Synthesis of 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylic acid and its derivatives

Article abstract of DOI:10.3987/COM-07-11303

Two new imidazo[1,2-a]pyridines, 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylic acid (4) and ethyl 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate (6) were prepared via cyclization of 2-aminopyfidin-3-ol (1) with bromopyruvic acid (2) and ethyl bromopyruvate (3), respectively. 8-Hydroxyimidazo[1,2-a]- pyridine-2-carboxylic acid (4) was successfully coupled with various amino acid derivatives via its active ester intermediate into the corresponding amides 22-27. O-protected ethyl 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate 11 was transformed into its hydrazide 13, acyl azide 14, and amide 15 derivatives.

Full text of DOI:10.3987/COM-07-11303

HETEROCYCLES, Vol. 75, No. 6, 2008
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HETEROCYCLES, Vol. 75, No. 6, 2008, pp. 1355 - 1370. © The Japan Institute of Heterocyclic Chemistry
Received, 14th December, 2007, Accepted, 8th February, 2008, Published online, 15th February, 2008. COM-07-11303
SYNTHESIS OF 8-HYDROXYIMIDAZO[1,2-a]PYRIDINE-2-CARBOX-
YLIC ACID AND ITS DERIVATIVES
Uroš Grošelj,1 Jure Bezenšek,1 Anton Meden,1 Jurij Svete,1* Branko
Stanovnik,1* Marko Oblak,2 Petra Štefanič Anderluh,2 and Uroš Urleb2
1Department of Organic Chemistry, Faculty of Chemistry and Chemical
Technology, University of Ljubljana, Aškerčeva 5, P.O. Box 537, 1000 Ljubljana,
Slovenia. E-mail: jurij.svete@fkkt.uni-lj.si, branko.stanovnik@fkkt.uni-lj.si
2Lek Pharmaceuticals d.d., Drug Discovery, Verovškova 57, 1526 Ljubljana,
Slovenia
Abstract – Two new imidazo[1,2-a]pyridines, 8-hydroxyimidazo[1,2-a]pyridine-
2-carboxylic acid (4) and ethyl 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate
(6) were prepared via cyclization of 2-aminopyridin-3-ol (1) with bromopyruvic
acid (2) and ethyl bromopyruvate (3), respectively. 8-Hydroxyimidazo[1,2-a]-
pyridine-2-carboxylic acid (4) was successfully coupled with various amino acid
derivatives via its active ester intermediate into the corresponding amides 22-27.
O-protected ethyl 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate 11 was
transformed into its hydrazide 13, acyl azide 14, and amide 15 derivatives.
INTRODUCTION
Numerous reactions resulting in the formation of the imidazo[1,2-a]pyridine ring system have been
reported. The majority of imidazo[1,2-a]pyridines have been prepared by the reaction of a variety of
2-aminopyridines with α-halocarbonyl compounds, usually a ketone or aldehyde. Other methods include
cyclizations of 2-aminopyridines with α-dioxo compounds, including α-oxocarboxylic acids derivatives,
1,5-dipolar cyclization, and a number of other reactions which either appear to lack generality for this
ring systems, or in which only poor yields have been obtained.1,2,3 Recently, a regioselective synthesis of
substituted imidazonaphthyridines, azacarbolines and cyclazines4 and vinyl substituted imidazo-
[1,2-a]pyridines5 have been reported.
Imidazo[1,2-a]pyridine system has been extensively investigated mainly because of important biological
applications, such as antibacterial,6 antifungal,7 antiviral,8 cardiotonic,9 acetylcholinesterase inhibitors,10
DNA binding ligands targeting drug-resistant bacteria,11 and phosphodiesterase 5 inhibiting activity.12

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Mur ligases play an essential role in the intracellular biosynthesis of bacterial peptidoglycan, the main
component of the bacterial cell wall.13 The critical biological function as well as an active site amenable
for small molecule inhibition as revealed by crystallographic structures14 make Mur ligases an attractive
target for the discovery of novel antibacterial agents.14,15 In this paper, we report the synthesis of
8-hydroxyimidazo[1,2-a]pyridine-2-carboxylic acid derivatives as potential inhibitors of Mur ligases.
RESULTS AND DISCUSSION
The starting compounds 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylic acid (4) and ethyl
8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate (6) were prepared in 39% and 38% yield, respectively,
by cyclocondensation of 2-aminopyridin-3-ol (1) with bromopyruvic acid (2) and ethyl bromopyruvate
(3), respectively.11 The formation of compound 6 proceeds via the intermediate 5, which was isolated
when the cyclization of 1 with ethyl bromopyruvate (3) was carried out in 1,2-dimethoxyethane at room
temperature. Treatment of intermediate 5 in ethanol under microwave irradiation at 120 °C gave
cyclocondensation product 6. Attempted formation of methyl ester of 4, compound 8, with excess of
diazomethane (7) performed in different solvents (ethanol, CH2Cl2, Et2O) failed completely probably due
to the zwitterionic nature of compound 4. The unreacted starting compound 4 was successfully recovered
(Scheme 1).
CO2Et
CO2H
OH
OH
OH
Br
Br
N
NH2
N
2
3
O
O
CO2Et
CO2H
N
N
N
MeOH, rt
THF, ∆
6
1
4
CO2Et
CH2N2
Br
EtOH, MW, 300 W
7
3
O
120 oC, 30 min, 3-5 bar
1,2-dimethoxyethane, rt
OH
OH
H
N
N
OH
CO2Et
CO2Me
N
N
Br
5
8
Scheme 1. Synthesis of starting compounds 4 and 6
Next, synthesis of the corresponding hydrazide from ester 6 was attempted. Reaction of 6 with two
equivalents of hydrazine monohydrate in ethanol at room temperature gave hydrazinium salt 9 due to the

