Three-component synthesis of 4-aroyl-2(1),4,5,7-Tetrahydropyrazolo[3,4-b] Pyridin-6-ones and their properties

Article abstract of DOI:10.1007/s10593-014-1502-7

Inspired by the concept of multicomponent reactions, a novel one-pot synthesis involving arylglyoxals, 5-aminopyrazoles, and Meldrum's acid has been developed and employed for the creation of a small library of 4-aroyl-2(1),4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones. The alkylation, acylation, reduction, and oxidation reactions of 4-aroyl-3-methyl-2,4,5,7- tetrahydropyrazolo[3,4-b]pyridin-6-ones have been studied.

Full text of DOI:10.1007/s10593-014-1502-7

Chemistry of Heterocyclic Compounds, Vol. 50, No. 4, July, 2014 (Russian Original Vol. 50, No. 4, April, 2014)
THREE-COMPONENT SYNTHESIS OF 4-AROYL-
2(1),4,5,7-TETRAHYDROPYRAZOLO[3,4-b]PYRIDIN-
6-ONES AND THEIR PROPERTIES
O. N. Petrova1, L. L. Zamigajlo1, I. M. Gella1,2, V. I. Musatov1, S. V. Shishkina1,
O. V. Shishkin1,2, E. V. Vashchenko1, A. V. Borisov3, and V. V. Lipson1,2,4
*
Inspired by the concept of multicomponent reactions, a novel one-pot synthesis involving arylglyoxals,
5-aminopyrazoles, and Meldrum's acid has been developed and employed for the creation of a small
library of 4-aroyl-2(1),4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones. The alkylation, acylation,
reduction, and oxidation reactions of 4-aroyl-3-methyl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones
have been studied.
Keywords: 5-aminopyrazoles, arylglyoxals, Meldrum's acid, tetrahydropyrazolo[3,4-b]pyridines, acylation,
alkylation, oxidation, reduction, three-component reaction.
In the last two decades, multicomponent reactions (MCRs) have been recognized as a highly powerful
synthetic strategy for the combinatorial synthesis of compound libraries and have received significant attention
[1-6]. A central issue in MCRs research is the synthesis of nitrogen heterocycles, since this group of organic
compounds holds a special place among pharmaceutically and agrochemically important natural and synthetic
products. Pyrazolopyridines among different azoloazines have received more attention as one of the "privileged
medicinal scaffolds" which are used for the development of new drug candidates of various applications.
Numerous methods for the synthesis of systems incorporating a pyrazolopyridine moiety have been reported
with respect to their different structures [7-17].
In the past several years, we and others have developed various MCRs based on the interaction of
Meldrum's acid or its derivatives with carbonyl compounds and different nitrogen-containing 1,3-binucleophiles
that can provide a facile route to partially hydrogenated fused heterocyclic systems for chemical and biomedical
purposes, some natural alkaloids, and their analogs [4-6, 17, 18]. For example, three-component reactions of
_______
*To whom correspondence should be addressed, e-mail: lipson@ukr.net.
1State Scientific Institution "Institute for Single Crystals" of National Academy of Sciences of Ukraine,
60 Lenina Ave., Kharkiv 61001, Ukraine; e-mail: olesya.demidchencko@yandex.ru, lalilali@mail.ru.
2V. N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv 61022, Ukraine; e-mail: info@karazin.ua.
3Enamine Ltd., 23 Alexandra Matrosova St., Kyiv 01103, Ukraine; e-mail: enamine@enamine.net.
4Antidiabetic Drug Laboratory, SI "V. Ya. Danilevsky Institute for Endocrine Pathology Problems", 10 Artema
St., Kharkiv 61002, Ukraine.
_________________________________________________________________________________________
Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 562-576, April, 2014. Original article
submitted March 14, 2014.
514
0009-3122/14/5004-0514©2014 Springer Science+Business Media New York

5-aminopyrazoles with aromatic, heterocyclic, or some aliphatic aldehydes and Meldrum's acid were shown to
provide facile access to 4-aryl-4,5,6,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones [17, 19-22]. Unfortunately, there
are only two reaction centers suitable for further chemical modification in their structure [21]. For this reason,
the introduction of a new chemically active group, such as the carbonyl moiety, in the tetra-hydro-
pyrazolo[3,4-b]pyridin-6-one scaffold is a synthetic task of high priority for us. We have selected arylglyoxals
as possible building blocks to be used in MCR with 5-aminopyrazoles and Meldrum's acid. They would be able
to provide an additional carbonyl group in target heterocycles. These 1,2-dicarbonyl compounds are widely
used in the design of different heterocycles [23]. Nevertheless, in the scientific literature there are no
publications concerning one-pot synthesis of tetrahydropyrazolo[3,4-b]pyridin-6-one derivatives on the base of
glyoxals, 5-aminopyrazoles, and Meldrum's acid.
Herein, we would like to report an easy and efficient procedure for synthesis of novel tetra-
hydropyrazolo[3,4-b]pyridin-6-ones via three-component condensation of Meldrum's acid, arylglyoxals, and
5-aminopyrazoles in alcohols and discuss some chemical transformations of the target compounds. The presence
of four nonequivalent nucleophilic centers in 3-substituted 5-aminopyrazoles provides various pathways for
their reactions with carbonyl 1,3-dielectrophiles, their synthetic precursors, or equivalents and opens up wide
possibilities for using these compounds in the synthesis of fused heterocyclic systems.
Earlier, it has been found that reactions of 5-amino-3-arylpyrazoles with methoxymethylene Meldrum's
acid derivative, as well as thermolysis of their pyrazolylaminomethylene derivatives, give pyrazolo[1,5-a]-
pyrimidines rather than pyrazolo[3,4-b]pyridines [24]. At the same time, three-component reactions of 5-amino-
3-methylpyrazole with aromatic, heterocyclic, or some aliphatic aldehydes and Meldrum's acid yielded
pyrazolo[3,4-b]pyridinones [20-22].
2 a Ar = Ph, b Ar = 4-MeC6H4, c Ar = 4-MeOC6H4, d Ar = 4-FC6H4, e Ar = 4-ClC6H4, f Ar = 4-BrC6H4, g Ar = 4-IC6H4,
h Ar = 2-Br-4-FC6H3, i Ar = 4-PhC6H4; 3 a–c R1 = H, a R2 = Me, b R2 = 4-MeC6H4, c R2 = 4-FC6H4, d–f R1 = Me, d R2 = Н,
e R2 = Me, f R2 = t-Bu, g–i R2 = Me, g R1 = cyclopentyl, h R1 = Ph, i R1 = 4-MeOC6H4; 4 a–i R2 = Me, a Ar = Ph, b Ar = 4-MeC6H4,
c Ar = 4-MeOC6H4, d Ar = 4-FC6H4, e Ar = 4-ClC6H4, f Ar = 4-BrC6H4, g Ar = 4-IC6H4, h Ar = 2-Br-4-FC6H3, i Ar = 4-PhC6H4;
4 j R2 = 4-MeC6H4, Ar = Ph; k–m R2 = 4-FC6H4, k Ar = Ph, l Ar = 4-MeOC6H4, m Ar = 4-FC6H4; 6 a–e R1 = Me, R2 = H, a Ar = Ph,
b Ar = 4-MeC6H4, c Ar = 4-MeOC6H4, d Ar = 4-FC6H4, e Ar = 4-BrC6H4; f R1 = R2 = Me, Ar = 4-BrC6H4; g,h R1 = Me, R2 = t-Bu,
g Ar = 4-FC6H4, h Ar = 4-BrC6H4; 6 i–l R1 = cyclopentyl, R2 = Me, i Ar = Ph, j Ar = 4-MeC6H4, k Ar = 4-MeOC6H4, l Ar = 4-FC6H4,
m,n R1 = Ph, R2 = Me, m Ar = 4-MeC6H4, n Ar = 4-MeOC6H4, o,p R1 = 4-MeOC6H4, R2 = Me; o Ar = 4-MeC6H4, p Ar = 4-FC6H4
515

