Application of Nickel Complexes with 1,3-Dicarbonyl Compounds for Synthesis of Fused 4-Aminopyridine-Based Systems

Article abstract of DOI:10.1134/S1070363220080101

Abstract: A potential of using nickel complexes with 1,3-dicarbonyl compounds for the transformation of heterocyclic aminonitriles into fused systems with a 4-aminopyridine core was evaluated. A possibility of introducing acidophobic groups into the molecules of fused compounds was shown.

Full text of DOI:10.1134/S1070363220080101

ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 8, pp. 1439–1446. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Obshchei Khimii, 2020, Vol. 90, No. 8, pp. 1231–1239.
Application of Nickel Complexes with 1,3-Dicarbonyl Compounds
for Synthesis of Fused 4-Aminopyridine-Based Systems
R. N. Vydzhaka, S. Ya. Panchishina, and V. S. Brovaretsa,*
a V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine,
Kiev, 02094 Ukraine
*e-mail: brovarets@bpci.kiev.ua
Received March 27, 2020; revised March 27, 2020; accepted April 10, 2020
Abstract—A potential of using nickel complexes with 1,3-dicarbonyl compounds for the transformation of het-
erocyclic aminonitriles into fused systems with a 4-aminopyridine core was evaluated. Apossibility of introducing
acidophobic groups into the molecules of fused compounds was shown.
Keywords: nickel complexes with 1,3-dicarbonyl compounds, oxadiazolo[3,4-b]pyridines, triazolo[4,5-b]-
pyridines, pyrazolo[3,4-b]pyridines
DOI: 10.1134/S1070363220080101
Over the past decades, much attention has been
given to the development and improvement of synthetic
approaches to the preparation of azoloazines. Among
such fused nitrogen-containing heterocycles, an important
place belongs to 4-aminopyridine derivatives, which are
promising scaffolds for the search for biologically active
compounds.
restrictions are imposed on the presence functional groups
in the molecules of the starting reagents;
– addition of carbonyl compounds to the nitrile group
of cyanoazoles in the presence of bases with further
transformation of intermediate products into azolopyridine
derivatives [20–24]. Alkali metal alcoholates, potassium
carbonate, amines or complexes of 1,3-dicarbonyl
compounds with transition metals are used as bases.
The literature data include the following approaches
to the synthesis of such compounds:
On the other hand, nickel acetylacetonate has been
known to add cyanogen [25] and other electrophilic
heterocyclic nitriles under mild conditions [24]. It is
also an effective catalyst for the preparation of Michael
adducts of acetylacetone with unsaturated compounds.
The yields of the final products are always significantly
higher than in traditional syntheses using strong bases
[26].
– reduction of nitro derivatives of azolopyridines,
however, this method is practically not used due to the
low availability of nitro derivatives [1–4];
– substitution of a halogen atom or alkoxyl group for
an amino group; the main disadvantage of this approach
is low availability of the corresponding halo- and
alkoxyazolopyridines [5–7];
The aim of this work is to evaluate the possibility of
using nickel complexes with 1,3-dicarbonyl compounds
for annulation of the pyridine ring to azole systems,
as well as to compare the results obtained with the
known data on the construction of such fused systems.
The following compounds were used as the model:
4-amino-1,2,5-oxadiazole-3-carbonitrile (the reaction
with acetylacetone nickel complex has been described in
[24]), 5-amino-1-benzyl-1H-1,2,3-triazole-4-carbonitrile
(similar in the acceptor properties of the nitrile group to
the nitrile group of oxadiazole) and 5-amino-1-phenyl-
1H-pyrazole-4-carbonitrile (annelated derivatives have
– substitution of the halogen atom with the azido group
followed by reduction to the amino group [8, 9];
– annulation of the azole fragment to the substituted
4-aminopyridine; this method is not often used, since
it requires the preparation of specifically substituted
4-aminopyridines [10–12];
– raction of heterocyclic aminonitriles with carbonyl
compounds in the presence of Lewis acids (ZnCl2,
AlCl3, SnCl4) is more often than others used to obtain
azolopyridines [13–19], however, the yield of final
products, as a rule, does not exceed 50%; significant
1439

1440
VYDZHAK et al.
Scheme 1.
Scheme 2.
been described in [17, 18], and the acceptor properties
of the nitrile group differ from those for the nitrile
group of oxadiazole), as well as nickel complexes with
acetylacetone and commercially available acetoacetic
acid esters.
addition of heterocyclic aminonitriles 2–4 directly to
nickel complexes at a 2 : 1 ratio.