HETEROCYCLES, Vol. 75, No. 6, 2008
1357
acidic nature of hydroxy group in position 8. Reactions of 6 with large excess of hydrazine monohydrate
at room temperature gave again hydrazinium salt 9, whereas the same reaction at elevated temperature led
to the inseparable mixture of products. In order to prevent the formation of undesired hydrazinium salt 9
and other similar salts, the 8-hydroxy group was protected. Treatment of 6 with tert-butyldimethylsilyl
chloride in DMF in the presence of imidazole gave TBDMS-protected compound 10,16 while Cs2CO3
catalyzed reaction of 6 with benzylbromide in THF furnished benzyl protected compound 11.17
Alternatively, cyclization of O-benzylated 2-aminopyridin-3-ol 12, prepared from 1 following the
modiefied literature procedure,18 with ethyl bromopyruvate (3) gave 11 in 27% overall yield. Compound
11 prepared via the sequence 1→6→11 was obtained in 21% overall yield. Reaction of compound 10
with basic hydrazine monohydrate in THF induced the TBDMS deprotection and formation of the
undesired hydrazinium salt 9. On the other hand, treatment of 11 with a large excess of hydrazine
monohydrate in refluxing THF yielded the desired hydrazide 13.19 Diazotization of hydrazide 13 gave
acyl azide 14.4 Finally, preparation of the amide 15 was undertaken. Reactions of 11 in liquid ammonia,
CHCl3/NH3(g), and ethanol/NH3(g) failed to give the desired product 15. Reaction of 11 in the mixture of
NH4OH (25% aq)/THF at room temperature for several days gave 15 in 28% conversion. On the other
hand, the same reaction in an avtoclave at elevated temperature (90 °C) gave amide 15 in full conversion
(Scheme 2).
Hydroxy acid 4 was used as the starting compound in the coupling reactions with amine 16 and amino
acid derivatives 17-21 to form the corresponding amidation products. Coupling of acid 4 with
2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) as activating agent failed to give the desired
amides. On the other hand, activation of 4 with bis(pentafluorophenyl) carbonate (BPC) in the presence of
Et3N followed by the addition of amine 16 or amino acid derivatives 17-21 gave the corresponding
amides 22-27.20 Using the BPC activation for the coupling of 4 with different heteroaromatic amines
failed completely. Hydrolysis of esters 23-25 with NaOH in a mixture of MeOH/H2O proceeded
smoothly to the acids 28-30, respectively (Scheme 3, Table 1).21
STRUCTURE DETERMINATION
The structures of compounds 4-6, 9-11, 13-15, 22-27, and 28-30 were determined by spectroscopic
1
13
methods (IR, H and C NMR, NOESY spectroscopy, MS) and by elemental analyses for C, H, and N.
Compounds 4-6, 9, 14, 22, 23, 27, 28, and 30 were not prepared in analytically pure form. Identities of
compounds 4, 6, 9, 14, 22, 23, 27, 28, and 30 were confirmed by 13C NMR and/or EI–HRMS.
Compounds 5 and 9 were characterized only by 1H NMR.

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HETEROCYCLES, Vol. 75, No. 6, 2008
Ph
H3N
O
NH2
N
O
NH2NH2xH2O
N
THF, ∆
CONH2
CO2Et
N
N
15
9
NH4OH (25%, aq.)
THF, 90oC
NH2NH2xH2O
EtOH, rt
autoclave
Ph
Si
O
OH
O
TBDMSCl
imidazole
DMF, rt
BnBr, Cs2CO3
THF, rt
N
N
N
CO2Et
CO2Et
CO2Et
N
N
N
11
6
10
NH2NH2xH2O
THF, ∆
Ph
Ph
CO2Et
O
O
Br
NaNO2
HCl, H2O
N
N
3
O
CONHNH2
CON3
EtOH, ∆
N
N
13
14
Ph
N
(n-Bu)4NBr
NaOH/H2O
BnCl
O
OH
NH2
NH2
CH2Cl2
N
12
1
Scheme 2. Transformations of compound 6
X-Ray structure analysis for compound 15
Single crystal X-ray diffraction data of compound 15 were collected at room temperature on a Nonius
Kappa CCD diffractometer using the Nonius Collect Software.22 DENZO and SCALEPACK23 were used
for indexing and scaling of the data and the structure was solved by means of SIR97.24 Refinement was
done using Xtal3.425 program package. Crystal structure was refined on F values using the full-matrix
least-squares procedure.

HETEROCYCLES, Vol. 75, No. 6, 2008
1359
OH
OH
BPC, Et3N, DMF, rt
O
N
N
N
R-NH2xHCl 16-21
CO2H
N
N
HN R
4
22-27
OH
OH
1) NaOH, MeOH
O
O
N
H2O, rt
2) HCl, H20, -5oC
CO2Me
R1
CO2H
R1
N
N
HN
HN
23-25
28-30
Scheme 3. Synthesis of coupling products 22-27 and methyl ester hydrolysis products 28-30
Table 1. Selected experimental data for compounds 22-30
Reaction
R
R1
Yield (%)
42
4→22
4→23
CO2Me
HN
CO2Me
4→24
4→25
48
40
OH
CO2Me
4→26
4→27
40
27
CN
CONH2
23→28
75
N
H
24→29
25→30
53
63
OH
H

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HETEROCYCLES, Vol. 75, No. 6, 2008
The non-hydrogen atoms were refined anisotropically, while the positions of hydrogen atoms were
geometrically calculated and their positional and isotropic atomic displacement parameters were not
refined. Absorption correction was not necessary. Regina26 weighting scheme was used. ORTEP-III27
drawings of the content of asymmetric units of amide 15 showing the atom-labeling scheme is presented
in Figure 1.
Crystallographic data (excluding structure factors) for the structure in this paper has been deposited with
the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 670122.
Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK [fax: +44(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk.
Figure 1. The asymmetric unit of compound 15. Ellipsoids are plotted at 50% probability level. H atoms
are drawn as circles of arbitrary radii
EXPERIMENTAL
1
Melting points were determined on a Kofler micro hot stage. The H NMR spectra were obtained on a
Bruker Avance DPX 300 at 300 MHz for 1H and 75.5 MHz for 13C nucleus, using DMSO–d6 and CDCl3,
with TMS as the internal standard, as solvents (δ in ppm, J in Hz). All NMR experiments were carried out