We found that a three-component condensation of equimolar amounts of Meldrum's acid (1),
arylglyoxals 2a-i, and 1,3-disubstituted 5-aminopyrazoles 3a-i under refluxing in ethanol leads to 4-aroyl-
tetrahydropyrazolo[3,4-b]pyridin-6-ones 4a-m, 6a-p with high yields. Products of the isomeric structures 5,
7-10 were not isolated (see the discussion below).
+
H
N
H
N
+
Me
H
N
C
N
N
Me
N
O
O
– CH3
– CH3OC6H4
O
NH
NH
NH
+
O
O
O
OMe
OMe
m/z 270 (8)
m/z 285 (12)
m/z 178 (11)
+ H – CH3OC6H4
– CH3OC6H4CO
H
N
H
H
N
+
N
Me
N
N
N
– CH3
O
C
+
+
NH
O
C
NH
NH
O
O
m/z 164 (10)
m/z 150 (52)
m/z 135 (100)
Fig. 1. Basic fragmentation paths for compound 4c in the EI mass spectrum.
The composition and structure of the obtained compounds 4a-m were confirmed by the results of
elemental analysis and spectral data.
In the IR spectra of compounds 4a,b,f, there was a set of typical absorption bands of cyclic amides in
the regions 3220-3124 (NH), 1648-1644 (C=O), and a carbonyl group band of the aroyl moiety at 1680-1664 cm-1.
With regard to the mass spectra, upon electron impact (EI) ionization all compounds 4a-m exhibit
similar behavior in their fragmentation, showing a molecular ion peak of low intensity along with a high-
intensity peak corresponding to the loss of the aroyl fragment and the base peak corresponding to
pyrazolo[3,4-b]pyridinone ion (Fig. 1).
However, these data do not permit an assignment to be made for the type of heterocycle fusion
(structures 4, 5, 8 vs. 9, 10) or the position of the aroyl group (structures 4, 5, 9 vs. 8, 10).
In the 1H NMR spectra of compounds 4a-m, signals of protons of two NH groups, methyl substituent in
pyrazole cycle, and aroyl fragment, as well as CH–CH2 moiety of a partially hydrogenated pyridinone ring were
present. The last one formed an ABX proton system. The presence of two broadened singlet signals of NH groups
at 11.68-12.39 and 10.03-10.33 ppm and the absence of a signal for a methine proton of the pyrazole ring speaks
in favor of assigning the obtained products to a pyrazolopyridine (compounds 4, 5 or 8) and not a
pyrazolopyrimidine series (compounds 9 or 10). The choice in favor of 4-aroyl isomer 4 was made on the basis
of an NOE experiment carried out for compound 4g (Fig. 2). Irradiation of the CH3 group protons at position 3
(1.84 ppm) causes the responses of the NH group proton of the pyrazole ring (11.75 ppm) and a CH proton at
position 4 of the bicyclic system (4.90 ppm) which indicates their close spatial disposition.
516

Fig. 2. Interactions in the NOE
spectrum of compound 4g.
Fig. 3. Molecular structure of compound 6c
according to X-ray diffraction data.
In the case of the N-1-substituted aminopyrazole taking part in the discussed three-component
condensation, only pyrazolopyridines 6a-p were obtained. The alternative structure 7 (R1 = Alk, Ar) was not
confirmed, since the magnetic coupling between the 6-CH and 7-NH protons of the partially hydrogenated
pyridine cycle was not observed in the 1H NMR spectrum. Finally the structure of the pyrazolopyridine 6c was
confirmed on the basis of single crystal X-ray structural analysis (Fig. 3). The tetrahydropyridine ring adopts a
twist-boat conformation (the puckering parameters [25] are S 0.53, Θ 48.3, Ψ 23.4). Deviations of the C(1) and
C(2) atoms from the mean plane of the remaining atoms of the ring are -0.26 and -0.64 Å, respectively. The
4 methoxybenzoyl substituent is located in the axial position (the C(8)–C(3)–C(4)–C(6) torsion angle is -94.1(1)°)
and it is almost orthogonal to the planar part of the pyrazolopyridine fragment (the C(4)–C(3)–C(8)–O(2)
torsion angle is 100.2(2)°). Such location of this substituent is caused, probably, by the steric repulsion between
the phenyl ring and the bicyclic fragment, as indicated by the shortened intramolecular contacts H(3)···C(14)
2.71 Å (the sum of the van der Waals radii [26] is 2.87 Å), C(14)···C(4) 3.38 Å, and C(14)···C(5) 3.38 Å
(3.42 Å).
Thus, the interaction of 3(5)-aminopyrazoles 3a-i with 2,2-dimethyl-1,3-dioxane-4,6-dione (1) and
arylglyoxals 2a-i is characterized by high regioselectivity and leads exclusively to the formation of the
4-aroylpyrazolo[3,4-b]pyridin-6-one systems 4 or 6. Such a direction of the process corresponds to the interaction
of the β-carbon atom of the possible intermediate A (in equilibrium with intermediate B), formed initially from
Meldrum's acid 1 and glyoxal 2, with the carbon nucleophilic center in the aminoazole molecule (intermediate
C), and the carbon atom of the C=O group of 1,3-dioxane-4,6-dione fragment with the exocyclic amino group.
O
H
Ar
O
NH2
Ar
O
Ar
O
O
O
O
N
R2
O
O
R1
N
3
2
1
O
+
O
O
O
O
– H2O
– 1
Me
Me
O
O
O
O
Me
Me
OH
OH
Me Me
B
Me
Me
A
1
O
O
Ar
R2
4 (R1 = H),
6 (R1 = Alk, Ar)
O
N
– H2O
Me
Me
N
NH2
O
O
R1
C
517

Chemical properties of the synthesized compounds were examined on the pyrazolopyridines 4a-c,f and
6n. We studied the transformations of these compounds upon alkylation, acylation, under oxidation conditions,
and in reactions with phenylhydrazine, aniline, and N-Boc-substituted piperidine carboxylic acid hydrazide.
Both secondary amino groups in the structure of the synthesized pyrazolopyridine 4c undergo an
electrophilic attack in the alkylation reaction producing the trimethyl derivative 11. However, in the case of
acylation only the amino group at the pyrazole ring takes part in the reaction (product 12). The alkylation with
methyl iodide in DMF/KOH medium in the presence of atmospheric oxygen is accompanied by oxidation of the
pyridine ring with the formation of N-methyl-substituted heteroaromatic derivative 13. The position of the
substituents in the pyrazole cycle was determined on the basis of the NOE experiment data. An NOE correlation
was found between proton signals of the 3-methyl group and N-methyl group (for compounds 11, 13) or N-acyl
fragment (for compound 12) of the pyrazole core. We have found that the oxidation of pyrazolopyridines 4a,b
easily occurs both in basic (Py or DMF/KOH) and acidic conditions (AcOH). The proof of heteroaromatization
of pyridine cycle is the disappearance of the signals of the ABX system and the presence of the signal of a
1
methine proton in the H NMR spectrum of compounds 13 and 14. Refluxing of the pyrazolopyridines 4a,b
with sodium borohydride in isopropyl alcohol yields hydroxy derivatives 15a,b.
14, 15 a Ar = Ph, b Ar = 4-MeC6H4
1
The Н NMR spectra of compounds 15a,b correspond to individual diastereomers, but not to isomer
mixtures. The diastereoselective formation of hydroxy compounds 15a,b could be explained by the attack of the
NaBH4-derived hydride ion on the C=O group carbon atom in pyrazolopyridines 4a,b from the less hindered
side, i.e., from the side opposite to the 3-methyl group. The values of the spin-spin coupling constants between
1
protons Ha and Hb in the Н NMR spectra of the reduction products 15a,b are 4.0 and 4.4 Hz, respectively,
which corresponds to the gauche orientation of the indicated hydrogen atoms.
Another series of chemical transformations of the synthesized compounds 4a-c, 6n investigated in this
study involves the carbonyl group of the aroyl fragment. The interaction of compound 4b with phenylhydrazine
(16a) in ethanol in the presence of hydrochloric acid allowed us to isolate ketoaminal 17. It should be expected
that attack by phenylhydrazine (16a) also takes place in the energetically more favorable conformation of
pyrazolopyridine 4b from the sterically less hindered side. Prolonged refluxing leads to the formation of
518

hydrazone 18a. However, the use of acetic acid as a solvent with compound 4a is accompanied by further
heteroaromatization of the pyridine ring (product 19). The interaction of pyrazolopyridine 4c with p-toluidine
(16b) leads to the formation of the expected azomethine 18b. Refluxing of the 1-substituted pyrazolopyridine
6n with a protected piperidine carboxylic acid hydrazide 16c in the mixture of EtOH and DMSO likewise yields
the corresponding hydrazide 20.
H
H
N
N
Me
OH
Me
N
Me
N
PhNHNH2
RNH2
16a,b
16a
R
N
4b
4b,c
NH
H+, EtOH
, 2 h
NH
HN
Ph
Ar
NH
17
O
O
18a,b
O
NHNH2
N
O
Me
Ph
N
H
N
N
Me
PhN
N
H
N
N
Boc
16c
16a
NH
BocN
4a
6n
AcOH
, 2.5 h
EtOH, DMSO
, 5 h
NH
O
Ar
O
19
MeO
20
18 a Ar = 4-MeC6H4, b Ar = 4-MeOC6H4; 16, 18 a R = NHPh, b R = 4-MeC6H4
To summarize, the investigation of three-component condensations involving aminopyrazoles,
arylglyoxals, and Meldrum's acid has shown that in all cases the reaction takes place regioselectively and leads to
the formation of pyrazolo[3,4-b]pyridinone systems. In the reactions of pyrazolo[3,4-b]pyridinones with
electrophilic reagents, the most nucleophilic is the N-2 atom of the pyrazole ring. Heteroaromatization of the
pyridine ring of pyrazolo[3,4-b]pyridinones takes place under the basic and acidic conditions. The presence of
the carbonyl group of the aroyl fragment opens additional opportunities for chemical modification of this
molecular platform.
EXPERIMENTAL
IR spectra were recorded in KBr on a Specord M-82 spectrometer. 1H NMR spectra were registered on a
Varian Mercury VX-200 instrument (200 MHz), and the 13C NMR spectra were registered on a Bruker AM-400
spectrometer (100 MHz) in DMSO-d6, using TMS as internal standard. Mass spectra were recorded on a Varian
1220 L mass spectrometer with direct injection of the sample (EI, 70 eV). Elemental analyses were made on a
Euro AE-3000 elemental analyzer. Melting points were determined on a Kofler apparatus and were not
corrected. Reactions were monitored by TLC (DC-Fertigfolien ALUGRAM Xtra SIL G/UV254) in CH2Cl2–
2-PrOH, 10:1, or EtOAc–toluene, 1:4, and visualized with UV light or iodine vapor. The starting materials were
purchased from commercial suppliers.
4-Aroyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-ones 4a-m and 4-Aroyl-1,4,5,7-tetrahydro-
6H-pyrazolo[3,4-b]pyridin-6-ones 6a-p (General Method). A mixture of 2,2-dimethyl-1,3-dioxane-4,6-dione
(1) (1 mmol), corresponding arylglyoxal 2 (1 mmol), and aminopyrazole 3 (1 mmol) in 8-10 ml EtOH was
refluxed for 1-1.5 h. The product was filtered off and washed with EtOH or MeOH. The products were
recrystallized from MeOH (compounds 4a-m) or EtOH (compounds 6a-p) and obtained as white powders.
519