The addition of oxadiazole 2 to compounds 1а–1i
occurred in methylene chloride at a temperature of 35–
40°С for 30–40 min. No addition of nickel complexes to
cyanotriazole 3 and cyanopyrazole 4 was observed. The
reaction with triazole 3 occured in boiling dichloroethane,
and in the case of pyrazole 4, the reaction was performed
upon heating in chlorobenzene at 100–110°С (Scheme 3).
Nickel complexes with 1,3-dicarbonyl compounds
werepreparedbymixingnickelchloride, thecorresponding
dicarbonyl compound, and sodium hydroxide in aqueous
ethanol (Scheme 1). The resulting precipitate was filtered
off, and dissolved in methylene chloride. The insoluble
solid was separated, the solvent was removed in vacuum,
and compounds 1а–1i were purified by crystallization
from aqueous ethanol in the hydrate form, which easily
lose water upon heating to 90–100°С in vacuum.
The ability of the nitrile group to attach nickel
complexes with 1,3-dicarbonyl compounds strongly
depends on the acceptor properties of the heterocyclic
fragment: the more pronounced are the acceptor
properties, the easier is the attachment process. The
presence of an electron-withdrawing group in the nickel
complex reduces its reactivity: the addition of compound
1i to oxadiazole 2 occurs upon reflux in dichloroethane.
The adducts of heterocyclic aminonitriles and complexes
1а–1i were not isolated in the individual state. They
were treated with acetic acid in ethanol to obtain fused
derivatives 5–7.
As described in [24], when using nickel acetylacetonate
1а as a catalyst for the addition of acetoacetic acid ethyl
ester to 4-amino-1,2,5-oxadiazole-3-carbonitrile 2, the
process proceeded rather quickly at first, but with time the
reaction slows down and stops. Therefore, it is necessary
to constantly monitor the reaction progress and add new
portions of the nickel complex 1a. After the solvent
evaporation and treatment of the reaction mixture with
acetic acid in ethanol, compounds 5а (8%) and 5c (85%)
were isolated by column chromatography (Scheme 2).
The formation of a mixture of compounds 5a and 5c is
explained by the addition of both acetoacetic ester and
acetylacetone, which is part of the nickel complex, to
the cyano group. Therefore, we decided to use nickel
complexes with the dicarbonyl compound that needs to
be reacted. To accelerate the process, we carried out the
The transformation of cyanofurazan 2 into oxa-
diazolo[3,4-b]pyridines 5b–5i proceeds rapidly. These
compounds were isolated in high yields in pure form
by crystallization. The conversion of cyanotriazole
3 to triazolo[4,5-b]pyridines 6 was accompanied by
slight resinification. Compounds 6а–6c were isolated
by crystallization; compounds 6d
, 6e, and 6g were
isolated using column chromatography on silica gel. The
synthesis of pyrazolo[3,4-b]pyridines 7 was accompanied
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APPLICATION OF NICKEL COMPLEXES WITH 1,3-DICARBONYL COMPOUNDS
1441
Scheme 3.
by significant resinification of the reaction mixture;
therefore, compounds 7а–7c can be purified only by
chromatography. This approach is convenient for the
preparation of compounds 5 and 6, while derivatives 7
are easier to obtain by reacting cyanopyrazole 4 with
dicarbonyl compounds in the presence of SnCl4, as
described in [17, 18].
of the proposed method is the strong effect of the nature
of the heterocyclic fragment on the ability of nickel
complexes to be attached to the nitrile group.
EXPERIMENTAL
IR spectra were recorded on a Vertex 70 spectrometer
from KBr pellets. 1H and 13C NMR spectra were registered
on a Bruker AVANCE DRX-500 instrument (500 and
125 MHz, respectively) from DMSO-d6 solution relative
to internal HMDS. Elemental analysis was carried out in
the Analytical Laboratory of the V.P. Kuhar Institute of
Bioorganic Chemistry and Petrochemistry of the National
Academy of Sciences of Ukraine. Melting points were
determined on a Fischer Johns apparatus.
Composition of compounds 5–7 was confirmed by
elemental analysis data, and structure was proved using
1
IR, H and 13C NMR spectroscopy. The IR spectra of
compounds 5b–5i contain absorption bands of stretching
vibrations of the C=O group, as well as stretching and
bending vibrations of the NH2 group. The IR spectra of
compounds 6 in the range of 1700–1580 cm–1 contain
three characteristic absorption bands of almost the
same intensity, as well as bands of stretching vibrations
4-Amino-1,2,5-oxadiazole-3-carbonitrile [27],
5-amino-1-benzyl-1Н-1,2,3-triazole-4-carbonitrile [28]
and 5-amino-1-phenyl-1Н-pyrazole-4-carbonitrile [29]
were obtained according to the appropriate methods.
