Five-membered 2,3-dioxoheterocycles: XCIV. Recyclization of 4,5-diaroyl-1H-pyrrole-2,3-diones under the action of 3-aminopyrazolo[3,4-b] pyridine. Crystal and molecular structure of substituted pyrido[2′, 3′:3,4]pyrazolo[1,5-a]pyrimidine

Article abstract of DOI:10.1134/S1070428013080186

1-Aryl-4,5-diaroyl-1H-pyrrole-2,3-diones react with 3-amino-4,6-dimethyl- 2H-pyrazolo[3,4-b]-pyridine affording N-aryl-2,3-diaroyl-8,10-dimethylpyrido [2′,3′:3,4]pyrazolo[1,5-a]pyrimidine-4-carboxamides.

Full text of DOI:10.1134/S1070428013080186

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 8, pp. 1203−1207. © Pleiades Publishing, Ltd., 2013.
Original English Text © P.S. Silaichev, P.A. Slepukhin, A.N. Maslivets, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 8, pp. 1219−1222.
Five-Membered 2,3-Dioxoheterocycles: ХСIV.*
Recyclization of 4,5-Diaroyl-1H-pyrrole-2,3-diones
under the Action of 3-Aminopyrazolo[3,4-b]pyridine.
Crystal and Molecular Structure
of Substituted Pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine
P. S. Silaicheva,b, P. A. Slepukhinc, and A. N. Maslivetsa,b
aPerm’State National Research University, Perm’, 614990 Russia
e-mail: koh2@psu.ru
bInstitute of Natural Sciences at Perm’State National Research University, Perm’, Russia
cPostovskii Institute of Organic Synthesis,
Ural Branch, Russian Academy of Sciences, Yekaterinburg, Russia
Received May 10, 2012
Abstract—1-Aryl-4,5-diaroyl-1Н-pyrrole-2,3-diones react with 3-amino-4,6-dimethyl-2Н-pyrazolo[3,4-b]-
pyridine affording N-aryl-2,3-diaroyl-8,10-dimethylpyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-4-carboxamides.
DOI: 10.1134/S1070428013080186
In reactions of 4,5-diaroyl-1Н-pyrrole-2,3-diones with
nucleophiles several reaction pathways can be realized
depending on the structure of the nucleophiles. Recycli-
zations were described of 4,5-diaroyl-1Н-pyrrole-2,3-
diones under the action of arylamines [2] and substituted
hydrazines [3] involving the carbon atoms in the position
5 and the carbonyl group of the aroyl substituent in the
position 4 of 1Н-pyrrole-2,3-diones, and also spiro-
bisheterocyclization under the action of acyclic [1] and
heterocyclic [4] enamines involving the carbon atoms in
the position 5 and the carbonyl group of the aroyl substitu-
ent in the position 5 of 1Н-pyrrole-2,3-dionesов. No pub-
lished data exist on the reactions of these pyrrolediones
with NH,NH-1,3-binucleophiles.
by XRD analysis of compound IIIe.
Compounds IIIа–IIIh are bright yellow crystalline
substances with high melting points, readily soluble in
DMF and DMSO, sparingly soluble in less polar solvents,
insoluble in alkanes and water, showing the negative re-
sult in the test for the presence of an enol hydroxyl with
alcoholic solution of iron(III) chloride.
IR spectra of compounds IIIа–IIIh contain character-
istic bands of the stretching vibrations of amide group NH
(3176–3266 cm–1), of keto and amide carbonyl groups as
two or three bands in the region 1649–1692 cm–1.
In the 1Н NMR spectra of compounds IIIа–IIIh along-
side the signals of the protons of the aromatic substituents
and the groups attached to them singlet signals of two
methyl groups in the positions 8 and 10 of the heterocyclic
system are observed at 2.67–2.81 ppm, of the proton Н9
(7.20–7.26 ppm) and the proton of the NH group in the
region 11.14–11.49 ppm. In the 13С NMR spectrum of
compound IIId beside the signals of the carbon atoms of
the aromatic fragments and aliphatic substituents linked
thereto the signals of carbon atoms are present belong-
ing to two keto and an amido carbonyl groups at 195.57,
195.51, and 166.48 ppm.
