Controllable synthesis of pyrazolo[3,4-b]pyridines or substituted malononitrile derivatives through multi-component reactions in ionic Liquid

Article abstract of DOI:10.1071/CH08290

A multi-component reaction of aldehyde, malononitrile, and 5-amino-3-methyl-1-phenylpyrazole was carried out smoothly in [bmim][BF ₄] without any added catalyst. Through this reaction, pyrazolo[3,4-b]pyridines or substituted malononitrile derivatives were obtained conveniently and controllably at different temperatures. The ionic liquid used can be easily recovered and efficiently reused for at least five runs.

Full text of DOI:10.1071/CH08290

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2009, 62, 382–388
www.publish.csiro.au/journals/ajc
Controllable Synthesis of Pyrazolo[3,4-b]pyridines
or Substituted Malononitrile Derivatives through
Multi-Component Reactions in Ionic Liquid
Xinying Zhang,A,B Xiaoyan Li,A Xuesen Fan,A,B Xia Wang,A Jianji Wang,A
and Guirong QuA
ASchool of Chemistry and Environmental Sciences, Henan Key Laboratory for Environmental
Pollution Control, Henan Normal University, Xinxiang, Henan 453007, China.
BCorresponding authors. Email: xyzh518@sohu.com; xuesen.fan@yahoo.com
A multi-component reaction of aldehyde, malononitrile, and 5-amino-3-methyl-1-phenylpyrazole was carried out smoothly
in [bmim][BF4] without any added catalyst. Through this reaction, pyrazolo[3,4-b]pyridines or substituted malononitrile
derivatives were obtained conveniently and controllably at different temperatures. The ionic liquid used can be easily
recovered and efficiently reused for at least five runs.
Manuscript received: 9 July 2008.
Final version: 31 December 2008.
Introduction
additives and catalysts was employed or volatile solvents were
used for the reaction to complete.Therefore, development of new
methods capable of inducing environmentally benign and effi-
cient preparation of pyrazolo[3,4-b]pyridine derivatives would
be of interest to synthetic chemists.
With an increasing prevalence of green chemistry, alternative
technologies that circumvent the use of volatile organic com-
pounds (VOCs) are of interest in organic synthesis.[1–4] One
respect in this field is the introduction and application of ionic
liquids (ILs) in organic synthesis. With the unique properties of
ILs, such as good solvating capability, wide liquid range, negligi-
ble vapour pressure, and ease of recycling, IL technology offers
a new and environmentally benign approach towards organic
synthesis. Many classical organic processes have successfully
proceeded in ILs. Recently, the utilization of ILs to promote the
selectivity of various organic reactions has also attracted much
attention.[5]
It is well known that the majority of new molecules enter-
ing clinical studies contain at least one heterocyclic moiety,
predominantly N-heterocycles. Therefore, the development of
novel methods for the preparation of nitrogen-containing hetero-
cyclic compounds is always in demand. As an example,
pyrazolo-pyridine derivatives are of interest for their appli-
cations as vasodilators, and hypotensive, hypoglycemic, anti-
inflammatory, analgesic, and antipyretic agents.[6–9] Because
of their importance, many methods have been reported for the
preparation of these interesting heterocyclic frameworks.[9,10]
In particular, pyrazolo[3,4-b]pyridine derivatives are usually
obtained through condensation and cyclization of amino-
pyrazole and compounds with an active methylene group or
α,β-unsaturated compounds.[11–14] More recently Tu et al.
reported that similar compounds could be obtained from
arylidenemalononitrile and aminopyrazole[15] or directly
from dialdehyde, aminopyrazole, and an active methylene
compound[16] under microwave irradiation conditions. Shi et al.
recently reported a three-component, one pot synthesis of
pyrazolo[3,4-b]pyridine derivatives in aqueous media using
sodium 1-dodecanesulfonate as catalyst.[17] However, with most
of these reported methods, either a combination of several
Multi-component reactions (MCRs) are special types of
organic reactions that afford complex products from the reac-
tion of three or more simple starting materials in one pot.
Because of their simple operation but good results, MCRs
have attracted much attention.[18–21] In the past several years,
our own interest has been focussed on the development of
novel methods for the preparation of various biologically
important heterocyclic compounds, such as benzopyran, 1,4-
dihydropyridine, xanthenedione, and quinoline by MCRs using
ILs as a novel reaction medium and/or promoter.[22–27] As a
continuation of our research in this field, herein we report
our recent study of the MCR of aldehyde, malononitrile, and
5-amino-3-methyl-1-phenylpyrazole in an IL, 1-butyl-3-methyl-
imidazolium tetrafluoroborate ([bmim][BF4]). From this reac-
tion, pyrazolo[3,4-b]pyridines or substituted malononitrile
derivatives are obtained controllably under different reaction
temperature conditions.