1
of the amino group. The H and 13C NMR spectra of
the synthesized compounds contain signals of all the
hydrogen and carbon atoms, respectively.
General procedure for the preparation of nickel
complexes with 1,3-dicarbonyl compounds 1a–1i.
To a solution of 4.76 g (0.02 mol) of nickel(II) chloride
hexahydrate in 50 mL of water were added 50 mL of
ethanol and 0.05 mol of a dicarbonyl compound. Next,
a solution of 1.6 g (0.04 mol) of sodium hydroxide in
20 mL of water was added With stirring and cooling to
The proposed approach for the annulation of
4-aminopyridine moiety to heterocyclic aminonitriles can
be an alternative in comparison with the existing synthetic
methods. Advantages of this method are simplicity and
possibility of introducing labile functional groups into
the molecules of fused systems. One of the disadvantages
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VYDZHAK et al.
0–5°С over 15 min. The mixture was stirred for 2 h, and
then the precipitate was filtered off, washed with water,
dried in air, and then dissolved in methylene chloride. The
resulting solution was filtered and evaporated in vacuum.
The residue was crystallized from aqueous ethanol, and
then dried in vacuum (1 mmHg) at 90–100°С for 2 h. The
characteristics of compound 1а are given in [24].
with a methanol gradient from 5 to 8%). Compounds 5а
(0.77 g, 8%) and 5c (9.44 g, 85%) were isolated.
1-(7-Amino-5-methyl[1,2,5]oxadiazolo[3,4-b]-
pyridin-6-yl)ethanone (5a). Pale yellow crystals, mp
194–196°С (ethanol) (mp 197–198°С [24]). IR spectrum,
ν, cm–1: 3277, 3142, 1650, 1622, 1597, 1541, 1508, 1449,
1
1378, 1358, 1308, 1258, 1189, 1088, 1030. Н NMR
Complex 1b. Yield 4.92 g (85.1%). Found, %: С
41.05; Н 4.82. C10H14NiO6. Calculated, %: С 41.57; Н
4.88.
spectrum, δ, ppm: 2.49 s (3Н, СН3), 2.55 s (3Н, СН3),
8.30 br. s (2Н, NH2). Found, %: C 49.75; Н 4.12; N 28.82.
C8H8N4O2. Calculated, %: C 50.00; Н 4.20; N 29.15.
Complex 1c. Yield 5.11 g (80.6%). Found, %: С
44.96; Н 5.83. C12H18NiO6. Calculated, %: С 45.47; Н
5.72.
Ethyl 7-amino-5-methyl[1,2,5]oxadiazolo[3,4-b]-
pyridine-6-carboxylate (5c). Colorless crystals, mp
178–179°С (ethanol) (mp 179–180°С [24]). IR spectrum,
ν, cm–1: 3349, 3270, 3174, 2991, 1677, 1623, 1515, 1443,
Complex 1d. Yield 7.27 g (82.4%). Found, %: С
59.37; Н 5.11. C22H22NiO6. Calculated, %: С 59.90; Н
5.03.
1
1381, 1361, 1276, 1203, 1098, 1078, 1030, 1004. Н
NMR spectrum, δ, ppm: 1.33 t (3Н, ОСН2СН3, 3JHH
7.1 Hz), 2.61 s (3Н, СН3), 4.35 q (2Н, ОСН2СН3, 3JHH
=
=
Complex 1e. Yield 5.08 g (68.1%). Found, %: С
51.09; Н 6.93. C16H26NiO6. Calculated, %: С 51.51; Н
7.02.
7.1 Hz), 8.57 br. s (2Н, NH2). Found, %: C 48.90; Н
4.77; N 24.97. C9H10N4O3. Calculated, %: C 48.65; Н
4.54; N 25.21.
Complex 1f. Yield 4.96 g (65.8%). Found, %: С 44.16;
Н 5.72. C14H22NiO8. Calculated, %: С 44.60; Н 5.88.
Compound 5c was also obtained from 0.55 g
(0.005 mol) of compound 2 and 0.79 g (0.0025 mol) of
nickel complex 1c. Yield 1.03 g (92.8%). The mixing
test of the samples of compound 5c obtained by different
methods did not give melting point depression. Their
spectral data are identical.
