Synthesis of derivatives of a new heterocyclic system pyrazolo[3,4-b] pyrido[1′,2′: 1,2]imidazo[4,5-d]pyridine

Article abstract of DOI:10.1007/s11172-006-0322-z

1-[4-Aminoarylpyrazolo[3,4-b]pyridin-5-yl]pyridinium chlorides undergo cyclization under reflux in tert-butanol in the presence of an excess of potassium tert-butoxide to form tetracyclic derivatives of pyrazolo[3,4-b] pyrido[1′,2′:1,2]imidazo[4,5-d]pyridine. The reaction scheme of the processes is proposed. The structures of the reaction products were confirmed by physicochemical methods.

Full text of DOI:10.1007/s11172-006-0322-z

Russian Chemical Bulletin, International Edition, Vol. 55, No. 4, pp. 735—740, April, 2006
735
Synthesis of derivatives of a new heterocyclic system
pyrazolo[3,4ꢀb]pyrido[1´,2´:1,2]imidazo[4,5ꢀd]pyridine
E. S. Komarova,a V. A. Makarov,b L. M. Alekseeva,b G. V. Avramenko,a and V. G. Granikbꢀ
aD. I. Mendeleev Russian University of Chemical Technology,
9 pl. Miusskaya, 125047 Moscow, Russian Federation.
Eꢀmail: yes.komarova@mail.ru
bState Research Center of Antibiotics,
3a ul. Nagatinskaya, 117105 Moscow, Russian Federation.
Fax: +7 (495) 231 4284. Eꢀmail: makarꢀcl@ropnet.ru
1ꢀ[4ꢀAminoarylpyrazolo[3,4ꢀb]pyridinꢀ5ꢀyl]pyridinium chlorides undergo cyclization unꢀ
der reflux in tertꢀbutanol in the presence of an excess of potassium tertꢀbutoxide to form
tetracyclic derivatives of pyrazolo[3,4ꢀb]pyrido[1´,2´:1,2]imidazo[4,5ꢀd]pyridine. The reacꢀ
tion scheme of the processes is proposed. The structures of the reaction products were conꢀ
firmed by physicochemical methods.
Key words: 2ꢀchloroacetamidoꢀ4ꢀcyanopyrazole, 1ꢀ[4ꢀaminopyrazolo[3,4ꢀb]pyridinꢀ5ꢀ
yl]pyridinium chloride, pyrazolo[3,4ꢀb]pyrido[1´,2´:1,2]imidazo[4,5ꢀd]pyridine, 4,5ꢀdiaminoꢀ
pyrazolo[3,4ꢀb]pyridine.
In recent years, it has been found1—3 that agents
activating the congitive functions, for example, antiꢀ
cholinesterase drugs, such as tacrine and amiridine
(4ꢀaminopyridine derivatives), can be used in the treatꢀ
ment of various asthenic states, central nervous sysꢀ
tem disorders, and intellectual amnestic disorders, which
cannot be presently effectively treated by therapeutic
agents.
The aim of the present study was to develop a proceꢀ
dure for the synthesis of such compounds of the aminoꢀ
pyrazolopyridine series.