Results and Discussion
Initially, 4-nitrobenzilidenemalononitrile (1a, Scheme 1), pre-
viously prepared from 4-nitrobenzaldehyde and malononitrile,
was treated with 5-amino-3-methyl-1-phenylpyrazole (2) in
[bmim][BF4] at room temperature. TLC analysis showed that
1a and 2 were consumed in 1 h to give a new substance. Based
on its mass spectrum and one and two-dimensional 2D NMR
spectra, this new substance was identified as 3a (Scheme 1), not
the expected 4a.
Our initial effort for the construction of pyrazolo[3,4-
b]pyridine scaffolds was continued. Thus, 1a was treated with 2
in [bmim][BF4] again, but at elevated temperatures. It was found
© CSIRO 2009
10.1071/CH08290
0004-9425/09/040382

Multi-Component Reactions in Ionic Liquid
383
that as the reaction temperature increased, another product was
formed along with 3a (based onTLCanalysis). Different temper-
ature conditions were tried and it was discovered that when the
reaction was run at 80◦C, only the second product was formed,
showing that at a higher temperature, 3 could be transformed
into 4 by a dehydrogenation step (presumably by atmospheric
oxygen). The product was in a solid state and was collected by
vacuum filtration. Subsequent structural analysis showed that it
was the desired product 4a (Scheme 1). Its identification was
based on 1H and 13C NMR analysis and mass spectrometry and
by comparison with an authentic compound prepared by a known
procedure.[15]
As mentioned previously, the art of performing efficient
chemical transformations that involve three or more compo-
nents in a single operation represents a fundamental target
of modern organic synthesis. This prompted us to study the
possibility of preparing 3a or 4a directly from the correspond-
ing aldehyde (5a), malononitrile (6), and 5-amino-3-methyl-1-
phenylpyrazole (2) in one pot.
To our delight, treatment of 5a, 6, and 2 in [bmim][BF4] at
room temperature afforded 3a in a yield of 95%, whereas the
same starting materials afforded 4a at 80◦C with a yield of 93%.
It should be noted here that the above results are of remarkable
interest because two different products can be obtained selec-
tively from the same starting materials under different but rather
mild conditions by a MCR.
Considering that with a free amino and two cyano groups,
compounds like 3a have the potential to be used as a useful
intermediate to construct new nitrogen-containing molecules,
and that pyrazolo-pyridine derivatives have found broad appli-
cations in medicinal chemistry, we found it was of importance
to investigate the scope and generality of the above preparative
processes. Thus, different substrates were studied (Scheme 2)
and the results are listed in Table 1 and Table 2.
temperature failed to produce 3h (Table 1, entry 8). However,
the pyrazolo-pyridine product 4h could be obtained from the
same starting materials at 80◦C, but with a low yield (Table 2,
entry 8). This is likely a result of the strong electron-donating
effect of the dimethylamino group, which results in a decrease
of the reactivity of the corresponding benzilidenemalononitrile
as a Michael-addition acceptor. In addition, aryl aldehydes with
group(s) in the ortho position gave lower yields of 4, probably
because of steric effects (Table 2, entry 19).
With the above products in hand, the initial structures of 4 and
3 assigned by mass spectrometry and NMR spectroscopy were
further confirmed by X-ray crystallographic analysis of 4a[28]
and 3d.[29]
Furthermore, one important feature of ILs as a reaction
medium is the possibility of its recovery and reuse. Our stud-
ies showed that reuse of [bmim][BF4] was feasible for all the
above procedures. At completion of the above reactions, corre-
sponding products were isolated accordingly and the IL phase
was concentrated and dried under reduced pressure for reuse.
No remarkable decrease in the efficiency of the reused IL was
observed after five rounds.
R
CN
H3C
[bmim][BF4]
r.t.
CN
NH2
N
N
N
H3C
Ph
3
CN
N
ϩ
R
CHO ϩ
NH2
R
N
N
CN
H3C
CN
Ph
2
5
6
[bmim][BF4]
NH2
N
80°C
Ph
It turned out that various aryl aldehydes or heterocyclic
aldehydes reacted smoothly with 6 and 2 to give 3 or 4
in reasonably high yields. In the meantime, aldehydes with
electron-withdrawing groups in the para or meta position of
the aryl ring gave relatively higher yields in a shorter reaction
time compared with aldehydes with electron-donating groups,
as shown in Table 1, entry 1 and entry 7; Table 2, entry 1 and
entry 7. It should also be noted that the three-component reac-
tion using 4-dimethylaminobenzaldehyde (5h) over 2d at room
4
Scheme 2.
