Synthesis of 6-hydrazino-3,4-dimethyl-1H-pyrazolo[3,4-d]pyrimidine and its application for the construction of a pyrazolo[4,3-e][1,2,4]triazolo[4,3-a] pyrimidine system

Article abstract of DOI:10.1007/s11172-013-0172-4

A new representative of heterocyclic hydrazines, viz., 6-hydrazino-3,4- dimethyl-1H-pyrazolo[3,4-d]pyrimidine (3) was synthesized from diacetyl ketene N,S-acetal. A condensation of hydrazine 3 with amide acetals or aldehydes and subsequent cyclization furnished pyrazolo[4,3-e][1,2,4]triazolo[4,3-a] pyrimidines, whose structure was confirmed by ¹H, ¹³C, and ¹H/¹⁵N HMBC NMR spectroscopy. Reactions of hydrazine 3 with acetylacetone, ethyl acetoacetate, diethyl malonate, and acetic anhydride were studied.

Full text of DOI:10.1007/s11172-013-0172-4

Russian Chemical Bulletin, International Edition, Vol. 62, No. 5, pp. 1248—1254, May, 2013
1248
Synthesis of 6ꢀhydrazinoꢀ3,4ꢀdimethylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidine
and its application for the construction
of a pyrazolo[4,3ꢀe][1,2,4]triazolo[4,3ꢀa]pyrimidine system
A. V. Komkov, A. S. Shashkov, S. V. Baranin, and V. A. Dorokhov†
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: svbar@ioc.ac.ru
A new representative of heterocyclic hydrazines, viz., 6ꢀhydrazinoꢀ3,4ꢀdimethylꢀ1Hꢀpyrꢀ
azolo[3,4ꢀd]pyrimidine (3) was synthesized from diacetyl ketene N,Sꢀacetal. A condensation
of hydrazine 3 with amide acetals or aldehydes and subsequent cyclization furnished pyrazoꢀ
lo[4,3ꢀe][1,2,4]triazolo[4,3ꢀa]pyrimidines, whose structure was confirmed by 1H, 13C, and
1H/15N HMBC NMR spectroscopy. Reactions of hydrazine 3 with acetylacetone, ethyl acetoꢀ
acetate, diethyl malonate, and acetic anhydride were studied.
Key words: diacetyl ketene N,Sꢀacetal, 5ꢀacetylꢀ6ꢀmethylꢀ2,4ꢀdi(methylsulfanyl)pyrimidine,
hydrazine, 6ꢀhydrazinoꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidine, amide acetals, aldehydes, condensaꢀ
tion, oxidative cyclization, pyrazolo[4,3ꢀe][1,2,4]triazolo[4,3ꢀa]pyrimidines, 6ꢀ(1Hꢀpyrazolꢀ
1ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidines.
Scheme 1
The present work is a continuation of our studies on
the application of diacetyl ketene N,Sꢀacetal1 obtained by
us in heterocyclic synthesis. Earlier this reagent was used
in the preparation of functionally substituted 2ꢀpyrimidiꢀ
nones,2 2ꢀpyrimidinethiones,3 4ꢀpyrimidinethiones,4,5
4ꢀmethylsulfanylꢀ and 4ꢀmethylsulfonylpyrimidines,5
4ꢀpyridinones,6 pyrazoles,7 pyridino[2,3ꢀd]pyrimidines,3,4
pyrimido[4,5ꢀd]pyrimidines,2,3 and pyrazolo[3,4ꢀd]pyrꢀ
imidines.5,7
Recently,3 the reaction of diacetyl ketene N,Sꢀacetal 1
and benzoylisothiocyanate with subsequent cyclization was
used to synthesize 5ꢀacetylꢀ6ꢀmethylꢀ2,4ꢀdi(methylꢀ
sulfanyl)pyrimidine (2) (Scheme 1). In order to prepare
new functionalized pyrazolo[3,4ꢀd]pyrimidines, we studꢀ
ied reactions of pyrimidine 2 with hydrazine hydrate. It
was found that reflux of compound 2 in hydrazine hydrate
led to the formation of 6ꢀhydrazinoꢀ3,4ꢀdimethylꢀ1Hꢀ
pyrazolo[3,4ꢀd]pyrimidine (3) in high yield, i.e., the pyrꢀ
azole ring closure was accompanied by the substitution for
the MeS group with the hydrazine one. It should be noted
that the use of milder conditions for this reaction (reflux
of the same mixture of reagents in butanol) gave 6ꢀmethylꢀ
sulfanylpyrazolopyrimidine 4, which upon reflux in hydrꢀ
azine hydrate was also converted to hydrazine 3.
Compound 3 is a white crystalline compound poorly
soluble in organic solvents. Its structure was confirmed by
mass spectrum and 1H and 13C NMR spectra.
Reagents and conditions: i. PhCONCS, C6H6, 20 C; ii. 1) MeONa,
MeOH, , 2) MeI, 20 C; iii. NH2NH2•H2O, ; iv. NH2NH2•
•H2O, BuOH, .
†
Deceased.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1248—1254, May, 2013.
1066ꢀ5285/13/6205ꢀ1248 © 2013 Springer Science+Business Media, Inc.

Pyrazolo[4,3ꢀe][1,2,4]triazolo[4,3ꢀa]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 5, May, 2013
1249
The reactivity of hydrazine 3 with respect to acetic
anhydride and ꢀdicarbonyl compounds was studied. It
was found that a prolonged reflux of hydrazine 3 with
a large excess of Ac2O in benzene resulted in the formaꢀ
tion of a white crystalline triacetylꢀsubstituted derivative 5
(Scheme 2), whose structure was confirmed by mass specꢀ
trum, 1H and 13C NMR spectra, and 2D 1H/15N HMBC
NMR spectrum (see Experimental).
tion peak with the protons of the 3´ꢀMe group; cf. with
 –78 for atom N(2´) in pyrazole 7).
A solventꢀfree heating of hydrazine 3 with diethyl maꢀ
lonate led to the formation of hydrazide 8, which failed to
be cyclized neither by reflux in acetic acid nor by treatꢀ
ment with MeONa in MeOH (Scheme 4).
Scheme 4
Scheme 2
Reagents and conditions: Ac2O, C6H6, .
The reaction of hydrazine 3 with ethyl acetoacetate or
acetylacetone upon reflux in acetic acid smoothly gave,
respectively, pyrazolo[3,4ꢀd]pyrimidinylꢀsubstituted pyrꢀ
azolone 6 or pyrazole 7 in high yields (Scheme 3).
Scheme 3
Reagents and conditions: i. EtO2CCH2CO2Et, 160—170 C.