HETEROCYCLES, Vol. 75, No. 6, 2008
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at 302 K. Optical rotations were measured on a Perkin-Elmer 241MC Polarimeter. Mass spectra were
recorded on an AutoSpecQ spectrometer and Q-TOF Premier spectrometer, IR spectra on a Perkin-Elmer
Spectrum BX FTIR spectrophotometer (ν in cm-1). Microanalyses were performed on a Perkin-Elmer
Series II CHN Analyser 2400. Column chromatography (CC) was performed on silica gel (Fluka, silica
gel 60, 0.04–0.06 mm).
8-Hydroxyimidazo[1,2-a]pyridine-2-carboxylic acid (4) A suspension of 2-aminopyridin-3-ol (1) (2.2
g, 20 mmol) in anhydrous MeOH (50 mL) was treated with bromopyruvic acid (2) (3.34 mL, 20 mmol) at
rt and the resulting mixture was stirred at rt for 24 h. The resulting precipitate was collected by filtration
to give 4. 39% yield (1.39 g) of a greyish-white solid; mp >350 °C. 1H NMR (DMSO-d6) δ: 6.53 (1H, dd,
J = 0.9; 7.5 Hz, Ar); 6.78 (1H, t, J = 7.2 Hz, Ar); 8.05 (1H, dd, J = 0.9; 6.9 Hz, Ar); 8.44 (1H, s, Ar);
10.57 (1H, br s, OH). m/z (EI) = 178 (M+); m/z (HRMS) Found: 178.038000 (M+); C10H10N2O3 requires:
m/z = 178.037842. Anal. Calcd for C8H6N2O3: C, 53.94; H, 3.39; N, 15.73. Found: C, 52.73; H, 3.78; N,
13.23. νmax (KBr) 3446, 3134, 3038, 2934, 1861, 1790, 1645, 1567, 1418, 1393, 1321, 1296, 1234, 1139,
1106, 1060, 1035, 897, 828, 781, 734, 623, 577, 532 cm–1.
2-(Ethoxycarbonyl)-2,8-dihydroxy-2,3-dihydro-1H-imidazo[1,2-a]pyridin-4-ium bromide (5) A
suspension of 2-aminopyridin-3-ol (1) (0.55 g, 5 mmol) in 1,2-dimethoxyethane (25 mL) was treated with
ethyl bromopyruvate (3) (0.975 g, 5 mmol) at rt. After stirring at rt for 5-10 min the suspension
completely dissolved. The reaction mixture was stirred at rt for 18 h. The resulting precipitate was
collected by filtration, suspended in MeCN (15 mL) and stirred at rt for 15 min. The suspension was
1
collected by filtration to give 5. 34% yield (0.550 g) of a white solid; mp 138-141 °C. H NMR
(DMSO-d6) δ: 1.27 (3H, t, J = 7.2 Hz, COOEt); 4.24 (2H, q, J = 7.2 Hz, COOEt); 4.68 (1H, d, J = 14.1
Hz, 1H of CH2); 5.08 (1H, d, J = 14.1 Hz, 1H of CH2); 6.96 (1H, dd, J = 6.3; 7.8 Hz, Ar); 7.37 (1H, d, J =
7.5 Hz, Ar); 7.80 (1H, br s); 7.83 (1H, d, J = 6.6 Hz, Ar); 10.45 (1H, br s, OH); 11.50 (1H, br s). Anal.
Calcd for C10H13BrN2O4: C, 39.36; H, 4.29; N, 9.18. Found: C, 39.90; H, 4.53; N, 8.00. νmax (KBr) 3344,
3190, 3011, 2946, 1926, 1869, 1743 (C=O), 1656, 1596, 1560, 1428, 1395, 1296, 1273, 1206, 1138, 1104,
1055, 1016, 921, 808, 785, 735 cm–1.
Ethyl 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate (6)
Procedure A: A suspension of 2-(ethoxycarbonyl)-2,8-dihydroxy-2,3-dihydro-1H-imidazo[1,2-a]-
pyridin-4-ium bromide (5) (0.153 g, 0.5 mmol) in EtOH (2 mL) was irradiated in a laboratory microwave
oven (P = 300 W, T = 120 °C, P = 3–5 bar) for 30 min. Volatile components were evaporated in vacuo
and the residue was purified by CC (ethyl acetate/ethanol, 10:1). Fractions containing the product were
combined and evaporated in vacuo to give 6. 38% yield (0.040 g) of a greyish-white solid.

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Procedure B: A suspension of 2-aminopyridin-3-ol (1) (5.858 g, 53.2 mmol) in anhydrous THF (120
mL) was treated with ethyl bromopyruvate (3) (6.65 mL, 53 mmol) at rt and heated at reflux for 40 h.
Volatile components were evaporated in vacuo, CH2Cl2 (200 mL) was added to the residue and the
mixture was washed with saturated aqueous sodium bicarbonate solution (100 mL). Aqueous phase was
additionally extracted twice with CH2Cl2 (50 mL). The combined organic phases were dried over
anhydrous Na2SO4, filtered, and the filtrate was evaporated in vacuo. The residue was purified by CC
(AcOEt/petroleum ether, 3:2 for elution of nonpolar impurities followed by AcOEt for elution of the
product 6). Fractions containing the product were combined and evaporated in vacuo to give 6. 38% yield
1
(4.200 g) of a greyish-white solid; mp 100-130 °C. H NMR (DMSO-d6) δ: 1.32 (3H, t, J = 7.2 Hz,
COOEt); 4.32 (2H, q, J = 7.2 Hz, COOEt); 6.55 (1H, dd, J = 0.9; 7.5 Hz, Ar); 6.80 (1H, deg t, J = 6.6; 7.5
Hz, Ar); 8.06 (1H, dd, J = 0.9; 6.9 Hz, Ar); 8.52 (1H, s, Ar); 10.59 (1H, br s, OH). 13C NMR (DMSO-d6)
δ: 15.1, 61.0, 106.4, 115.2, 119.5, 119.7, 135.4, 140.9, 147.7, 163.6. m/z (EI) = 206 (M+); m/z (HRMS)
Found: 206.069850 (M+); C10H10N2O3 requires: m/z = 206.069142. Anal. Calcd for C10H10N2O3: C,
58.25; H, 4.89; N, 13.59. Found: C, 56.21; H, 4.79; N, 12.14. νmax (KBr) 3144, 3115, 2976, 2928, 2541,
1709 (C=O), 1550, 1489, 1475, 1451, 1401, 1384, 1340, 1298, 1256, 1239, 1177, 1137, 1113, 1094, 1030,
991, 926, 909, 869, 840, 817, 779, 758, 740, 729, 714 cm–1.
Hydrazinium 2-(ethoxycarbonyl)imidazo[1,2-a]pyridin-8-olate (9)
Procedure A: A solution of ethyl 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate (6) (0.103 g, 0.5
mmol) in anhydrous EtOH (2 mL) was treated with hydrazine monohydrate (0.049 mL, 1 mmol) and
stirred at rt for 48 h. The resulting white precipitate was collected by filtration and washed with ethanol (2
mL) and Et2O (5 mL) to give 9. 67% yield (0.080 g) of a greyish-white solid.
Procedure B: A solution of ethyl 8-(tert-butyldimethylsilyloxy)imidazo[1,2-a]pyridine-2-carboxylate
(10) (0.091 g, 0.28 mmol) in anhydrous THF (2 mL) was treated with hydrazine monohydrate (0.016 mL,
0.33 mmol) at rt and heated at reflux for 5 h. The resulting precipitate was collected by filtration and
washed with EtOH (2 mL) and Et2O (5 mL) to give 9. 43% yield (0.029 g) of a greyish-white solid.
Melting point: 157-163 °C. 1H NMR (DMSO-d6) δ: 1.32 (3H, t, J = 7.2 Hz, COOEt); 4.31 (2H, q, J = 7.2
+
Hz, COOEt); 4.51 (5H, br s, NH2NH3 ); 6.47 (1H, dd, J = 0.9; 7.5 Hz, Ar); 6.77 (1H, deg t, J = 6.9; 7.2
Hz, Ar); 7.98 (1H, dd, J = 0.9; 6.6 Hz, Ar); 8.49 (1H, s, Ar). Anal. Calcd for C10H14N4O3: C, 50.41; H,
5.92; N, 23.52. Found: C, 53.24; H, 5.44; N, 19.03. νmax (KBr) 3446, 3140, 1721 (C=O), 1552, 1525,
1490, 1399, 1387, 1318, 1305, 1226, 1176, 1130, 1030, 985, 775, 734 cm–1.
Ethyl 8-(tert-butyldimethylsilyloxy)imidazo[1,2-a]pyridine-2-carboxylate (10) A solution of ethyl
8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate (6) (0.279 g, 1.35 mmol), tert-butyldimethylsilyl
chloride (0.408 g, 2.71 mmol), and imidazole (0.368 g, 5.40 mmol) in DMF (5 mL) was stirred at rt for