At boiling a solution in anhydrous toluene of
1-aryl-4,5-diaroyl-1H-pyrrole-2,3-diones Iа–Ih [5]
and 3-amino-4,6-dimethyl-2Н-pyrazolo[3,4-b]pyridine
(II) [6] in a ratio 1:1 during 2–3 h (TLC monitoring)
we obtained in good yields N-aryl-2,3-diaroyl-8,10-
dimethylpyrido[2',3':3,4]-pyrazolo[1,5-a]pyrimidine-4-
carboxamides IIIа–IIIh,** whose structure was proved
–––––––––––––––––
* For Communication XCIII, see [1]
** For preliminary communication, see [7].
1203

SILAICHEV et al.
1204
Scheme.
Me
NH2
NH
O
O
2
Me
OH
Ar
Ar2
O
O
N
Me
N
Me
H
N
II
O
N
N
O
N
Ar1
NH
Ar1
Ar2
N
Ar2
O
Iа_Ih
Ar1
NH
Ar1
HN
O
O
O
O
O
Ar2
O
H
Ar2
O
N
N
N
N
_H2O
N
N
N
Ar2
N
Me
Ar2
Me
Me
Me
IIIа_IIIh
Ar1 = Ph, Ar2 = Ph (а), C6H4Me-4 (b), C6H3Me2-2,5 (c); Ar1 = C6H4Me-4, Ar2 = C6H4Me-4 (d), C6H3Me2-2,5 (e); Ar1 = C6H4OMe-4,
Ar2 = Ph (f), C6H4Me-4 (g), C6H3Me2-2,5 (h).
Structure of the molecule of 2,3-bis(2,5-dimethylbenzoyl)-8,10-dimethyl-N-(4-tolyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-
4-carboxamide (IIIe), according to XRD data shown in thermal ellipsoids of 50% probability.
To confirm the structure of obtained compounds
IIIа–IIIh and to establish the features of their spatial ar-
rangement compound IIIe was subjected to XRD analysis
(see the figure).
The spatial arrangement of compound IIIe is fairly
typical for this class substance. The conformation of the
molecule is governed, on the one hand, by the presence
of intramolecular hydrogen bond of the NH⋯N type fix-
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FIVE-MEMBERED 2,3-DIOXOHETEROCYCLES: ХСIV.
1205
1
ing the amide group in the heterocycle plane, and on the
other hand, by the mutual repulsion of carbonyl fragments
pushing the aroyl fragments from this plane.
mulls in mineral oil. Н and 13С NMR spectra were
registered on a spectrometer BrukerAM-400 at operating
frequencies 400 (1Н) and 100 MHz (13С) in DMSO-d6,
internal reference TMS. The homogeneity of compounds
synthesized was proved by TLC on Silufol plates, eluent
benzene–ethyl acetate, 5 : 1, development in iodine vapor.
2,3-Dibenzoyl-8,10-dimethyl-N-phenyl-
pyrido-[2',3':3,4]pyrazolo[1,5-a]pyrimidine-4-
carboxamide (IIIа). Asolution of 1 mmol of compound
Iа and 1.0 mmol of compound II in 20 ml of anhydrous
toluene was boiled for 3 h. On cooling the separated
precipitate was filtered off and recrystallized from
toluene. Yield 78%, mp 259–260°С. IR spectrum, cm–1:
3184 (NH), 1691 (C=O), 1675 (C=O), 1659 (C=O).
1Н NMR spectrum, δ, ppm: 2.70 s (3H, Me), 2.80 s (3H,
Me), 7.19–8.13 group of signals (16Harom), 11.49 s (1H,
NH). Found, %: C 73.15; H 4.38; N 13.30. С32H23N5О3.
Calculated, %: C 73.13; H 4.41; N 13.33.
The formation of compounds IIIа–IIIh occurs ap-
parently due to the initial addition of the primary amino
group of compound II to the carbon atom in the position
5 of 1H-pyrrole-2,3-diones Iа–Ih, the opening of the
pyrroledione ring at the N1–C5 bond and subsequent in-
tramolecular cyclization involving the endocyclic amino
group of compound II and the keto carbonyl group of the
oxamoyl moiety.