The structure of a colorless compound 8 was confirmed
by physicochemical methods. It should be noted that in
1
1
the H and 13C NMR spectra and 2D H—15N HMBC
NMR spectrum, a double set of signals for the hydrazide
fragment is observed, indicating the presence of Eꢀ and
Zꢀisomers in molecule 8. This fact, apparently, is explained
by the slow rotation around the N—CO bond in the hydrꢀ
azide fragment.
Reagents and conditions: i. MeCOCH2COOEt, AcOH, ;
ii. MeCOCH2COMe, AcOH, .
The structure of colorless compounds 6 and 7 was conꢀ
firmed by mass spectra, 1H and 13C NMR spectra, and 2D
1H—15N HMBC NMR spectra. It should be noted that
pyrazolone 6 exclusively exists in the enamine form, which
Further studies of the reactivity of hydrazine 3 showed
that it can be used for the construction of pyrazolo[4,3ꢀe]ꢀ
[1,2,4]triazolo[4,3ꢀa]pyrimidines. The molecules with the
pyrazolotriazolopyrimidine structure contain two fragꢀ
ments isomeric to purines: the pyrazolopyrimidine and
the triazolopyrimidine ones. Compounds having such fragꢀ
ment are of interest because of their biological properties.
Thus, for example, some of similar compounds are known
to be selective human A3 adenosine receptor antagonists,8,9
1
was indicated by the H NMR spectra in DMSOꢀd6 and
CDCl3. This is probably due to the presence in molecule 6
of a strong intramolecular hydrogen bond stabilizing the
enamine form. The oxy form of the pyrazole ring in comꢀ
pound 6 is excluded based on the 2D 1H/15N HMBC
NMR spectrum, in which a characteristic upfield chemiꢀ
cal shift for atom N(2´) is observed ( –164, the correlaꢀ

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 5, May, 2013
Komkov et al.
exhibit antiinflammatory activity,10—12 or belong to the
class of strong xantineoxidase inhibitors.13
of compounds 9a,b and 10a,b was confirmed by spectroꢀ
scopic methods. Their mass spectra (EI) are characterized
by strong peaks of molecular ions (the tricycles 10a,b virꢀ
tually give no fragmentation). The 1H NMR spectrum of
amidrazone 9a (CDCl3) exhibits a singlet for the proton
CH= at  7.65, whereas for pyrazolotriazolopyrimidine
10a (DMSOꢀd6) the singlet for proton H(8) is found at
 9.26. The 2D 1H—15N HMBC NMR spectrum of comꢀ
pound 10b is shown in Fig. 1.
We found that reflux of hydrazine 3 with an excess of
dimethylformamide or dimethylacetamide dimethylacetal in
benzene led to the formation of amidrazones 9a,b, which in
refluxing oꢀxylene were converted to pyrazolo[4,3ꢀe]ꢀ
[1,2,4]triazolo[4,3ꢀa]pyrimidines 10a,b, i.e., the cyclization
took place at atom N(7) of the pyrimidine ring of amiderꢀ
azines 9, rather than at atom N(5), which would result in
the formation of the alternative structure 11a,b (Scheme 5).
The presence of the upfield signal for atom N(9) at
 –208 and the downfield signal for atom N(7) in the
region  –102 (the correlation peaks of the protons of
8ꢀMe group, respectively, with atoms N(9) and N(7)) conꢀ
firmed the structure of compound 10b and excluded the
formation of tricycle 12b, in which chemical shifts for
both N atoms should be found in the low field region (the
correlation peaks of the protons of 7ꢀMe group with atoms
N(6) and N(8)). Besides, in the spectrum of the alternaꢀ
tive structure 11b chemical shift for atom N(5) in both
correlation peaks with the 4ꢀMe and 6ꢀMe protons should
be identical and found in the high field. The actual chemꢀ
ical shift for atom N(5) is observed at  –140 (the correlaꢀ
tion peak only with the protons of the 4ꢀMe group; cf. also
with  –136 for atom N(5) in amidrazone 9b), that conꢀ
firms the structure 10b. The highꢀfield chemical shift for
atom N(2) at  –159 (the correlation peak with the proꢀ
tons of the 3ꢀMe group) in compound 10b indicates the
position of the proton at atom N(2) in the pyrazole ring
(cf. with  –85 for atom N(2) in amidrazone 9b, which has
a proton at atom N(1)). Chemical shifts for proton H(8)
Scheme 5
1
in the H NMR spectrum ( 9.26) and atom C(8) in the
13C NMR spectrum ( 132.44) in compound 10a also conꢀ
firm its structure and exclude the formation of compound
12a (cf.14 with  9.25 for H(3) and  135.8 for C(3) in
compound A,  8.26 for H(2) and  156.3 for C(2) in
compound B in the 1H and 13C NMR spectra recorded in
DMSOꢀd6 for R = H).
R = H (a), Me (b)
Reagents and conditions: i. (MeO)2C(R)NMe2, C6H6, ; ii. oꢀxylꢀ
ene, .
To sum up, the data of the 2D 1H—15N HMBC NMR
spectra unambiguously confirm the structure 10a,b and
exclude the structures 11a,b and 12a,b.
Besides, a possibility of the formation of other alternaꢀ
tive structures (12a,b), i.e., the Dimroth rearrangement
products, was excluded based on the spectroscopic data.
Thus, it is known14 that the 1,2,4ꢀtriazolo[4,3ꢀa]pyrꢀ
imidine system (A), being a fragment of heterocycles 10a,b,
can undergo isomerization to the thermodynamically more
stable [1,5ꢀa] system (B) either thermally, or under acidic
or basic conditions.
Continuing with the studies of the reactivity of hydrꢀ
azine 3, we found that it reacted with aromatic aldehydes,
resulting in obtaining of white crystalline hydrazones
13a,b. When this reaction was run in refluxing acetic acid
in the presence of sulfuric acid, the aldehydes also underwent
condensation at the methyl group of the pyrimidine ring,
which led to the formation of compounds 14a,b as yellow
crystals (Scheme 6). Hydrazones 13a,b were converted to
pyrazolotriazolopyrimidines 15a,b, similar in structure to
compounds 10a,b, by the oxidative cyclization using CuCl2
according to the method suggested in the work.15
The structure of pyrazolotriazolopyrimidines 15a,b was
established by spectroscopic methods.
