Controlled Switching of Multicomponent Heterocyclizations of 5-Amino-N-arylpyrazole-4-carboxamides, 1,3-Cyclohaxanediones and Aldehydes

FULL PAPER

DOI: 10.1002/ejoc.201200669

Controlled Switching of Multicomponent Heterocyclizations of 5-Amino-N-arylpyrazole-4-carboxamides, 1,3-Cyclohexanediones, and Aldehydes

Valentin A. Chebanov,*[a,b] Vyacheslav E. Saraev,[a] Svetlana V. Shishkina,[a]

Oleg V. Shishkin,[a,b] Vladimir I. Musatov,[a] and Sergey M. Desenko[a,b]

Keywords: Multicomponent reactions / Heterocycles / Chemoselectivity / Combinatorial chemistry / Synthetic methods

Multicomponent heterocyclization of 5-amino-N-arylpyraz-ole-4-carboxamides, 1,3-cyclohexanediones, and aromaticaldehydes was studied, and reaction conditions allowing se-lective switching between two directions were found. Whenthe reaction was carried out under thermal heating or ultra-sonication at room temperature, formation of linear pyrazolo-quinoline-3-carboxamides was observed. Isomeric angular

IntroductionHeterocycles containing a pyrazole ring are important

targets in synthetic and medicinal chemistry, because thisfragment is a key moiety in numerous biologically activecompounds such as Allopurinol (I), Viagra (II), Zaleplon(III), Celebrex (IV) (Figure 1), and others.[1] Therefore, thechemistry of a range of aminopyrazoles, as promising build-ing blocks in preparative organic chemistry for the synthesisof fused heterocycles containing the pyrazole core, has beenextensively investigated for a long time. The scope andlimitations of this chemistry has been reported in severalreviews[2] covering, in detail, the general pattern of reactiv-ity of 3(5)-aminopyrazoles, 4-aminopyrazoles, 1-aminopyr-azoles, and some diaminopyrazoles in two- and multicom-ponent reactions.

3(5)-Aminopyrazoles are the most attractive startingpoints for the study of multicomponent heterocyclizationsfrom several viewpoints. First, there are a number of pos-sible ways to introduce different substituents in the pyrazolering,[2a] which allows the combinatorial potential of suchbuilding blocks to be increased. Secondly, the presence ofseveral non-equivalent nucleophilic reaction centers in thesecompounds can cause additional variability of the direc-tions of their multicomponent reactions, which gives an op-portunity to enlarge molecular diversity of the final hetero-

[a] Division of Functional Materials Chemistry, SSI “Institute forSingle Crystals” NAS of Ukraine,Lenin Ave. 60, Kharkiv 61001, UkraineFax: +38-057-341-02-73E-mail: [email protected]: http://chem.isc.kharkov.com/

[b] Faculty of Chemistry, V.N. Karazin Kharkiv NationalUniversity,Svobody sq. 4, Kharkiv 61077, UkraineSupporting information for this article is available on theWWW under http://dx.doi.org/10.1002/ejoc.201200669.

Eur. J. Org. Chem. 2012, 5515–5524 © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 5515

heterocycles were obtained by ultrasonic-assisted synthesisat ambient temperature in the presence of HCl catalyst.Treatment with 2 equiv. of 1,3-diketone in boiling N,N-di-methylformamide/HCl gave a mixture of pyrazoloquinoline-3-carboxamides and unusual acridin-10-yl-pyrazole-4-carb-oxamides, which showed hindered rotation of the pyrazolefragment around the C–N bond.

Figure 1. Some examples of pyrazole-containing biologically activecompounds.

cycles. However, this second feature only becomes an ad-vantage when suitable methodologies are available that al-low selective switching of the reaction from one directionto another, otherwise, two or more pathways may proceedsimultaneously to generate complex mixtures of final com-pounds.[3]

The development of methods for tuning the selectivity ofmulticomponent reactions involving 3(5)-aminopyrazoleswas illustrated in several resent publications by their hetero-cyclizations with triethyl orthoesters and p-substitutedbenzoylacetonitriles,[4] or with aldehydes and cyclopentan-one,[5] acetoacetamides,[6a] pyruvic acids,[6b–6d] 1,3-cyclo-hexanediones,[6e–6g] or barbituric acids.[6h] In most of thesearticles, nonclassical activation methods such as microwaveand ultrasonic irradiation together with different types ofcatalysts and reaction media were required.

Multicomponent heterocyclizations of 5-aminopyrazole-4-carboxamides may also proceed in several alternative di-rections; the formation of the new heterocycle ring can in-

V. A. Chebanov et al.FULL PAPERvolve the participation of pyrazole NH2 and endocyclic NH(structure V, Figure 2),[6a–6c,7] pyrazole NH2 and carbox-amide NH2 (structure VI),[8] or only pyrazole NH2 (struc-ture VII).[6b]

Figure 2. Possible reaction products of heterocyclizations of 5-ami-nopyrazole-4-carboxamides.

There is also an additional possibility of the formationof position isomers for each of these structures, which in-creases the challenge of generating 5-aminopyrazole-4-carboxamides selectively in multicomponent reactions. Inthe present article we disclose our efforts to selectivelyswitch the course of multicomponent reactions with 5-amino-N-arylpyrazole-4-carboxamides, 1,3-cyclohexane-diones, and aromatic aldehydes by means of variation ofthe reaction conditions through the application of ultra-sonication.

Results and DiscussionAs anticipated, on the basis of earlier results with other

aminoazoles,[3a,3b] the three-component reaction of 5-amino-N-arylpyrazole-4-carboxamides 1a–c, aromatic alde-hydes 2a–e, and 1,3-cyclohexanediones 3a and 3b in boilingN,N-dimethylformamide (DMF) for 15 min led to the isola-tion of pyrazoloquinoline-3-carboxamides 4a–w in 59–92%yields (Scheme 1, Table 1). The same results were found

Scheme 1. Three-component reaction of 5-amino-N-arylpyrazole-4-carboxamides, 1,3-cyclohexanediones, and aromatic aldehydes.

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Table 1. Synthesis of compounds 4, 5, and 7.

Aminopyrazole Aldehyde Diketone ProductR R1 R2 Yield [%]

1a Ph 2c 4-CH3C6H4 3a Me 4a 79[a]

1a Ph 2b 4-CH3OC6H4 3a Me 4b 85[a]

1a Ph 2d 4-ClC6H4 3a Me 4c 71[a]

1a Ph 2e 4-CO2HC6H4 3a Me 4d 71[a]

1b 4-MeC6H4 2a Ph 3a Me 4e 86[a]

1b 4-MeC6H4 2c 4-MeC6H4 3a Me 4f 87[a]

1b 4-MeC6H4 2b 4-MeOC6H4 3a Me 4g 78[a]

1b 4-MeC6H4 2d 4-ClC6H4 3a Me 4h 92[a]

1b 4-MeC6H4 2e 4-CO2HC6H4 3a Me 4i 65[a]

1c 4-ClC6H4 2a Ph 3a Me 4j 89[a]

1c 4-ClC6H4 2c 4-MeC6H4 3a Me 4k 90[a]

1c 4-ClC6H4 2b 4-MeOC6H4 3a Me 4l 59[a]

1c 4-ClC6H4 2d 4-ClC6H4 3a Me 4m 64[a]

1c 4-ClC6H4 2e 4-CO2HC6H4 3a Me 4n 78[a]

1a Ph 2a Ph 3b H 4o 69[a]

1a Ph 2c 4-MeC6H4 3b H 4p 79[a]

1a Ph 2d 4-ClC6H4 3b H 4q 89[a]

1b 4-MeC6H4 2a Ph 3b H 4r 79[a]

1b 4-MeC6H4 2c 4-MeC6H4 3b H 4s 91[a]

1b 4-MeC6H4 2d 4-ClC6H4 3b H 4t 90[a]

1c 4-ClC6H4 2a Ph 3b H 4u 70[a]

1c 4-ClC6H4 2c 4-MeC6H4 3b H 4v 75[a]

1c 4-ClC6H4 2d 4-ClC6H4 3b H 4w 63[a]

1b 4-MeC6H4 2a Ph 3a Me 5a 68[b],[c]

1a Ph 2c 4-MeC6H4 3a Me 5b 71[b],[c]

1a Ph 2d 4-ClC6H4 3a Me 5c 63[b],[c]

1b 4-MeC6H4 2d 4-ClC6H4 3a Me 5d 65[b],[c]

1b 4-MeC6H4 2f 4-FC6H4 3a Me 5e 78[b],[c]

1b 4-MeC6H4 2c 4-MeOC6H4 3a Me 5f 75[b],[c]

1b 4-MeC6H4 2d 4-ClC6H4 3a Me 7a 35[c]

1b 4-MeC6H4 2b 4-MeOC6H4 3a Me 7b 30[c]

[a] Reaction in boiling DMF. [b] Reaction in DMF/HCl underultrasonication. [c] 2 equiv. of dimedone were used.

Controlled Switching of Multicomponent Heterocyclizations

when the heterocyclization was carried out in acetic acid orDMF at room temperature under ultrasonication, althoughsome previously published articles[6a,6b,6e,6h] had givengrounds to expect, in this case, the formation of anothertype of final product.