Complex 1g. Yield 5.32 g (77.1%). Found, %: С
48.35; Н 6.39. C14H22NiO6. Calculated, %: С 48.74; Н
6.43.
Complex 1h. Yield 5.24 g (71.0%). Found, %: С
51.79; Н 5.94. C16H22NiO6. Calculated, %: С 52.07; Н
6.01.
Methyl 7-amino-5-methyl[1,2,5]oxadiazolo[3,4-b]-
pyridine-6-carboxylate (5b). To a solution of 1.1 g
(0.01 mol) of compound 2 in 50 mL of methylylene
chloride were added 1.44 g (0.005 mol) of nickel complex
1b and two drops of acetoacetic acid methyl ester. The
mixture was stirred for 30 min at 35–40°С, then the
solvent was evaporated in vacuum. To the residue were
added 20 mL of ethanol and 3 mL of acetic acid. The
resulting mixture was boiled for 1 h, then ethanol was
partially evaporated in vacuum, and 30 mL of water was
added to the residue. The precipitate was filtered off,
washed with water, and compound 5b was purified by
crystallization. Yield 1.91 g (91.8%), mp 193–194°С
(ethanol–water, 2 : 1). IR spectrum, ν, cm–1: 3349, 3270,
3174, 2991, 1677, 1623, 1515, 1443, 1381, 1361, 1276,
Complex 1i. Yield 5.09 g (65.4%). Found, %: С 36.59;
Н 3.69. C12H14F4NiO6. Calculated, %: С 37.06; Н 3.63.
1-(7-Amino-5-methyl[1,2,5]oxadiazolo[3,4-b]-
pyridin-6-yl)ethanone (5а) and ethyl 7-amino-5-
methyl[1,2, 5]oxadiazolo[3,4-b]pyridine-6-carboxylate
(5c). To a solution of 5.5 g (0.05 mol) of compound 2
in 150 mL of methylene chloride were added 9.75 g
(0.075 mol) of ethyl acetoacetate and 0.39 g (0.0015 mol)
of nickel complex 1а. The mixture was stirred at 35–40°С.
After 6 h, 0.13 g of complex 1а was added, and after 4 h,
0.13 g of complex 1а was added, and stirring was continued
for another 12 h. The solvent was evaporated in vacuum,
150 mL of ethanol and 10 mL of acetic acid were added to
the residue. The resulting mixture was refluxed for 2 h, and
then the solvent was evaporated in vacuum. 50 mLof water
was added to the residue, the precipitate was filtered off and
washed with water. The resulting mixture of the reaction
products was separated by column chromatography on
silica gel (eluent—chloroform–ethyl acetate, 75 : 15
1
1203, 1098, 1078, 1030, 1004. Н NMR spectrum, δ,
ppm: 2.59 s (3Н, СН3), 3.86 s (3Н, ОСН3), 8.67 br. s (2Н,
NH2). 13С NMR spectrum, δС, ppm: 28.0, 52.5, 102.6,
140.3, 145.9, 158.4, 167.3, 170.2. Found, %: C 46.31;
Н 3.82; N 27.10. C8H8N4O3. Calculated, %: С46.16; Н
3.87; N 26.91.
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APPLICATION OF NICKEL COMPLEXES WITH 1,3-DICARBONYL COMPOUNDS
1443
7.4 Hz), 4.36 q (2Н, ОСН2СН3, 3JHH = 7.1 Hz), 8.45 br. s
Benzyl 7-amino-5-methyl[1,2,5]oxadiazolo[3,4-b]-
pyridine-6-carboxylate (5d) was prepared similarly
from 0.55 g (0.005 mol) of compound 2 and 1.11 g
(0.0025 mol) of nickel complex 1d. Yield 1.25 g (88%),
mp 159–161°С (ethanol–water, 3 : 1). IR spectrum, ν,
cm–1: 3348, 3270, 3178, 3035, 1679, 1626, 1601, 1513,
13
(2Н, NH2). С NMR spectrum, δС, ppm: 13.1, 14.3, 32.3,
61.6, 103.4, 140.2, 145.4, 158.7, 167.0, 173.9. Found, %:
C 51.05; Н 5.22; N 23.53. C10H12N4O4. Calculated, %:
C 50.84; Н 5.12; N 23.72.