Alkylation of 3ꢀaminoꢀ4ꢀcyanopyrazole (1)5 with
oꢀchlorobenzyl chloride in methanol in the presence of
potassium carbonate afforded a mixture of isomeric
pyrazole derivatives, viz., 3ꢀaminoꢀ1ꢀ(2ꢀchlorobenzyl)ꢀ
4ꢀcyanopyrazole (2) and 5ꢀaminoꢀ1ꢀ(2ꢀchlorobenzyl)ꢀ4ꢀ
cyanopyrazole (3) (Scheme 1). Pyrazole 2 was isolated in
individual state in 57% yield after double crystallization
from ethanol. The 1H NMR spectrum of 2 (DMSOꢀd6, δ)
shows signals at 5.20 (s, 2 H, N(1)CH2), 5.64 (br.s, 2 H,
NH2), 7.13—7.49 (m, 4 H, C6H4), and 8.24 (s, 1 H,
H(5)). The structure of compound 2 was established based
on the NOEDIFF spectrum. In the case of saturation of
the signal of the methylene group (δ 5.20), a response
for H(5) was observed, which indicates that the proton
at position 5 of the pyrazole ring is in the proximity to
the methylene group. An increase in the intensity of
the signal for H(5) due to NOE was 12%. The assignꢀ
ment of some signals of the 5ꢀNH2 isomer 3 in the isoꢀ
meric mixture of compounds 2 and 3 (for example, the
signal at δ 7.64 (s, 1 H, H(3)) was made based on the
comparison of the 1H NMR spectra of compound 2
and its phenylꢀsubstituted analog 8 6 (DMSOꢀd6, δ: 6.55
(br.s, 2 H, NH2); 7.40—7.55 (m, 5 H, Ph); 7.76 (s, 1 H,
H(3)), which can be considered as a model of the 5ꢀNH2
isomer, and the ratio of pyrazole 2 to 3 was estimated
at 4 : 1.
Tacrine
Amiridine
These drugs are used in the treatment of various
dementias, although primarily as auxiliary pharmaceutiꢀ
cals. Hence, there is a strong need to design new effective
pharmaceuticals, which can provide approaches to the
treatment of the aboveꢀmentioned diseases and to design
new drugs, which can improve memory. The design of
compounds serving as activators of the congitive funcꢀ
tions is one of the main ways of struggling against these
diseases.
In this connection, investigations of approaches to the
synthesis of compounds containing the 4ꢀaminopyridine
fragment hold promise in designing new pharmaceuticals
for the treatment of neurodegenerative diseases, for exꢀ
ample, of Alzheimer's disease.4
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 710—714, April, 2006.
1066ꢀ5285/06/5504ꢀ0735 © 2006 Springer Science+Business Media, Inc.

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Komarova et al.
Scheme 1
Chloroacetylation of compound 2 in dioxane in the
tion, a small amount of yet another compound was present
in the reaction mixture. Based on the physicochemical
data, we assigned the structure of 2ꢀ(2ꢀchlorobenzyl)ꢀ
2,4ꢀdihydroꢀ5Hꢀpyrazolo[3,4ꢀb]pyrido[1´,2´:1,2]imidꢀ
azo[4,5ꢀd]pyridinꢀ5ꢀone (7) to the latter compound.
A further investigation demonstrated that refluxing of
pyridinium salt 5 with 2 equiv. of potassium tertꢀbutoxide
in tertꢀbutanol for 2 days afforded tetracyclic compound 7
in 80.5% yield.
Somewhat better results were obtained by refluxing
bicyclic pyridinium salt 6 with 2 moles of potassium
tertꢀbutoxide in tertꢀbutanol for 1 day. In this case, comꢀ
pound 7 was synthesized in 90% yield.
In the next step of our investigation, we used 5ꢀaminoꢀ
4ꢀcyanoꢀ1ꢀphenylpyrazole (8)6 as the starting comꢀ
pound analogously to pyrazole 2. The reaction of comꢀ
pound 8 with chloroacetyl chloride smoothly produced
chloroacetyl derivative 9, whose treatment with pyridine
gave 1ꢀ(4ꢀcyanoꢀ1ꢀphenylpyrazolꢀ5ꢀylaminocarbonylmeꢀ
thyl)pyridinium chloride (10) in 97% yield (Scheme 2).
