic acid (15).
Yield 0.158 g (66%). Mp >370°C (EtOH). 1H NMR
spectrum (DMSO-d6 + D2O), δ, ppm (J, Hz): 7.28 (1H, dd,
J = 8.4, J = 4.8, H-6); 8.02 (1H, br. d, J = 7.6, H-7); 8.08
(2H, dd, J = 6.8, J = 1.6, H-2',6'); 8.26 (2H, dd, J = 6.8,
J = 1.6, H-3',5'); 8.34 (1H, br. dd, J = 4.4, J = 0.8, H-5).
Mass spectrum, m/z (Irel, %): 240 [M+H]+ (100). Found, %:
C 60.14; H 4.48; N 16.01. C13H9N3O2. Calculated (with
7.7% H2O), %: C 60.27; H 4.36; N 16.22.
4-(6-Chloro-3H-imidazo[4,5-b]pyridin-2-yl)benzoic acid
(16). Yield 0.126 g (46%). Mp >370°C (DMF–EtOH,
5:95). 1H NMR spectrum (DMSO-d6 + NaH + D2O),
δ, ppm (J, Hz): 7.68 (1H, d, J = 2.8, H-7); 7.87 (2H, d, J = 8.0,
H-2',6'); 7.90 (1H, d, J = 2.8, H-5); 8.16 (2H, d, J = 8.4,
H-3',5'). 13C NMR spectrum (DMSO-d6 + NaH + D2O),
δ, ppm: 171.2; 164.5; 159.7; 140.1; 139.7; 137.7; 137.3;
129.6; 126.4; 121.6; 120.7. Mass spectrum, m/z (Irel, %):
272 [M–H]+ (100), 274 [M–H+2]+ (33). Found, %: C 56.63;
H 2.82; N 15.44. C13H8ClN3O2. Calculated (with 0.7%
H2O), %: C 56.67; H 3.00; N 15.25.
3-(3-Benzyl-3H-imidazo[4,5-b]pyridin-2-yl)benzoic acid
(17). Yield 0.151 g (46%). Mp 218–220°C (2-PrOH).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 5.62 (2H,
s, PhCH2); 6.97–6.99 (2H, m, H-3,5 Ph); 7.18–7.25 (3H, m,
H-2,4,6 Ph); 7.36 (1H, dd, J = 8.4, J = 5.2, H-6); 7.63 (1H,
t, J = 8.0, H-5'); 7.98 (1H, d, J = 8.0, H-6'); 8.07 (1H, d, J = 8.0,
H-4'); 8.17 (1H, dd, J = 8.0, J = 1.6, H-7); 8.30 (1H, s,
H-2'); 8.39 (1H, dd, J = 5.2, J = 1.2, H-5). 13C NMR
spectrum (DMSO-d6), δ, ppm: 167.3 (C=O); 153.7; 149.3;
144.9 (C-5); 137.5; 135.2; 133.5 (C-6'); 132.1; 131.5
(C-4'); 130.8; 130.4 (C-2'); 130.0 (C-5'); 129.4 (C-2,6 Ph);
128.1 (C-4 Ph); 127.9 (C-7); 126.9 (C-3,5 Ph); 119.7 (C-6);
46.7(CH2). Mass spectrum, m/z (Irel, %): 330 [M+H]+
(100). Found, %: C 70.30; H 4.92; N 11.90. C20H15N3O2.
Calculated (with 2.7% H2O and 4.4% 2-PrOH), %:
C 70.52; H 5.13; N 11.89.
2-(3H-Imidazo[4,5-b]pyridin-2-yl)benzoic acid (11).
Yield 0.065 g (27%). Mp 269–270°C (DMF–EtOH, 5:95).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.23 (1H,
dd, J = 8.0, J = 4.8, H-6); 7.62 (1H, td, J = 7.6, J = 1.6,
H-5'); 7.68 (1H, td, J = 7.6, J = 1.2, H-4'); 7.77 (1H, dd,
J = 7.6, J = 1.2, H-6'); 7.83 (1H, dd, J = 7.6, J = 1.2, H-3');
7.97 (1H, dd, J = 8.0, J = 1.6, H-7); 8.32 (1H, dd, J = 4.8,
J = 1.6, H-5). Mass spectrum, m/z (Irel, %): 240 [M+H]+
(100). Found, %: C 63.34; H 4.22; N 16.56. C13H9N3O2.
Calculated (with 3.6% H2O), %: C 62.89; H 4.06; N 16.92.
2-(3H-Imidazo[4,5-c]pyridin-2-yl)benzoic acid (12).
Yield 0.057 g (24%). Mp 271–272°C (DMF–EtOH, 5:95).
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.67–7.69 (2H,
m, H-4',5'); 7.80 (1H, d, J = 5.6, H-7); 7.88–7.91 (1H, m,
H-6'); 8.04–8.06 (1H, m, H-3'); 8.38 (1H, d, J = 6.0, H-6);
9.01 (1H, s, H-4). Mass spectrum, m/z (Irel, %): 240 [M+H]+
(100). Found, %: C 59.87; H 4.70; N 16.44. C13H9N3O2.
Calculated (with 7.7% H2O), %: C 60.27; H 4.36; N 16.22.
3-(3H-Imidazo[4,5-b]pyridin-2-yl)benzoic acid (13).
2-(3-Benzyl-1H-imidazo[4,5-b]pyridin-2-yl)benzoic acid
(18). Purified by column chromatography, eluent CH2Cl2–
MeOH–AcOH, 50:10:0.2. Yield 0.072 g (22%). Mp 226–
1
228°C. H NMR spectrum (CD3OD), δ, ppm (J, Hz): 4.92
1
Yield 0.187 g (78%). Mp >370°C (EtOH). H NMR spect-
and 4.93 (2H total, 2s, PhCH2); 6.89–6.91 (2H, m, H-3,5
Ph); 7.11–7.16 (3H, m, H-2,4,6 Ph); 7.22 (1H, d, J = 7.2,
H-6'); 7.37 (1H, dd, J = 8.0, J = 4.8, H-6); 7.56 (1H, td,
J = 7.2, J = 0.8, H-5'); 7.66 (1H, td, J = 7.6, J = 0.8, H-4');
rum (DMSO-d6 + NaH + D2O), δ, ppm (J, Hz): 7.01–7.04
(1H, m, H-6); 7.42 (1H, t, J = 7.6, H-5'); 7.87 (1H, d,
J = 8.0, H-5); 7.94 (1H, d, J = 7.6, H-6'); 8.14 (1H, d,
729