HETEROCYCLES, Vol. 75, No. 6, 2008
1363
24 h. The reaction mixture was poured into water (200 mL) and extracted with petroleum ether (4x50
mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and the filtrate was
evaporated in vacuo. The residue was purified by CC (ethyl acetate/petroleum ether, 1:3). Fractions
containing the product were combined and evaporated in vacuo to give 10. 78% yield (0.251 g) of a white
solid; mp 85-90 °C. 1H NMR (CDCl3) δ: 0.33 (6H, s, 2xMe); 1.05 (9H, s, t-Bu); 1.41 (3H, t, J = 7.2 Hz,
COOEt); 4.41 (2H, q, J = 7.2 Hz, COOEt); 6.57 (1H, dd, J = 0.9; 7.2 Hz, Ar); 6.70 (1H, deg t, J = 6.9; 7.2
Hz, Ar); 7.78 (1H, dd, J = 0.9; 6.6 Hz, Ar); 8.13 (1H, s, Ar). 13C NMR (CDCl3) δ: -4.2, 14.4, 18.7, 25.9,
60.9, 111.0, 114.0, 117.8, 119.6, 136.2, 142.6, 146.4, 163.5. Anal. Calcd for C16H24N2O3Si: C, 59.97; H,
7.55; N, 8.74. Found: C, 59.81; H, 7.70; N, 8.62. νmax (KBr) 3462, 3144, 3107, 2956, 2855, 1715 (C=O),
1550, 1473, 1383, 1361, 1343, 1309, 1273, 1252, 1217, 1187, 1114, 1100, 1054, 1031, 976, 905, 839, 824,
794, 779, 757, 741, 695 cm–1.
Ethyl 8-(benzyloxy)imidazo[1,2-a]pyridine-2-carboxylate (11)
Procedure A: A mixture of ethyl 8-hydroxyimidazo[1,2-a]pyridine-2-carboxylate (6) (0.104 g, 0.5
mmol), Cs2CO3 (0.326 g, 1 mmol), and benzyl bromide (118 µl, 1 mmol) in THF (5 mL) was stirred at rt
for 24 h. Volatile components were evaporated in vacuo and the residue was suspended in CH2Cl2 (70
mL) and washed with NaHSO4 (aq sat) (50 mL) and water (50 mL). The organic phase was dried over
anhydrous Na2SO4, filtered, and the filtrate was evaporated in vacuo. The residue was purified by CC
(AcOEt/petroleum ether, 2:1). Fractions containing the product were combined and evaporated in vacuo
to give 11. The product 11 was recrystallized from the mixture of AcOEt /n-heptane. 55% yield (0.082 g)
of a white solid; mp 158-165 °C. 1H NMR (CDCl3) δ: 1.42 (3H, t, J = 7.2 Hz, COOEt); 4.45 (2H, q, J =
7.2 Hz, COOEt); 5.34 (2H, s, CH2); 6.48 (1H, br d, J = 7.2 Hz, Ar); 6.68 (1H, deg t, J = 6.9; 7.5 Hz, Ar);
7.31-7.40 (3H, m, 3H of Ph); 7.46-7.50 (2H, m, 2H of Ph); 7.74 (1H, dd, J = 0.9; 6.9 Hz, Ar); 8.15 (1H, s,
Ar). 13C NMR (CDCl3) δ: 14.4, 61.0, 70.8, 103.6, 113.8, 118.0, 119.0, 127.4, 128.1, 128.6, 135.9, 136.3,
140.2, 148.7, 163.2. m/z (EI) = 296 (M+); m/z (HRMS) Found: 296.116650 (M+); C17H16N2O3 requires:
m/z = 296.116093. Anal. Calcd for C17H16N2O3: C, 68.91; H, 5.44; N, 9.45. Found: C, 68.70; H, 5.33; N,
9.39. νmax (KBr) 3447, 3147, 3108, 1717 (C=O), 1543, 1481, 1438, 1398, 1383, 1350, 1296, 1264, 1212,
1182, 1130, 1105, 1067, 1021, 978, 791, 762, 748, 736, 701 cm–1.
Procedure B: A solution of 3-(benzyloxy)pyridin-2-amine (12) (0.400g, 2.0 mmol) in anhydrous EtOH
(10 mL) was treated with ethyl bromopyruvate (3) (0.39g, 2.0 mmol) and stirred under reflux for 2h.
Volatile components were evaporated in vacuo, the oily residue was crystallized by addition of water (20
mL), and collected by filtration to give raw product 11. The raw product 11 was dissolved in hot EtOH (3
mL) and precipitated by addition of water (20 mL). The resulting precipitate was collected by filtration
to give pure 11. 55% yield (0.326 g) of a white solid.