Amidrazones 9a,b are well soluble in chloroform,
whereas pyrazolotriazolopyrimidines 10a,b are poorly solꢀ
uble in organic solvents, including DMSO. The structure
Unlike for tricycles 10a,b, the molecular ion peak in
the mass spectrum (EI) of compound 15b appeared to be

Pyrazolo[4,3ꢀe][1,2,4]triazolo[4,3ꢀa]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 5, May, 2013
1251

–220
–208
N(9)
–200
–180
–160
–159
N(2)
N(5)
–140
–120
–100
–140
–102
N(7)
3.00 2.98 2.96 2.94 2.92 2.90 2.88 2.86 2.84 2.82 2.80
Fig. 1. 2D 1H—15N HMBC NMR spectrum of compound 10b.

Scheme 6
weak, and was absent in the spectrum of heterocycle 15a.
However, in the high resolution mass spectra obtained by
electrospray ionization (ESI), the peaks of the ions
[M + H]+ were observed for compounds 15a,b, that conꢀ
firmed the formation of suggested pyrazolotriazolopyrꢀ
imidines. The 2D 1H—15N HMBC NMR spectrum of
compound 15b exhibited a downfield signal for N(5)
at  –127 (the correlation peak of the 4ꢀMe protons
with atom N(5)) and an upfield signal N(2) in the region
 –171 (the correlation peak of the 3ꢀMe protons with
atom N(2)). The 13C NMR spectra exhibit the signal
for atom C(8) at  145.80 in compound 15a and  145.04
in heterocycle 15b (cf. the data in Ref. 14: the chemiꢀ
cal shifts  144.8 for C(3) and  165.6 for C(2), respectꢀ
ively, in compounds A and B for R = Ar). The spectral
data given unambiguously confirm the structure of comꢀ
pounds 15a,b.
It should be noted that earlier,16,17 it was reported that
only 4ꢀiminoꢀ1,5ꢀdiphenylpyrazolo[4,3ꢀe][1,2,4]triazoloꢀ
[4,3ꢀa]pyrimidines were synthesized from 5ꢀaminoꢀ1ꢀpheꢀ
nylꢀ1Hꢀpyrazoloꢀ4ꢀcarboxylic acid amide
Ar = 4ꢀEtOC6H4 (a), 4ꢀBrC6H4 (b)
In conclusion, we suggested an approach to the conꢀ
struction of the little studied pyrazolo[4,3ꢀe][1,2,4]ꢀ
Reagents and conditions: i. ArCHO, EtOH, ; ii. ArCHO, AcOH,
H2SO4, ; iii. CuCl2, DMF, 110 C.

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Komkov et al.
(5 mL) was refluxed for 8 h until complete dissolution, cooled to
20 C, and diluted with light petroleum (12 mL). A precipitate
formed was filtered off and washed with light petroleum to obtain
a white compound 5 (0.071 g, 58%), m.p. 192—193 C. Found (%):
C, 51.48; H, 5.35; N, 27.36. C13H16N6O3. Calculated (%): C, 51.30;
H, 5.30; N, 27.62. MS, m/z (Irel (%)): 304 [M]+ (1), 262 [M –
– COCH2]+ (55), 220 [M – 2 COCH2]+ (55), 178 [M – 3 COCH2]+
(100), 149 [M – 3 COCH2 – N2 – H]+ (40). 1H NMR (CDCl3),
: 2.17 (s, 3 H, MeCONH); 2.63 (s, 3 H, MeCON); 2.65 (s, 3 H,
3ꢀMe); 2.77 (s, 3 H, MeCON); 2.78 (s, 3 H, 4ꢀMe); 8.46 (br.s, 1 H,
NH). 13C NMR (CDCl3), : 15.13 (3ꢀMe); 20.79, 22.50, 24.17,
25.39 (3 MeCON, 4ꢀMe); 112.64 (C(3a)); 146.78 (C(3)); 156.37,
158.17 (C(6), C(7a)); 164.84 (C(4)); 167.94 (NCO); 169.41
(NHCO); 170.73 (NCO). 15N NMR (CDCl3), : –240 (NH)
(correlation with proton NH); –213 (NH—NCOMe) (correlaꢀ
tion with proton NH); –115 (N(5)) (correlation with protons
4ꢀMe); –70 (N(2)) (correlation with protons 3ꢀMe).
triazolo[4,3ꢀa]pyrimidine system based on diacetyl ketene
N,Sꢀacetal.
Experimental
1
H NMR spectra were recorded on a Bruker AMꢀ300
spectrometer (300 MHz), 13C NMR spectra and 2D 1H—13
C
1
and H—15N HMBC NMR spectra were recorded on a Bruker
Avance 600 spectrometer (600, 150, and 60.8 MHz for 1H, 13C,
and 15N, respectively). Residual signals of the deuterated solꢀ
vents (7.27 for CDCl3 and 2.50 for DMSOꢀd6) were used as
references in the 1H NMR spectra, whereas in the 13C NMR
spectra as those were used the multiplet signals of the deuterated
solvents (39.50 for DMSOꢀd6 and 77.00 for CDCl3). The signals
in the H and 13C NMR spectra of NMR spectra were assigned
1
based on the 2D 1H—13C HMBC NMR spectra. Chemical shifts
for 15N were measured relative to the external standard MeNO2
(the upfield chemical shifts are given as negative values) based on
the analysis of the 2D 1H—15N HMBC NMR spectra. IR spectra
were recorded on a SpecordꢀM 82 spectrometer, mass spectra
were measured on a Kratos MSꢀ30 instrument (EI, 70 eV, temperꢀ
ature of the ionizing chamber 250 C, direct injection of comꢀ
pounds). High resolution mass spectra were recorded on a Bruker
micrOTOF II instrument using electrospray ionization (ESI).
The measurements were performed on the positive ions (capillary
voltage 4500 V). The masses range scanning (m/z 50—3000 Da),
external and internal calibration (Electrospray Calibrant Soluꢀ
tion, Fluka). Solutions of samples in methanol were injected
with a syringe, the flow rate 3 L min–1. Sprayer gas nitrogen
(4 L min–1), interface temperature 180 C. Amide acetals purchased
from Lancaster and aldehydes from Acros were used in the synꢀ
theses. 5ꢀAcetylꢀ6ꢀmethylꢀ2,4ꢀdi(methylsulfanyl)pyrimidine (2)
was synthesized according to the procedure p ublished earlier.3
6ꢀHydrazinoꢀ3,4ꢀdimethylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidine
(3). A mixture of pyrimidine 2 (0.456 g, 2 mmol) and hydrazine
hydrate (6 mL, 123 mmol) was refluxed for 4 h and cooled to
20 C. A precipitate was filtered off and washed with ethanol
(6 mL) to obtain a white hydrazine 3 (0.306 g, 86%), m.p. >360 C.