Nevertheless, the direction of this multicomponent reac-tion was changed by additional application of acid catalysis;the treatment of aminopyrazoles 1a,b, aldehydes 2a,c,d,f,and dimedone 3a in either EtOH or DMF containing cata-lytic amounts of HCl under ultrasonic irradiation at ambi-ent temperature, gave exclusively the position isomeric pyr-azoloquinoline-3-carboxamide 5a–f (63–78 %). The yieldsof the heterocyclizations were slightly higher in ethanol,whereas the purity of the final compounds (TLC, HPLCand NMR analysis) was higher in DMF. In both cases, afterisolation of pyrazoloquinolines 5, which was further char-acterized by chromatography without additional purifica-tion, insignificant amounts of compounds 4, 6, and 9 werefound in the mother liquor.

It is worth noting that there are only a few publicationsconcerning multicomponent reactions of aminoazoles, alde-hydes, and cyclic active methylene compounds in which thealdehyde component reacts with the exocyclic NH2 insteadof the endocyclic nucleophilic centers. For example, such acyclization of 3-amino-1,2,4-triazole and cyclohexanonewas previously described[9a] and, recently, was also reportedthe condensation of aminopyrazoles, aldehydes, and somecyclic ketones.[9b,9c] However, in most cases, the formationof angular-type azoloazines such as 5 was observed as sidereactions in low yields[10] or the reaction involved triethylorthoesters,[4] DMF,[11] or DMF/DMA[12] instead of alde-hyde.

All the heterocyclization reactions mentioned above werealso carried out under standard magnetic stirring instead ofin an ultrasonic bath. However, under these conditions thereaction proceeded with a significant decrease in both theyield and the purity of the final compounds, and requiredan increase in the reaction time (up to 24 h). This result isconnected, in our opinion, with better mass transfer and

Scheme 2. Third direction of the multicomponent heterocyclization.

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homogenization of the reaction mixture under ultra-sonication in comparison with mechanical stirring.

Switching the direction of this multicomponent heterocy-clization may arise as a result of the influence of acid cata-lyst and temperature regime on the stability of azomethines6, which are anticipated to be intermediates in the reactionleading to compounds 5.[6a–6c] Indeed, it was establishedthat treatment of compounds 6a–d with 1,3-diketone 3a atroom temperature under ultrasonic irradiation in the pres-ence of HCl yielded heterocycles 5a–d, whereas boiling thesame starting materials in pure DMF or ultrasonicatingthem in pure DMF or AcOH always led to decompositionof the azomethines and isolation of pyrazoloquinolines4a,c,e,h. The latter compounds were also obtained, in allcases, in the presence of triethylamine.

Another unusual result was found when aminopyrazole1b, aldehyde 2b,d, and dimedone 3a were treated in a 1:1:2ratio in boiling DMF containing a catalytic amount of HCl(Scheme 2). In this case, a precipitate was isolated that con-tained two visually different types of crystals, which wereseparated mechanically with the help of an optical micro-scope. The first type of compound was identified withoutadditional purification as pyrazoloquinoline-3-carboxamide4g,h (40–50%), whereas the second was first crystallizedfrom EtOH/H2O (2:3), which allowed the structure of5-(1,8-dioxo-1,2,3,4,5,6,7,8-octahydroacridin-10-yl)-pyr-azole-4-carboxamides 7a,b to be assigned. The yields ofthese reaction products were in the 30–35% range.

Thus, 5-amino-N-arylpyrazole-4-carboxamide, being atypical 1,3-binucleophile with high reactivity of both pyr-azole NH2 and endocyclic NH reaction centers, in this caseplays the role of a primary amine. Unfortunately, attemptsto elaborate a preparative multicomponent procedure forthe selective synthesis of 7 were unsuccessful; conventionalthermal or microwave heating at a wide range of tempera-tures or ultrasonication carried out in numerous solvents(primary alcohols, DMF, HOAc) led to mixtures of severalproducts including heterocycles 4, 7, and 9. A sequentialapproach involving preliminary production of Michael ad-

V. A. Chebanov et al.FULL PAPERduct 8[13] and its further treatment with aminopyrazole 1aalso yielded pyrazoloquinoline 4 as the main product andxanthenedione 9 as a minor product.

All the compounds synthesized were identified with thehelp of elemental analysis, mass spectrometry, NMR spec-troscopy and X-ray diffraction analysis.

The 1H NMR spectra of heterocycles 4 showed the fol-lowing signals: singlets for cyclohexanone methyl groups atδ = 0.9 and 1.0 ppm (compounds 4a–n), four doublet sig-nals (J ≈ 16 Hz) for two CH2 groups (compounds 4a–n), orseveral multiplet signals for three CH2 groups (compounds4o–w), singlets for CH of the pyrimidine ring (δ = 6.1–6.2 ppm) and of the pyrazole ring (δ = 8.0–8.1 ppm), abroad signal at δ = 9.7–9.8 ppm for both pyrimidine andcarboxamide NH, signals of aromatic fragments withinrange of δ = 6.6–7.9 ppm as well as all necessary signals ofthe other terminal substituents.

The 1H NMR spectra of angular quinozalines 5, in com-parison with the spectra of linear heterocycles 4, showedshifts of some signals. In particular, downfield shifts of thesignals of all protons of the cyclohexanone moiety (by 0.1–0.2 ppm) and upfield shifts of the signals of the pyrimidineCH and NH protons (by 0.6 and 1.5 ppm, respectively),were found. A clear dependence of the 1H NMR chemicalshift of this NH proton on the structure of the azoloazineskeleton was previously described in several publications.[13]

Additionally, it is worth noting that the pyrimidine CH andNH moieties appeared in the spectra as doublets (J = 2.3–2.5 Hz) and showed cross-peaks in COSY and NOESY ex-periments.

The structure of heterocycles 5 was unequivocally estab-lished by X-ray diffraction analysis of a single crystal ofcompound 5c (Figure 3). It was found that the dihydropyr-imidine and cyclohexenone rings of the tricyclic fragmentadopt a distorted sofa conformation. The puckering param-eters[14] are S = 0.46, Θ = 54.6°, Ψ = 11.7° for the dihy-dropyrimidine ring and S = 0.71, Θ = 41.9°, Ψ = 9.5° forthe cyclohexenone ring. The chlorophenyl substituent is al-most orthogonal to the plane of the partially saturated het-erocycle and is turned relatively to the C8–C9 bond [the

Figure 3. Molecular structure of compound 5c according to X-raydiffraction data.


C3–C8–C9-C13 and C8–C9–C13–C18 torsion angles are–92.4(2)° and 32.9(3)°, respectively]. The formation of theN4-H···O1� (0.5 + x, 0.5 – y, –0.5 + z) intermolecular hy-drogen bond leads to an elongation of the N4–C19[1.364(3) Å] and O1–C7 [1.234(2) Å] bonds compared totheir mean values[15] (1.334 and 1.210 Å, respectively).

The 1H NMR spectra of acridinediones 7 exhibited sing-lets for four CH3 groups (δ = 0.7 and 0.8 ppm), multipletsfor the CH2 groups of the cyclohexanone rings (δ = 1.7–2.4 ppm), singlets for 9-CH (δ ≈ 4.9 ppm), pyrazole CH (δ≈ 8.6 ppm), pyrazole NH (δ ≈ 10.0 ppm), and carboxamideNH (δ ≈ 13.5 ppm). Signals arising from the aromatic rings(δ = 6.5–7.7 ppm) and other substituents were also foundat the appropriate positions.

However, detailed analysis of the 1H NMR spectra ofheterocycles 7 measured at 20 °C revealed a doubling of allthe signals and further complication of the multiplets fromthe aromatic rings. Such spectral characteristics may indi-cate the occurrence of hindered rotation of one of the sub-stituents and the appearance of axial chirality. This assump-tion was confirmed by temperature-dependence 1H NMRexperiments that showed that increasing the temperaturefrom 20 to 150 °C led to averaging of the doubled signalsright up to their complete convergence (Figure 4).

Figure 4. Dependence of the 1H NMR spectra of compound 7a onthe temperature.

In our opinion, such rotamerism is due to restricted rota-tion of the whole pyrazole fragment around the C–N bond(Figure 5), as previously described for N-aryl-substitutedacridinediones.[16]

Figure 5. Hindered rotation of the pyrazolyl substituent around theC–N bond.

Conclusions

The direction of multicomponent heterocyclization of5-amino-N-arylpyrazole-4-carboxamides, 1,3-cyclohexane-


diones, and aromatic aldehydes can be efficiently controlledby changing the reaction parameters. Treatment of thestarting materials under neutral conditions or in the pres-ence of Et3N in boiling DMF or with the help of ultra-sonication in AcOH at room temperature yields N,9-diaryl-8-oxo-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazoline-3-carboxamides 4. In the case of ultrasonic-assisted reactionsat room temperature, addition of HCl switches the directiontowards formation of the position-isomeric N,5-diaryl-6-oxo-4,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinazoline-3-carboxamide 5. Change of selectivity of the heterocycli-zation depends on the stability of azomethines 6 as the in-termediates of the last reaction.