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3-(Benzyloxy)pyridin-2-amine (12)18 To a suspension of 2-amino-3-hydroxypyridine (2.2 g, 20 mmol)
in CH2Cl2 were added (n-Bu)4NBr (0.07 g, 0.22 mmol) and aqueous NaOH (10 mL, 40%). After a minute
of stirring, the suspension dissolved and benzyl chloride (2.9 g, 21.4 mmol) was added. The reaction
mixture was stirred for 16 h at rt. The organic phase was separated and the aqueous phase was diluted
with water (10 mL) and extracted with CH2Cl2 (3x10 mL). The combined organic phases were dried over
anhydrous Na2SO4, filtered, and the filtrate was evaporated in vacuo to give crude 12. Crude 12 was
purified by recrystallization from EtOH. 49% yield (1.963 g) of a yellow solid; mp 89-91 °C, lit.18 mp
1
97-99 °C. H NMR (CDCl3) δ: 4.70 (2H, s, NH2); 5.09 (2H, s, CH2); 6.6 (1H, dd, J = 5.1; 7.8 Hz, Ar);
6.98 (1H, dd, J = 1.2; 7.8 Hz, Ar); 7.34-7.46 (5H, m, Ph); 7.70 (1H, dd, J = 1.3; 5.1 Hz, Ar).
8-(Benzyloxy)imidazo[1,2-a]pyridine-2-carbohydrazide
(13)
A
mixture
of
ethyl
8-(benzyloxy)imidazo[1,2-a]pyridine-2-carboxylate (11) (0.297 g, 1.0 mmol), and hydrazine
monohydrate (1.5 mL) in THF (7 mL) was refluxed for 5 h. The reaction mixture was cooled to rt, Et2O
(15 mL) was added and the resulting precipitate was collected by filtration and washed with Et2O (10 mL).
The collected raw product was suspended in cooled water (50 mL, 5 °C) stirred for 10 minutes and the
suspension was collected by filtration and washed with cooled water (100 mL, 5 °C) to give 13. 78%
yield (0.220 g) of a white solid; mp 185-187 °C. 1H NMR (DMSO-d6) δ: 4.42 (2H, br s, NH2); 5.31 (2H, s,
CH2); 6.80-6.88 (2H, m, 2H of Ar); 7.34-7.47 (3H, m, 3H of Ph); 7.50-7.54 (2H, m, 2H of Ph); 8.18 (1H,
dd, J = 1.2; 6.0 Hz, Ar); 8.34 (1H, s, Ar); 9.49 (1H, br s; NH). 13C NMR (DMSO-d6) δ: 70.1, 103.9, 112.9,
115.4, 120.2, 128.2, 128.3, 128.5, 136.2, 138.1, 138.7, 147.6, 161.1. m/z (EI) = 282 (M+); m/z (HRMS)
Found: 282.112200 (M+); C15H14N4O2 requires: m/z = 282.111676. Anal. Calcd for C15H14N4O2: C,
63.82; H, 5.00; N, 19.85. Found: C, 63.67; H, 4.96; N, 19.80. νmax (KBr) 3416, 3333, 3143, 1646 (C=O),
1576, 1563, 1546, 1480, 1456, 1444, 1400, 1387, 1343, 1310, 1267, 1102, 1068, 997, 974, 941, 913, 865,
767, 760, 731, 696 cm–1.
8-(Benzyloxy)imidazo[1,2-a]pyridine-2-carbonyl
azide
(14)
To
a
suspension
of
8-(benzyloxy)imidazo[1,2-a]pyridine-2-carbohydrazide (13) (0.282 g, 1.0 mmol) in water (10 mL) was
added hydrochloric acid (37%, 0.20 mL, ~2 mmol) at rt. The resulting mixture was cooled to 0 °C and
aqueous NaNO2 (0.5 M, 5 mL, 2.5 mmol) was added slowly. The reaction mixture was stirred at 0 °C for
1.5 h. The resulting white precipitate was collected by filtration and washed with water (30 mL). The
filtrate was suspended in CH2Cl2 (150 mL) and washed with NaHCO3 (aq sat) (50 mL). The organic
phase was dried over anhydrous Na2SO4, filtered, and the filtrate was evaporated in vacuo. The residue
was dissolved in a minimal amount of CH2Cl2 and precipitated by addition of n-heptane. The resulting
precipitate was collected by filtration to give 14. 51% yield (0.150 g) of a grayish-white solid; mp
1
125-140 °C (decomposition with extrusion of N2). H NMR (DMSO-d6) δ: 5.30 (2H, s, CH2); 6.84-6.96