Pyrido[2’,3’:3,4]pyrazolo[1,5-a]pyrimidines at-
tract attention of researchers as potential biologi-
cally active compounds. Some of them exhibit cy-
totoxic action [8]. The described methods of the
synthesis of this heterocyclic system are based on the
reaction of 2-aminopyrazolo[1,5-а]pyrimidines or
3-aminopyrazolo[3,4-b]pyridines with 1,3-dicarbonyl
compounds [8–15], of 3-aminopyrazolo-[3,4-b]pyridines
with N-aryl-3-oxobutanethioamides [16], α,β-unsaturated
carbonyl compounds [8, 14, 17], with compounds con-
taining in their composition enol, enethiol, or enamine
moieties with one or two electron-acceptor groups in the
β-position of these fragments [12–14, 17–22]. Besides the
pyrido[2',3':3,4]pyrazolo-[1,5-a]pyrimidines can be syn-
thesized from 3-(N,N-dimethylaminomethyleneamino)
pyrazolo[3,4-b]pyridines obtained by the reaction of
3-aminopyrazolo-[3,4-b]pyridines with DMF and РОCl3
and 1-phenylpropan-2-one [17] or the cyanoacetic acid
derivatives [13, 23–25], and also by oxidation of tetra-
hydropyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidines pre-
pared by successive reactions of 3-aminopyrazolo[3,4-b]
pyridines with aldehydes and alkenes [26]. However
there is no published information on the synthesis of
pyrido[2',3':3,4]pyrazolo[1,5-a]-pyrimidines with several
electron-acceptor substituents in the pyrimidine ring.
Compounds IIIb–IIIh were prepared similarly.
8,10-Dimethyl-2,3-di(4-toluoyl)-N-phenyl-
pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-
4-carboxamide (IIIb). Yield 86%, mp 279–280°С
(ethyl acetate). IR spectrum, cm–1: 3260 (NH), 1686
(C=O), 1661 (C=O). 1Н NMR spectrum, δ, ppm: 2.28 s
(3H, Me), 2.43 s (3H, Me), 2.70 s (3H, Me), 2.81s (3H,
Me), 7.18–8.04 group of signals (14Harom), 11.41 s (1H,
NH). Found, %: C 73.70; H 4.94; N 12.60. С32H27N5О3.
Calculated, %: C 73.76; H 4.92; N 12.65.
2,3-Bis(2,5-dimethylbenzoyl)-8,10-dimethyl-N-
phenylpyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-
4-carboxamide (IIIc). Yield 84%, mp 281–282°С (ethyl
acetate). IR spectrum, cm–1: 3186 (NH), 1682 (C=O),
1
1663 (C=O). Н NMR spectrum, δ, ppm: 1.99 s (3H,
Me), 2.27 s (3H, Me), 2.28 s (3H, Me), 2.46 s (3H, Me),
2.68 s (3H, Me), 2.70 s (3H, Me), 7.10–7.63 group of
signals (12Harom), 11.27 s (1H, NH). Found, %: C 74.38;
H 5.36; N 12.06. С36H31N5О3. Calculated, %: C 74.34;
H 5.37; N 12.04.
8,10-Dimethyl-N-(4-tolyl)-2,3-di(4-toluoyl)-
pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-
4-carboxamide (IIId). Yield 83%, mp 267–268°С (ethyl
acetate). IR spectrum, cm–1: 3176 (NH), 1684 (C=O),
The reaction we describe is an example of the new
recyclization direction of substituted 4,5-diaroyl-1Н-
pyrrole-2,3-diones under the action of a nucleophilic
reagent, and also an example of the synthesis of a fused
heterocyclic system pyrido[2',3':3,4]pyrazolo[1,5-a]-
pyrimidine with previously inaccessible combination of
substituents.