The third direction of the multicomponent cyclizationwith formation of 5-(1,8-dioxo-1,2,3,4,5,6,7,8-octahydro-acridin-10-yl)pyrazole-4-carboxamides 7 is observed as aside process when 2 equiv. of dimedone react with 1 equiv.of 5-amino-N-arylpyrazole-4-carboxamides and 1 equiv. ofaromatic aldehyde in boiling DMF in the presence of cata-lytic amounts of HCl. The acridinediones obtained displayhindered rotation of the pyrazole moiety around the C–Nbond and exhibit axial chirality.

Experimental SectionGeneral: The melting points of all compounds synthesized weredetermined with a Gallenkamp melting point apparatus. NMRspectra were recorded in [D6]DMSO at 500 MHz (125 MHz for13C) or at 200 MHz (50 MHz for 13C) with Bruker Avance andVarian Mercury VX-200 spectrometers. Chemical shifts (δ) aregiven in ppm relative to TMS as internal standard. Mass spectrawere measured with a GC–MS Varian 1200L (ionizing voltage70 eV) instrument using direct input of compounds. Elementalanalyses were determined with a EuroVector EA-3000. AnalyticalHPLC analysis was carried out with a Bischoff module chromato-graph on a C18 reversed-phase analytical column (119�3 mm,particle size 5 mm) or a reversed-phase column (150�4.6 mm, par-ticle size 5 mm) at 25 °C using a mobile phase A [water/acetonitrile,90:10 (v/v) + 0.1% TFA] and B (MeCN + 0.1% TFA) at a flowrate of 1.0 mL/min. The following gradient was applied: linear in-crease from solution 30% B to 100 % B in 8 min, hold at 100%solution B for 7 min. TLC analyses were performed on pre-coated(silica gel 60 HF254) plates. Ultrasonication was carried out with astandard ultrasonic bath operating at 44.2 kHz. Microwave experi-ments were performed with an Emrys Creator EXP from BiotageAB (Uppsala, Sweden) in a single-mode microwave cavity(2.45 GHz). Solvents, 1,3-cyclohexanediones and aromatic alde-hydes were commercially available and used without additional pu-rification. Aminopyrazoles 1a–c were obtained by a known meth-od,[6b] azomethines 6a–d were obtained from the correspondingaminoazoles and aldehydes.[17]

X-ray Diffraction Data: Colorless crystals of 5c (C25H23N4O2Cl);monoclinic; 293 K; a = 8.926(5), b = 21.999(5), c = 11.413(5) Å, β= 100.629(5)°; V = 2203(2) Å3; M = 446.92; Z = 4; space groupP21/n; dcalcd. = 1.348 g/cm3; μ(Mo-Kα) = 0.204 mm–1; F(000) = 936.Intensities of 11649 reflections (3800 independent, Rint = 0.041)were measured with an Xcalibur-3 diffractometer (graphite-mono-chromated Mo-Kα radiation, CCD detector, ω-scaning, 2θmax =50°). The structure was solved by direct methods using theSHELXTL package.[18] Positions of the hydrogen atoms were lo-


cated from electron density difference maps and refined by the “ri-ding” model with Uiso = nUeq of the carrier atom (n = 1.5 formethyl groups and n = 1.2 for other hydrogen atoms). Full-matrixleast-squares refinement against F2 in anisotropic approximationfor non-hydrogen atoms using 3763 reflections converged to wR2= 0.096 [R1 = 0.040 for 1917 reflections with F � 4σ(F), S = 0.856].CCDC-871752 contains the supplementary crystallographic datafor this paper. These data can be obtained free of charge from TheCambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Typical Procedure for the Thermal Synthesis of 6,6-Dimethyl-8-oxo-N-phenyl-9-p-tolyl-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazol-ine-3-carboxamide (4a): A mixture containing 5-amino-N-phenyl-1H-pyrazolo-4-carboxamide (1a; 0.3 g, 1.5 mmol), 4-methylbenz-aldehyde (2c; 0.18 g, 1.5 mmol), and 5,5-dimethylcyclohexane-1,3-dione (3a; 0.21 g, 1.5 mmol) in DMF (2 mL) was heated to refluxfor 15 min. After cooling to ca. 50 °C, an EtOH/H2O (1:1, 4 mL)mixture was added, and the precipitate formed was filtered, washedwith ethanol, and air-dried. Yield: 0.51 g (79%); m.p. 259–261 °C.1H NMR ([D6]DMSO, 200 MHz): δ = 0.91 (s, 3 H, CH3), 1.02 (s,3 H, CH3), 2.06 (d, J = 16.2 Hz, 1 H, CH2), 2.20 (s, 3 H, CH3),2.21 (d, J = 16.2 Hz, 1 H, CH2), 2.64 (d, J = 17.2 Hz, 1 H, CH2),2.76 (d, J = 17.2 Hz, 1 H, CH2), 6.12 (s, 1 H, 9-CH), 6.92–7.78 (m,9 H, ArH), 8.05 (s, 1 H, pyrazole CH), 9.77 (br. s, 1 H, NH), 9.79(br. s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 21.12,27.21, 29.25, 32.67, 50.34, 57.74, 100.26, 106.67, 120.48, 123.76,127.20, 129.1, 129.24, 137.26, 138.65, 139.49, 139.81, 139.86,149.63, 161.59, 193.52 ppm. MS (EI, 70 eV): m/z (%) = 427 (32)[M+], 426 (37), 425 (19), 336 (13), 335 (36), 334 (59), 333 (87), 332(78), 306 (81), 305 (79), 304 (19), 250 (34), 249 (43), 248 (18), 243(16), 242 (100), 241 (59), 186 (20), 185 (23), 157 (16), 149 (25), 148(24), 115 (15). C26H26N4O2 (426.52): calcd. C 73.22, H 6.14, N13.14; found C 73.01, H 6.12, N 13.09.

Typical Procedure for the Ultrasonic-Assisted Synthesis of 6,6-Di-methyl-8-oxo-N-phenyl-9-p-tolyl-4,5,6,7,8,9-hexahydropyrazolo-[5,1-b]quinazoline-3-carboxamide (4a): A mixture containing 5-amino-N-phenyl-1H-pyrazolo-4-carboxamide (1a ; 0 .3 g,1.5 mmol), 4-methylbenzaldehyde (2c; 0.18 g, 1.5 mmol) and 5,5-dimethylcyclohexane-1,3-dione (3a; 0.21 g, 1.5 mmol) was ultra-sonicated in AcOH (2 mL) for 45 min. After cooling, an EtOH/H2O (1:1, 4 mL) mixture was added, and the precipitate formedwas filtered, washed with ethanol, and air-dried.

9-(p-Methoxyphenyl)-6,6-dimethyl-8-oxo-N-phenyl-4,5,6,7,8,9-hexa-hydropyrazolo[5,1-b]quinazoline-3-carboxamide (4b): Yield: 85 %;m.p. 165–167 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.93 (s, 3H, CH3), 1.02 (s, 3 H, CH3), 2.05 (d, J = 16.3 Hz, 1 H, CH2), 2.21(d, J = 16.3 Hz, 1 H, CH2), 2.63 (d, J = 17.4 Hz, 1 H, CH2), 2.77(d, J = 17.4 Hz, 1 H, CH2), 3.67 (s, 3 H, OCH3), 6.12 (s, 1 H, CH-9), 6.63–7.86 (m, 9 H, ArH), 8.06 (s, 1 H, CH), 9.75 (s, 1 H, NH),9.78 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ =27.25, 29.25, 32.61, 50.35, 55.53, 57.44, 100.23, 106.71, 114.06,120.48, 123.76, 128.48, 129.09, 134.95, 138.62, 139.49, 139.76,149.57, 159.11, 161.61, 193.56 ppm. MS (EI, 70 eV): m/z (%) = 442(10) [M], 350 (22), 349 (66), 348 (39), 322 (34), 321 (56), 320 (21),266 (17), 242 (46), 241 (43), 186 (14), 148 (220), 122 (15), 111 (27),96 (46), 94 (20), 92 (19), 91 (24), 83 (100), 79 (40), 77 (40), 65 (19),64 (29), 60 (14), 57 (49). C26H26N4O3 (442.52): calcd. C 70.57, H5.92, N 12.66; found C 70.31, H 5.90, N 12.61.

9-(p-Chlorophenyl)-6,6-dimethyl-8-oxo-N-phenyl-4,5,6,7,8,9-hexa-hydropyrazolo[5,1-b]quinazoline-3-carboxamide (4c): Yield: 71 %;m.p. 251–253 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.91 (s, 3H, CH3), 1.02 (s, 3 H, CH3), 2.07 (d, J = 16.2 Hz, 1 H, CH2), 2.21

V. A. Chebanov et al.FULL PAPER(d, J = 16.2 Hz, 1 H, CH2), 2.64 (d, J = 17.2 Hz, 1 H, CH2), 2.76(d, J = 17.2 Hz, 1 H, CH2), 6.18 (s, 1 H, CH-9), 6.95–7.83 (m, 9H, ArH), 8.09 (s, 1 H, CH), 9.81 (s, 1 H, NH), 9.85 (s, 1 H,NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 27.31, 29.11,32.65, 50.28, 57.44, 100.40, 106.10, 120.5, 123.82, 128.75, 129.11,129.18, 132.63, 138.92, 139.43, 139.77, 141.60, 149.97, 161.48,193.60 ppm. MS (EI, 70 eV): m/z (%) = 446 (9) [M], 355 (22), 354(47), 327 (20), 326 (37), 270 (14), 242 (60), 241 (55), 149 (35), 112(22), 111 (26), 110 (15), 94 (42), 93 (95), 92 (45), 90 (14), 83 (24),77 (34), 74 (16), 71 (14), 67 (29), 66 (45), 65 (28), 57 (58), 56 (34),55 (53), 54 (100). C25H23ClN4O2 (446.94): calcd. C 67.18, H 5.19,Cl 7.93, N 12.54; found C 66.89, H 5.17, Cl 7.95, N 12.49.