4-Benzoyl-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4a). Yield 62%, mp
274-276°C. IR spectrum, ν, cm-1: 3220-3160 (NH), 1680 (HNC=O), 1644 (ArC=O), 1592 (C=C), 1524 (C=N).
1H NMR spectrum, δ, ppm (J, Hz): 1.82 (3H, s, 3-CH3); 2.59 (1H, dd, J = 16.2, J = 2.8) and 2.70 (1H, dd, J = 16.2,
J = 6.2, 5-CH2); 4.95 (1H, dd, J = 6.0, J = 3.0, 4-CH); 7.52 (2H, t, J = 7.4, H-3,5 Ph); 7.64 (1H, t, J = 7.0, H-4
Ph); 7.99 (2H, d, J = 7.4, H-2,6 Ph); 10.10 (1H, br. s, 7-NH); 11.73 (1H, br. s, 2-NH). 13C NMR spectrum,
δ, ppm: 10.4 (CH3); 35.0 (C-4); 36.4 (C-5); 97.1 (C-3a); 129.1 (C-3,5 Ph); 129.2 (C-2,6 Ph); 133.8 (C-4 Ph);
135.5 (C-1 Ph); 136.5 (C-3); 149.8 (C-7a); 169.9 (CONH); 199.8 (COAr). Mass spectrum, m/z (Irel, %):
255 [M]+ (17), 151 (14), 150 (100), 149 (15), 132 (22), 105 (44), 77 (19). Found, %: С 65.94; Н 5.20; N 16.39.
С14Н13N3О2. Calculated, %: С 65.87; Н 5.13; N 16.46.
3-Methyl-4-(4-methylbenzoyl)-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4b). Yield
61%, mp 274-276°C. IR spectrum, ν, cm-1: 3164-3136 (NH), 1664 (HNC=O), 1648 (ArC=O), 1604 (C=C),
1524 (C=N). 1H NMR spectrum, δ, ppm (J, Hz): 1.84 (3H, s, 3-CH3); 2.37 (3H, s, CH3C6H4); 2.55 (1H, dd, J = 15.8,
J = 3.4) and 2.68 (1H, dd, J = 15.8, J = 6.4, 5-CH2); 4.92 (1H, dd, J = 6.2, J = 3.4, 4-CH); 7.32 (2H, d, J = 7.8,
H-3,5 Ar); 7.90 (2H, d, J = 7.6, H-2,6 Ar); 10.10 (1H, br. s, 7-NH); 11.72 (1H, br. s, 2-NH). Mass spectrum, m/z
(Irel, %): 269 [M]+ (12), 150 (67), 149 (10), 119 (100), 91 (32). Found, %: С 67.01; Н 5.69; N 15.69.
С15Н15N3О2. Calculated, %: С 66.90; Н 5.61; N 15.60.
4-(4-Methoxybenzoyl)-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4c). Yield 64%,
1
mp 202-204°C. H NMR spectrum, δ, ppm (J, Hz): 1.88 (3H, s, 3-CH3); 2.57 (1H, dd, J = 16.2, J = 3.8) and
2.69 (1Н, dd, J = 16.2, J = 6.2, 5-CH2); 3.84 (3H, s, OCH3); 4.91 (1H, dd, J = 6.0, J = 3.8, 4-CH); 7.05 (2H, d,
J = 8.8, H-3,5 Ar); 8.01 (2H, d, J = 8.6, H-2,6 Ar); 10.03 (1H, br. s, 7-NH); 11.68 (1H, br. s, 2-NH). Mass
spectrum, m/z (Irel, %): 285 [M]+ (12), 178 (11), 164 (10), 150 (52), 135 (100), 107 (19). Found, %: С 63.04;
Н 5.22; N 14.65. С15Н15N3О3. Calculated, %: С 63.15; Н 5.30; N 14.73.
4-(4-Fluorobenzoyl)-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4d). Yield
1
44%, mp 316-318°C. H NMR spectrum, δ, ppm (J, Hz): 1.84 (3H, s, 3-CH3); 2.59 (1H, dd, J = 17.8, J = 1.8)
and 2.63 (1H, dd, J = 17.8, J = 6.6, 5-CH2); 4.96 (1H, dd, J = 6.4, J = 1.8, 4-CH); 7.36 (2H, d, J = 8.0, H-3,5
Ar); 8.01 (2H, d, J = 8.2, H-2,6 Ar); 10.11 (1H, br. s, 7-NH); 11.75 (1H, br. s, 2-NH). Mass spectrum, m/z (Irel,
%): 273 [M]+ (14), 240 (10), 178 (14), 150 (49), 123 (100). Found, %: С 61.64; Н 4.50; N 15.29. С14Н12FN3О2.
Calculated, %: С 61.53; Н 4.43; N 15.38.
4-(4-Chlorobenzoyl)-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4e). Yield
73%, mp 340-342°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.84 (3H, s, CH3); 2.59 (1H, dd, J = 16.2, J = 2.8) and
2.68 (1H, dd, J = 16.2, J = 6.2, 5-CH2); 4.94 (1H, dd, J = 6.2, J = 2.8, 4-CH); 7.60 (2H, d, J = 8.0, H-3,5 Ar);
13
8.02 (2H, d, J = 8.2, H-2,6 Ar); 10.12 (1H, br. s, 7-NH); 11.77 (1H, br. s, 2-NH). C NMR spectrum, δ, ppm:
10.4 (3-CH3); 34.8 (C-4); 36.4 (C-5); 96.9 (C-3a); 129.4 (C-3,5 Ar); 131.1 (C-2,6 Ar); 135.2 (C-1 Ar); 135.5
(C-3); 138.8 (C–Cl); 149.8 C-7a); 169.7 (CONH); 198.7 (COAr). Mass spectrum, m/z (Irel, %): 291 [M (37Cl)]+
(3), 289 [M (35Cl)]+ (8), 150 (100), 141 (24), 139 (78), 132 (78), 111 (27), 107 (10). Found, %: С 57.96; Н 4.09;
N 14.42. С14Н12ClN3О2. Calculated, %: С 58.04; Н 4.17; N 14.50.
4-(4-Bromobenzoyl)-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4f). Yield 72%,
mp 342-344°C. IR spectrum, ν, cm-1: 3164–3124 (NH), 1672 (HNC=O), 1648 (ArC=O), 1524 (C=N). 1H NMR
spectrum, δ, ppm (J, Hz): 1.84 (3H, s, CH3); 2.59 (1H, dd, J = 16.2, J = 2.8) and 2.68 (1H, dd, J = 16.2, J = 6.6,
5-CH2); 4.93 (1H, dd, J = 6.4, J = 2.8, 4-CH); 7.72 (2H, d, J = 8.2, H-3,5 Ar); 7.96 (2H, d, J = 8.2, H-2,6 Ar);
10.11 (1H, br. s, 7-NH); 11.78 (1H, br. s, 2-NH). Found, %: С 50.42; Н 3.53; N 12.65. С14Н12BrN3О2.
Calculated, %: С 50.32; Н 3.62; N 12.57.
4-(4-Iodobenzoyl)-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4g). Yield 68%,
mp 328-330°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.84 (3H, s, CH3); 2.59 (1H, dd, J = 16.2, J = 2.4) and 2.67
(1H, dd, J = 16.2, J = 6.2, 5-CH2); 4.90 (1H, dd, J = 6.0, J = 2.6, 4-CH); 7.75 (2H, d, J = 7.8, H-3,5 Ar); 7.91
13
(2H, d, J = 8.0, H-2,6 Ar); 10.10 (1H, br. s, 7-NH); 11.75 (1H, br. s, 2-NH). C NMR spectrum, δ, ppm: 10.4
(3-CH3); 34.9 (C-4); 36.3 (C-5); 96.9 (C-3a); 102.4 (C–I); 130.8 (C-2,6 Ar); 135.5 (C-1 Ar); 135.8 (C-3); 138.2
520