Found (%): C, 47.22; H, 5.68; N, 47.25. C7H10N6. Calculated
(%): C, 47.18; H, 5.66; N, 47.16. MS, m/z (Irel (%)): 178 [M]+
(100), 149 [M – NNH]+ (28), 148 [M – NNH2]+ (12), 133
[M – NNH – NH2]+ (11). 1H NMR (DMSOꢀd6), : 2.46 (s, 3 H,
3ꢀMe); 2.56 (s, 3 H, 4ꢀMe); 4.15 (br.s, 2 H, NH2); 7.92 (br.s,
1 H, NH); 12.30 (br.s, 1 H, NHpyrazole). 13C NMR (DMSOꢀd6 +
+ CF3COOH), : 14.49 (3ꢀMe); 21.96 (4ꢀMe); 108.40 (C(3a));
143.06 (C(3)); 155.92, 159.31 (C(6), C(7a)); 165.06 (C(4)).
3,4ꢀDimethylꢀ6ꢀmethylsulfanylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidꢀ
ine (4). A mixture of pyrimidine 2 (0.16 g, 0.7 mmol) and hydrꢀ
azine hydrate (0.85 mL, 17.5 mmol) in BuOH (5 mL) was reꢀ
fluxed for 3 h and cooled to 20 C. A precipitate was filtered off
and washed with BuOH (5 mL) and light petroleum to obtain
a white compound 4 (0.09 g, 65%), m.p. 237—240 C (subl.).
Found (%): C, 49.63; H, 5.21; N, 28.72; S, 16.22. C8H10N4S.
Calculated (%): C, 49.46; H, 5.19; N, 28.84; S, 16.51. MS, m/z
(Irel (%)): 194 [M]+ (100), 193 [M – H]+ (44), 163 [M – H –
–2 Me]+ (15), 148 [M – SCH2]+ (34), 133 [M – SCH2 – Me]+
(19), 121 [M – MeSCN]+ (30). 1H NMR (CDCl3), : 2.68
(s, 6 H, 2 Me); 2.79 (s, 3 H, Me); 10.75 (br.s, 1 H, NH).
3,4ꢀDimethylꢀ6ꢀ(3ꢀmethylꢀ5ꢀoxoꢀ1H,2Hꢀpyrazolꢀ1ꢀyl)ꢀ1Hꢀ
pyrazolo[3,4ꢀd]pyrimidine (6). A mixture of (0.142 g, 0.8 mmol)
hydrazine 3 and ethyl acetoacetate (0.40 mL, 3.2 mmol) in AcOH
(4 mL) was refluxed for 7 h. The reaction mixture was allowed to
stand at 20 C for 12 h. A precipitate was filtered off, washed
with chloroform (2 mL) to obtain colorless compound 6 (0.137 g,
70%), m.p. 354—356 C (decomp.). Found (%): C, 54.21;
H, 4.83; N, 34.48. C11H12N6O. Calculated (%): C, 54.09;
H, 4.95; N, 34.41. MS, m/z (Irel (%)): 244 [M]+ (100), 216
[M – CO]+ (8), 203 [M – MeCN]+ (11), 148 (19), 147 (11), 133
(12). IR (KBr), /cm–1: 3250—2750 (NH, CH); 1636 (CO);
1
1595, 1512, 1484, 1444. H NMR (DMSOꢀd6), : 2.15 (s, 3 H,
3´ꢀMe); 2.62 (s, 3 H, 3ꢀMe); 2.81 (s, 3 H, 4ꢀMe); 5.44 (s, 1 H,
H(4´)); 12.51 (br.s, 1 H, N(2´)H); 13.43 (br.s, 1 H, N(1)H).
1H NMR (CDCl3), : 2.43 (s, 3 H, 3´ꢀMe); 2.72 (s, 3 H, 3ꢀMe);
2.91 (s, 3 H, 4ꢀMe); 5.52 (s, 1 H, H(4´)); 12.50 (br.s, 1 H, NH).
13C NMR (DMSOꢀd6 + CF3COOH), :12.97, 14.16 (3ꢀMe,
3´ꢀMe); 21.56 (4ꢀMe); 90.30 (C(4´)); 110.46 (C(3a)); 143.86 (C(3));
151.37 (C(3´)); 151.49, 155.07 (C(6), C(7a)); 158.63 (C(5´)); 164.52
(C(4)). 15N NMR (DMSOꢀd6 + CF3COOH), : –164 (N(2´))
(correlation with protons 3´ꢀMe); –150 (N(5)) (correlation with
protons 4ꢀMe); –76 (N(2)) (correlation with protons 3ꢀMe).
3,4ꢀDimethylꢀ6ꢀ(3,5ꢀdimethylꢀ1Hꢀpyrazolꢀ1ꢀyl)ꢀ1Hꢀpyrꢀ
azolo[3,4ꢀd]pyrimidine (7). A mixture of hydrazine 3 (0.125 g,
0.7 mmol) and acetylacetone (0.29 mL, 2.8 mmol) in AcOH
(4 mL) was refluxed for 4 h. The reaction mixture was allowed to
stand at 20 C for 12 h. A precipitate was filtered off and washed
with light petroleum (10 mL) to obtain colorless compound 7
(0.122 g, 72%), m.p. 310—312 C. Found (%): C, 59.32; H, 5.85;
N, 34.70. C12H14N6. Calculated (%): C, 59.49; H, 5.82; N, 34.69.
MS, m/z (Irel (%)): 242 [M]+ (100), 227 [M – Me]+ (26), 201
[M – MeCN]+ (12), 163 (15), 148 (12), 102 (35). 1H NMR
(DMSOꢀd6), : 2.21 (s, 3 H, 3´ꢀMe); 2.60 (s, 3 H, 5´ꢀMe); 2.64
(s, 3 H, 3ꢀMe); 2.82 (s, 3 H, 4ꢀMe); 6.11 (s, 1 H, H(4´)); 13.37
(br.s, 1 H, NH). 13C NMR (DMSOꢀd6), : 13.02 (3´ꢀMe); 13.93
(5´ꢀMe); 14.10 (3ꢀMe); 21.84 (4ꢀMe); 108.81 (C(4´)); 109.80
(C(3a)); 141.55 (C(5´)); 142.20 (C(3)); 148.79 (C(3´)); 153.86,
155.48 (C(6), C(7a)); 163.87 (C(4)). 15N NMR (DMSOꢀd6),
: –164 (N(1´)) (correlation with protons 5´ꢀMe and proton H(4´));
–125 (N(5)) (correlation with protons 4ꢀMe); –78 (N(2´)) (corꢀ
relation with protons 3´ꢀMe); –74 (N(2)) (correlation with proꢀ
tons 3ꢀMe).