HETEROCYCLES, Vol. 75, No. 6, 2008
1365
(2H, m, 2H of Ar); 7.37-7.46 (3H, m, 3H of Ph); 7.50-7.54 (2H, m, 2H of Ph); 8.19 (1H, dd, J = 0.9; 6.6
Hz, Ar); 8.67 (1H, s, Ar). 13C NMR (DMSO-d6) δ: 70.1, 104.4, 114.1, 120.2, 120.3, 128.0, 128.2, 128.5,
135.1, 136.1, 140.0, 147.8, 167.6. m/z (EI) = 293 (M+); m/z (HRMS) Found: 293.091600 (M+);
C15H11N5O2 requires: m/z = 293.091275. Anal. Calcd for C15H11N5O2: C, 61.43; H, 3.78; N, 23.88.
Found: C, 61.25; H, 3.81; N, 22.90. νmax (KBr) 3448, 2158 (N3), 1693 (C=O), 1543, 1478, 1454, 1435,
1383, 1353, 1292, 1263, 1186, 1104, 1064, 1049, 976, 949, 845, 801, 781, 760, 739, 701 cm–1.
8-(Benzyloxy)imidazo[1,2-a]pyridine-2-carboxamide
(15)
A
mixture
of
ethyl
8-(benzyloxy)imidazo[1,2-a]pyridine-2-carboxylate (11) (0.593 g, 2.0 mmol), NH4OH (aq, 25%) (15 mL),
and THF (10 mL) was heated in an autoclave for 48 h. The reaction mixture was cooled to rt, the excess
NH3 and THF were evaporated on a heating plate, the residue was cooled to rt, and the resulting
precipitate was collected by filtration and washed with water (10 mL) to give 15. 80% yield (0.428 g) of a
1
white solid; mp 230-234 °C. H NMR (DMSO-d6) δ: 5.30 (2H, s, CH2); 6.79-6.88 (2H, m, 2H of Ar);
7.30 (1H, br s, 1H of NH2); 7.34-7.46 (3H, m, 3H of Ph); 7.50-7.54 (2H, m, 2H of Ph); 7.68 (1H, br s, 1H
of NH2); 8.18 (1H, dd, J = 1.2; 6.3 Hz, Ar); 8.32 (1H, s, Ar). 13C NMR (DMSO-d6) δ: 70.1, 103.7, 113.0,
115.8, 120.2, 128.2, 128.4, 128.5, 136.1, 138.5, 139.2, 147.6, 164.2. m/z (EI) = 267 (M+); m/z (HRMS)
Found: 267.101000 (M+); C15H13N3O2 requires: m/z = 267.100777. Anal. Calcd for C15H13N3O2: C,
67.40; H, 4.90; N, 15.72. Found: C, 67.38; H, 4.85; N, 15.58. νmax (KBr) 3468, 3285, 1661, 1583, 1544,
1455, 1400, 1384, 1357, 1316, 1276, 1187, 1101, 974, 918, 784, 746 cm–1.
General Procedure for Amidation of 8-Hydroxyimidazo[1,2-a]pyridine-2-carboxylic acid (4) with
BPC as the Activating Reagent.
Triethylamine (0.280 mL, 2 mmol) was added to a suspension of 8-hydroxyimidazo-
[1,2-a]pyridine-2-carboxylic acid (4) (0.356 g, 2 mmol) in anhydrous dimethylformamide (10 mL), and
the mixture was stirred at rt for 10 min. Bis(pentafluorophenyl) carbonate (BPC) (0.946 g, 2.4 mmol) was
added and the mixture was stirred at rt for 12 h. Then, amine hydrochloride 16-21 (2 mmol) and
triethylamine (0.560 ml, 4.0 mmol) was added and the mixture was stirred at rt for 12 h. Reaction mixture
was evaporated in vacuo (0.1 Torr/ 60 °C) to remove all volatile components and the residue was purified
by CC. Compounds 22-26 were prepared in this manner. In the case of compound 27, the residue was
suspended in MeOH (11 mL) and stirred at rt for 12 h. The suspension was collected by filtration, the
filtrate suspended in MeOH/CHCl3 (MeOH/CHCl3 = 10 mL/5 mL), and stirred at rt for 12 h. The
suspension was collected by filtration and washed with Et2O (15 ml) to give pure 27.
N-Benzyl-8-hydroxyimidazo[1,2-a]pyridine-2-carboxamide (22) Benzylamine hydrochloride (16)
(0.287 g); CC (first elution of nonpolar impurities with AcOEt/petroleum ether = 5:1, followed by elution

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HETEROCYCLES, Vol. 75, No. 6, 2008
1
of the product 22 with ethyl acetate); 35% yield (0.188 g) of a white solid; mp 199-202 °C. H NMR
(DMSO-d6) δ: 4.48 (2H, d, J = 6.3 Hz, CH2); 6.55 (1H, dd, J = 0.9; 7.5 Hz, Ar); 6.76 (1H, dd, J = 6.9; 7.4
Hz, Ar); 7.23-7.36 (1H, m, Ar); 8.07 (1H, dd, J = 0.9; 6.7 Hz, Ar); 8.33 (1H, s, Ar); 8.68 (1H, t, J = 6.3
13
Hz, CONH); 10.50 (1H, br s, Ar-OH). C NMR (DMSO-d6) δ: 42.1, 105.1, 113.7, 115.4, 118.7, 126.7,
127.4, 128.2, 138.6, 139.2, 139.8, 146.8, 162.2. m/z (EI) = 267 (M+); m/z (HRMS) Found: 267.101230
(M+); C15H13N3O2 requires: m/z = 267.100777. Anal. Calcd for C15H13N3O2: C, 67.40; H, 4.90; N, 15.72.
Found: C, 67.11; H, 4.76; N, 15.50. νmax (KBr) 3420, 3026, 2926, 1651 (C=O), 1609, 1575, 1545, 1493,
1447, 1401, 1364, 1346, 1298, 1248, 1232, 1055, 890, 726 cm–1.
(S)-Methyl 2-(8-hydroxyimidazo[1,2-a]pyridine-2-carboxamido)-3-(1H-indol-3-yl)propanoate (23)
L-Tryptophan methyl ester hydrochloride (17) (0.510 g); CC (AcOEt); 42% yield (0.320 g) of a
yellowish-white solid; mp 108-115 °C; [α]58918 +183.9 (c 0.17, CHCl3). 1H NMR (DMSO-d6) δ: 3.34 (2H,
CH2); 3.65 (3H, s, COOMe); 4.84-4.91 (1H, m, CH); 6.55 (1H, dd, J = 0.9; 7.5 Hz, Ar); 6.75-6.80 (1H, m,
Ar); 6.93-6.98 (1H, m, Ar); 7.03-7.08 (1H, m, Ar); 7.14 (1H, d, J = 2.4 Hz, Ar); 7.33 (1H, d, J = 7.8 Hz,
Ar); 7.50 (1H, d, J = 7.8 Hz, Ar); 8.06 (1H, dd, J = 0.9; 6.6 Hz, Ar); 8.17 (1H, d, J = 8.1 Hz, CONH);
13
8.34 (1H, s, Ar); 10.53 (1H, br s, Ar-OH); 10.87 (1H, br s, NH). C NMR (CDCl3) δ: 27.2, 52.2, 52.7,
107.2, 108.8, 111.5, 114.8, 116.3, 118.0, 118.6, 119.2, 122.0, 122.4, 127.1, 136.3, 137.7, 139.7, 145.6,
162.4, 172.9. m/z (EI) = 378 (M+); m/z (HRMS) Found: 378.133520 (M+); C20H18N4O4 requires: m/z =
378.132805. Anal. Calcd for C20H18N4O4: C, 63.48; H, 4.79; N, 14.81. Found: C, 60.71; H, 4.80; N, 13.61.
νmax (KBr) 3387, 1739 (C=O), 1648 (C=O), 1572, 1518, 1483, 1457, 1438, 1400, 1356, 1346, 1295, 1215,
1179, 1091, 739 cm–1.
(S)-Methyl
3-hydroxy-2-(8-hydroxyimidazo[1,2-a]pyridine-2-carboxamido)propanoate
(24)
L-Serine methyl ester hydrochloride (18) (0.311 g); CC (AcOEt/MeOH = 20:1); 48% yield (0.272 g) of a
18
1
pink-orange solid; mp 210-215 °C; [α]589 +40.7 (c 0.16, CHCl3/MeOH = 5:1). H NMR (DMSO-d6) δ:
3.68 (3H, s, COOMe); 3.75 (1H, br d, J = 11.4 Hz, Hα of CH2); 3.91 (1H, br d, J = 10.8 Hz, Hβ of CH2);
4.60-4.65 (1H, m, CH); 5.33 (1H, br s, Ser-OH); 6.58 (1H, d, J = 7.5 Hz, Ar); 6.79 (1H, deg t, J = 6.9; 7.2
Hz, Ar); 8.08 (1H, d, J = 6.6 Hz, Ar); 8.18 (1H, d, J = 8.4 Hz, CONH); 8.37 (1H, s, Ar); 10.57 (1H, br s,
Ar-OH). 13C NMR (DMSO-d6) δ: 52.1, 54.1, 61.5, 105.4, 113.9, 115.7, 118.7, 137.8, 139.3, 146.8, 162.0,
171.0. m/z (EI) = 279 (M+); m/z (HRMS) Found: 279.086250 (M+); C12H13N3O5 requires: m/z =
279.085521. Anal. Calcd for C12H13N3O5: C, 51.61; H, 4.69; N, 15.05. Found: C, 51.34; H, 4.80; N, 14.82.
ν
max (KBr) 3346, 3159, 3128, 3089, 1744 (C=O), 1645 (C=O), 1576, 1557, 1535, 1491, 1464, 1438, 1403,
1330, 1301, 1248, 1233, 1213, 1184, 1154, 1097, 1051, 1042, 1002, 732 cm–1.