The reaction of sodium methoxide with salt 10 in
methanol or storage of salt 10 in an aqueous alkaline
presence of potassium carbonate afforded the correspondꢀ
ing chloroacetyl derivative 4, which was used in the furꢀ
ther synthesis of the target 4ꢀaminopyrazolo[3,4ꢀb]pyriꢀ
dine. Taking into account the possibility of the use of
various pyridinium salts7,8 in heterocyclic synthesis, comꢀ
pound 4 was used in the reaction with pyridine at room
temperature to prepare 1ꢀ[1ꢀ(2ꢀchlorobenzyl)ꢀ4ꢀcyanoꢀ
pyrazolꢀ3ꢀylaminocarbonylmethyl]pyridinium chloride
(5) (95% yield). A high CHꢀacidity of the methylene unit
located between the electronꢀwithdrawing carbonyl and
pyridinium substituents ensures cyclization involving the
nitrile group. Actually, the reaction of sodium methoxide
with salt 5 in methanol or heating of this salt in aqueous
alkaline solution produced pyrazolo[3,4ꢀb]pyridinone 6
in 54% yield. The structure of the latter was established by
elemental analysis, 1H NMR spectroscopy, and mass specꢀ
trometry.
It should be noted that the reaction mixture contained,
along with pyridinium chloride 6, the starting pyrazole 2,
i.e., under these conditions, the reaction at the pyridine
nitrogen atom was accompanied by deacylation. In addiꢀ

Pyrazolopyridoimidazopyridine
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 4, April, 2006
737
Scheme 2
solution afforded 1ꢀ[4ꢀaminoꢀ6(7H )ꢀoxoꢀ1ꢀphenylꢀ1Hꢀ
pyrazolo[3,4ꢀb]pyridinꢀ5ꢀyl]pyridinium chloride (11) in
61% yield. Simultaneously, the reaction gave the starting
5ꢀaminoꢀ4ꢀcyanoꢀ1ꢀphenylpyrazole. Recall that cyclizaꢀ
tion of salt 5 under the same conditions was also accomꢀ
panied by analogous deacylation.
It is worthwhile to discuss the pathway of unusual
cyclization giving rise to tetracyclic compounds 7 and 12.
Let us consider the transformation of pyridinium salt 11
as an example (Scheme 3).
Scheme 3
Refluxing of pyridinium chloride 10 in tertꢀbutanol
with a twofold excess of tertꢀpotassium butoxide for 8 days
afforded 3ꢀphenylꢀ3,4ꢀdihydroꢀ5Hꢀpyrazolo[3,4ꢀb]pyriꢀ
do[1´,2´:1,2]imidazo[4,5ꢀd]pyridinꢀ5ꢀone (12) in 72%
yield. Compound 12 of higher quality was synthesized
more rapidly by refluxing pyridinium chloride 11 in
tertꢀbutanol with 2 moles of potassium tertꢀbutoxide. The
structures of the reaction products were established by
spectroscopic methods.
As can be seen from Schemes 1 and 2, the reactions of
both 1ꢀ(oꢀchlorobenzyl)ꢀsubstituted 3ꢀaminoꢀ4ꢀcyanoꢀ
pyrazole 2 and 1ꢀphenylꢀsubstituted 5ꢀaminoꢀ4ꢀcyanoꢀ
pyrazole 8 follow the same pathway, i.e., these reactions
have a general character. We observed the difference in
the behavior of intermediates in studies of the transforꢀ
mation of the pyridinium fragment into the amino group
typical of pyridinium salts.6,7,9 We failed to find condiꢀ
tions for this transformation of compound 6, whereas
pyridinium salt 11 was decomposed by heating with 50%
aqueous hydrazine hydrate for several days. The subseꢀ
quent treatment of the product with a methanolic soluꢀ
tion of hydrogen chloride afforded 4,5ꢀdiaminoꢀ6(7H )ꢀ
oxoꢀ1ꢀphenylꢀ1Hꢀpyrazolo[3,4ꢀb]pyridine 13 in high
yield.

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Russ.Chem.Bull., Int.Ed., Vol. 55, No. 4, April, 2006
Komarova et al.
were recorded on a Bruker ACꢀ300 spectrometer in DMSOꢀd6.
The purity of the reaction products was checked and the
course of the reactions was monitored by TLC on Merck TLC
Silicagel 60 F254 plates (hexane—acetone (3 : 1) as the eluent;
chloroform—methanol (10 : 1) with the addition of a drop of
ammonia, visualization with UV light). The melting points were
determined on an Electrothermal 9100 instrument (UK).