9-(p-Carboxyphenyl)-6,6-dimethyl-8-oxo-N-phenyl-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazoline-3-carboxamide (4d): Yield:71%; m.p. 305–307 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.89(s, 3 H, CH3), 1.01 (s, 3 H, CH3), 2.05 (d, J = 16.1 Hz, 1 H, CH2),2.21 (d, J = 16.1 Hz, 1 H, CH2), 2.64 (d, J = 17.3 Hz, 1 H, CH2),2.76 (d, J = 17.3 Hz, 1 H, CH2), 6.24 (s, 1 H, CH-9), 6.91–7.90 (m,9 H, ArH), 8.08 (s, 1 H, CH), 9.83 (s, 1 H, NH), 9.89 (br. s, 1H, NH), 12.93 (br. s, 1 H, COOH) ppm. 13C NMR ([D6]DMSO,125 MHz): δ = 27.22, 29.13, 32.64, 50.27, 57.83, 100.45, 106.07,120.51, 123.82, 127.53, 129.10, 129.86, 130.60, 138.96, 139.43,139.85, 147.15, 150.06, 161.50, 167.45, 193.58 ppm. MS (EI,70 eV): m/z (%) = 456 (10) [M], 364 (27), 363 (34), 336 (22), 335(19), 243 (16), 242 (100), 186 (23), 158 (16), 149 (14), 129 (29), 128(12), 127 (19), 115 (27), 111 (17), 110 (43), 107 (34), 106 (19), 105(14), 104 (13), 103 (13), 101 (13), 98 (16), 97 (28), 96 (17), 95 (16),94 (26), 93 (88), 91 (22). C26H24N4O4 (456.50): calcd. C 68.41, H5.30, N 12.27; found C 67.18, H 5.28, N 12.23.

6,6-Dimethyl-8-oxo-9-phenyl-N-p-tolyl-4,5,6,7,8,9-hexahydropyr-azolo[5,1-b]quinazoline-3-carboxamide (4e): Yield: 86%; m.p. 245–247 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.90 (s, 3 H, CH3),1.02 (s, 3 H, CH3), 1.94–2.33 (m, 2 H, CH2), 2.25 (s, 3 H, CH3),2.62 (d, J = 17.1 Hz, 1 H, CH2), 2.74 (d, J = 17.1 Hz, 1 H, CH2),6.16 (s, 1 H, CH-9), 7.01–7.65 (m, 9 H, ArH), 8.05 (s, 1 H, CH),9.73 (br. s, 1 H, NH), 9.78 (br. s, 1 H, NH) ppm. 13C NMR ([D6]-DMSO, 125 MHz): δ = 20.95, 27.23, 29.21, 32.64, 50.32, 57.98,100.36, 106.50, 120.54, 127.25, 128.03, 128.71, 129.50, 132.72,136.90, 138.67, 139.78, 142.69, 149.81, 161.40, 193.54 ppm. MS(EI, 70 eV): m/z (%) = 427 (18) [M+], 426 (55) [M], 349 (156), 321(16), 320 (80), 319 (90), 239 (14), 292 (72), 291 (43), 243 (19), 242(100), 236 (38), 186 (16), 107 (34), 106 (21) ppm. C26H26N4O2

(426.52): calcd. C 73.22, H 6.14, N 13.14; found C 72.91, H 6.12,N 13.09.

6,6-Dimethyl-8-oxo-N,9-bis(p-tolyl)-4,5,6,7,8,9-hexahydropyr-azolo[5,1-b]quinazoline-3-carboxamide (4f): Yield: 87%; m.p. 260–262 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.90 (s, 3 H, CH3),1.02 (s, 3 H, CH3), 1.94–2.33 (m, 2 H, CH2), 2.20 (s, 3 H, CH3),2.25 (s, 3 H, CH3), 2.62 (d, J = 17.1 Hz, 1 H, CH2), 2.74 (d, J =17.1 Hz, 1 H, CH2), 6.12 (s, 1 H, CH-9), 7.01–7.70 (m, 8 H, ArH),8.03 (s, 1 H, CH), 9.70 (br. s, 2 H, HNH) ppm. 13C NMR ([D6]-DMSO, 125 MHz): δ = 20.95, 21.11, 27.22, 29.25, 32.62, 50.34,57.72, 100.29, 106.63, 120.53, 127.18, 129.23, 129.49, 132.70,136.91, 137.25, 138.57, 139.74, 139.87, 149.64, 161.43, 193.50. ppm.MS (EI, 70 eV): m/z (%) = 441 (26) [M+], 440 (80) [M], 349 (14),335 (20), 334 (92), 333 (99), 307 (20), 306 (59), 250 (38), 243 (20),242 (100), 186 (16), 107 (44), 106 (29). C27H28N4O2: C 73.61, H6.41, N 12.72; found C 73.32, H 6.39, N 12.67.

9-(4-Methoxyphenyl)-6,6-dimethyl-8-oxo-N-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazoline-3-carboxamide (4g): Yield:78%; m.p. 257–259 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.92(s, 3 H, CH3), 1.02 (s, 3 H, CH3), 1.90–2.33 (m, 2 H, CH2), 2.25


(s, 3 H, CH3), 2.61 (d, J = 17.6 Hz, 1 H, CH2), 2.75 (d, J = 17.6 Hz,1 H, CH2), 3.67 (s, 3 H, OCH3), 6.11 (s, 1 H, CH-9), 6.94–7.22 (m,4 H, ArH), 6.75 (d, J = 8.4 Hz, 2 H, ArH), 7.52 (d, J = 8.4 Hz, 2H, ArH), 8.03 (s, 1 H, CH), 9.70 (br. s, 2 H, HNH) ppm. 13C NMR([D6]DMSO, 125 MHz): δ = 20.95, 27.27, 29.24, 32.62, 50.36,55.54, 57.41, 100.26, 106.66, 114.06, 120.53, 128.45, 129.49, 132.69,134.96, 136.91, 138.55, 139.68, 149.59, 159.10, 161.44, 193.54 ppm.MS (EI, 70 eV): m/z (%) = 456 (9) [M], 350 (22), 349 (28), 348 (11),322 (12), 321 (20), 320 (13), 242 (23), 108 (24), 107 (80), 106 (100),105 (64), 92 (14), 91 (14), 83 (32), 82 (26), 79 (15), 78 (20), 77 (31).C27H28N4O3 (456.54): calcd. C 71.03, H 6.18, N 12.27; found C70.73, H 6.16, N 12.22.

9-(4-Chlorophenyl)-6,6-dimethyl-8-oxo-N-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazoline-3-carboxamide (4h): Yield:92%; m.p. 284–286 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.90(s, 3 H, CH3), 1.01 (s, 3 H, CH3), 1.92–2.36 (m, 2 H, CH2), 2.24(s, 3 H, CH3), 2.63 (d, J = 17.6 Hz, 1 H, CH2), 2.75 (d, J = 17.6 Hz,1 H, CH2), 6.17 (s, 1 H, CH-9), 6.96–7.75 (m, 8 H, ArH), 8.06 (s,1 H, CH), 9.74 (s, 1 H, NH), 9.84 (s, 1 H, NH) ppm. 13C NMR ([D6]-DMSO, 125 MHz): δ = 20.95, 27.31, 29.11, 32.65, 50.28, 57.42,100.44, 106.07, 120.56, 128.74, 129.16, 129.50, 132.61, 132.75,136.86, 138.84, 139.70, 141.62, 149.97, 161.32, 193.58 ppm. MS(EI, 70 eV): m/z (%) = 461 (6) [M+], 461 (19) [M], 356 (14), 355(27), 354 (41), 353 (67), 327 (17), 326 (39), 325 (17), 270 (26), 243(16), 242 (100), 186 (14), 107 (19), 106 (42). C26H25N4O2 (425.51):calcd. C 67.75, H 5.47, Cl 7.69, N 12.15; found C 67.49, H 5.45,Cl 7.71, N 12.11.