1
1664 (C=O), 1649 (C=O). Н NMR spectrum, δ, ppm:
2.28 s (3H, Me), 2.30 s (3H, Me), 2.43 s (3H, Me), 2.70 s
(3H, Me), 2.81 s (3H, Me), 7.19–8.04 group of signals
(13Harom), 11.36 s (1H, NH). 13С NMR spectrum, δ, ppm:
23.23 (Me), 25.64 (Me), 26.26 (Me), 26.47 (Me), 30.52
(Me), 110.04 (C10a), 124.82–149.36 (Сarom), 150.08 (C10),
154.46 (C6a), 161.49 (C4), 166.48 (CONH), 169.56 (C2),
EXPERIMENTAL
IR spectra of compounds obtained were recorded on
a spectrophotometer Perkin Elmer Spectrum Two from
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

SILAICHEV et al.
1206
195.51 (CO), 195.57 (CO). Found, %: C 74.00; H 5.11;
N 12.30. С35H29N5О3. Calculated, %: C 74.06; H 5.15;
N 12.34.
NH). Found, %: C 72.00; H 4.97; N 11.96. С35H29N5О4.
Calculated, %: C 72.03; H 5.01; N 12.00.
2,3-Bis(2,5-dimethylbenzoyl)-8,10-dimethyl-N-
(4-methoxyphenyl)pyrido[2',3':3,4]pyrazolo[1,5-
a]-pyrimidine-4-carboxamide (IIIh). Yield 72%, mp
266–267°С. IR spectrum, cm–1: 3181 (NH), 1692 (C=O),
2,3-Bis(2,5-dimethylbenzoyl)-8,10-dimethyl-N-
(4-tolyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-
4-carboxamide (IIIe). Yield 79%, mp 215–216°С
(toluene). IR spectrum, cm–1: 3188 (NH), 1689 (C=O),
1
1678 (C=O), 1661. Н NMR spectrum, δ, ppm: 2.12
1
1673 (C=O), 1665 (C=O). Н NMR spectrum, δ, ppm:
s (3H, Me), 2.27 s (3H, Me), 2.28 s (3H, Me), 2.46 s
(3H, Me), 2.68 s (3H, Me), 2.70 s (3H, Me), 3.76 s (3Н,
Mе), 6.95–7.63 group of signals (11Harom), 11.14 s (1H,
NH). Found, %: C 72.64; H 5.45; N 11.43. С37H33N5О4.
Calculated, %: C 72.65; H 5.44; N 11.45.
2.12 s (3H, Me), 2.27 s (3H, Me), 2.28 s (3H, Me), 2.30 s
(3H, Me), 2.46 s (3H, Me), 2.67 s (3H, Me), 2.70 s (3H,
Me), 7.10–7.63 group of signals (11Harom), 11.20 s (1H,
NH). Found, %: C 74.64; H 5.54; N 11.78. С37H33N5О3.
Calculated, %: C 74.60; H 5.58; N 11.76.
ACKNOWLEDGMENTS
XRD experiment on compound IIIe was carried out
along standard procedure [27] on a four-circle automatic
diffractometer Xcalibur S (λMoKα 0.71073 Å, 295(2) K,
ω/2θ-scanning with a scan step 1°). In the experiment a
yellow prismatic crystal was used of the size 0.25 × 0.20 ×
0.15 mm. The correction for extinction was not introduced
due to its negligible value (μ 0.082 mm–1). The crystal is
triclinic, space group P-1, a 10.0418(15), b 11.8931(12),
c 14.0578(15) Å, α 86.919(8), β 69.547(11), γ 87.175(10)
deg, V 1569.9(3) Å3, Z 2. Within the dispersion angles
2.72 < θ < 26.37° 13697 reflections were collected,
among them 6392 independent (Rint 0.0273), 2758 re-
flections with I > 2σ(I), completeness of the experiment
for θ 26.37° was 99.5%. The structure was solved by the
direct method and refined by the full-matrix least-squares
method with respect to F2 using a SHELXTL software
[28]. The final refinement parameters are as follows: R1
0.0458, wR2 0.1048 [I > 2σ(I)], R1 0.1056, wR2 0.1109
(for all reflections), GООF 1.000,Δρ 0.297/–0.212 ēÅ–3.
The study was carried out under the financial support
of the Ministry of Education and Science of the Russian
Federation, of the Ministry of Education of Perm’ Krai
(MIG competition) and of the Russian Foundation for
Basic Research (grants nos. 12-03-00696, 12-03-31157,
13-03-96009).
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