The physicochemical characteristics and elemental analysis
data for the reaction products are given in Table 1.
3ꢀAminoꢀ1ꢀ(2ꢀchlorobenzyl)ꢀ4ꢀcyanopyrazole (2). A suspenꢀ
sion of pyrazole 1 (14 g, 13 mmol), oꢀchlorobenzyl chloꢀ
ride (22.8 g, 14.3 mmol), and potassium carbonate (26.8 g,
19.4 mmol) in ethanol (50 mL) was refluxed with stirring for
3 days. The reaction mixture was cooled and then water (500 mL)
was added. After 1 day, the yellow precipitate of chloroꢀ
benzylpyrazole 2 that formed was filtered off, washed with waꢀ
ter, and recrystallized from ethanol.
3ꢀChloroacetamidoꢀ1ꢀ(2ꢀchlorobenzyl)ꢀ4ꢀcyanopyrazole (4).
A solution of chloroacetyl chloride (11.7 g, 10.3 mmol) in diꢀ
oxane (15 mL) was slowly added dropwise with vigorous stirring
to a mixture of chlorobenzylpyrazole 2 (16 g, 6.9 mmol) and
potassium carbonate (14.3 g, 10.3 mmol) at 60 °C for 1 h. The
reaction mixture was refluxed with stirring for 3 days and cooled.
Then water (1000 mL) was added, and the precipitate of 4 that
formed was filtered off and recrystallized from ethanol. 1H NMR,
δ: 4.26 (s, 2 H, CH2Cl); 5.42 (s, 2 H, N(1)CH2); 7.24—7.53 (m,
4 H, C6H4); 8.66 (s, 1 H, H(5)); 10.95 (br.s, 1 H, NH).
It is reasonable to assume that the synthesis of tetraꢀ
cyclic compound 12 occurs through bicyclic pyridinium
salt 11 as the key intermediate (this is also true for the
reaction in which monocyclic salt 10 is used as the priꢀ
mary starting compound, which is initially transformed
into 11). The subsequent treatment of pyridinium chloꢀ
ride 11 with potassium tertꢀbutoxide afforded comꢀ
pound 14 followed by the proton abstraction from the
primary amino group at position 4 of the bicyclic comꢀ
pound giving rise to zwitterion 15. Apparently, this is the
rateꢀdetermining step of the process as a whole, which is
responsible for the long time of transformation 11 → 12.
The addition of the resulting amide anion at the α posiꢀ
tion of the pyridine ring afforded dihydro derivative 16,
whose oxidation with atmospheric oxygen gave tetracyclic
derivative 12 (tetracyclic compound 7 is generated analoꢀ
gously). It should be noted that the reaction of potassium
tertꢀbutoxide with pyridinium chloride 10 under argon
did not produce tetracyclic compound 12, i.e., oxidation
is a necessary step. If intermediate 16 cannot be oxidized
(under anaerobic conditions, when argon is passed through
the solution), deacylation of compound 10 giving rise to
compound 8 becomes the major reaction.
1ꢀ[1ꢀ(2ꢀChlorobenzyl)ꢀ4ꢀcyanopyrazolꢀ3ꢀylaminocarbonylꢀ
methyl]pyridinium chloride monohydrate (5). A solution of comꢀ
pound 4 (17 g, 5.5 mmol) in pyridine (170 mL) was stirred at
~20 °C for 3 h, during which a white precipitate was formed in
the flask. Isopropyl alcohol (50 mL) was added to the reaction
Experimental
The mass spectra (EI) were obtained on a Finnigan SSQꢀ710
mass spectrometer using a direct inlet system. The NMR spectra
Table 1. Physicochemical characteristics and elemental analysis data for compounds 2, 4—7, and 9—13
Comꢀ Yield
M.p.