(C-3,5 Ar); 149.8 (C-7a); 169.7 (CONH); 199.3 (COAr). Mass spectrum, m/z (Irel, %): 381 [M]+ (12), 164 (16),
132 (100), 127 (21), 95 (40). Found, %: С 44.20; Н 3.28; N 10.91. С14Н12IN3О2. Calculated, %: С 44.11;
Н 3.17; N 11.02.
4-(2-Bromo-4-fluorobenzoyl)-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4h).
Yield 58%, mp 171-173°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.48 (3H, s, CH3); 2.54 (1H, dd, J = 15.8, J = 2.8)
and 2.61 (1H, dd, J = 15.8, J = 5.4, 5-CH2); 4.52 (1H, dd, J = 5.4, J = 2.8, 4-CH); 7.40 (1H, dd, J = 8.4, J = 2.0,
H-5 Ar); 7.62-7.70 (2H, m, H-3,6 Ar); 10.14 (1H, br. s, 7-NH); 11.78 (1H, br. s, 2-NH). 13C NMR spectrum, δ,
ppm: 9.2 (3-CH3); 33.4 (C-4); 41.0 (C-5); 94.8 (C-3a); 115.2 (С-5 Ar); 115.4 (С-3 Ar); 121.1 (C–Br); 131.0
(С-6, Ar); 136.1 (С-1 Ar); 137.5 (C-3); 149.8 (C-7a); 163.8 (C–F); 169.4 (CONH); 199.8 (COAr). Found, %:
С 47.86; Н 3.23; N 12.03. С14Н11BrFN3О2. Calculated, %: С 47.75; Н 3.15; N 11.93.
4-[(1,1'-Biphenyl)-4-carbonyl]-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4i).
Yield 49%, mp 290-292°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.89 (3H, s, CH3); 2.62 (1H, dd, J = 16.8, J = 2.8)
and 2.70 (1H, dd, J = 17.0, J = 6.0, 5-CH2); 4.99 (1H, dd, J = 6.0, J = 2.8, 4-CH); 7.41-7.51 (3H, m, H-3,4,5
Ph); 7.73-7.85 (4H, m, H-2,6 Ph, H-3,5 Ar); 8.09 (2H, d, J = 7.8, H-2,6 Ar); 10.10 (1H, br. s, 7-NH); 11.73 (1H,
br. s, 2-NH). Mass spectrum, m/z (Irel, %): 332 [M+Н]+ (22), 331 [M]+ (100), 316 (21), 254 (11), 181 (53),
178 (15), 153 (17), 150 (43), 136 (12). Found, %: С 72.56; Н 5.09; N 12.57. С20Н17N3О2. Calculated, %:
С 72.49; Н 5.17; N 12.68.
4-Benzoyl-3-(p-tolyl)-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4j). Yield 70%, mp
282-284°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.27 (3H, s, CH3); 2.56 (1H, dd, J = 16.0, J = 2.4) and 3.03 (1H,
dd, J = 16.2, J = 7.0, 5-CH2); 5.22 (1H, dd, J = 7.0, J = 2.6, 4-CH); 7.12-7.38 (6H, m, H-2,3,5,6 Ar, H-3,5 Ph);
7.55 (1H, t, J = 7.5, H-4 Ph); 7.83 (2H, d, J = 7.4, H-2,6 Ph); 10.33 (1H, br. s, 7-NH); 12.39 (1H, br. s, 2-NH). Mass
spectrum, m/z (Irel, %): 331 [M]+ (10), 254 (14), 240 (19), 226 (100), 163 (10), 135 (12). Found, %: С 72.54; Н 5.24;
N 12.59. С20Н17N3О2. Calculated, %: С 72.49; Н 5.17; N 12.68.
4-Benzoyl-3-(4-fluorophenyl)-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4k). Yield 49%,
1
mp 315-317°C. H NMR spectrum, δ, ppm (J, Hz): 2.58 (1H, dd, J = 15.4, J = 2.4) and 2.91 (1H, dd, J = 16.2,
J = 7.2, 5-CH2); 5.16 (1H, dd, J = 7.2, J = 2.4, 4-CH); 7.10 (2H, t, J = 7.5, H-3,5 Ar); 7.30-7.54 (5H, m, H-3,4,5
Ph, H-2,6 Ar); 7.80 (2H, d, J = 7.8, H-2,6 Ph); 10.16 (1H, br. s, 7-NH); 12.30 (1H, br. s, 2-NH). Found, %:
С 67.96; Н 4.28; N 12.62. С19Н14FN3О2. Calculated, %: С 68.05; Н 4.21; N 12.53.
3-(4-Fluorophenyl)-4-(4-methoxybenzoyl)-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (4l).
Yield 43%, mp 302-304°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.55 (1H, d, J = 16.5) and 2.89 (1H, dd, J = 16.8,
J = 6.8, 5-CH2); 3.83 (3H, s, OCH3); 5.00 (1H, d, J = 6.8, 4-CH); 6.84 (2H, d, J = 8.4, H-3,5 ArCO); 7.11 (2H,
dd, J = 8.0, J = 2.2, H-3,5 Ar); 7.42 (2H, t, J = 8.2, H-2,6 Ar); 7.82 (2H, d, J = 8.4, H-2,6 ArCO); 10.16 (1H,
br. s, 7-NH); 12.31 (1H, br. s, 2-NH). Found, %: С 65.82; Н 4.48; N 11.44. С20Н16FN3О3. Calculated, %:
С 65.75; Н 4.41; N 11.50.
4-(4-Fluorobenzoyl)-3-(4-fluorophenyl)-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
(4m).
1
Yield 41%, mp 305-307°C. H NMR spectrum, δ, ppm (J, Hz): 2.56 (1H, d, J = 16.5) and 2.89 (1H, dd,
J = 16.2, J = 6.2, 5-CH2); 5.16 (1H, d, J = 6.2, 4-CH); 7.03-7.14 (4H, m, H-3,5 Ar, H-3,5 ArCO); 7.42 (2H, dd,
J = 8.4, J = 5.0, H-2,6 Ar); 7.88 (2H, dd, J = 8.0, J = 5.6, H-2,6 ArCO); 10.19 (1H, br. s, 7-NH); 12.32 (1H,
br. s, 2-NH). Mass spectrum, m/z (Irel, %): 353 [M]+ (12), 231 (20), 230 (100), 123 (36), 95 (34), 76 (15). Found,
%: С 64.62; Н 3.63; N 12.00. С19Н13F2N3О2. Calculated, %: С 64.59; Н 3.71; N 11.89.
4-Benzoyl-1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (6a). Yield 51%, mp
1
175-177°C. H NMR spectrum, δ, ppm (J, Hz): 2.55 (1H, dd, J = 16.2, J = 4.2) and 2.70 (1H, dd, J = 16.2,
J = 6.2, 5-CH2); 3.60 (3H, s, NCH3); 4.92 (1H, dd, J = 6.2, J = 4.2, 4-CH); 6.93 (1H, s, 3-CH); 7.91-7.81 (3H,
m, H-3,4,5 Ph); 8.06 (2H, d, J = 7.6, H-2,6 Ph); 10.60 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 255 [M]+
(7), 150 (100), 105 (22), 77 (19). Found, %: С 65.76; Н 5.01; N 16.62. С14Н13N3О2. Calculated, %: С 65.87;
Н 5.13; N 16.46.
521