1ꢀAcetylꢀ6ꢀ(1,2ꢀdiacetyl)hydrazinoꢀ3,4ꢀdimethylꢀ1Hꢀpyrꢀ
azolo[3,4ꢀd]pyrimidine (5). A mixture of hydrazine 3 (0.072 g,
0.4 mmol) and acetic anhydride (0.30 mL, 3.2 mmol) in benzene
3,4ꢀDimethylꢀ6ꢀ[2ꢀ(ethoxycarbonyl)acetyl]hydrazinoꢀ1Hꢀ
pyrazolo[3,4ꢀd]pyrimidine (8). A mixture of hydrazine 3 (0.064 g,
0.36 mmol) and ethyl malonate (2.0 mL, 13.2 mmol) was heated

Pyrazolo[4,3ꢀe][1,2,4]triazolo[4,3ꢀa]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 5, May, 2013
1253
in an oil bath at 160—170 C for 5 h and cooled to 20 C.
A precipitate was filtered off and washed with light petroleum
(10 mL) to obtain colorless compound 8 (0.074 g, 70%), m.p.
266—268 C. Found (%): C, 49.28; H, 5.55; N, 28.71. C12H16N6O3.
Calculated (%): C, 49.31; H, 5.52; N, 28.75. MS, m/z (Irel (%)):
3,4ꢀDimethylꢀ2Hꢀpyrazolo[4,3ꢀe][1,2,4]triazolo[4,3ꢀa]ꢀ
pyrimidine (10a). Amidrazone 9a (0.065 g, 0.28 mmol) was reꢀ
fluxed in oꢀxylene (5 mL) for 8 h and cooled to 20 C. A precipꢀ
itate was filtered off and washed with chloroform (5 mL) to
obtain compound 10a (0.042 g, 80%), m.p. > 360 C. Found (%):
C, 50.82; H, 4.48; N, 44.44. C8H8N6. Calculated (%): C, 51.06;
H, 4.28; N, 44.66. MS, m/z (Irel (%)): 188 [M]+ (100), 101 (38),
83 (33). 1H NMR (DMSOꢀd6), : 2.72 (s, 3 H, 3ꢀMe); 2.76 (s, 3 H,
4ꢀMe); 9.26 (s, 1 H, H(8)); 13.60 (br.s, 1 H, NH). 13C NMR
(DMSOꢀd6), : 11.33 (3ꢀMe); 22.90 (4ꢀMe); 103.80 (C(3a));
132.44 (C(8)); 139.66 (C(3)); 153.70 (C(5a)); 161.15 (C(4))
(chemical shifts for C(3a) and C(5a) were obtained from the 2D
1H/13C HMBC NMR spectrum, whereas that of C(9a) was not
found because of the low solubility of compound 10a in DMSOꢀd6).
13C NMR (DMSOꢀd6 + CF3COOH), : 12.06 (3ꢀMe); 23.92
(4ꢀMe); 107.62 (C(3a)); 134.53 (C(8)); 143.00, 149.35 (C(5a),
C(9a)); 143.29 (C(3)); 171.80 (C(4)). 15N NMR (DMSOꢀd6 +
+ CF3COOH), : –214 (N(9)) (correlation with proton H(8));
–163 (N(2)) (correlation with protons 3ꢀMe); –148 (N(5)) (corꢀ
relation with protons 4ꢀMe).
292 [M]+ (55), 247 [M – C2H5O]+ (15), 220 [M – C2H4
–
– CO2]+ (10), 205 [M – CH2CO2Et]+ (26), 178 [M – C2H4 –
– CO2 – CH2CO] (100), 149 (87). IR (KBr), /cm–1: 3282,
3213, 3144, 3014, 1746 (CO2Et); 1671 (CON); 1619, 1596, 1554,
1517. 1H NMR (DMSOꢀd6),  (for major/minor isomer, the
ratio 3.5 : 1): 1.28/1.12 (t, 3 H, MeCH2, J = 7.2 Hz); 2.50/2.50
(s, 3 H, 3ꢀMe); 2.61/2.61 (s, 3H , 4ꢀMe); 3.30/3.22 (s, 2 H,
CH2); 4.10/4.00 (q, 2 H, CH2O, J = 7.2 Hz); 8.97/9.20 (br.s, 1 H,
NH); 10.0/9.35 (br.s, 1 H, NHCO); 12.72/12.91 (br.s, 1 H,
N(1)H). 13C NMR (DMSOꢀd6),  (for major/minor isomer):
13.98/13.85 (MeCH2); 14.49/14.49 (3ꢀMe); 21.91/21.91 (4ꢀMe);
40.68/39.46 (CH2); 60.50/60.25 (CH2O); 106.96/106.96 (C(3a));
142.03/142.03 (C(3)); 156.73/156.73 (C(7a)); 161.15/161.15
(C(6)); 163.53/163.53 (C(4)); 164.70/170.65 (NCO); 167.21/167.00
(COO). 15N NMR (DMSOꢀd6),  (for major/minor isomer):
–278/–274 (NHpyrim) (correlation with proton NHCO in major
isomer and NHpyrim in minor isomer); –249/–248 (NHCO)
(correlation with protons NHCO and CH2 in both isomers);
–203/–201 (N(1)) (correlation with proton N(1)H); –138/–138
(N(5)) (correlation with protons 4ꢀMe); –85/–85 (N(2)) (corꢀ
relation with protons 3ꢀMe and N(1)H).
3,4,8ꢀTrimethylꢀ2Hꢀpyrazolo[4,3ꢀe][1,2,4]triazolo[4,3ꢀa]ꢀ
pyrimidine (10b) was synthesized similarly to compound 10a by
reflux of amidrazone 9b in oꢀxylene. The yield was 79%, m.p.
> 360 C. Found (%): C, 53.38; H, 4.90; N, 41.28. C9H10N6.
Calculated (%): C, 53.45; H, 4.99; N, 41.56. MS, m/z (Irel (%)):
202 [M]+ (100), 132 (4), 101 (13). 1H NMR (DMSOꢀd6
+
3,4ꢀDimethylꢀ6ꢀ(dimethylaminomethylidene)hydrazinoꢀ1Hꢀ
pyrazolo[3,4ꢀd]pyrimidine (9a). A mixture of hydrazine 3 (0.089 g,
0.5 mmol) and DMF dimethyl acetal (0.13 mL, 1.0 mmol) in
benzene (4 mL) was refluxed for 4 h and cooled to 20 C.