Table 1. Preparation of compound 3 in [bmim][BF4]
Reaction conditions: 1 mmol of 5, 6, and 2; 1 mL of [bmim][BF4]; room
temperature
Entry
R
Product
Reaction
time [h]
Yield
[%]
NO2
1
2
3
4
5
6
7
8
p-NO2C6H4
C6H5
p-FC6H4
p-ClC6H4
p-BrC6H4
p-CH3C6H4
p-CH3OC6H4
p-N(CH3)2C6H4
4-pyridyl
m-NO2C6H4
m-FC6H4
m-ClC6H4
m-BrC6H4
m-CH3C6H4
3-pyridyl
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
1.5
1.5
4
4
4
95
94
92
95
93
92
80
0
83
89
90
94
92
93
89
92
92
90
88
[bmim][BF4]
r.t.
CN
H3C
CN
NH2
N
4
N
12
48
4
3
3
3
3
3
3
4
4
4
4
Ph
3a
H3C
9
CN
CN
10
11
12
13
14
15
16
17
18
19
NO2
N
C
C
O2N
ϩ
NH2
N
H
Ph
2
1a
H3C
CN
[bmim][BF4]
N
80°C
o-FC6H4
N
NH2
N
o-ClC6H4
o-BrC6H4
o-NO2C6H4
Ph
4a
Scheme 1.

384
X. Zhang et al.
It has also been reported that compared with classical organic
longer reaction time was needed and the yields were lower.When
the reaction was run at 80◦C in toluene or in refluxing ethanol or
THF, it gave a mixture of 3a and 4a together with other uniden-
tified by-products. Moreover, using [bmim][BF4] as the reaction
medium made the separation process much easier. For example,
in [bmim][BF4], 4a is in a solid state and could be conveniently
isolated with high purity through vacuum filtration. However,
when ethanol, toluene, or THF was used, a complicated mix-
ture was formed and 4a could only be obtained through column
chromatography.
The accelerating effect of [bmim][BF4] in the above reac-
tions may be attributed to the acidity of the proton attached at
the 2-position of the imidazolium moiety and its ability to act
as a hydrogen-bond donor.[30] The formation of the O–H hydro-
gen bond from [bmim]+ to the carbonyl oxygen and the N–H
hydrogen bond from [bmim]+ to the cyano nitrogen increases
the polarity and thus reactivity of the carbonyl group and the
cyano group (Scheme 3), which consequently benefits the whole
reaction process including the initial Knoevenagel condensation
between an aldehyde and malononitrile, subsequent Michael-
addition reaction, and the following cyclization process when
the reaction was run at 80◦C.
In summary, we have demonstrated that an IL, [bmim][BF4],
canbeusedasbothareactionmediumandpromoterforthethree-
component reaction of aldehydes, malononitrile, and 5-amino-
3-methyl-1-phenylpyrazole to give pyrazolo[3,4-b]pyridines or
substituted malononitriles in high yields at different reaction
temperatures. Compared with literature methods, the notable
features of the procedures presented here are excellent selec-
tivity, atom economy, mild conditions, cleaner reaction profiles,
simple operation process together with convenient and efficient
recovery and reuse of the reaction medium.
solvents, ILs not only possess a green nature, but also offer a sim-
pler operational process and/or enhanced reactivity and better
yields. This was demonstrated by comparing [bmim][BF4] with
several classical organic solvents including ethanol, toluene, and
tetrahydrofuran (THF). The following is the results (shown in
Table 3) of investigations using 5a, 6, and 2 as model substrates.