HETEROCYCLES, Vol. 75, No. 6, 2008
1367
Methyl 2-(8-hydroxyimidazo[1,2-a]pyridine-2-carboxamido)acetate (25) Glycine methyl ester
1
hydrochloride (19) (0.251 g); CC (AcOEt); 40% yield (0.200 g) of a white solid; mp 175-178 °C. H
NMR (DMSO-d6) δ: 3.66 (3H, s, COOMe); 4.06 (2H, d, J = 6.3 Hz, CH2); 6.57 (1H, dd, J = 0.9; 7.5 Hz,
Ar); 6.77 (1H, deg t, J = 6.6; 7.5 Hz, Ar); 8.07 (1H, dd, J = 0.9; 6.6 Hz, Ar); 8.34 (1H, s, Ar); 8.54 (1H, br
t, J = 6.0 Hz, CONH); 10.55 (1H, br s, Ar-OH). 13C NMR (DMSO-d6) δ: 40.6, 51.7, 105.2, 113.7, 115.5,
118.8, 138.1, 139.3, 146.8, 162.6, 170.4. m/z (EI) = 249 (M+); m/z (HRMS) Found: 249.075660 (M+);
C11H11N3O4 requires: m/z = 249.074956. Anal. Calcd for C11H11N3O4: C, 53.01; H, 4.45; N, 16.86.
Found: C, 52.81; H, 4.57; N, 16.65. νmax (KBr) 3379, 3132, 1725 (C=O), 1650 (C=O), 1581, 1556, 1527,
1493, 1465, 1434, 1422, 1405, 1344, 1295, 1267, 1249, 1238, 1181, 1091, 1051, 1030, 1000, 954, 893,
852, 772, 735 cm–1.
N-(Cyanomethyl)-8-hydroxyimidazo[1,2-a]pyridine-2-carboxamide
(26)
Aminoacetonitrile
hydrochloride (20) (0.185 g); CC (AcOEt); 40% yield (0.176 g) of a greyish-white solid; mp 250-255 °C.
1H NMR (DMSO-d6) δ: 4.27 (2H, d, J = 6.0 Hz, CH2); 6.58 (1H, d, J = 7.5 Hz, Ar); 6.79 (1H, deg t, J =
6.9; 7.2 Hz, Ar); 8.08 (1H, d, J = 6.6 Hz, Ar); 8.41 (1H, s, Ar); 8.98 (1H, br deg t, J = 5.4; 5.7 Hz,
CONH); 10.60 (1H, br s, Ar-OH). m/z (EI) = 216 (M+); m/z (HRMS) Found: 216.065320 (M+);
C10H8N4O2 requires: m/z = 216.064726. Anal. Calcd for C10H8N4O2: C, 55.55; H, 3.73; N, 25.91. Found:
C, 55.49; H, 3.75; N, 25.61. νmax (KBr) 3377, 3161, 3121, 1677 (C=O), 1578, 1560, 1517, 1485, 1400,
1387, 1378, 1301, 1280, 1236, 1213, 956, 773, 735 cm–1.
N-(2-Amino-2-oxoethyl)-8-hydroxyimidazo[1,2-a]pyridine-2-carboxamide
(27)
Glycinamide
hydrochloride (21) (0.221 g); 27% yield (0.130 g) of a grey solid; mp 230-235 °C. 1H NMR (DMSO-d6)
δ: 3.90 (2H, d, J = 5.4 Hz, CH2); 6.56 (1H, dd, J = 0.9; 7.5 Hz, Ar); 6.77 (1H, deg t, J = 6.9; 7.2 Hz, Ar);
7.12 (1H, br s, 1H of CONH2); 7.45 (1H, br s, 1H of CONH2); 8.07 (1H, dd, J = 0.9; 6.6 Hz, Ar); 8.17
(1H, br t, J = 5.4 Hz, CONH); 8.33 (1H, s, Ar); 10.57 (1H, br s, Ar-OH). 1H NMR (DMSO-d6 + D2O) δ:
3.93 (2H, s, CH2); 6.62 (1H, d, J = 7.5 Hz, Ar); 6.82 (1H, deg t, J = 6.9; 7.2 Hz, Ar); 8.10 (1H, d, J = 6.6
Hz, Ar); 8.36 (1H, s, Ar). m/z (EI) = 234 (M+); m/z (HRMS) Found: 234.075860 (M+); C10H10N4O3
requires: m/z = 234.075290. Anal. Calcd for C10H10N4O3: C, 51.28; H, 4.30; N, 23.92. Found: C, 49.36; H,
4.46; N, 24.19. νmax (KBr) 3373, 3191, 1670 (C=O), 1649 (C=O), 1640, 1577, 1556, 1523, 1487, 1455,
1429, 1404, 1297, 1267, 1247, 1094, 773, 737 cm–1.
General Procedure for the Methyl Ester Hydrolysis of Compounds 23-25.
NaOH (1 M in H2O, 1.5 mL) was added to a suspension of compound 23-25 (0.65 mmol) in MeOH (3
mL) and the resulting solution was stirred at rt for 24 h. The reaction mixture was cooled to -5 °C
followed by addition of HCl (1 M in H2O, 1.5 mL) and H2O (2 mL, 4 °C). The reaction mixture was