1-Methyl-4-(4-methylbenzoyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (6b). Yield
54%, mp 197-199°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.43 (3H, s, CH3); 2.62 (1H, dd, J = 16.0, J = 4.0) and
2.71 (1H, dd, J = 16.2, J = 6.4, 5-CH2); 3.60 (3H, s, NCH3); 4.86 (1H, dd, J = 6.2, J = 3.8, 4-CH); 6.88 (1H, s,
3-CH); 7.33 (2H, d, J = 8.0, H-3,5 Ar); 7.94 (2H, d, J = 7.8, H-2,6 Ar); 10.56 (1H, br. s, 7-NH). Mass spectrum,
m/z (Irel, %): 269 [M]+ (10), 213 (14), 150 (100), 119 (20). Found, %: С 67.01; Н 5.50; N 15.56. С15Н15N3О2.
Calculated, %: С 66.90; Н 5.61; N 15.60.
4-(4-Methoxybenzoyl)-1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (6c). Yield 56%,
1
mp 170-172°C. H NMR spectrum, δ, ppm (J, Hz): 2.64 (1H, dd, J = 16.2, J = 4.4) and 2.70 (1H, dd, J = 16.2,
J = 6.0, 5-CH2); 3.61 (3H, s, NCH3); 3.88 (3H, s, OCH3); 4.84 (1H, dd, J = 6.0, J = 4.4, 4-CH); 6.90 (1H, s,
3-CH); 7.02 (2H, d, J = 8.6, H-3,5 Ar); 8.01 (2H, d, J = 8.6, H-2,6 Ar); 10.55 (1H, br. s, 7-NH). Mass spectrum,
m/z (Irel, %): 285 [M]+ (8), 239 (10), 178 (11), 150 (100), 135 (27). Found, %: С 63.06; Н 5.41; N 14.68.
С15Н15N3О3. Calculated, %: С 63.15; Н 5.30; N 14.73.
4-(4-Fluorobenzoyl)-1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (6d). Yield 77%,
1
mp 177-179°C. H NMR spectrum, δ, ppm (J, Hz): 2.65 (1H, dd, J = 16.4, J = 3.6) and 2.71 (1H, dd, J = 16.2,
J = 6.0, 5-CH2); 3.60 (3H, s, NCH3); 4.90 (1H, dd, J = 6.0, J = 3.4, 4-CH); 6.92 (1H, s, 3-CH); 7.29 (2H, d,
J = 8.4, H-3,5 Ar); 8.14 (2H, dd, J = 8.0, J = 7.6, H-2,6 Ar); 10.59 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel,
%): 273 [M]+ (8), 151 (10), 150 (100), 123 (18), 106 (5), 105 (22). Found, %: С 61.61; Н 4.37; N 15.47.
С14Н12FN3О2. Calculated, %: С 61.53; Н 4.43; N 15.38.
4-(4-Bromobenzoyl)-1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (6e). Yield 71%,
1
mp 217-219°C. H NMR spectrum, δ, ppm (J, Hz): 2.64 (1H, dd, J = 15.6, J = 4.8) and 2.70 (1H, dd, J = 15.8,
J = 6.2, 5-CH2); 3.60 (3H, s, NCH3); 4.89 (1H, dd, J = 6.2, J = 4.4, 4-CH); 6.93 (1H, s, 3-CH); 7.70 (2H, d,
J = 8.6, H-3,5 Ar); 8.00 (2H, d, J = 8.6, H-2,6 Ar); 10.60 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 335
[M (81Br)]+ (4), 333 [M (79Br)]+ (5), 320 (11), 318 (12), 279 (9), 277 (10), 239 (14), 185 (27), 183 (29), 178
(10), 150 (100), 124 (12). Found, %: С 50.41; Н 3.57; N 12.49. С14Н12BrN3О2. Calculated, %: С 50.32; Н 3.62;
N 12.57.
4-(4-Bromobenzoyl)-1,3-dimethyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (6f). Yield
1
65%, mp 252-254°C. H NMR spectrum, δ, ppm (J, Hz): 1.73 (3H, s, 3-CH3); 2.56 (1H, dd, J = 15.6, J = 2.2)
and 2.74 (1H, dd, J = 16.2, J = 6.6, 5-CH2); 3.50 (3H, s, NCH3); 4.89 (1H, dd, J = 6.6, J = 2.2, 4-CH); 7.74 (2H,
d, J = 8.4, H-3,5 Ar); 7.93 (2H, d, J = 8.6, H-2,6 Ar); 10.54 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 349
(5) [M (81Br)]+, 347 (6) [M (79Br)]+, 253 (11), 185 (11), 183 (12), 164 (100), 150 (38). Found, %: С 51.83;
Н 3.97; N 11.98. С15Н14BrN3О2. Calculated, %: С 51.74; Н 4.05; N 12.07.
3-(tert-Butyl)-4-(4-fluorobenzoyl)-1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
1
(6g). Yield 63%, mp 267-269°C. H NMR spectrum, δ, ppm (J, Hz): 1.08 (9H, s, C(CH3)3); 2.38 (1H, d,
J = 16.0) and 2.98 (1H, dd, J = 16.0, J = 6.4, 5-CH2); 3.63 (3H, s, NCH3); 5.06 (1H, d, J = 6.2, 4-CH); 7.28 (2H,
t, J = 7.0, H-3,5 Ar); 8.16 (2H, dd, J = 7.2, J = 6.8, H-2,6 Ar); 10.57 (1H, br. s, 7-NH). 13C NMR spectrum, δ,
ppm: 30.3 (C(CH3)3); 32.9 (C(CH3)3); 35.1 (NCH3); 36.3 (C-4); 37.4 (C-5); 96.1 (C-3a); 116.6 (C-3(5) Ar);
116.8 (C-5(3) Ar); 131.8 (C-2(6) Ar); 132.1 (C-6(2) Ar); 141.6 (C-1 Ar); 154.4 (C-3); 164.9 (C-7a); 166.9 (C–F);
168.9 (CONH); 199.1 (COAr). Mass spectrum, m/z (Irel, %): 329 [M]+ (15), 234 (11), 206 (100), 123 (56), 95
(12). Found, %: С 65.72; Н 6.02; N 12.85. С18Н20FN3О2. Calculated, %: С 65.64; Н 6.12; N 12.76.
4-(4-Bromobenzoyl)-3-(tert-butyl)-1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
1
(6h). Yield 68%, mp 303-305°C. H NMR spectrum, δ, ppm (J, Hz): 1.28 (9H, s, C(CH3)3); 2.55 (1H, d,
J = 16.0) and 3.08 (1H, dd, J = 16.0, J = 6.8, 5-CH2); 3.84 (3H, s, NCH3); 5.28 (1H, d, J = 6.8, 4-CH); 7.74 (2H,
d, J = 7.6, H-3,5 Ar); 8.07 (2H, d, J = 7.6, H-2,6 Ar); 11.11 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 391
[M (81Br)]+ (4), 389 [M (79Br)]+ (5), 207 (32), 206 (100), 150 (63). Found, %: С 55.32; Н 5.09; N 10.85.
С18Н20BrN3О2. Calculated, %: С 55.40; Н 5.17; N 10.77.
4-Benzoyl-1-cyclopentyl-3-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
(6i).
Yield 59%, mp 221-223°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.60-1.67 (2H, m) and 1.82-1.91 (2H, m, 2СH2);
522