Ethyl 7-amino-5-cyclopropyl[1,2,5]oxa-
diazolo[3,4-b]pyridine-6-carboxylate (5h) was prepared
similarly from 0.55 g (0.005 mol) of compound 2 and
0.93 g (0.0025 mol) of nickel complex 1h. Yield 1.04 g
(83.9%), mp 158–160°С (ethanol–water, 3 : 1). IR
spectrum, ν, cm–1: 3378, 3275, 3184, 2992, 1681, 1627,
1597, 1535, 1505, 1450, 1400, 1270, 1205, 1092, 1011. 1Н
NMR spectrum, δ, ppm: 0.97–1.04 m (2Н, cyclopropyl),
1.12–1.18 m (2Н, cyclopropyl), 1.32 t (3Н, ОСН2СН3,
3JHH = 7.1 Hz), 2.37–2.46 m (1Н, cyclopropyl), 4.37 q
(2Н, ОСН2СН3, 3JHH = 7.1 Hz), 8.31 br. s (2Н, NH2). 13С
NMR spectrum, δС, ppm: 12.3, 14.4, 17.5, 61.8, 104.9,
140.1, 144.2, 158.9, 167.1, 173.3. Found, %: C 53.01; Н
4.99; N 22.83. C11H12N4O4. Calculated, %: C 53.22; Н
4.87; N 22.57.
1
1438, 1385, 1362, 1307, 1271, 1202, 1077. Н NMR
spectrum, δ, ppm: 2.60 s (3Н, СН3), 5.37 s (2Н, СН2),
7.34–7.48 m (5Н, С6Н5), 8.52 br. s (2Н, NH2). 13С NMR
spectrum, δС, ppm: 28.3, 67.1, 102.5, 128.6, 128.9, 130.0,
136.2, 140.3, 146.4, 158.5, 166.9, 170.1. Found, %: C
58.96; Н 4.32; N 20.01. C14H12N4O3. Calculated, %:
С59.15; Н 4.25; N 19.71.
tert-Butyl 7-amino-5-methyl[1,2,5]oxadiazolo[3,4-b]-
pyridine-6-carboxylate (5e) was prepared similarly
from 0.55 g (0.005 mol) of compound 2 and 0.94 g
(0.0025 mol) of nickel complex 1e. Yield 1.03 g (82%),
mp 174–175°С (ethanol–water, 1 : 1). IR spectrum, ν,
cm–1: 3378, 3278, 3182, 3145, 2978, 1683, 1624, 1514,
1442, 1371, 1295, 1252, 1206, 1163, 1103, 1082, 1031.
1Н NMR spectrum, δ, ppm: 1.58 s [9Н, С(СН3)3], 2.63 s
(3Н, СН3), 8.55 br. s (2Н, NH2). 13С NMR spectrum, δС,
ppm: 28.4, 28.8, 83.0, 103.8, 140.3, 146.2, 158.3, 166.6,
170.1. Found, %: C 52.64; Н 5.80; N 22.11. C11H14N4O3.
Calculated, %: C 52.79; Н 5.64; N 22.39.
Ethyl 7-amino-5-(difluoromethyl)[1,2,5]oxa-
diazolo[3,4-b]pyridine-6-carboxylate (5i). 0.97 g
(0.0025 mol) of nickel complex 1c and two drops of
ethyl 4,4-difluoro-3-oxobutanoate were added to a
solution of 0.55 g (0.005 mol) of compound 2 in 20 mL
of dichloroethane. The mixture was refluxed for 8 h.
Compound 5i was isolated similarly to compound 5b.
Yield 0.97 g (75.2%), mp 119–120°С (benzene–ethanol,
1 : 1). IR spectrum, ν, cm–1: 3395, 3273, 1685, 1607,
1518, 1408, 1381, 1288, 1208, 1133, 1094, 1066, 1018.
2-Methoxyethyl 7-amino-5-methyl[1,2,5]oxa-
diazolo[3,4-b]pyridine-6-carboxylate (5f) was prepared
similarly from 0.55 g (0.005 mol) of compound 2 and
0.95 g (0.0025 mol) of nickel complex 1f. Yield 0.98 g
(78%), mp 126–128°С (benzene–ethanol, 4 : 1). IR
spectrum, ν, cm–1: 3372, 3276, 3206, 2998, 2939, 2841,
1679, 1641, 1599, 1538, 1516, 1449, 1381, 1287, 1201,
1Н NMR spectrum, δ, ppm: 1.33 t (3Н, ОСН2СН3, 3JHH
=
3
7.2 Hz), 4.38 q (2Н, ОСН2СН3, JHH = 7.2 Hz), 7.30 t
(1Н, CHF2, 2JHF = 53.6 Hz), 9.15 d (2Н, NH2). Found,
%: C 41.61; Н 3.26; N 21.43. C9H8F2N4O3. Calculated,
%: C 41.87; Н 3.12; N 21.70.