1368
HETEROCYCLES, Vol. 75, No. 6, 2008
stirred at -5 °C for 1 h. The resulting precipitate was collected by filtration and washed with H2O (5 mL,
4 °C). Compounds 28-30 were prepared in this manner.
(S)-2-(8-Hydroxyimidazo[1,2-a]pyridine-2-carboxamido)-3-(1H-indol-3-yl)propanoic acid (28)
21
Prepared from compound 23 (0.246 g); 75% yield (0.178 g) of a white solid; mp 178-185 °C; [α]589
+20.2 (c 0.25, DMSO). 1H NMR (DMSO-d6) δ: 3.31-3.34 (2H,m, CH2); 4.78-4.85 (1H, m, CH); 6.59 (1H,
d, J = 6.9 Hz, Ar); 6.80 (1H, t, J = 6.9; 7.2 Hz, Ar); 6.91-6.96 (1H, m, Ar); 7.02-7.07 (1H, m, Ar); 7.12
(1H, d, J = 2.4 Hz, Ar); 7.32 (1H, d, J = 7.8 Hz, Ar); 7.53 (1H, d, J = 8.1 Hz, Ar); 8.07-8.10 (2H, m,
CONH, 1H of Ar); 8.37 (1H, s, Ar); 10.61 (1H, br s, Ar-OH); 10.86 (1H, br s, NH); 12.97 (1H, br s,
COOH). 13C NMR (DMSO-d6) δ: 27.3, 52.5, 106.1, 109.4, 111.4, 114.2, 115.7, 118.3, 118.5, 118.8,
121.0, 123.7, 127.4, 136.1, 137.3, 138.9, 146.5, 161.5, 173.2. m/z (EI) = 364 (M+); m/z (HRMS) Found:
364.118000 (M+); C19H16N4O4 requires: m/z = 364.117155. Anal. Calcd for C19H16N4O4: C, 62.63; H,
4.43; N, 15.38. Found: C, 59.19; H, 4.60; N, 14.40. νmax (KBr) 3406, 3125, 1653, 1577, 1520, 1488, 1458,
1400, 1340, 1300, 1230, 1094, 734 cm–1.
(S)-3-Hydroxy-2-(8-hydroxyimidazo[1,2-a]pyridine-2-carboxamido)propanoic acid (29) Prepared
21
from compound 24 (0.182 g); 53% yield (0.092 g) of a brownish-white solid; mp 255-258 °C; [α]589
+37.8 (c 0.16, DMSO). 1H NMR (DMSO-d6) δ: 3.75 (1H, dd, J = 3.4; 10.9 Hz, Hα of CH2); 3.91 (1H, dd,
J = 3.8; 10.9 Hz, Hβ of CH2); 4.50-4.55 (1H, m, CH); 5.27 (1H, br s, OH); 6.56-6.59 (1H, m, Ar); 6.79
(1H, deg t, J = 6.8; 7.5 Hz, Ar); 8.06-8.12 (2H, m, CONH, 1H of Ar); 8.37 (1H, s, Ar); 10.62 (1H, br s,
Ar-OH); 12.71 (1H, br s, COOH). 13C NMR (DMSO-d6) δ: 54.1, 61.6, 105.5, 113.9, 115.6, 118.8, 138.0,
139.3, 146.7, 161.9, 172.0. m/z (EI) = 266 (MH+); m/z (HRMS) Found: 266.0772 (MH+); C11H12N3O5
requires: m/z = 266.0777. Anal. Calcd for C11H11N3O5: C, 49.81; H, 4.18; N, 15.84. Found: C, 49.75; H,
4.39; N, 15.55. νmax (KBr) 3437, 3312, 3118, 2452, 1630, 1578, 1508, 1463, 1430, 1338, 1293, 1247,
1231, 1112, 1056, 1041, 953, 788, 739 cm–1.
2-(8-Hydroxyimidazo[1,2-a]pyridine-2-carboxamido)acetic acid (30) Prepared from compound 25
1
(0.162 g); 63% yield (0.097 g) of a brownish-white solid; mp 293-300 °C. H NMR (DMSO-d6) δ: 3.98
(2H, d, J = 5.7 Hz, CH2); 6.56 (1H, dd, J = 0.9; 7.5 Hz, Ar); 6.77 (1H, deg t, J = 6.6; 7.5 Hz, Ar); 8.07
(1H, dd, J = 0.9; 6.6 Hz, Ar); 8.34 (1H, s, Ar); 8.35 (1H, br t, J = 6.0 Hz, CONH); 10.55 (1H, br s,
Ar-OH); 12.62 (1H, br s, COOH). 13C NMR (DMSO-d6) δ: 40.7, 105.3, 113.8, 115.5, 118.8, 138.2, 139.3,
146.8, 162.5, 171.3. m/z (EI) = 236 (MH+); m/z (HRMS) Found: 236.0660 (MH+); C10H10N3O4 requires:
m/z = 236.0671. Anal. Calcd for C10H9N3O4: C, 51.07; H, 3.86; N, 17.87. Found: C, 49.40; H, 4.45; N,
17.15. νmax (KBr) 3481, 3316, 3118, 2451, 1633, 1578, 1508, 1451, 1423, 1338, 1306, 1286, 1237, 1094,
946, 838, 789, 739 cm–1.

HETEROCYCLES, Vol. 75, No. 6, 2008
1369
ACKNOWLEDGEMENTS
This work was supported by the funds from Lek Pharmaceuticals d.d., the European Union FP6
Integrated Project EUR-INTAFAR (Project n° LSHM-CT-2004-512138) under the thematic priority Life
Sciences, Genomics and Biotechnology for Health.
The financial support from the Ministry of Higher Education, Science and Technology, Slovenia through
grants P0-0502-0103, P1-0179, and J1-6689-0103-04 is gratefully acknowledged.
Crystallographic data were collected on the Kappa CCD Nonius diffractometer in the Laboratory of
Inorganic Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia.
We acknowledge with thanks the financial contribution of the Ministry of Science and Technology,
Republic of Slovenia through grant Packet X-2000 and PS-511-102, which thus made the purchase of the
apparatus possible.
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