9-(4-Carboxyphenyl)-6,6-dimethyl-8-oxo-N-(p-tolyl)-4,5,6,7,8,9-hexa-hydropyrazolo[5,1-b]quinazoline-3-carboxamide (4i): Yield: 65 %;m.p. �310 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.89 (s, 3 H,CH3), 1.01 (s, 3 H, CH3), 1.95–2.33 (m, 2 H, CH2), 2.24 (s, 3 H,CH3), 2.63 (d, J = 17.5 Hz, 1 H, CH2), 2.75 (d, J = 17.5 Hz, 1 H,CH2), 6.23 (s, 1 H, CH-9), 7.11 (d, J = 8.3 Hz, 2 H, ArH), 7.25 (d,J = 8.1 Hz, 2 H, ArH), 7.57 (d, J = 8.3 Hz, 2 H, ArH), 7.83 (d, J

= 8.1 Hz, 2 H, ArH), 8.06 (s, 1 H, CH), 9.76 (s, 1 H, NH), 9.87(br. s, 1 H, NH), 12.87 (br. s, 1 H, COOH) ppm. 13C NMR ([D6]-DMSO, 125 MHz): δ = 20.95, 27.22, 29.13, 32.64, 50.27, 57.81,100.49, 106.03, 120.55, 127.50, 129.51, 129.85, 130.65, 132.76,136.87, 138.89, 139.79, 147.17, 150.08, 161.34, 167.46, 193.55 ppm.MS (EI, 70 eV): m/z (%) = 471 (20) [M+], 470 (22) [M], 365 (22),364 (62), 363 (100), 362 (57), 337 (27), 336 (50), 335 (47), 334 (16),242 (43), 241 (34), 149 (20),148 (17), 129 (17), 128 (15), 108 (23),107 (44), 106 (92), 105 (32), 97 (24), 84 (24), 83 (42), 82 (39), 77(24), 76 (25), 73 (26), 72 (30), 70 (27), 69 (33), 68 (25), 57 (40), 56(60), 55 (79), 54 (36). C27H26N4O4 (470.53): calcd. C 68.92, H 5.57,N 11.91; found C 68.65, H 5.55, N 11.87.

N-(4-Chlorophenyl)-6,6-dimethyl-8-oxo-9-phenyl-4,5,6,7,8,9-hexa-hydropyrazolo[5,1-b]quinazoline-3-carboxamide (4j): Yield: 89 %;m.p. 295–298 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.91 (s, 3H, CH3), 1.02 (s, 3 H, CH3), 2.06 (d, J = 16.3 Hz, 1 H, CH2), 2.22(d, J = 16.3 Hz, 1 H, CH2), 2.64 (d, J = 16.9 Hz, 1 H, CH2), 2.76(d, J = 16.9 Hz, 1 H, CH2), 6.17 (s, 1 H, CH-9), 7.03–7.51 (m, 6H, ArH), 7.52–7.85 (m, 3 H, ArH), 8.04 (s, 1 H, CH), 9.80 (s, 1 H,NH), 9.90 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ= 27.22, 29.21, 32.63, 50.31, 58.01, 100.14, 106.59, 121.97, 127.27,127.38, 128.06, 128.72, 129.01, 138.46, 138.75, 139.92, 142.62,149.78, 161.58, 193.56 ppm. MS (EI, 70 eV): m/z (%) = 447 (7)[M+], 446 (14) [M], 321 (15), 320 (80), 319 (100), 292 (53), 291(30), 243 (15), 242 (98), 236 (38), 186 (17), 127 (32). C25H23ClN4O2

(446.94): calcd. C 67.18, H 5.19, Cl 7.93, N 12.54; found C 66.90,H 5.17, Cl 7.97, N 12.49.

N-(4-Chlorophenyl)-6,6-dimethyl-8-oxo-9-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazoline-3-carboxamide (4k): Yield:


90%; m.p. 302–304 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.91(s, 3 H, CH3), 1.02 (s, 3 H, CH3), 2.03 (d, J = 16.3 Hz, 1 H, CH2),2.20 (s, 3 H, CH3), 2.24 (d, J = 16.3 Hz, 1 H, CH2), 2.62 (d, J =17.7 Hz, 1 H, CH2), 2.74 (d, J = 17.7 Hz, 1 H, CH2), 6.12 (s, 1 H,CH-9), 6.92–7.83 (m, 8 H, ArH), 8.03 (s, 1 H, CH), 9.76 (s, 1 H,NH), 9.90 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ= 21.11, 27.22, 29.24, 32.62, 50.33, 57.75, 75.98, 100.08, 106.72,121.95, 127.20, 127.36, 129.00, 129.24, 137.28, 138.48, 138.64,138.65, 139.81, 139.89, 149.60, 161.60, 193.54 ppm. MS (EI,70 eV): m/z (%) = 461 (5) [M+], 460 (17) [M], 335 (15), 334 (84),333 (96), 307 (14), 306 (66), 305 (40), 250 (42), 243 (14), 242 (100),186 (15), 129 (13), 127 (26). C26H25ClN4O2 (460.96): calcd. C 67.75,H 5.47, Cl 7.69, N 12.15; found C 67.48, H 5.45, Cl 7.73, N 12.10.

N-(4-Chlorophenyl)-9-(4-methoxyphenyl)-6,6-dimethyl-8-oxo-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazoline-3-carboxamide (4l):Yield: 59 %; m.p. 303–306 °C. 1H NMR ([D6]DMSO, 200 MHz): δ= 0.93 (s, 3 H, CH3), 1.02 (s, 3 H, CH3), 2.05 (d, J = 16.3 Hz, 1H, CH2), 2.21 (d, J = 16.3 Hz, 1 H, CH2), 2.61 (d, J = 17.1 Hz, 1H, CH2), 2.77 (d, J = 17.1 Hz, 1 H, CH2), 3.67 (s, 3 H, OCH3),6.11 (s, 1 H, CH-9), 6.81 (d, J = 8.7 Hz, 2 H, ArH), 7.07 (d, J =8.7 Hz, 2 H, ArH), 7.38 (d, J = 8.9 Hz, 2 H, ArH), 7.73 (d, J =8.9 Hz, 2 H, ArH), 8.03 (s, 1 H, CH), 9.75 (s, 1 H, NH), 9.90 (s, 1H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 27.27, 29.24,32.62, 50.34, 55.55, 57.43, 100.04, 106.74, 114.07, 121.95, 127.35,128.47, 129.01, 134.89, 138.48, 138.63, 139.82, 149.57, 159.12,161.60, 193.56, 194.59 ppm. MS (EI, 70 eV): m/z (%) = 476 (8) [M],350 (47), 349 (100), 348 (58), 322 (54), 321 (43), 266 (28), 265 (22),242 (46), 241 (23), 186 (14), 185 (17), 129 (16), 127 (26), 126 (186),83 (19), 57 (21), 56 (24). C26H25ClN4O3 (476.96): calcd. C 65.47,H 5.28, Cl 7.43, N 11.75; found C 65.21, H 5.26, Cl 7.47, N 11.71.

N,9-Bis(4-chlorophenyl)-6,6-dimethyl-8-oxo-4,5,6,7,8,9-hexahydro-pyrazolo[5,1-b]quinazoline-3-carboxamide (4m): Yield: 64 %; m.p.�310 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.91 (s, 3 H, CH3),1.02 (s, 3 H, CH3), 2.07 (d, J = 16.3 Hz, 1 H, CH2), 2.21 (d, J =16.3 Hz, 1 H, CH2), 2.61 (d, J = 17.0 Hz, 1 H, CH2), 2.77 (d, J =17.0 Hz, 1 H, CH2), 6.18 (s, 1 H, CH-9), 7.16 (d, J = 8.8 Hz, 2 H,ArH), 7.32 (d, J = 9.8 Hz, 2 H, ArH), 7.37 (d, J = 9.8 Hz, 2 H,ArH), 7.72 (d, J = 8.8 Hz, 2 H, ArH), 8.06 (s, 1 H, CH), 9.86 (br.s, 1 H, NH), 9.93 (br. s, 1 H, NH) ppm. 13C NMR ([D6]DMSO,125 MHz): δ = 27.32, 29.11, 32.65, 50.28, 57.44, 100.22, 106.15,121.98, 127.40, 128.75, 129.02, 129.18, 132.64, 138.43, 138.93,139.85, 141.55, 149.95, 161.50, 193.60 ppm. MS (EI, 70 eV): m/z(%) = 480 (10) [M], 356 (18), 355 (30), 354 (55), 353 (74), 326 (37),325 (23), 270 (34), 243 (15), 242 (100), 186 (18), 129 (12), 127 (40),99 (12). C25H22Cl2N4O2 (481.38): calcd. C 62.38, H 4.61, Cl 17.73,N 11.64; found C 62.13, H 4.60, Cl 17.81, N 11.60.

9-(4-Carboxyphenyl)-N-(4-chlorophenyl)-6,6-dimethyl-8-oxo-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazoline-3-carboxamide(4n): Yield: 78%; m.p.� 310 °C. 1H NMR ([D6]DMSO, 200 MHz):δ = 0.89 (s, 3 H, CH3), 1.02 (s, 3 H, CH3), 2.05 (d, J = 16.1 Hz, 1H, CH2), 2.21 (s, J = 16.1 Hz, 1 H, CH2), 2.64 (d, J = 17.4 Hz, 1H, CH2), 2.76 (d, J = 17.4 Hz, 1 H, CH2), 6.24 (s, 1 H, CH-9), 7.26(d, J = 8.4 Hz, 2 H, ArH), 7.38 (d, J = 9.0 Hz, 2 H, ArH), 7.72 (d,J = 9.0 Hz, 2 H, ArH), 7.83 (d, J = 8.4 Hz, 2 H, ArH), 8.06 (s, 1H, CH), 9.89 (br. s, 1 H, NH), 9.94 (br. s, 1 H, NH), 12.97 (br. s,1 H, COOH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 27.22,29.13, 32.64, 50.26, 57.83, 100.27, 106.11, 121.89, 127.53, 129.02,129.86, 130.60, 138.44, 138.96, 139.92, 147.11, 150.04, 161.51,167.44, 193.58 ppm. MS (EI, 70 eV): m/z (%) = 492 (4) [M + 2],491 (5) [M+], 490 (12) [M], 365 (19), 364 (98), 363 (84), 337 (12),336 (48), 335 (32), 280 (22), 243 (13), 242 (100), 186 (18), 149 (23),129 (33), 128 (16), 127 (66), 115 (14), 11 (18), 110 (43), 107 (17),


101 (15), 99 (27), 93 (19), 91 (19). C26H23ClN4O4 (490.95): calcd.C 63.61, H 4.72, Cl 7.22, N 11.41; found C 63.34, H 4.70, Cl 7.25,N 11.37.