1.95 (3H, s, 3-CH3); 1.99-2.08 (4H, m, 2СH2); 2.82-2.94 (2H, m, 5-CH2); 4.40-4.53 (1H, m, J = 7.0, (CH2)2CH);
4.77 (1H, dd, J = 6.0, J = 4.0, 4-CH); 7.50 (2H, t, J = 7.2, H-3,5 Ph); 7.61 (1H, t, J = 7.2, H-4 Ph); 7.99 (2H, d,
J = 7.4, H-2,6 Ph); 10.34 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 323 [M]+ (13), 219 (17), 218 (100),
150 (28), 105 (14), 77 (13). Found, %: С 70.47; Н 6.48; N 13.05. С19Н21N3О2. Calculated, %: С 70.57; Н 6.55;
N 12.99.
1-Cyclopentyl-3-methyl-4-(4-methylbenzoyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
(6j). Yield 76%, mp 176-178°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.54-1.59 (2H, m, СH2); 1.80-1.89 (9H, m,
3-CH3, 3СH2); 2.10 (3H, s, CH3C6H4); 2.60 (1H, dd, J = 16.4, J = 2.4) and 2.70 (1H, dd, J = 15.8, J = 6.2,
5-CH2); 4.52-4.63 (1H, m, (CH2)2CH); 4.86 (1H, dd, J = 6.2, J = 2.4, 4-CH); 7.28 (2H, d, J = 8.6, H-3,5 Ar);
8.09-8.13 (2H, d, J = 8.6, H-2,6 Ar); 10.39 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 338 [M+Н]+ (20),
337 [M]+ (100), 322 (11), 218 (16), 149 (12), 119 (17), 91 (10). Found, %: С 71.27; Н 6.95; N 12.53.
С20Н23N3О2. Calculated, %: С 71.19; Н 6.87; N 12.45.
1-Cyclopentyl-4-(4-methoxybenzoyl)-3-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
(6k). Yield 58%, mp 215-217°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.53-1.59 (2H, m, СH2); 1.83-1.90 (9H, m,
3-CH3, 3СH2); 2.60 (1H, dd, J = 15.6, J = 2.6) and 2.69 (1H, dd, J = 15.8, J = 6.6, 5-CH2); 3.87 (3H, s, OCH3);
4.53−4.64 (1H, m, (CH2)2CH); 4.82 (1H, dd, J = 6.6, J = 2.6, 4-CH); 7.02 (2H, d, J = 8.6, H-3,5 Ar); 8.01 (2H, d,
13
J = 8.6, H-2,6 Ar); 10.35 (1H, br. s, 7-NH). C NMR spectrum, δ, ppm: 13.4 (3-CH3); 24.6 (2CH2); 31.9 (CH2);
32.4 (CH2); 35.3 (C-4); 35.9 (C-5); 56.1 (OCH3); 57.1 ((CH2)2CH); 96.2 (C-3a); 114.5 (C-3,5 Ar); 128.8 (C-1 Ar);
131.5 (H-2,6 Ar); 140.1 (C-4 Ar); 143.0 (C-3); 163.9 (C-7a); 170.3 (CONH); 198.5 (COAr). Mass spectrum, m/z
(Irel, %): 354 [M+Н]+ (21), 353 [M]+ (100), 338 (12), 322 (19), 284 (14), 270 (12), 218 (22), 149 (11), 135 (31).
Found, %: С 68.05; Н 6.65; N 12.00. С20Н23N3О3. Calculated, %: С 67.97; Н 6.56; N 11.89.
1-Cyclopentyl-4-(4-fluorobenzoyl)-3-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (6l).
1
Yield 39%, mp 229-231°C. H NMR spectrum, δ, ppm (J, Hz): 1.53-1.58 (2H, m, СH2); 1.80-1.89 (9H, m,
3-CH3, 3СH2); 2.58 (1H, dd, J = 16.0, J = 2.4) and 2.70 (1H, dd, J = 16.4, J = 6.8, 5-CH2); 4.51-4.62 (1H, m,
(CH2)2CH); 4.85 (1H, dd, J = 6.8, J = 2.4, 4-CH); 7.28 (2H, t, J = 8.8, H-3,5 Ar); 8.11 (2H, dd, J = 8.8, J = 5.2,
H-2,6 Ar); 10.39 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 341 [M]+ (11), 272 (10), 218 (100), 136 (12).
Found, %: С 66.95; Н 6.01; N 12.40. С19Н20FN3О2. Calculated, %: С 66.85; Н 5.91; N 12.31.
3-Methyl-4-(4-methylbenzoyl)-1-phenyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (6m).
Yield 64%, mp 187-189°C. IR spectrum, ν, cm-1: 3320-3252 (NH), 1640 (C=O), 1572 (C=C), 1508 (C=N).
1H NMR spectrum, δ, ppm (J, Hz): 1.86 (3H, s, 3-CH3); 2.05 (3H, s, CH3C6H4), 2.65 (1H, d, J = 15.6) and 2.88
(1H, dd, J = 15.4, J = 6.2, 5-CH2); 5.05 (1H, d, J = 6.0, 4-CH); 7.32-7.68 (7H, m, H Ph, H-3,5 Ar); 8.06 (2H, d,
13
J = 7.0, H-2,6 Ar); 10.40 (1H, br. s, 7-NH). C NMR spectrum, δ, ppm: 13.0 (3-CH3); 31.2 (CH3C6H4); 35.1
(C-4); 36.6 (C-5); 98.8 (C-3a); 123.4 (C-2,6 Ph); 127.4 (C-4 Ph); 129.3 (C-2,6 Ar); 129.3 (C-3,5 Ar); 129.7
(C-3,5 Ph); 134.1 (C-1 Ar); 136.3 (C-1 Ar); 138.3 (C-4 Ar); 140.4 (C-3); 145.7 (C-7a); 170.3 (CONH); 199.2
(COAr). Mass spectrum, m/z (Irel, %): 345 [M]+ (17), 330 (10), 268 (13), 226 (100), 119 (43). Found, %:
С 72.95; Н 5.64; N 12.25. С21Н19N3О2. Calculated, %: С 73.03; Н 5.54; N 12.17.
4-(4-Methoxybenzoyl)-3-methyl-1-phenyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
(6n). Yield 82%, mp 192-194°C. IR spectrum, ν, cm-1: 3324-3252 (NH), 1640 (C=O), 1580 (C=C), 1508
1
(C=N). H NMR spectrum, δ, ppm (J, Hz): 2.06 (3H, s, 3-CH3); 2.68 (1H, d, J = 15.8) and 2.82-3.01 (1H, dd,
J = 16.0, J = 6.0, 5-CH2); 3.78 (3H, s, OCH3); 5.29 (1H, d, J = 6.0, 4-CH); 6.95 (2H, d, J = 8.4, H-3,5 Ar);
7.72-7.43 (5H, m, H Ph); 7.79 (2H, d, J = 8.4, H-2,6 Ar); 10.35 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %):
361 [M]+ (18), 284 (11), 226 (100), 135 (38). Found, %: С 69.86; Н 5.21; N 11.71. С21Н19N3О3. Calculated, %:
С 69.79; Н 5.30; N 11.63.
1-(4-Methoxyphenyl)-3-methyl-4-(4-methylbenzoyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
1
(6o). Yield 61%, mp 187-189°C. H NMR spectrum, δ, ppm (J, Hz): 1.91 (3H, s, 3-CH3); 2.44 (3H, s,
CH3C6H4); 2.65 (1H, dd, J = 16.2, J = 3.2) and 2.79 (1H, dd, J = 16.4, J = 6.4, 5-CH2); 3.82 (3H, s, OCH3); 4.90
(1H, dd, J = 6.2, J = 3.0, 4-CH); 6.96 (2H, d, J = 9.0, H-3,5 Ar); 7.30-7.36 (4H, m, H-2,6 Ar, H-3,5 ArCO);
7.97 (2H, d, J = 7.8, H-2,6 ArCO); 10.14 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 376 [M+Н]+ (44), 375
523

[M]+ (19), 360 (10), 346 (18), 315 (13), 268 (10), 256 (100), 239 (15), 177 (10), 107 (11). Found, %: С 70.45;
Н 5.57; N 11.10. С22Н21N3О3. Calculated, %: С 70.38; Н 5.64; N 11.19.
4-(4-Fluorobenzoyl)-1-(4-methoxyphenyl)-3-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-
1
6-one (6p). Yield 54%, mp 170-172°C. H NMR spectrum, δ, ppm (J, Hz): 1.90 (3H, s, 3-CH3); 2.65 (1H, dd,
J = 15.4, J = 1.8) and 2.78 (1H, dd, J = 15.8, J = 6.8, 5-CH2); 3.82 (3H, s, OCH3); 4.98 (1H, dd, J = 6.6, J = 2.4,
4-CH); 6.96 (2H, d, J = 8.6, H-3,5 Ar); 7.28-7.36 (4H, m, H-2,6 Ar, H-3,5 ArCO); 8.16 (2H, dd, J = 8.6,
J = 5.4, H-2,6 ArCO); 10.17 (1H, br. s, 7-NH). Mass spectrum, m/z (Irel, %): 379 [M]+ (17), 257 (24), 256 (100),
123 (23), 95 (27). Found, %: С 66.57; Н 4.69; N 11.01. С21Н18FN3О2. Calculated, %: С 66.48; Н 4.78; N 11.08.
4-(4-Methoxybenzoyl)-2,3,7-trimethyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
(11).
Sodium hydride (0.05 g, 2.1 mmol) was added to a stirred solution of compound 4c (0.285 g, 1.0 mmol) in DMF
(2 ml). After the hydrogen evolution had subsided, methyl iodide (0.13 ml, 2.1 mmol) was added dropwise to
the reaction mixture, and the stirring was continued for 30 min. Then distilled water (20 ml) was added to the
reaction mixture, and the white precipitate was filtered off, washed on the filter with water, and crystallized
from EtOH. Yield 37%, white powder, mp 225-227°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.28 (3H, s, 3-CH3);
2.55 (1H, dd, J = 16.2, J = 4.0) and 2.63 (1H, dd, J = 16.2, J = 6.2, 5-CH2); 3.48 (3H, s, 7-CH3); 3.72 (3H, s,
2-CH3); 3.79 (3H, s, OCH3); 5.56 (1H, dd, J = 6.0, J = 4.0, 4-CH); 6.98 (2H, d, J = 8.0, H-3,5 Ar); 7.90 (2H, d,
J = 8.2, H-2,6 Ar). Found, %: С 65.27; Н 6.01; N 13.48. С17Н19N3О3. Calculated, %: С 65.16; Н 6.11; N 13.41.
2-Acetyl-4-(4-bromobenzoyl)-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (12).
Sulfuric acid (1-2 drops) was added to a stirred solution of compound 4f (0.334 g, 1 mmol) in acetic anhydride
(5 ml), and reaction mixture was stirred for 10-15 min at room temperature. Distilled water (50 ml) was added,
and the white precipitate was filtered off, washed on the filter with warm water, and crystallized from MeOH.
Yield 53%, white powder, mp 274-276°C. IR spectrum, ν, cm-1: 3296-3250 (NH), 1712 (MeC=O), 1676 (C=O),
1
1604 (C=C), 1532 (C=N). H NMR spectrum, δ, ppm (J, Hz): 2.22 (3H, s, 3-CH3); 2.44 (3H, s, CH3CO); 2.56
(1H, d, J = 16.6) and 2.79 (1H, dd, J = 16.6, J = 6.8, 5-CH2); 5.11 (1H, d, J = 5.2, 4-CH); 7.75 (2H, d, J = 8.4,
H-3,5 Ar); 7.96 (2H, d, J = 8.4, H-2,6 Ar); 10.17 (1H, br. s, 7-NH). Found, %: С 50.99; Н 3.68; N 11.25.
С16Н14BrN3О3. Calculated, %: С 51.08; Н 3.75; N 11.17.
4-(4-Bromobenzoyl)-2,3,7-trimethyl-2,7-dihydro-6H-pyrazolo[3,4-b]pyridin-6-one (13). A mixture of
compound 4f (0.334 g, 1.0 mmol), powdered KOH (0.12 g, 2.1 mmol), and methyl iodide (0.13 ml, 2.1 mmol)
was dissolved in DMF (2 ml) and stirred for 2 h. Then distilled water (20 ml) and a few drops of dilute
hydrochloric acid (to the pH ~7) were added to this solution. The pale-yellow precipitate was filtered off,
washed on the filter with water, and crystallized from ethanol. Yield 48%, pale-yellow powder, mp 229-231°C.
1H NMR spectrum, δ, ppm (J, Hz): 2.06 (3H, s, 3-CH3); 3.44 (3H, s, 7-NCH3); 3.79 (3H, s, 2-CH3); 6.18 (1H, s,
13
5-CH); 7.74–7.84 (4H, m, H Ar). C NMR spectrum, δ, ppm: 10.5 (3-CH3); 28.6 (7-CH3); 37.2 (2-CH3); 86.2
(C-3a); 101.3 (C–Br); 132.2 (C-2,6 Ar); 132.8 (C-3,5 Ar); 134.7 (C-5); 135.0 (C-1 Ar); 137.0 (C-4 Ar); 142.4 (C-3);
149.7 (C-4); 161.6 (C-7a); 170.1 (CONH); 193.3 (COAr). Mass spectrum, m/z (Irel, %): 362 [M+Н (81Br)]+ (40), 360
[M+Н (79Br)]+ (42), 361 [M (81Br)]+ (99), 359 [M (79Br)]+ (100), 344 (17), 342 (18), 333 (50), 331 (52), 332
(81), 330 (83), 304 (11), 302 (12), 185 (50), 183 (52), 157 (39), 155 (40). Found, %: С 53.26; Н 4.01; N 11.58.
С16Н14BrN3О2. Calculated, %: С 53.35; Н 3.92; N 11.67.
4-Benzoyl-3-methyl-2,7-dihydro-6H-pyrazolo[3,4-b]pyridin-6-one (14a). A. A solution of compound 4a
(0.255 g, 1 mmol) in pyridine (5 ml) was refluxed for 8 h. The solution was cooled, and the yellow precipitate
was filtered off and washed on the filter with MeOH. Yield 60%, yellow powder, mp 265-267°C.
B. A solution of compound 4a (0.255 g, 1 mmol) in acetic acid (5 ml) was refluxed for 5 h. The solution
was cooled, and the yellow precipitate was filtered and washed on the filter with MeOH. Yield 63%, yellow
powder, mp 264-266°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.97 (3H, s, 3-CH3); 6.06 (1H, s, 5-CH); 7.56 (2H,
d, J = 7.4, H-3,5 Ph); 7.72 (1H, t, J = 7.0, H-4 Ph); 7.87 (2H, d, J = 7.4, H-2,6 Ph), 11.92 (1H, br. s, 7-NH);
12.96 (1H, br. s, 2-NH). 13C NMR spectrum, δ, ppm: 11.3 (3-CH3); 84.49 (C-3a); 129.4 (C-2,6 Ph);
524