1
1108, 1073, 1019. Н NMR spectrum, δ, ppm: 2.50 s
(3Н, СН3), 3.32 s (3Н, ОСН3), 3.65–3.69 m (2Н,
ОСН2СН2ОСН3), 4.41–4.45 m (2Н, ОСН2СН2ОСН3),
8.90 br. s (2Н, NH2). 13С NMR spectrum, δС, ppm:
27.9, 58.4, 64.0, 69.8, 102.5, 140.2, 146.1, 158.4, 166.6,
170.2. Found, %: C 46.83; Н 4.72; N 22.43. C10H12N4O4.
Calculated, %: C 46.62; Н 4.80; N 22.21.
1-(7-Amino-3-benzyl-5-methyl-3Н[1,2,3]tri-
azolo[4,5-b]pyridin-6-yl)ethanone (6а). To a solution
of 0.50 g (0.0025 mol) of compound 3 in 15 mL of
dichloroethane were added 0.32 g (0.0013 mol) of nickel
complex 1а and two drops of acetylacetone. The mixture
was refluxed for 16 h; compound 6а was isolated similarly
to compound 5b. Yield 0.51 g (72.5%), mp 158–160°С
(ethanol). IR spectrum, ν, cm–1: 3419, 3293, 3234, 3186,
1629, 1581, 1486, 1448, 1419, 1342, 1273, 1222, 1109.
1Н NMR spectrum, δ, ppm: 2.51 s (3Н, СН3), 2.54 s
(3Н, СН3), 5.76 s (2Н, СН2), 7.27–7.37 m ( 5Н, C6H5),
7.71 br. s ( 2Н, NH2). 13С NMR spectrum, δС, ppm: 25.9,
32.7, 49.5, 114.9, 127.2, 128.1, 128.4, 129.2, 136.7, 145.8,
Ethyl 7-amino-5-ethyl[1,2,5]oxadiazolo[3,4-b]-
pyridine-6-carboxylate (5g) was prepared similarly
from 0.55 g (0.005 mol) of compound 2 and 0.87 g
(0.0025 mol) of nickel complex 1g. Yield 1.07 g (90.7%),
mp 150–151°С (ethanol–water, 3 : 1). IR spectrum, ν, cm–1:
3373, 3020, 2991, 2970, 1688, 1638, 1598, 1504, 1445,
1382, 1284, 1248, 1206, 1110, 1016. 1Н NMR spectrum,
δ, ppm: 1.19 t (3Н, СН2СН3, 3JHH = 7.4 Hz), 1.32 t (3Н,
ОСН2СН3, 3JHH = 7.1 Hz), 2.93 q (2Н, СН2СН3, 3JHH
=
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VYDZHAK et al.
146.1, 159.3, 203.9. Found, %: C 63.81; Н 5.49; N 25.07.
C15H15N5O. Calculated, %: C 64.04; Н 5.37; N 24.89.
1340, 1306, 1282, 1253, 1164,1112.1Н NMR spectrum,
δ, ppm: 1.60 s [9Н, С(СН3)3], 2.68 s (3Н, СН3), 5.71 s
(2Н, СН2С6Н5), 7.27–7.37 m (5Н, С6Н5), 7.87 br. s (2Н,
NH2). Found, %: C 63.91; Н 6.35; N 20.48. C18H21N5O2.
Calculated, %: C 63.70; Н 6.24; N 20.63.
Methyl 7-amino-3-benzyl-5-methyl-3Н[1,2,3]tri-
azolo[4,5-b]pyridine-6-carboxylate (6b) was prepared
similarly from 0.50 g (0.0025 mol) of compound 3 and
0.41 g (0.0013 mol) of nickel complex 1b. Yield 0.51 g
(72.5%), mp 167–169°С (methanol). IR spectrum, ν,
cm–1: 3397, 3279, 3229, 3177, 1678, 1638, 1583, 1428,
Ethyl 7-amino-3-benzyl-5-ethyl-3Н[1,2,3]tri-
azolo[4,5-b]pyridine-6-carboxylate (6g) was prepared
similarly from 0.50 g (0.0025 mol) of compound 3 and
0.36 g (0.0013 mol) of nickel complex 1g. Compound 6g
was isolated by column chromatography (hexane–ethyl
acetate, 7 : 2). Yield 0.52 g (64.2%), mp 151–152°С
(ethanol). IR spectrum, ν, cm–1: 3392, 3275, 3229,
3179,1669, 1632, 1583, 1478, 1443, 1375, 1334, 1248,
1
1385, 1364, 1339, 1277, 1249, 1102, 1071. Н NMR
spectrum, δ, ppm: 2.61 s (3Н, СН3), 3.85 s (3Н, OСН3),
5.75 s (2Н, СН2С6Н5), 7.27–7.38 m (5Н, C6H5), 7.92 br. s
(2Н, NH2). Found, %: C 60.88; Н 5.17; N 23.30.