N,9-Diphenyl-8-oxo-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazol-ine-3-carboxamide (4o): Yield: 69 %; m.p. 208–210 °C. 1H NMR([D6]DMSO, 200 MHz): δ = 1.65–2.08 (m, 2 H, CH2), 2.12–2.36(m, 2 H, CH2), 2.55–2.80 (m, 1 H, CH2), 2.82–3.06 (m, 1 H, CH2),6.19 (s, 1 H, CH-9), 6.94–7.44 (m, 8 H, ArH), 7.60–7.83 (m, 2 H,ArH), 8.07 (s, 1 H, CH), 9.79 (br. s, 1 H, NH), 9.89 (br. s, 1 H,NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 21.15, 26.78,36.81, 57.71, 100.27, 107.55, 120.49, 123.78, 127.78, 128.03, 128.75,129.09, 138.71, 139.47, 139.74, 142.59, 151.88, 161.55, 193.87 ppm.MS (EI, 70 eV): m/z (%) = 385 (5) [M+], 384 (18), 292 (43), 291(61), 264 (40), 263 (25), 236 (13), 214 (100), 93 (14). C23H20N4O2


N-Phenyl-8-oxo-9-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]-quinazoline-3-carboxamide (4p): Yield: 79%; m.p. 180–183 °C. 1HNMR ([D6]DMSO, 200 MHz): δ = 1.49–2.10 (m, 2 H, CH2), 2.08–2.42 (m, 2 H, CH2), 2.20 (s, 3 H, CH3), 2.53–3.09 (m, 2 H, CH2),6.15 (s, 1 H, CH), 6.80–7.21 (m, 5 H, ArH), 7.18–7.51 (m, 2 H,ArH), 7.56–7.84 (m, 2 H, ArH), 8.06 (s, 1 H, CH), 9.79 (br. s, 1 H,NH), 9.85 (br. s, 1 H, NH) ppm. 1 3C NMR ([D6 ]DMSO,125 MHz): δ = 21.11, 21.18, 26.77, 36.83, 57.44, 100.20, 107.69,120.48, 123.76, 127.18, 129.09, 129.26, 137.26, 138.62, 139.48,139.72, 139.77, 151.70, 161.57, 193.88 ppm. MS (EI, 70 eV): m/z(%) = 399 (9) [M+], 398 (30) [M], 306 (54), 305 (86), 278 (61), 277(33), 250 (14), 215 (13), 214 (100), 93 (16). C24H22N4O2 (398.46):calcd. C 72.34, H 5.57, N 14.06; found C 72.16, H 5.55, N 14.00.

9-(4-Chlorophenyl)-8-oxo-N-phenyl-4,5,6,7,8,9-hexahydropyrazolo-[5,1-b]quinazoline-3-carboxamide (4q): Yield: 89 %; m.p. 217–220 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 1.68–2.08 (m, 2 H,CH2), 2.09–2.36 (m, 2 H, CH2), 2.54–2.79 (m, 1 H, CH2), 2.86–3.06 (m, 1 H, CH2), 6.20 (s, 1 H, CH-9), 6.92–7.48 (m, 7 H, ArH),7.53–7.84 (m, 2 H, ArH), 8.09 (s, 1 H, CH), 9.81 (s, 1 H, NH), 9.95(s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 21.14,26.79, 36.78, 57.18, 100.34, 107.11, 120.50, 123.81, 128.75, 129.10,129.21, 132.65, 138.88, 139.43, 139.66, 141.51, 152.05, 161.47,193.90 ppm. MS (EI, 70 eV): m/z (%) = 418 (16) [M], 327 (24), 326(34), 325 (55), 299 (12), 298 (32), 297 (16), 270 (12), 215 (13), 214(100), 93 (22). C23H19ClN4O2 (418.88): calcd. C 65.95, H 4.57, Cl8.46, N 13.38; found C 65.79, H 4.56, Cl 8.50, N 13.34.

9-Phenyl-8-oxo-N-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]-quinazoline-3-carboxamide (4r): Yield: 79%; m.p. 283–285 °C. 1HNMR ([D6]DMSO, 200 MHz): δ = 1.68–2.05 (m, 2 H, CH2), 2.11–2.36 (m, 2 H, CH2), 2.24 (s, 3 H, CH3), 2.56–2.79 (m, 1 H, CH2),2.80–3.07 (m, 1 H, CH2), 6.19 (s, 1 H, CH-9), 7.00–7.39 (m, 7 H,ArH), 7.41–7.71 (m, 2 H, ArH), 8.05 (s, 1 H, CH), 9.73 (s, 1 H,NH), 9.87 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ= 20.95, 21.15, 26.78, 36.81, 57.70, 100.31, 107.53, 120.54, 127.27,128.01, 128.74, 129.49, 132.71, 136.90, 138.64, 139.68, 142.62,151.86, 161.40, 193.84 ppm. MS (EI, 70 eV): m/z (%) = 399 (7)[M+], 398 (25) [M], 292 (49), 291 (60), 264 (41), 263 (26), 236 (13),215 (14), 214 (100), 107 (22), 106 (14). C24H22N4O2 (398.46): calcd.C 72.34, H 5.57, N 14.06; found C 72.17, H 5.55, N 14.01.

8-Oxo-9,N-bis(4-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quin-azoline-3-carboxamide (4s): Yield: 91%; m.p. 209–212 °C. 1H NMR([D6]DMSO, 200 MHz): δ = 1.71–2.07 (m, 2 H, CH2), 2.09–2.35(m, 2 H, CH2), 2.20 (s, 3 H, CH3), 2.24 (s, 3 H, CH3), 2.55–3.07(m, 2 H, CH2), 6.14 (s, 1 H, CH), 6.90–7.25 (m, 6 H, ArH), 7.47–7.72 (m, 2 H, ArH), 8.03 (s, 1 H, CH.), 9.72 (br. s, 2 H, 2NH) ppm.13C NMR ([D6]DMSO, 125 MHz): δ = 20.94, 21.11, 21.17, 26.77,

V. A. Chebanov et al.FULL PAPER36.82, 57.42, 100.23, 107.65, 120.52, 127.17, 129.25, 129.49, 132.69,136.91, 137.24, 138.54, 139.64, 139.80, 151.70, 161.41, 193.80 ppm.MS (EI, 70 eV): m/z (%) = 413 (5) [M+], 412 (20) [M], 306 (53),305 (100), 304 (43), 278 (54), 277 (67), 246 (16), 215 (12), 214 (89),213 (77), 107 (14), 106 (20), 77 (11), 55 (22), 24 (17). C25H24N4O2


9-(4-Chlorophenyl)-8-oxo-N-(p-tolyl)-4,5,6,7,8,9-hexahydropyr-azolo[5,1-b]quinazoline-3-carboxamide (4t): Yield: 90%; m.p. 270–273 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 1.66–2.07 (m, 2 H,CH2), 2.10–2.36 (m, 2 H, CH2), 2.24 (s, 3 H, CH3), 2.57–2.80 (m,1 H, CH2), 2.81–3.05 (m, 1 H, CH2), 6.19 (s, 1 H, CH-9), 7.01–7.43 (m, 6 H, ArH), 7.45–7.71 (m, 2 H, ArH), 8.06 (s, 1 H, CH),9.75 (s, 1 H, NH), 9.93 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO,125 MHz): δ = 20.94, 21.14, 26.80, 36.78, 57.17, 100.39, 107.09,120.55, 128.74, 129.20, 129.49, 132.63, 132.74, 136.87, 138.81,139.60, 141.54, 152.03, 161.32, 193.87 ppm. MS (EI, 70 eV): m/z(%) = 434 (9) [M + 2], 432 (27) [M], 327 (31), 326 (49), 325 (69),298 (43), 2697 (19), 214 (100), 107 (60), 106 (21). C24H21ClN4O2


N-(4-Chlorophenyl)-8-oxo-9-phenyl-4,5,6,7,8,9-hexahydropyrazolo-[5,1-b]quinazoline-3-carboxamide (4u): Yield: 70%; m.p.� 310 °C.1H NMR ([D6]DMSO, 200 MHz): δ = 1.67–2.07 (m, 2 H, CH2),2.11–2.37 (m, 2 H, CH2), 2.56–2.79 (m, 1 H, CH2), 2.80–3.06 (m,1 H, CH2), 6.19 (s, 1 H, C9-H), 7.05–7.31 (m, 5 H, ArH), 7.37 (d,J = 8.8 Hz, 2 H, ArH), 7.72 (d, J = 8.8 Hz, 2 H, ArH), 8.04 (s, 1H, CH), 9.89 (br. s, 1 H, NH), 9.91 (br. s, 1 H, NH) ppm. 13CNMR ([D6]DMSO, 125 MHz): δ = 21.15, 26.77, 36.81, 57.72,100.08, 107.59, 121.97, 127.28, 127.36, 128.04, 128.74, 129.00,138.46, 138.71, 139.82, 142.54, 151.85, 161.56, 193.86 ppm. MS(EI, 70 eV): m/z (%) = 418 (11) [M], 292 (79), 291 (82), 264 (43),263 (27), 236 (15), 214 (100), 127 (25). C23H19ClN4O2 (418.88):calcd. C 65.95, H 4.57, Cl 8.46, N 13.38; found C 65.70, H 4.57,Cl 8.48, N 13.35.