130.3 (C-3,5 Ph); 135.0 (C-1 Ph); 136.8 (C-5); 144.3 (C-4 Ph); 147.8 (C-3); 149.2 (C-4); 150.3 (C-7a); 163.1
(CONH); 194.5 (COAr). Mass spectrum, m/z (Irel, %): 254 [M+Н]+ (21), 253 [M]+ (100), 252 [M-Н]+ (10), 225
(68), 224 (55), 105 (83), 77 (52). Found, %: С 66.49; Н 4.29; N 16.51. С14Н11N3О2. Calculated, %: С 66.40;
Н 4.38; N 16.59.
3-Methyl-4-(4-methylbenzoyl)-2,7-dihydro-6H-pyrazolo[3,4-b]pyridin-6-one (14b). Powdered of
KOH (0.057 g, 1 mmol) was added to a solution of compound 4b (0.269 g, 1 mmol) in DMF (2 ml), and the
reaction mixture was stirred for 3 h. Then distilled water (20 ml) and a few drops of dilute hydrochloric acid (to
pH ~7) were added to this solution. The yellow precipitate was filtered, washed on the filter with water, and
crystallized from EtOH. Yield 63%, yellow powder, mp 273-275°C. IR spectrum, ν, cm-1: 3364-3312 (NH),
1652 (C=O), 1604 (C=С), 1556 (C=N). 1H NMR spectrum, δ, ppm (J, Hz): 1.98 (3H, s, 3-CH3); 2.37 (3H, s,
CH3C6H4); 6.03 (1H, s, 5-CH); 7.37 (2H, d, J = 8.2, H-3,5 Ar); 7.69 (2H, d, J = 8.0, H-2,6 Ar); 11.89 (1H, br. s,
7-NH); 12.97 (1H, br. s, 2-NH). 13C NMR spectrum, δ, ppm: 13.1 (3-CH3); 21.8 (CH3C6H4); 79.6 (C-3a); 130.2
(C-2,6 Ar); 130.4 (C-3,5 Ar); 133.3 (C-1 Ar); 134.7 (C-5); 144.5 (C-4 Ar); 145.8 (C-3,4); 150.4 (C-7a); 163.2
(CONH); 193.9 (COAr). Found, %: С 67.31; Н 5.00; N 15.64. С15Н13N3О2. Calculated, %: С 67.40; Н 4.90;
N 15.72.
4-[Hydroxy(aryl)methyl]-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-ones
15a,b
(General Method). NaBH4 (0.04 g, 1 mmol) was added to a solution of compound 4a or 4b (1 mmol) in
2-PrOH (18-20 ml), and the obtained mixture was refluxed for 3-3.5 h. After cooling, the white precipitate that
formed was filtered off, washed on the filter with warm i-PrOH, and crystallized from ethanol.
4-[Hydroxy(phenyl)methyl]-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
(15a).
Yield 92%, mp 278-280°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.45 (3H, s, 3-CH3); 2.27 (1H, d, J = 16.0) and
2.56 (1H, dd, J = 15.8, J = 7.6, 5-CH2); 2.91-2.97 (1H, m, 4-CH); 4.53 (1H, d, J = 4.0, CHOH); 5.26 (1H, br. s,
OH); 7.10-7.25 (5H, m, Ph); 9.87 (1H, br. s, 7-NH); 11.50 (1H, br. s, 2-NH). Found, %: С 65.43; Н 5.92;
N 16.23. С14Н15N3О2. Calculated, %: С 65.35; Н 5.88; N 16.33.
4-[Hydroxy(p-tolyl)methyl]-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
(15b).
Yield 83%, mp 313-315°C. IR spectrum, ν, cm-1: 3300–3260 (NH, OH, H-bond), 1648 (C=O), 1616 (C=C),
1
1524 (C=N). H NMR spectrum, δ, ppm (J, Hz): 1.55 (3H, s, 3-CH3); 2.23 (1H, d, J = 15.4) and 2.57 (dd, 1H,
J = 15.4, J = 8.0, 5-CH2); 2.25 (3H, s, CH3C6H4); 2.88-2.94 (1H, m, 4-CH); 4.46 (1H, t, J = 4.4, CHOH); 5.20
(1H, d, J = 4.2, OH); 6.99 (2H, d, J = 8.0, H-3,5 Ar); 7.06 (2H, d, J = 8.0, H-2,6 Ar); 9.88 (1H, br. s, 7-NH);
11.51 (1H, br. s, 2-NH). Found, %: С 66.51; Н 6.41; N 15.40. С15Н17N3О2. Calculated, %: С 66.40; Н 6.32;
N 15.49.
4-[Hydroxy(2-phenylhydrazinyl)(p-tolyl)methyl]-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]-
pyridin-6-one (17). A mixture of compound 4b (0.269 g, 1 mmol) and phenylhydrazine (16a) (0.098 ml,
1 mmol) in EtOH (8-10 ml) with a catalytic amount of HCl (3-4 drops) was refluxed for 2 h. After cooling, a
pale-yellow precipitate formed. The precipitate was filtered off and washed twice on the filter with EtOH. Yield
42%, pale- yellow powder, mp 260-262°C. IR spectrum, ν, cm-1: 3220–3140 (NH), 1660 (C=O), 1600 (C=С),
1
1500 (C=N). H NMR spectrum, δ, ppm (J, Hz): 1.41 (3H, s, 3-CH3); 2.37 (3H, s, CH3C6H4); 2.65 (1H, dd,
J = 15.0, J = 7.0) and 2.87 (1H, d, J = 15.0, 5-CH2); 3.81 (1H, br. s, OH); 4.00 (1H, d, J = 6.8, 4-CH); 6.67 (1H,
t, J = 7.0, H-4 Ph); 7.04-7.13 (7H, m, H-2,3,5,6 Ph, H-3,5 Ar, NHPh); 7.30 (2H, d, J = 7.4, H-2,6 Ar); 8.36 (1H,
d, J = 9.4, NHC(OH)); 10.06 (1H, br. s, 7-NH); 11.56 (1H, br. s, 2-NH). 1H NMR spectrum (DMSO-d6+D2O),
δ, ppm (J, Hz): 1.39 (3H, s, 3-CH3); 2.31 (3H, s, CH3C6H4); 2.60 (1H, dd, J = 16.0, J = 6.4) and 2.84 (1H, d,
J = 16.2, 5-CH2); 3.97 (1H, d, J = 6.0, 4-CH); 6.63 (1H, t, J = 6.8, H-4 Ph); 6.95-7.09 (6H, m, H-2,3,5,6 Ph,
H-3,5 Ar); 7.25 (2H, d, J = 7.4, H-2,6 Ar). 13C NMR spectrum, δ, ppm: 9.0 (3-CH3); 21.5 (CH3C6H4); 36.4
(С-5); 36.8 (C-4); 79.6 (C-3a); 99.8 (C–OH); 113.1 (C-2,6 Ph); 118.9 (C-4 Ph); 129.0 (C-2,6 Ar); 130.2 (C-3,5
Ar); 131.2 (C-3,5 Ph); 135.1 (C-1 Ar); 138.5 (C-4 Ar); 146.8 (C-3); 149.1 (C-1 Ph); 159.8 (C-7a); 170.6
(CONH). Mass spectrum, m/z (Irel, %): 376 [M–Н]+ (11), 359 (21), 150 (100), 149 (58), 132 (16), 121 (14), 93
(51), 92 (92), 91 (15), 65 (47). Found, %: С 66.76; Н 6.19; N 18.62. С21Н23N5О2. Calculated, %: С 66.83;
Н 6.14; N 18.55.
525