C15H15N5O2. Calculated, %: C 60.60; Н 5.09; N 23.55.
1
Ethyl 7-amino-3-benzyl-5-methyl-3Н[1,2,3]tri-
azolo[4,5-b]pyridine-6-carboxylate (6c) was prepared
similarly from 0.50 g (0.0025 mol) of compound 3 and
0.36 g (0.0013 mol) of nickel complex 1c. Yield 0.52 g
(66.7%), mp 125–127°С (ethanol). IR spectrum, ν, cm–1:
3427, 3296, 3244, 3192, 1694, 1640, 1583, 1477, 1364,
1314, 1276, 1245, 1104, 1082, 1017. 1Н NMR spectrum,
δ, ppm: 1.33 t (3Н, ОСН2СН3, 3JHH = 7.1 Hz), 2.64 s
(3Н, СН3), 4.35 q (2Н, ОСН2СН3, 3JHH = 7.1 Hz), 5.76 s
(2Н, СН2С6Н5), 7.28–7.37 m (5Н, С6Н5), 7.92 br. s (2Н,
NH2). 13С NMR spectrum, δС, ppm: 14.5, 27.4, 49.5,
61.2, 103.3, 127.1, 128.1, 128.4, 129.2, 136.6, 145.9,
148.7, 162.4, 168.2. Found, %: C 61.58; Н 5.67; N 22.64.
C16H17N5O2. Calculated, %: C 61.72; Н 5.50; N 22.49.
1097, 1069. Н NMR spectrum, δ, ppm: 1,20 t (3Н,
СН2СН3, 3JHH = 7.4 Hz), 1.31 t (3Н, ОСН2СН3, 3JHH
=
7.1 Hz), 2.92 q (2Н, СН2СН3, 3JHH = 7.4 Hz), 4.33 q
(2Н, ОСН2СН3, 3JHH = 7.1 Hz), 5.74 s ( 2Н, СН2С6Н5),
7.26–7.37 m (5Н, С6Н5), 7.75 br. s (2Н, NH2). 13С NMR
spectrum, δС, ppm: 14.2, 14.4, 31.6, 49.6, 61.3, 103.7,
126.8, 128.2, 128.4, 129.1, 136.5, 146.0, 148.1, 166.3,
168.1. Found, %: C 62.59; Н 6.01; N 21.28. C17H19N5O2.
Calculated, %: C 62.76; Н 5.89; N 21.52.
1-(4-Amino-6-methyl-1-phenyl-1Н-pyrazolo[3,4-b]-
pyridin-5-yl)ethanone (7a). To a solution of 0.46 g
(0.0025 mol) of compound 3 in 15 mL of chlorobenzene
were added 0.32 g (0.0013 mol) of nickel complex 1a and
two drops of acetylacetone. The resulting mixture was
stirred at 100–110°С for 30 h. Compound 7a was isolated
by column chromatography (hexane–ethyl acetate, 5 : 2).
Yield 0.27 g (40.6%), mp 196–198°С (ethanol) (mp
166–168°С [18]). 1Н NMR spectrum, δ, ppm: 2.54 s (3Н,
СН3), 2.58 s (3Н, СН3), 7.29–7.32 m (1Нar), 7.50–7.54 m
(2НAr), 7.62 br. s (2Н, NH2), 8.24–8.28 m (2НAr), 8.48 s
(1Н, С3Н). Found, %: C 67.91; Н 5.45; N 20.67.
C15H14N4O. Calculated, %: C 67.65; Н 5.30; N 21.04.