N-(4-Chlorophenyl)-8-oxo-9-(p-tolyl)-4,5,6,7,8,9-hexahydropyr-azolo[5,1-b]quinazoline-3-carboxamide (4v): Yield: 75 %; m.p. 290–292 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 1.70–2.05 (m, 2 H,CH2), 2.09–2.33 (m, 2 H, CH2), 2.20 (s, 3 H, CH3), 2.55–2.77 (m,1 H, CH2), 2.80–3.03 (m, 1 H, CH2), 6.14 (s, 1 H, CH-9), 6.92–7.14 (m, 4 H, ArH), 7.36 (d, J = 8.8 Hz, 2 H, ArH), 7.72 (d, J =8.8 Hz, 2 H, ArH), 8.03 (s, 1 H, CH), 9.86 (br. s, 1 H, NH), 9.90(br. s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 21.10,21.16, 26.77, 36.82, 57.45, 100.02, 107.73, 121.95, 127.19, 127.35,128.99, 129.26, 137.27, 138.48, 138.62, 139.74, 139.80, 151.66,161.59, 193.82 ppm. MS (EI, 70 eV): m/z (%) = 434 (7) [M + 2],432 (24) [M], 431 (21) [M–], 306 (80), 305 (100), 304 (55), 279 (37),277 (54), 249 (20), 248 (16), 214 (80), 213 (76), 128 (19), 127 (28),126 (19). C24H21ClN4O2 (432.91): calcd. C 66.59, H 4.89, Cl 8.19,N 12.94; found C 66.32, H 4.89, Cl 8.23, N 12.90.

N,9-Bis(4-chlorophenyl)-8-oxo-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]-quinazoline-3-carboxamide (4w): Yield: 63%; m.p. 298–302 °C. 1HNMR ([D6]DMSO, 200 MHz): δ = 1.71–2.06 (m, 2 H, CH2), 2.11–2.38 (m, 2 H, CH2), 2.57–2.79 (m, 1 H, CH2), 2.79–3.04 (m, 1 H,CH2), 6.19 (s, 1 H, CH-9), 7.17 (d, J = 8.6 Hz, 2 H, ArH), 7.32 (d,J = 8.6 Hz, 2 H, ArH), 7.37 (d, J = 8.8 Hz, 2 H, ArH), 7.72 (d, J

= 8.8 Hz, 2 H, ArH), 8.06 (s, 1 H, CH), 9.99 (br. s, 2 H, NH) ppm.13C NMR ([D6]DMSO, 125 MHz): δ = 21.14, 26.79, 36.78, 57.21,100.17, 107.17, 121.97, 127.40, 128.74, 128.99, 129.22, 132.67,138.44, 138.87, 139.74, 141.47, 151.98, 161.51, 193.88 ppm. MS(EI, 70 eV): m/z (%) = 453 (8) [M+], 452 (8) [M], 328 (21), 327 (50),326 (87), 325 (89), 299 (24), 298 (44), 270 (16), 215 (13), 214 (100),


128 (20), 127 (25), 126 (30), 55 (32), 54 (28). C23H18Cl2N4O2


Typical Procedure for the Ultrasonic-Assisted Synthesis of 8,8-Di-methyl-6-oxo-5-phenyl-N-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo-[1,5-a]quinazoline-3-carboxamide (5a): A mixture of 5-amino-N-(p-tolyl)-1H-pyrazole-4-carboxamide (1b; 0.22 g, 1 mmol), dimedone(3a; 0.28 g, 2 mmol), benzaldehyde (2a; 0.11 g, 1 mmol) and DMF(1.5 mL) containing a catalytic amount of HCl in a round-bottomflask, was irradiated in an ultrasonic bath (44.2 kHz) for 45 min.The reaction mixture was cooled to room temperature and anEtOH/H2O (1:1, 4 mL) mixture was added. After cooling, the crys-tals formed were removed by filtration, washed with EtOH/H2O(1:1) and dried in air. Yield: 0.29 g (68%); m.p. 235–238 °C. 1HNMR ([D6]DMSO, 200 MHz): δ = 0.98 (s, 3 H, CH3), 1.08 (s, 3H, CH3), 2.24 (d, J = 16.0 Hz, 1 H, CH2), 2.26 (s, 3 H, ArCH3),2.36 (d, J = 16.0 Hz, 1 H, CH2), 2.75 (d, J = 18.5 Hz, 1 H, CH2),3.03 (d, J = 18.5 Hz, 1 H, CH2), 5.59 (d, J = 2.6 Hz, 1 H, CH),6.96–7.65 (m, 9 H, ArH), 8.09 (d, J = 2.6 Hz, 1 H, NH), 8.23 (s, 1H, CH), 9.53 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz):δ = 20.91, 27.39, 29.23, 32.53, 37.00, 50.21, 50.35, 97.35, 112.22,120.27, 126.37, 128.01, 129.01, 129.45, 132.36, 137.10, 142.75,143.82, 147.45, 148.53, 161.53, 195.26 ppm. MS (EI, 70 eV): m/z(%) = 426 (15) [M], 349 (16), 320 (33), 319 (71), 318 (57), 242 (100),241 (80), 186 (53), 185 (47), 149 (71), 148 (75), 107 (59), 106 (54),82 (40), 57 (54), 56 (68), 55 (74), 44 (29), 41 (42). C26H26N4O2


8,8-Dimethyl-6-oxo-N-phenyl-5-(p-tolyl)-4,5,6,7,8,9-hexahydropyr-azolo[1,5-a]quinazoline-3-carboxamide (5b): Yield: 71%; m.p. 225–227 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.98 (s, 3 H, CH3),1.08 (s, 3 H, CH3), 2.20 (s, 3 H, ArCH3), 2.24 (d, J = 16.6 Hz, 1H, CH2), 2.36 (d, J = 16.6 Hz, 1 H, CH2), 2.75 (d, J = 18.3 Hz, 1H, CH2), 3.03 (d, J = 18.3 Hz, 1 H, CH2), 5.54 (d, J = 2.4 Hz, 1H, CH), 6.85–7.19 (m, 5 H, ArH), 7.18–7.38 (m, 2 H, ArH), 7.53–7.74 (m, 2 H, ArH), 8.08 (d, J = 2.4 Hz, 1 H, NH), 8.25 (s, 1 H,CH), 9.59 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO,125 MHz): δ= 21.11, 27.40, 29.24, 32.53, 36.99, 49.97, 50.37, 97.30, 112.34,120.19, 123.45, 126.32, 129.05, 129.53, 137.24, 139.68, 140.90,142.69, 147.30, 148.59, 161.68, 195.22 ppm. MS (EI, 70 eV): m/z(%) = 426 (7) [M+], 334 (27), 333 (56), 332 (35), 305 (25), 242 (97),241 (100), 185 (21), 149 (19), 92 (26). C26H26N4O2 (426.52): calcd.C 73.22, H 6.14, N 13.14; found C 72.91, H 6.12, N 13.11.

5-(4-Chlorophenyl)-8,8-dimethyl-6-oxo-N-phenyl-4,5,6,7,8,9-hexahy-dropyrazolo[1,5-a]quinazoline-3-carboxamide (5c): Yield: 63%; m.p.154–156 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.97 (s, 3 H,CH3), 1.08 (s, 3 H, CH3), 2.22 (d, J = 16.1 Hz, 1 H, CH2), 2.38 (d,J = 16.1 Hz, 1 H, CH2), 2.75 (d, J = 18.4 Hz, 1 H, CH2), 3.04 (d,J = 18.4 Hz, 1 H, CH2), 5.58 (d, J = 3.0 Hz, 1 H, CH), 6.90–7.10(m, 1 H, ArH), 7.18–7.45 (m, 6 H, ArH), 7.54–7.74 (m, 2 H, ArH),8.20 (d, J = 3.0 Hz, 1 H, NH), 8.27 (s, 1 H, CH), 9.63 (s, 1 H,NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 27.41, 29.18,32.52, 37.00, 49.75, 50.30, 97.38, 111.86, 120.20, 123.49, 128.32,129.03, 132.62, 139.65, 142.77, 142.86, 147.64, 148.40, 161.64,195.27 ppm. MS (EI, 70 eV): m/z (%) = 448 (21) [M + 2], 447 (20)[M+], 446 (55) [M], 445 (20) [M–], 242 (86), 186 (67), 158 (22), 94(20), 93 (100), 65 (19). C25H23ClN4O2 (446.94): calcd. C 67.18, H5.19, Cl 7.93, N 12.54; found C 66.96, H 5.17, Cl 7.96, N 12.50.