3-Methyl-4-[(2-phenylhydrazono)(p-tolyl)methyl]-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-
6-one (18a). A mixture of compound 4b (0.269 g, 1 mmol) and phenylhydrazine (16a) (0.098 ml, 1 mmol) in
EtOH (8-10 ml) with a catalytic amount of HCl (3-4 drops) was refluxed for 4 h. The solution was cooled, and
the yellow precipitate was filtered off and washed twice on the filter with EtOH. Yield 64%, mp 340-342°C.
1H NMR spectrum, δ, ppm (J, Hz): 1.36 (3H, s, 3-CH3); 2.34 (3H, s, CH3C6H4); 2.62 (1H, dd, J = 15.0, J = 7.0)
and 2.85 (1H, d, J = 15.4, 5-CH2); 3.98 (1H, d, J = 6.8, 4-CH); 6.72 (1H, t, J = 7.2, H-4 Ph); 6.98-7.10 (6H, m,
H-2,3,5,6 Ph, H-3,5 Ar); 7.27 (2H, d, J = 8.0, H-2,6 Ar); 8.34 (1H, br. s, NH–N=); 10.04 (1H, br. s, 7-NH);
11.55 (1H, br. s, 2-NH). Found, %: С 70.09; Н 5.96; N 19.56. С21Н21N5О. Calculated, %: С 70.17; Н 5.89;
N 19.48.
4-[(4-Methoxyphenyl)(p-tolylimino)methyl]-3-methyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-
6-one (18b). A mixture of compound 4c (0.285 g, 1 mmol) and p-toluidine (16b) (0.107 g, 1 mmol) in xylene
(7-8 ml) was refluxed for 8 h. The solution was cooled, and the beige precipitate was filtered off, washed twice
on the filter with xylene, and crystallized from MeOH. Yield 64%, mp 334-336°C. IR spectrum, ν, cm-1:
1
3228-3180 (NH), 1664 (C=O), 1584 (C=C), 1504 (C=N). H NMR spectrum, δ, ppm (J, Hz): 2.22 (3H, s,
3-CH3); 2.29 (3H, s, CH3C6H4); 2.53 (1H, d, J = 16.4) and 2.96 (1H, dd, J = 16.4, J = 7.2, 5-CH2); 3.86 (3H, s,
OСH3); 5.18 (1H, d, J = 7.0, 4-CH); 7.13 (2H, d, J = 8.0, H-3,5 ArN); 7.22 (2H, d, J = 8.0, H-2,6 ArN); 7.45
(2H, d, J = 8.4, H-3,5 Ar); 7.68 (2H, d, J = 8.4, H-2,6 Ar); 10.36 (1H, br. s, 7-NH); 12.39 (1H, br. s, 2-NH).
Found, %: С 70.65; Н 6.01; N 15.04. С22Н22N4О2. Calculated, %: С 70.57; Н 5.92; N 14.96.
3-Methyl-4-[phenyl(2-phenylhydrazono)methyl]-2,7-dihydro-6H-pyrazolo[3,4-b]pyridin-6-one (19).
A solution of compound 4a (0.255 g, 1 mmol) and phenylhydrazine (16a) (0.098 ml, 1 mmol) in acetic acid
(10 ml) was refluxed for 2.5 h. After cooling, the pale-yellow precipitate was filtered off, washed on the filter
1
with warm water, and crystallized from EtOH. Yield 80%, mp 314-316°C. H NMR spectrum, δ, ppm (J, Hz):
1.87 (3H, s, 3-CH3); 5.92 (1H, s, 5-CH); 6.75 (1H, t, J = 7.8, H-4 PhN); 7.14-7.34 (7H, m, H-3,4,5 Ph, H-2,3,5,6
PhN); 7.56 (2H, d, J = 7.4, H-2,6 Ph); 9.26 (1H, br. s, NH–N=); 11.80 (1H, br. s, 7-NH); 12.70 (1H, br. s,
2-NH). Mass spectrum, m/z (Irel, %): 343 [M]+ (100), 343 [M-H]+ (55), 251 (11), 167 (11), 148 (14), 105 (33),
92 (12), 77 (52). Found, %: С 70.03; Н 5.07; N 20.33. С20Н17N5О. Calculated, %: С 69.96; Н 4.99; N 20.40.
tert-Butyl 4-({2-[(4-Methoxyphenyl)(3-methyl-6-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]-
pyridin-4-yl)methylidene]hydrazino}carbonyl)piperidine-1-carboxylate (20). A solution of compound 6n
(0.361 g, 1 mmol) and 1-tert-butylpiperidine-4-carbohydrazide (16c) (0.200 g, 1 mmol) in a mixture EtOH–DMSO,
2:1 (~6 ml) was refluxed for 5 h. After cooling, the pale-yellow precipitate was filtered off and washed on the
filter with EtOH. Yield 68%, mp 93-95°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.37 (9H, s, C(CH3)3); 1.91 (3H,
s, 3-CH3); 2.35-2.43 (2H, m, CH2); 2.51-2.92 (6H, m, 5-CH2, 2CH2); 3.73-3.80 (2H, m, CH2); 3.85 (3H, s,
OCH3); 3.88-4.04 (1H, m, CHC=O); 5.01 (1H, d, J = 4.0, 4-CH); 7.02–7.10 (3H, m, H-3,5 Ar, NH–N=); 7.34
(1H, t, J = 7.6, H-4 Ph); 7.40-7.45 (4H, m, H-2,3,5,6 Ph); 8.07 (2H, d, J = 8.6, H-2,6 Ar); 10.38 (1H, br. s,
7-NH). Mass spectrum, m/z (Irel, %): 485 [M-Boc]+ (2), 227 (21), 226 (100), 135 (22), 77 (10). Found, %:
С 65.60; Н 6.47; N 14.24. С32Н38N6О5. Calculated, %: С 65.51; Н 6.53; N 14.32.
X-ray Diffraction Study of Compound 6c. The colorless crystals (crystallized from EtOH) of
compound 6с (C15H15N3O3) are monoclinic. At 293 K: a 13.7791(7), b 10.9180(6), c 9.1462(6) Å; β 92.870(5)°;
V 1374.2(1) Å3; Mr 285.30; Z 4; space group P21/c; dcalc 1.379 g/сm3; (MoKα) 0.098 mm-1, F(000) 600.
Intensities of 13261 reflections (4000 independent, Rint 0.029) were measured on an Xcalibur-3 diffractometer
(graphite monochromator, CCD detector, ω-scanning, 2max 60). The structure was solved by the direct method
using the SHELXTL package [27]. The positions of hydrogen atoms were found from electron density
difference maps and refined by ''rider'' model with Uiso = nUeq (n = 1.5 for methyl group and n = 1.2 for other
hydrogen atoms) for the carrier atom. The hydrogen atom of the NH group was refined in isotropic
approximation. Full-matrix least-squares refinement against F2 in anisotropic approximation for non-hydrogen
atoms using 3934 reflections converged to wR2 0.140 (R1 0.049 for 2534 reflections with F > 4σ(F), S 1.003).
The final atomic coordinates and crystallographic data for molecule 6c have been deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 981626).
526

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