Of the four solvents studied, [bmim][BF4] gave the highest
yields for 3a (95%, Table 3, entry 1) and 4a (93%, Table 3,
entry 2) within the shortest reaction time at room temperature
or at 80◦C, respectively. With ethanol, toluene, or THF as sol-
vent, product 3a could be obtained at room temperature, but a
Table 2. Preparation of compound 4 in [bmim][BF4]
Reaction conditions: 1 mmol of 5, 6, and 2; 1 mL of [bmim][BF4]; 80◦C
Entry
R
Product
Reaction
time [h]
Yield
[%]
1
2
3
4
5
6
7
8
p-NO2C6H4
C6H5
p-FC6H4
p-ClC6H4
p-BrC6H4
p-CH3C6H4
p-CH3OC6H4
p-N(CH3)2C6H4
4-pyridyl
m-NO2C6H4
m-FC6H4
m-ClC6H4
m-BrC6H4
m-CH3C6H4
3-pyridyl
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
10
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
93
82
84
85
83
80
81
50
75
87
80
80
78
80
77
79
80
78
61
9
10
11
12
13
14
15
16
17
18
19
o-FC6H4
Experimental
o-ClC6H4
o-BrC6H4
o-NO2C6H4
Melting points were measured by a Kofler micromelting point
apparatus and were uncorrected. 1H and 13C NMR spectra were
determined on a Bruker AC 400 spectrometer as (D6)DMSO
solutions. Chemical shifts (δ) are expressed in ppm downfield
from the internal standard tetramethylsilane and coupling con-
stants J are given in Hz. Mass spectra were recorded on a
Bruker Esquire 3000 mass spectrometer. Elemental analyses
were performed on an EA-1110 instrument.
Table 3. Preparation of 3a or 4a in different solvents
Entry
Solvent
Temp.
[◦C]
Product
Reaction
time [h]
Yield
[%]
General Procedure for the Preparation of
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)(aryl)-
methyl)malononitrile (3)
1
2
3
4
5
6
7
8
[bmim][BF4]
[bmim][BF4]
Ethanol
Ethanol
Toluene
Toluene
THF
r.t.
80
r.t.
Reflux
r.t.
80
r.t.
Reflux
3a
4a
3a
1.5
10
24
24
24
24
24
24
95
93
61
3a + 4a
50 + 20
To 1 mL of [bmim][BF4] were added aldehyde 5 (1 mmol), mal-
ononitrile 6 (1 mmol), and 5-amino-3-methyl-1-phenylpyrazole
2(1 mmol).Thereactionmixturewasstirredatroomtemperature
for a certain period of time to complete the reaction (monitored
by TLC). Upon completion, the reaction mixture was extracted
3a
47
3a + 4a
3a
3a + 4a
48 + 11
65
52 + 19
THF
R
ϩ
N
H
N
H3C
CN
N
Bu
Me
C
C
N
C
N
N
H
O
NH2
N
Me
N
Bu
Me
N
H
H
H
N
ϩ
Ph
ϩ
3
ϩ
N
N
C
R
N
Me
Bu
Bu
Scheme 3.

Multi-Component Reactions in Ionic Liquid
385
with ether (2 mL × 5). The ether extracts were combined and
concentrated. The residue was recrystallized from 95% ethanol
to give 3 with high purity. The IL layer was dried at 100◦C under
reduced pressure to recover the IL.
7.29 (t, 1H, J 7.6, Ar-H), 7.36 (d, 2H, J 8.0, Ar-H), 7.45 (t,
2H, J 7.6, Ar-H), 7.52 (d, 2H, J 8.0, Ar-H), 7.62 (d, 2H, J 8.0,
Ar-H). δC 14.1, 26.7, 98.5, 114.2, 114.4, 121.0, 123.4, 126.7,
129.5, 130.1, 132.0, 138.0, 139.3, 145.5, 146.5. m/z (ESI) 428,
430 [M + Na]+. (Found: C 59.19, H 3.99, N 17.15. Calc. for
C20H16BrN5: C 59.13, H 3.97, N 17.24%.)
General Procedure for the Preparation of 6-Amino-4-aryl-
5-cyano-3-methyl-1-phenylpyrazolo[3,4-b]pyridine (4)
To 1 mL of [bmim][BF4] were added aldehyde 5 (1 mmol), mal-
ononitrile 6 (1 mmol), and 5-amino-3-methyl-1-phenylpyrazole
2 (1 mmol). The reaction mixture was stirred at 80◦C for a cer-
tain period of time to complete the reaction (monitored byTLC).
Upon completion, the mixture was cooled to room temperature
and 2 mL of 50% ethanol in water was added. The solid precip-
itated was collected by vacuum filtration and rinsed with water
andethanol, andthendriedtogive 4withhighpurity.TheILlayer
was dried at 100◦C under reduced pressure to recover the IL.