Benzyl 7-amino-3-benzyl-5-methyl-3Н[1,2,3]tri-
azolo[4,5-b]pyridine-6-carboxylate (6d) was prepared
similarly from 0.50 g (0.0025 mol) of compound 3 and
0.56 g (0.0013 mol) of nickel complex 1d. Compound 6d
was isolated by column chromatography (hexane–ethyl
acetate, 3 : 1). Yield 0.76 g (81.7%), mp 134–135°С
(hexane–ethyl acetate, 1:1). IR spectrum, ν, cm–1: 3395,
3279, 3232, 3182, 1673, 1631, 1584, 1492, 1422, 1381,
1
1336, 1275, 1237, 1104. Н NMR spectrum, δ, ppm:
Methyl 4-amino-6-methyl-1-phenyl-1Н-pyra-
zolo[3,4-b]pyridine-5-carboxylate (7b) was prepared
similarly from 0.46 g (0.0025 mol) of compound 4 and
0.41 g (0.0013 mol) of nickel complex 1b. Compound 7b
was isolated by column chromatography (hexane–ethyl
acetate, 3 : 1). Yield 0.15 g (21.3%), mp 128–129°С
(methanol) (mp 125–126°С [17]). 1Н NMR spectrum, δ,
ppm: 2.66 s (3Н, СН3), 3.85 s (3Н, OСН3), 7.26–7.30 m
(1НAr), 7.51–7.55 m (2НAr), 7.70 br. s (2Н, NH2), 8.24–
8.28 m (2НAr), 8.50 s (1Н, С3Н). Found, %: C 63.59; Н
5.11; N 20.14. C15H14N4O2. Calculated, %: C 63.82; Н
5.00; N 19.85.
2.76 s (3Н, СН3), 5.36 s (2Н, СН2С6Н5), 5.72 s (2Н,
СН2С6Н5), 7.23–7.45 m (10Н, C6H5), 7.85 br. s (2Н,
NH2). Found, %: C 67.82; Н 5.21; N 18.49. C21H19N5O2.
Calculated, %: C 67.55; Н 5.13; N 18.75.
tert-Butyl 7-amino-3-benzyl-5-methyl-3Н[1,2,3]tri-
azolo[4,5-b]pyridine-6-carboxylate (6e) was prepared
similarly from 0.50 g (0.0025 mol) of compound 3 and
0.47 g (0.0013 mol) of nickel complex 1e. Compound 6e
was isolated by column chromatography (hexane–ethyl
acetate, 4 : 1). Yield 0.47 g (55.3%), mp 177–179°C
(hexane–ethyl acetate, 2 : 1). IR spectrum, ν, cm–1:
3413, 3285, 3238, 3186,1681, 1631, 1588, 1389, 1366,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 8 2020

APPLICATION OF NICKEL COMPLEXES WITH 1,3-DICARBONYL COMPOUNDS
1445
11. Mascal, M., Hext, N.M., Warmuth, R., Arnall-Culiford, J.R.,
Moore, M.H., and Turkenburg, J.R., J. Org. Chem., 1999,
vol. 64, no. 23, p. 8479.
Ethyl 4-amino-6-methyl-1-phenyl-1Н-pyra-
zolo[3,4-b]pyridine-5-carboxylate (7c) was prepared
similarly from 0.46 g (0.0025 mol) of compound 4 and
0.41 g (0.0013 mol) of nickel complex 1c. Compound 6d
was isolated by column chromatography (hexane–ethyl
acetate, 3 : 1). Yield 0.23 g (31.1%), mp 130–131°С
https://doi.org/10.1021/jo990719t
12. Komarova, E.S., Makarov, V.A., Alekseeva, L.M.,
Avramenko, G.V., and Granik, V.G., Russ. Chem. Bull.,
2007, vol. 56, no. 11, p. 2337.
1
(ethanol) (mp 130–132°С [18]). Н NMR spectrum, δ,
ppm: 1.33 t (3Н, ОСН2СН3, 3JHH = 7.2 Hz), 2.66 s (3Н,
СН3), 4.34 q (2Н, ОСН2СН3, 3JHH = 7.2 Hz), 7.26–7.30 m
(1НAr), 7.51–7.55 m (2НAr), 7.76 br. s (2Н, NH2), 8.23–
8.27 m (2НAr), 8.51 s (1Н, С3Н). Found, %: C 65.14; Н
5.59; N 19.17. C16H14N4O2. Calculated, %: C 64.85; Н
5.44; N 18.91.
https://doi.org/10.1007/s11172-007-0369-5
13. Silva, D., Chioua, M., Samadi, A., Carmo, C., Jimero, M.-L.,
Mendes, E., Rios, C., Romero, A., Villarroya, M.,
Lopez, M., and Marco-Contelles, J., Eur. J. Med. Chem.,
2011, vol. 46, no. 9, p. 4676.
https://doi.org/10.1016/j.ejmech.2011.05.068
14. Corre, L., Tak-Tak, L., Guillard, A., Prestat, G., Gravier-
Delletier, C., and Busca, D., Org. Biomol. Chem., 2015,
vol. 13, no. 2, p. 409.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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