A precipitate was filtered off, then chloroform (5 mL) was added
to this precipitate, the undissolved residue of the unreacted hydrꢀ
azine 3 was filtered off, chloroform was evaporated in vacuo, the
residue was washed with light petroleum to obtain amidrazone
9a (0.085 g, 73%), m.p. >360 C. Found (%): C, 51.22; H, 6.36;
N, 41.82. C10H15N7. Calculated (%): C, 51.49; H, 6.48; N, 42.03.
MS, m/z (Irel (%)): 233 [M]+ (100), 189 [M – Me2N]+ (52), 178
[M – MeNCN]+ (45), 163[M – Me2NCN]+ (94). 1H NMR
(CDCl3), : 2.52 (s, 3 H, 3ꢀMe); 2.61 (s, 3 H, 4ꢀMe); 2.93 (s, 6 H,
NMe2);7.65 (s, 1 H, CH=); 8.02 (br.s, 1 H, NH); 12.05 (br.s,
1 H, NHpyrazole). 13C NMR (CDCl3), : 14.96 (3ꢀMe); 22.25
(4ꢀMe); 38.07 (NMe2); 106.96 (C(3a)); 142.99 (C(3)); 154.45
(CH=); 157.48, 160.29 (C(6), C(7a)); 163.85 (C(4)). 15N NMR
(CDCl3), : –310 and –240 (NMe2 and NH) (correlation with
proton CH=); –136 (N(5)) (correlation with protons 4ꢀMe);
–85 (N(2)) (correlation with protons 3ꢀMe).
3,4ꢀDimethylꢀ6ꢀ[1ꢀ(dimethylamino)ethylidene]hydrazinoꢀ
1Hꢀpyrazolo[3,4ꢀd]pyrimidine (9b). A mixture of hydrazine 3
(0.10 g, 0.56 mmol) and dimethylacetamide dimethyl acetal
(0.33 mL, 2.24 mmol) in benzene (4 mL) was refluxed for 8 h.
Then, the reaction mixture was treated similarly as described for
amidrazone 9a to obtain amidrazone 9b (0.072 g, 52%), m.p.
> 360 C. Found (%): C, 53.18; H, 6.78; N, 39.36. C11H17N7.
Calculated (%): C, 53.42; H, 6.93; N, 39.65. MS, m/z (Irel (%)):
247 [M]+ (12), 163 (6), 101 (100). 1H NMR (CDCl3), : 2.11
(s, 3 H, Me); 2.53 (s, 3 H, 3ꢀMe); 2.62 (s, 3 H, 4ꢀMe); 2.99(s, 6 H,
NMe2); 7.59 (br.s, 1 H, NH); 12.08 (br.s, 1 H, NHpyrazole).
13C NMR (CDCl3), : 12.95 (Me); 14.93 (3ꢀMe); 22.19 (4ꢀMe);
38.63 (NMe2); 106.90 (C(3a)); 142.80 (C(3)); 157.47, 160.30
(C(6), C(7a)); 161.24 (C—NMe2); 163.62 (C(4)). 15N NMR
(CDCl3), : –136 (N(5)) (correlation with protons 4ꢀMe);
–85 (N(2)) (correlation with protons 3ꢀMe).
+ CF3COOH), : 2.83 (s, 3 H, 3ꢀMe); 2.91 (s, 3 H, 4ꢀMe); 2.95
(s, 3 H, 8ꢀMe); 14.70 (br.s, 1 H, NH). 13C NMR (DMSOꢀd6 +
+ CF3COOH), : 11.70 (3ꢀMe); 12.34 (8ꢀMe); 23.67 (4ꢀMe);
107.00 (C(3a)); 142.15 (C(3)); 143.47 (C(8)); 144.39, 149.37 (C(5a),
C(9a)); 170.59 (C(4)). 15N NMR (DMSOꢀd6 + CF3COOH),
: –208 (N(9)) (correlation with protons 8ꢀMe); –159 (N(2))
(correlation with protons 3ꢀMe); –140 (N(5)) (correlation with
protons 4ꢀMe); –102 (N(7)) (correlation with protons 8ꢀMe).
3,4ꢀDimethylꢀ6ꢀ(4ꢀethoxybenzylidene)hydrazinoꢀ1Hꢀpyrazoꢀ
lo[3,4ꢀd]pyrimidine (13a). A mixture of hydrazine 3 (0.078 g,
0.44 mmol) and 4ꢀethoxybenzaldehyde (0.12 mL, 0.88 mmol) in
EtOH (5 mL) was refluxed for 4 h and cooled to 20 C. A precipꢀ
itate was filtered off and washed with light petroleum to obtain
a white compound 13a (0.125 g, 92%), m.p. 274—275 C.
Found (%): C, 61.79; H, 6.05; N, 27.10. C16H18N6O. Calculatꢀ
ed (%): C, 61.92; H, 5.85; N, 27.08. 1H NMR (DMSOꢀd6),
: 1.31 (t, 3 H, MeCH2, J = 7.0 Hz); 2.50 (s, 3 H, 3ꢀMe); 2.62
(s, 3 H, 4ꢀMe); 4.05 (q, 2 H, CH2, J = 7.0 Hz); 6.95 (d, 2 H, C6H4,
J = 7.8 Hz); 7.58 (d, 2 H, C6H4, J = 7.8 Hz); 8.08 (br.s, 1 H,
CH=); 11.12 (br.s, 1 H, NH); 12.81 (br.s, 1 H, NHpyrazole).
6ꢀ(4ꢀBromobenzylidene)hydrazinoꢀ3,4ꢀdimethylꢀ1Hꢀpyrazoꢀ
lo[3,4ꢀd]pyrimidine (13b) was synthesized similarly to compound
13a from hydrazine 3 and 4ꢀbromobenzaldehyde. The yield was
85%, m.p. 345—347 C. Found (%): C, 48.53; H, 4.00; N, 24.69.
C14H13BrN6. Calculated (%): C, 48.71; H, 3.79; N, 24.35.
1H NMR (DMSOꢀd6), : 2.50 (s, 3 H, 3ꢀMe); 2.62 (s, 3 H,
4ꢀMe); 7.60 (s, 4 H, C6H4); 8.11 (s, 1 H, CH=); 11.38 (br.s, 1 H,
NH); 12.88 (br.s, 1 H, NHpyrazole).
