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.

1203

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]pyrimidineP. S. Silaicheva,b, P. A. Slepukhinc, and A. N. Maslivetsa,b

aPerm’ State National Research University, Perm’, 614990 Russiae-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.

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].

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.

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

1204 SILAICHEV et al.

N

O

O

Ar1

OAr2

O

Ar2N

OH

O

Ar1

OAr2

Ar2O

HN

N NHN

MeMe

NNN

NMe

Me

Ar2

O

Ar2

O_H2O

Iа_Ih

II

IIIа_IIIh

N NNH

NH2Me

Me

N

NN

N

O

NHOO

Ar2

Ar2

O

Me Me

H

Ar1

HN OAr1

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).

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 fi gure).

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.

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 fi x-

Scheme.

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1205FIVE-MEMBERED 2,3-DIOXOHETEROCYCLES: ХСIV.

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.

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.

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.

EXPERIMENTAL

IR spectra of compounds obtained were recorded on a spectrophotometer Perkin Elmer Spectrum Two from

mulls in mineral oil. 1Н and 13С NMR spectra were registered on a spectrometer Bruker AM-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 -Dibenzoy l -8 ,10 -d imethy l -N -pheny l -pyrido-[2',3':3,4]pyrazolo[1,5-a]pyrimidine-4-carboxamide (IIIа). A solution 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.

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), 1663 (C=O). 1Н 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), 1664 (C=O), 1649 (C=O). 1Н 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),

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

1206 SILAICHEV et al.

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.

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), 1673 (C=O), 1665 (C=O). 1Н NMR spectrum, δ, ppm: 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.

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 refl ections were collected, among them 6392 independent (Rint 0.0273), 2758 re-fl ections with I > 2σ(I), completeness of the experiment for θ 26.37° was 99.5%. The structure was solved by the direct method and refi ned by the full-matrix least-squares method with respect to F2 using a SHELXTL software [28]. The fi nal refi nement parameters are as follows: R1 0.0458, wR2 0.1048 [I > 2σ(I)], R1 0.1056, wR2 0.1109 (for all refl ections), GООF 1.000, Δρ 0.297/–0.212 ēÅ–3.

2,3-Dibenzoyl-8,10-dimethyl-N-(4-methoxyphenyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidin-4-carboxamide (IIIf). Yield 73%, mp 310–311єС (ethyl acetate). IR spectrum, cm–1: 3266 (NH), 1682 (C=O), 1673 (C=O), 1655 (C=O). 1Н NMR spectrum, δ, ppm: 2.71 s (3H, Me), 2.80 s (3H, Me), 3.76 s (1Н, OMe), 6.86–8.11 group of signals (15Harom), 11.36 s (1H, NH). Found, %: C 71.28; H 4.57; N 12.63. С33H25N5О4. Calculated, %: C 71.34; H 4.54; N 12.61.

8,10-Dimethyl-N-(4-methoxyphenyl)-2,3-di(4-toluoyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-4-carboxamide (IIIg). Yield 77%, mp 253–254єС. IR spectrum, cm–1: 3194 (NH), 1678 (C=O), 1667 (C=O). 1Н NMR spectrum, δ, ppm: 2.28 s (3H, Me), 2.42 s (3H, Me), 2.69 s (3H, Me), 2.80 s (3H, Me), 3.76 s (3Н, ОMе), 6.95–8.03 group of signals (13Harom), 11.33 c (1H,

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), 1678 (C=O), 1661. 1Н NMR spectrum, δ, ppm: 2.12 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.

ACKNOWLEDGMENTS

The study was carried out under the fi nancial 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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