/°С
Found
Calculated
Molecular
formula
MS ([M]+),
m/z (Irel (%))
(%)
poꢀ
(%)
und
С
Н
N
2
90
86
94
54
80
57
97
61
74
70
144—146
179—180
229—231
355—356
358—360
149—151
210—212
355—357
335—337
262—264
56.74
56.78
50.38
50.51
53.28
53.21
55.84
55.68
61.82
61.81
55.28
55.29
60.05
60.09
60.11
60.09
67.56
67.77
51.97
51.90
4.03
3.90
3.31
3.26
4.24
4.22
4.02
3.89
3.56
3.46
3.47
3.48
4.19
4.15
4.19
4.15
3.76
3.68
4.38
4.36
23.97
24.08
17.93
18.12
17.23
17.24
18.16
18.04
19.73
20.02
21.66
21.49
20.62
20.61
19.97
20.61
23.25
23.24
25.29
25.22
C11H9ClN4
232 (47)
309 (9)
4
C13H10Cl2N4O
5
C18H15Cl2N5O•
•Н2О
C18H15Cl2N5O
352 (86)
352 (72)
349 (90)
260 (33)
304 (14)
304 (87)
301 (90)
241 (100)
6
7
C18H12ClN5O
C12H9ClN4O
C17H14ClN5O
C17H14ClN5O
C17H11N5O
9
10
11
12
13
C12H12ClN5O

Pyrazolopyridoimidazopyridine
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 4, April, 2006
739
mixture and the mixture was stored in a refrigerator at 5 °C.
After 1 day, the precipitate of pyridinium chloride 5 was filtered
off, washed with cold isopropyl alcohol, and recrystallized from
the same solvent. 1H NMR, δ: 5.44 (s, 2 H, N(1)CH2); 5.72 (s,
2 H, N(1´)CH2); 7.29—7.53 (m, 4 H, C6H4); 8.21 (m, 2 H,
H(3´), H(5´)); 8.65 (s, 1 H, H(5)); 8.69 (m, 1 H, H(4´)); 9.05
(m, 1 H, H(2´), H(6´)); 11.44 (br.s, 1 H, NH).
1ꢀ[4ꢀAminoꢀ2ꢀ(2ꢀchlorobenzyl)ꢀ6(7H )ꢀoxoꢀ2Hꢀpyrazoꢀ
lo[3,4ꢀb]pyridinꢀ5ꢀyl]pyridinium chloride (6). Sodium methoxide
(2.8 g, 5.14 mol) was added to a suspension of pyridinium chloꢀ
ride 5 (10 g, 2.57 mmol) in methanol (100 mL). The reaction
mixture was heated with stirring for 3 days and cooled. Then a
HCl(9%)/MeOH solution and activated carbon were added.
The precipitate containing the carbon was filtered off through a
funnel with silica gel. The redꢀbrown filtrate was concentrated
in vacuo to dryness. The precipitate that formed was treated with
acetone and filtered off. Pyridinium chloride 6 was isolated by
crystallization from isopropyl alcohol. 1H NMR, δ: 5.53 (s, 2 H,
N(2)CH2); 7.27—7.54 (m, 6 H, NH2, C6H4); 8.24 (m, 2 H,
H(3´), H(5´)); 8.41 (s, 1 H, H(3)); 8.70 (m, 1 H, H(4´)); 8.96
(m, 2 H, H(2´), H(6´)); 11.54 (br.s, 1 H, NH).
2ꢀ(2ꢀChlorobenzyl)ꢀ2,4ꢀdihydroꢀ5Hꢀpyrazolo[3,4ꢀb]pyriꢀ
do[1´,2´:1,2]imidazo[4,5ꢀd]pyridinꢀ5ꢀone (7). A. A suspension
of pyridinium chloride 6 (5 g, 1.29 mmol) and potassium
tertꢀbutoxide (2.88 g, 2.58 mmol) in tertꢀbutanol (30 mL) was
heated with stirring for 1 day. The reaction mixture was cooled
and water (100 mL) was added. Then the reaction mixture was
acidified with aqueous hydrochloric acid to pH ~5 and stored
at 5 °C. After 1 day, the precipitate of 7 that formed was filtered
off, washed with water, and recrystallized from DMF.