6ꢀ(4ꢀEthoxybenzylidene)hydrazinoꢀ4ꢀ[2ꢀ(4ꢀethoxyphenyl)ꢀ
vinyl]ꢀ3ꢀmethylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidine (14a). Acetic acid
(5 mL) and concentrated H2SO4 (3 drops) were added to a mixꢀ
ture of hydrazine 3 (0.089 g, 0.50 mmol) and 4ꢀethoxybenzaldeꢀ
hyde (0.28 mL, 2.0 mmol), and the mixture was refluxed for 3 h
and cooled to 20 C. A precipitate was filtered off, treated with
aqueous NH3, washed with water, and dried to obtain a yellow
compound 14a (0.203 g, 92%), m.p. 288—289 C. Found (%):

1254
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 5, May, 2013
Komkov et al.
C, 67.67; H, 5.98; N, 18.68. C25H26N6O2. Calculated (%):
C, 67.85; H, 5.92; N, 18.99. MS, m/z (Irel (%)): 442 [M]+ (10),
295 [M – EtOC6H4CN]+ (66), 163 [EtOC6H4CHNNH2]+
(100), 121 [EtOC6H4]+ (70). 1H NMR (DMSOꢀd6), : 1.34
(t, 3 H, MeCH2, J = 7.2 Hz); 1.35 (t, 3 H, MeCH2, J = 7.2 Hz);
2.64 (s, 3 H, 3ꢀMe); 4.06 (q, 2 H, CH2O, J = 7.2 Hz); 4.08
pound 15a from hydrazone 13b. The yield was 31%, m.p.
>360 C. HRMS (MCBP) (ESI): found: m/z 343.0299 (for isoꢀ
tope 79Br) [M + H]+, 345.0286 (for isotope 81Br) [M + H]+.
C14H11BrN6. Calculated: [M + H]+ = 343.0301 (for isotope
79Br) and 345.0281 (for isotope 81Br). MS (EI), m/z (Irel (%)):
342 [M]+(12) for isotope 79Br, 344 [M]+ (10) for isotope 81Br,
184 (70), 183 (49), 182 (55), 163 (28),148 (54), 147 (47), 91
(100). 1H NMR (DMSOꢀd6), : 2.71 (s, 3 H, 3ꢀMe); 2.76 (s, 3 H,
4ꢀMe); 7.76 (d, 2 H, C6H4, J = 7.2 Hz); 8.11 (d, 2 H, C6H4,
J = 7.2 Hz); 13.50 (br.s, 1 H, NH). 13C NMR (DMSOꢀd6), :
11.34 (3ꢀMe); 23.05 (4ꢀMe); 104.78 (C(3a)); 123.32, 126.46
(pꢀCC H , ipsoꢀCC H ); 130.94, 131.30 (oꢀCC H , mꢀCC H ); 139.02
(q, 2 H, CH2O, J = 7.2 Hz); 6.98 (d, 2 H, mꢀHC H C=N
,
J = 8.4 Hz); 7.01 (d, 2 H, mꢀHC H C=C, J = 8.4 Hz); 7.43 6(d4, 1 H,
6
4
PyrimꢀCH=, J = 15.6 Hz); 7.61 (d, 2 H, oꢀHC H C=N, J = 8.4 Hz);
6
4
7.70 (d, 2 H, oꢀHC H C=C, J = 8.4 Hz); 8.00 (d, 1 H, C6H4CH=,
6
4
J = 15.6 Hz); 8.13 (s, 1 H, CH=N); 11.04 (br.s, 1 H, NH); 12.90
(br.s, 1 H, NHpyrazole). 13C NMR (DMSOꢀd6), : 14.54 (Me—CH2);
14.60 (Me—CH2); 15.14 (3ꢀMe); 63.16 (CH2); 63.29 (CH2);
105.74 (C(3a)); 114.68 (mꢀCC H C=N); 114.96 (mꢀCC H C=C); 119.88
6
4
6
4
4
(C(3)); 144.28 (C(9a)); 145.04 (C(8)); 1565.03 (C(56a)4); 161.46
(C(4)). 15N NMR (DMSOꢀd6, : –171 (N(2)) (correlation with
protons 3ꢀMe); –127 (N(5)) (correlation with protons 4ꢀMe).
6
4
6 4
(PyrimꢀCH=); 127.78 (oꢀCC H C=N); 127.82 (ipsoꢀCC H C=N
,
6
4
ipsoꢀCC H C=C); 129.60 (oꢀCC H C=C); 137.27 (C6H46C4H=);
6
4
6
4
141.38 (CH=N); 141.75 (C(3)); 157.88 (C(4)); 158.23 (C(6));
References
158.32 (C(7a)); 159.22 (pꢀCC H C=N); 159.90 (pꢀCC H C=C).
6
4
6
6ꢀ(4ꢀBromobenzylidene)hydrazinoꢀ4ꢀ[2ꢀ(4ꢀbrom4ophenyl)ꢀ
vinyl]ꢀ3ꢀmethylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidine (14b). Acetic acid
(5 mL) and conc. H2SO4 (3 drops) were added to a mixture of
hydrazone 13b (0.060 g, 0.17 mmol) and 4ꢀbromobenzaldehyde
(0.064 g, 0.35 mmol), and the mixture was refluxed for 4 h and
cooled to 20 C. A precipitate was filtered off, treated with aqueꢀ
ous NH3, washed with water, and dried to obtain a yellow comꢀ
pound 14b (0. 086 g, 97%), m.p. 303—305 C. Found (%): C, 48.92;
H, 3.44; N, 16.12. C21H16Br2N6. Calculated (%): C, 49.24;
H, 3.15; N, 16.41. 1H NMR (DMSOꢀd6), : 2.65 (s, 3 H, 3ꢀMe);
7.61 (d, 1 H, PyrimꢀCH=, J = 15.6 Hz); 7.63 (s, 4 H, C6H4C=N);
1. V. A. Dorokhov, M. F. Gordeev, E. M. Shashkova, A. V.
Komkov, V. S. Bogdanov, Bull. Acad. Sci. USSR. Div. Chem.
Sci. (Engl. Transl.), 1991, 40, 2274 [Izv. Akad. Nauk SSSR,
Ser. Khim., 1991, 2600].
2. V. A. Dorokhov, M. F. Gordeev, A. V. Komkov, V. S. Bogꢀ
danov, Bull. Acad. Sci. USSR. Div. Chem. Sci. (Engl. Transl.),
1991, 40, 2267 [Izv. Akad. Nauk SSSR, Ser. Khim., 1991, 2593].
3. V. Dorokhov, A. Komkov, S. Baranin, ARKIVOC, 2003, 14,
178 (www.arkatꢀusa.org, volume 2003, 14).