5-(4-Chlorophenyl)-8,8-dimethyl-6-oxo-N-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinazoline-3-carboxamide (5d): Yield:65%; m.p. 218–220 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.97(s, 3 H, CH3), 1.08 (s, 3 H, CH3), 2.23 (s, 3 H, ArCH3), 2.17 (d, J


= 15.7 Hz, 1 H, CH2), 2.43 (d, J = 15.7 Hz, 1 H, CH2), 2.73 (d, J

= 18.5 Hz, 1 H, CH2), 3.02 (d, J = 18.5 Hz, 1 H, CH2), 5.57 (d, J

= 2.4 Hz, 1 H, CH), 7.08 (d, J = 8.1 Hz, 2 H, ArH), 7.21 (d, J =8.4 Hz, 2 H, ArH), 7.34 (d, J = 8.4 Hz, 2 H, ArH), 7.52 (d, J =8.1 Hz, 2 H, ArH), 8.15 (d, J = 2.4 Hz, 1 H, NH), 8.24 (s, 1 H,CH), 9.56 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ= 20.92, 27.41, 29.18, 32.53, 36.99, 49.73, 50.30, 97.42, 111.86,120.27, 128.31, 129.03, 129.46, 132.40, 132.60, 137.08, 142.79,142.83, 147.65, 148.33, 161.48, 195.27 ppm. MS (EI, 70 eV): m/z(%) = 460 (3) [M], 353 (15), 243 (15), 242 (44), 241 (29), 186 (19),108 (14), 107 (70), 106 (100), 78 (19). C26H25ClN4O2 (460.96):calcd. C 67.75, H 5.47, Cl 7.69, N 12.15; found C 67.61, H 5.46,Cl 7.72, N 12.11.

5-(4-Fluorophenyl)-8,8-dimethyl-6-oxo-N-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinazoline-3-carboxamide (5e): Yield:78%; m.p. 146–149 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.98(s, 3 H, CH3), 1.07 (s, 3 H, CH3), 2.23 (s, 3 H, ArCH3), 2.24 (d, J

= 16.2 Hz, 1 H, CH2), 2.36 (d, J = 16.2 Hz, 1 H, CH2), 2.73 (d, J

= 18.5 Hz, 1 H, CH2), 3.02 (d, J = 18.5 Hz, 1 H, CH2), 5.57 (d, J

= 2.3 Hz, 1 H, CH), 6.98–7.37 (m, 6 H, ArH), 7.38–7.62 (m, 2 H,ArH), 8.12 (d, J = 2.3 Hz, 1 H, NH), 8.24 (s, 1 H, CH), 9.55 (s, 1H, NH) ppm. 13C NMR ([D6]DMSO, 125 MHz): δ = 20.91, 27.43,29.18, 32.53, 36.98, 49.65, 50.31, 97.39, 112.09, 115.70, 115.87,120.27, 128.47, 129.45, 132.39, 137.08, 140.14, 142.79, 147.52,148.35, 160.97, 161.51, 195.26 ppm. MS (EI, 70 eV): m/z (%) = 444(6) [M], 338 (11), 242 (25), 108 (15), 107 (71), 106 (100), 78 (15).C26H25FN4O2 (444.51): calcd. C 70.25, H 5.67, F 4.27, N 12.60;found C 69.95, H 5.66, F 4.29, N 12.56.

5-(4-Methoxyphenyl)-8,8-dimethyl-6-oxo-N-(p-tolyl)-4,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinazoline-3-carboxamide (5f): Yield:75%; m.p. 168–171 °C. 1H NMR ([D6]DMSO, 200 MHz): δ = 0.99(s, 3 H, CH3), 1.08 (s, 3 H, CH3), 2.22 (s, 3 H, ArCH3), 2.23 (d, J

= 14.2 Hz, 1 H, CH2), 2.34 (d, J = 14.2 Hz, 1 H, CH2), 2.75 (d, J

= 14.2 Hz, 1 H, CH2), 3.04 (d, J = 14.2 Hz, 1 H, CH2), 3.66 (s, 3H, ArOCH3), 5.50 (d, J = 2.3 Hz, 1 H, CH), 6.73–6.99 (m, 2 H,ArH), 7.00–7.33 (m, 4 H, ArH), 7.40–7.69 (m, 2 H, ArH), 8.02 (d,J = 2.3 Hz, 1 H, NH), 8.22 (s, 1 H, CH), 9.53 (s, 1 H, NH) ppm.13C NMR ([D6]DMSO,125 MHz): δ = 20.91, 27.45, 29.24, 32.53,36.97, 49.69, 50.37, 55.54, 97.34, 112.43, 114.06, 114.35, 120.25,120.54, 127.63, 128.45, 129.45, 132.35, 136.00, 137.11, 142.64,147.19, 148.46, 159.14, 161.54, 195.21 ppm. MS (EI, 70 eV): m/z(%) = 457 (14) [M+], 456 (45) [M], 350 (26), 349 (62), 348 (46), 322(27), 321 (40), 242 (53), 243 (34), 186 (24), 149 (23), 108 (22), 107(80), 106 (100), 83 (39), 77 (52). C27H28N4O3 (456.54): calcd. C71.03, H 6.18, N 12.27; found C 70.88, H 6.16, N 12.23.

Typical Procedure for the Synthesis of 5-[9-(4-Chlorophenyl)-3,3,6,6-tetramethyl-1,8-dioxo-1,2,3,4,5,6,7,8-octahydroacridin-10(9H)-yl]-N-(p-tolyl)-1H-pyrazole-4-carboxamide (7a): A mixture of 5-amino-N-(p-tolyl)-1H-pyrazole-4-carboxamide (1b; 0.32 g, 1.5 mmol), di-medone 3a (0.42 g, 3 mmol), 4-chlorobenzaldehyde (2d; 0.21 g,1.5 mmol) and DMF (2 mL) with a catalytic amount of HCl washeated to reflux for 15 min. The reaction mixture was cooled to50–60 °C, and EtOH/H2O (1:1, 4 mL) was added. The precipitateformed was removed by filtration, washed with EtOH/H2O (1:1),and dried in air. To obtain an analytical sample of compound 7ait was mechanically separated from compound 4h and recrystallizedfrom EtOH/H2O (2:3). Yield: 0.3 g (35%); m.p. �300 °C. 1H NMR([D6]DMSO, 200 MHz): δ = 0.68 (0.71) (s, 3 H, CH3), 0.84 (0.86)(s, 3 H, CH3), 1.69–2.41 (m, 8 H, 4CH2), 2.24 (2.26) (s, 3 H,ArCH3), 4.87 (4.94) (s, 1 H, CH), 6.93–7.38 (m, 5 H, ArH), 7.41–7.82 (m, 3 H, ArH), 8.57 (8.65) (s, 1 H, CH), 9.92 (10.00) (s, 1 H,NH), 13.20 (s, 1 H, NH) ppm. MS (EI, 70 eV): m/z (%) = 584 (7)


[M + 2], 583 (12) [M+], 582 (26) [M+], 473 (30), 472 (89), 471 (100),110 (17), 109 (14), 108 (36), 107 (64), 106 (87), 105 (49), 83 (27).C34H35ClN4O3 (583.13): calcd. C 70.03, H 6.05, Cl 6.08, N 9.61;found C 69.75, H 6.03, Cl 6.11, N 9.58.

5- [9- (4-Methoxyphenyl ) -3 ,3 ,6 ,6- te t ramethyl -1 ,8-dioxo-1,2,3,4,5,6,7,8-octahydroacridin-10(9H)-yl]-N-(p-tolyl)-1H-pyr-azole-4-carboxamide (7b): Yield: 30 %; m.p. �300 °C. 1H NMR([D6]DMSO, 200 MHz): δ = 0.69 (0.72) (s, 3 H, CH3), 0.84 (0.86)(s, 3 H, CH3), 1.70–2.30 (m, 8 H, 4CH2), 2.24 (2.25) (s, 3 H,ArCH3), 3.64 (3.66) (s, 3 H, ArOCH3), 4.83 (4.89) (s, 1 H, CH),6.52–7.68 (m, 8 H, ArH), 8.53 (8.64) (s, 1 H, CH), 9.90 (10.00) (s,1 H, NH), 13.52 (br. s, 1 H, NH) ppm. MS (EI, 70 eV): m/z (%) =578 (6) [M], 471 (14), 108 (66), 107 (100), 106 (87), 92 (48), 82 (28),78 (29), 77 (64). C35H38N4O4 (578.71): calcd. C 72.64, H 6.62, N9.68; found C 72.35, H 6.03, Cl 6.61, N 9.65.

Supporting Information (see footnote on the first page of this arti-cle): 1H and 13C NMR spectra for the compounds synthesized.

Acknowledgments

The authors thank Dr. Vataliy Polovinko (Enamine Ltd., Ukraine)and Dr. Dmytro Sysoev (Konstanz University, Germany) for meas-uring some NMR spectra.

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Published Online: August 15, 2012

Controlled Switching of Multicomponent Heterocyclizations of 5-Amino-N-arylpyrazole-4-carboxamides, 1,3-Cyclohaxanediones and Aldehydes

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