1ꢀ[4ꢀAminoꢀ6(7H )ꢀoxoꢀ1ꢀphenylꢀ1Hꢀpyrazolo[3,4ꢀb]pyriꢀ
dinꢀ5ꢀyl]pyridinium chloride (11). A suspension of pyridinium
chloride 10 (6.1 g, 1.8 mmol) and sodium methoxide (1.94 g,
3.6 mmol) in methanol (100 mL) was refluxed for 3 days. The
reaction mixture was cooled and filtered. The filtrate was acidiꢀ
fied with a HCl(9%)/MeOH solution to pH ~6, and the inorꢀ
ganic precipitate that formed was filtered off. The resulting filꢀ
trate was concentrated in vacuo to 20 mL. The precipitate of
pyridinium salt 11 was filtered off, washed with methanol, and
recrystallized from methanol. 1H NMR, δ: 7.40 (m, 1 H, H(4″);
7.54 (m, 2 H, H(3″), H(5″)); 7.61 (br.s, 2 H, NH2); 7.83 (m,
2 H, H(2″), H(6″)); 8.30 (m, 2 H, H(3´), H(5´)); 8.46 (s, 1 H,
H(3)); 8.72 (m, 1 H, H(4´)); 9.01 (m, 2 H, H(2´), H(6´)); 11.31
(br.s, 1 H, NH(C(5)).
3ꢀPhenylꢀ3, 4ꢀdihydroꢀ5Hꢀpyrazolo[3, 4ꢀb]pyriꢀ
do[1´,2´:1,2]imidazo[4,5ꢀd]pyridinꢀ5ꢀone (12). A. A suspension
of pyridinium salt 11 (5 g, 1.47 mmol) and potassium tertꢀbutꢀ
oxide (3.29 g, 2.94 mmol) in tertꢀbutanol (50 mL) was refluxed
with stirring for 5 days. The reaction mixture was cooled, water
(500 mL) was added, and the mixture was acidified with hydroꢀ
chloric acid to pH ~5. After 2 h, the precipitate of pyrazoloꢀ
pyridine 12 that formed was recrystallized from DMF.
B. A suspension of pyridinium chloride 10 (5 g, 1.47 mmol)
and potassium tertꢀbutoxide (4.12 g, 3.68 mmol) in tertꢀbutanol
(30 mL) was refluxed with stirring for 8 days. The reaction
mixture was cooled, water (500 mL) was added, and the mixture
was acidified with hydrochloric acid to pH ~5. After 1 day, the
precipitate that formed was filtered off and recrystallized from
DMF in the presence of carbon; Rf 0.8 (chloroform—methaꢀ
nol, 10 : 1).
B. A suspension of pyridinium chloride 5 (2 g, 0.51 mmol)
and potassium tertꢀbutoxide (1.15 g, 1.03 mmol) in tertꢀbutanol
was refluxed with stirring for 2 days. The reaction mixture
was cooled, water (200 mL) was added, and the mixture was
acidified with aqueous hydrochloride acid to pH ~5. The paleꢀ
yellow precipitate of 7 that formed was filtered off, washed with
water, and twice recrystallized from DMF. 1H NMR, δ: 5.57 (s,
2 H, N(2)CH2); 7.13, 7.35, and 7.50 (all m, 1 H, 2 H, 1 H,
C6H4); 7.22 (m, 1 H, H(8)); 7.65 (m, 1 H, H(9)); 7.80 (m,
1 H, H(10)); 8.57 (s, 1 H, H(1)); 9.36 (m, 1 H, H(7)); 11.86
(br.s, 1 H, NH).
Attempts to perform cyclization of salt 10 in the absence of
atmospheric oxygen. A suspension of pyridinium chloride 10
(0.3 g, 0.088 mmol) and potassium tertꢀbutoxide (0.19 g,
0.17 mmol) in tertꢀbutanol (10 mL) was refluxed with stirring
under argon for 1 day, after which the TLC test of the reaction
mixture showed the presence of pyridinium salt 10 and one
unidentified product. Then water (10 mL) was added and the
reaction mixture was acidified with hydrochloric acid to pH ~5.