4. V. A. Dorokhov, A. V. Komkov, E. M. Shashkova, V. S. Bogꢀ
danov, M. N. Bochkarev, Russ. Chem. Bull. (Engl. Transl.),
1993, 42, 1848 [Izv. Akad. Nauk, Ser. Khim., 1993, 1932].
5. A. V. Komkov, V. A. Voronkova, A. S. Shashkov, V. A. Doroꢀ
khov, Russ. Chem. Bull., (Int. Ed.), 2012, 61, 332 [Izv. Akad.
Nauk, Ser. Khim., 2012, 330].
7.65 (d, 2 H, mꢀHC H C=C, J = 7.8 Hz); 7.73 (d, 2 H,
6
oꢀHC H C=C, J = 7.8 Hz);47.99 (d, 1 H, C6H4CH=, J = 15.6 Hz);
6
8.16 (s,41 H, CH=N); 11.34 (br.s, 1 H, NH); 13.00 (br.s, 1 H,
NHpyrazole). 13C NMR (DMSOꢀd6), : 15.08 (3ꢀMe); 106.29
(C(3a)); 121.83 (pꢀCC H C=N); 122.89 (pꢀCC H C=C); 123.42 (Pyꢀ
6
4
6 4
6. V. A. Dorokhov, M. A. Prezent, V. S. Bogdanov, Russ. Chem.
Bull. (Engl. Transl.), 1995, 44, 1080 [Izv. Akad. Nauk, Ser.
Khim., 1995, 1118].
7. V. A. Dorokhov, A. V. Komkov, B. I. Ugrak, Russ. Chem.
Bull. (Engl. Transl.), 1993, 42, 1364 [Izv. Akad. Nauk, Ser.
Khim., 1993, 1429].
8. P. G. Baraldi, B. Cacciari, R. Romagnoli, G. Spalluto, K.ꢀN.
Klotz, E. Leung, K. Varani, S. Gessi, S. Merighi, P. A. Borea,
J. Med. Chem., 1999, 42, 4473.
9. P. G. Baraldi, B. Cacciari, R. Romagnoli, G. Spalluto,
S. Moro, K.ꢀN. Klotz, E. Leung, K. Varani, S. Gessi,
S. Merighi, P. A. Borea, J. Med. Chem., 2000, 43, 4768.
10. F. Russo, S. Guccione, G. Romeo, L. Scolaro, S. Pucci, A. Carꢀ
uso, V. Cutuli, M. Amico Roxas, Eur. J. Med. Chem., 1992, 27, 73.
11. Pat. US 4 053474, 1977, Chem. Abstrs, 1978, 88, 37826s.
12. Pat. US 4 124764, 1978, Chem. Abstrs, 1979, 90, 87508b.
13. N. Tomohisa, F. Takayunki, E. Kazuki, J. Chem. Soc., Perꢀ
kin Trans. 1, 2000, 33.
rimꢀCH=); 128.14 (oꢀCC H C=N); 129.90 (oꢀCC H C=C); 131.71
6
4
4
(mꢀCC H C=N); 131.98 (mꢀCC H C=C); 134.57 (i6psoꢀCC H C=C);
4
6
6
4
134.606(ipsoꢀCC H C=N); 136.29 4(C6H4CH=); 140.13 (CH=N);
4
141.85 (C(3)); 1657.37 (C(4)); 158.02 (C(6)); 158.26 (C(7a)).
8ꢀ(4ꢀEthoxyphenyl)ꢀ3,4ꢀdimethylꢀ2Hꢀpyrazolo[4,3ꢀe][1,2,4]ꢀ
triazolo[4,3ꢀa]pyrimidine (15a). Dimethylformamide (4 mL) was
added to hydrazone 13a (0.10 g, 0.32 mmol) and heated until
complete dissolution, then CuCl2 (0.086 g, 0.64 mmol) was addꢀ
ed, and the reaction mixture was heated in an oil bath for 2.5 h.
DMF was evaporated in vacuo. Aqueous ammonia (5 mL) was
added to the residue, a precipitate was filtered off and washed
with water until the washings ceased to be colored in violet.
A black precipitate obtained was extracted with refluxing methaꢀ
nol (3×50 mL) to yield the reaction product 15a. Methanol was
evaporated in vacuo, the residue was washed with chloroform
(5 mL) to obtain a yellowish compound 15a (0.028 g, 28%), m.p.
265—268 C. HRMS (MCBP) (ESI): found: m/z 309.1449
[M + H]+. C16H16N6O. Calculated: [M + H]+ = 309.1458. MS
(EI), m/z (Irel (%)): 216 (9), 184 (33), 182 (49), 148 (25), 138
(39), 121 (30), 91 (100), 57 (80). 1H NMR (DMSOꢀd6), : 1.36
(t, 3 H, MeCH2, J = 6.0 Hz); 2.71 (s, 3 H, 3ꢀMe); 2.73 (s, 3 H,
14. A. Salgado, C. Varela, A. M. Garcia Collazo, P. Pevarello,
Magn. Reson. Chem., 2010, 48, 614.
15. M. Ciesielski, D. Pufky, M. Döring, Tetrahedron, 2005, 61, 5942.
16. A. Davoodnia, R. Zhiani, M. Roshani, M. Bakavoli, M. Bashꢀ
ash, Phosphorus, Sulfur, Silicon Rel. Elem., 2007, 182, 1219.
17. N. Seifi, M. H. ZahediꢀNiaki, M. R. Barzegari, A. Davoodnia,
R. Zhiani, A. A. Kaju, J. Mol. Catal. A: Chem., 2006, 260, 77.
4ꢀMe); 4.11 (q, 2 H, CH2, J = 6.0 Hz); 7.07 (d, 2 H, HC H
,
6
4
J = 7.2 Hz); 8.06 (d, 2 H, HC H , J = 7.2 Hz); 14.10 (br.s, 1 H,
6
4
NH). 13C NMR (DMSOꢀd6), : 11.30 (3ꢀMe); 14.46 (MeCH2); 23.00
(4ꢀMe); 63.17 (CH2); 104.62 (C(3a)); 113.91 (mꢀCC H ); 119.35
4
(ipsoꢀCC H ); 130.47 (oꢀCC H ); 138.74 (C(3)); 144.630 (C(9a));
6
4
6
145.80 (C(8)); 154.70 (C(5a))4; 159.63 (pꢀCC H ); 160.85 (C(4)).
6
4
8ꢀ(4ꢀBromophenyl)ꢀ3,4ꢀdimethylꢀ2Hꢀpyrazolo[4,3ꢀe][1,2,4]ꢀ
triazolo[4,3ꢀa]pyrimidine (15b) was synthesized similarly to comꢀ
Received October 30, 2012;
in revised form February 4, 2013