The precipitate that formed was filtered off, washed with water,
and recrystallized from ethanol in the presence of carbon.
5ꢀAminoꢀ4ꢀcyanoꢀ1ꢀphenylpyrazole was obtained in a yield of
1
5ꢀ(2ꢀChloroacetamido)ꢀ4ꢀcyanoꢀ1ꢀphenylpyrazole (9). A soꢀ
lution of chloroacetyl chloride (29.2 g, 25.8 mmol) in dioxane
(35 mL) was slowly added dropwise with vigorous stirring to a
suspension of phenylpyrazole 8 (31.7 g, 17 mmol) in potassium
carbonate (35.6 g, 25.8 mmol) at 60 °C for 1 h. The reaction
mixture was refluxed with stirring for 3 days and cooled. Then
water (1000 mL) was added and NaHCO3 was added to pH ~7.
The white precipitate of 9 that formed was filtered off and reꢀ
crystallized from water. 1H NMR, δ: 4.33 (s, 2 H, CH2Cl); 7.54
(m, 5 H, Ph); 8.32 (s, 1 H, H(3)); 10.96 (br.s, 1 H, NH).
1ꢀ[4ꢀCyanoꢀ1ꢀphenylpyrazolꢀ5ꢀylaminocarbonylmethyl]pyriꢀ
dinium chloride (10). A solution of compound 9 (5 g, 1.29 mmol)
in pyridine (60 mL) was stirred at 40 °C. After 30 min, the white
precipitate was obtained. The reaction mixture was continued to
be stirred at ~20 °C for 4 h. Pyrazolopyridinium chloride 10 that
formed was filtered off, washed with cold isopropyl alcohol, and
0.18 g. H NMR, δ: 7.27 (m, 1 H, H(8)); 7.49 (m, 1 H, H(4´);
7.58 (m, 2 H, H(3´), H(5´)); 7.72 (m, 3 H, H(2´), H(6´), H(9));
7.84 (m, 1 H, H(10)); 8.32 (s, 1 H, H(1)); 9.34 (m, 1 H, H(7));
12.40 (br.s, 1 H, NH).
4,5ꢀDiaminoꢀ6(7H)ꢀoxoꢀ1ꢀphenylꢀ1Hꢀpyrazolo[3,4ꢀb]pyriꢀ
dine (13). A solution of pyridinium salt 11 (1.4 g, 4.1 mmol) in a
50% aqueous hydrazine hydrate solution was refluxed with stirꢀ
ring for 24 h. The reaction mixture was cooled, diluted with
water (140 mL), and carefully acidified with dilute aqueous
hydrochloric acid to pH ~7.5. The white precipitate that formed
was rapidly filtered off, transferred to a flask, and immediately
treated with HCl(9%)/MeOH. Pyrazolopyridine hydrochloride
13 that formed was filtered off and recrystallized from ethanol.
1H NMR, δ: 6.35 (br.s, 2 H, NH2); 7.27 (m, 1 H, H(4´)); 7.48
(m, 2 H, H(3´), H(5´)); 8.09 (m, 2 H, H(2´), H(6´)); 8.14
(s, 1 H, H(3)).
1
recrystallized from the same solvent. H NMR, δ: 5.89 (s, 2 H,
This study was financially supported by the Federal
Agency for Science and Innovations of the Ministry of
Education and Science of the Russian Federation (State
N(1´)CH2); 7.47—7.71 (m, 5 H, Ph); 8.20 (m, 3 H, H(3´),
H(5´), H(3)); 8.68 (m, 1 H, H(4´)); 9.08 (m, 1 H, H(2´), H(6´));
12.14 (br.s, 1 H, NH).

740
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 4, April, 2006
Komarova et al.
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Received February 8, 2006;
in revised form April 10, 2006