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(4-methylphenyl)methyl)malononitrile (3f)
White solid. Mp 146–148◦C. δH 1.88 (s, 3H, CH3), 2.26 (s, 3H,
CH3), 4.95 (d, 1H, J 10.8, CH), 5.41 (br s, 2H, NH2), 5.68 (d, 1H,
J 10.8, CH), 7.17–7.27 (m, 5H, Ar-H), 7.42 (t, 2H, J 8.0, Ar-H),
7.50 (d, 2H, J 7.6, Ar-H). δC 13.7, 20.7, 26.5, 99.0, 113.9, 114.3,
123.0, 126.2, 127.3, 129.1, 129.2, 135.2, 136.7, 139.1, 145.0,
146.2. m/z (ESI) 364 [M + Na]+. (Found: C 73.93, H 5.66, N
20.41. Calc. for C21H19N5: C 73.88, H 5.61, N 20.51%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(4-nitrophenyl)methyl)malononitrile (3a)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(4-methoxylphenyl)methyl)malononitrile (3g)
Pale yellow solid. Mp 134–136◦C. δH 1.89 (s, 3H, CH3), 5.24
(d, 1H, J 10.8, CH), 5.52 (br s, 2H, NH2), 5.85 (d, 1H, J 10.8,
CH), 7.29 (t, 1H, J 6.8, Ar-H), 7.43 (t, 2H, J 8.0, Ar-H), 7.49
(d, 2H, J 8.0, Ar-H), 7.66 (d, 2H, J 8.0, Ar-H), 8.27 (d, 2H, J
8.4, Ar-H). δC 13.7, 26.2, 40.1, 97.6, 113.5, 113.9, 123.1, 124.0,
126.4, 128.8, 129.2, 138.9, 145.4, 145.6, 146.1, 146.8. m/z (ESI)
395 [M + Na]+. (Found: C 64.62, H 4.43, N 22.47. Calc. for
C20H16N6O2: C 64.51, H 4.33, N 22.57%.)
White solid. Mp 148–150◦C. δH 1.91 (s, 3H, CH3), 3.74 (s, 3H,
OCH3), 4.95 (d, 1H, J 11.2, CH), 5.45 (br s, 2H, NH2), 5.70 (d,
1H, J 11.2, CH), 6.95 (d, 2H, J 8.4, Ar-H), 7.26–7.32 (m, 3H,
Ar-H), 7.44 (t, 2H, J 7.6, Ar-H), 7.52 (d, 2H, J 7.6, Ar-H). δC
14.1, 27.1, 55.5, 99.4, 114.4, 114.7, 123.3, 126.5, 129.0, 129.5,
130.5, 139.4, 145.3, 146.5, 158.8. m/z (ESI) 380 [M + Na]+.
(Found: C 70.65, H 5.48, N 19.50. Calc. for C21H19N5: C 70.57,
H 5.36, N 19.59%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-
4-yl)(phenyl)methyl)malononitrile (3b)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(pyridin-4-yl)methyl)malononitrile (3i)
White solid. Mp 131–132◦C. δH 1.88 (s, 3H, CH3), 5.02 (d, 1H,
J 10.8, CH), 5.45 (br s, 2H, NH2), 5.73 (d, 1H, J 10.8, CH),
7.25–7.52 (m, 10H, Ar-H). δC 13.7, 26.5, 98.9, 113.9, 114.2,
123.0, 126.2, 127.5, 128.7, 129.1, 138.2, 139.0, 145.1, 146.2.
m/z (ESI) 350 [M + Na]+. (Found: C 73.30, H 5.20, N 21.49.
Calc. for C20H17N5: C 73.37, H 5.23, N 21.39%.)
White solid. Mp 144–145◦C. δH 1.87 (s, 3H, CH3), 5.13 (d, 1H,
J 10.8, CH), 5.59 (br s, 2H, NH2), 5.84 (d, 1H, J 10.8, CH), 7.30
(t, 1H, J 7.2,Ar-H), 7.40 (d, 2H, J 4.8, C5H4N), 7.45 (t, 2H, J 7.6,
Ar-H), 7.52 (d, 2H, J 7.6, Ar-H), 8.61 (d, 2H, J 4.8, C5H4N). δC
14.0, 26.1, 97.6, 113.9, 114.3, 122.9, 123.4, 126.8, 129.6, 139.2,
145.9, 146.5, 147.1, 150.5. m/z (ESI) 351 [M + Na]+. (Found:
C 69.55, H 4.95, N 25.50. Calc. for C19H16N6: C 69.50, H 4.91,
N 25.59%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(4-fluorophenyl)methyl)malononitrile (3c)
White solid. Mp 154–156◦C. δH 1.91 (s, 3H, CH3), 5.05 (d, 1H, J
10.8, CH), 5.50 (br s, 2H, NH2), 5.76 (d, 1H, J 11.2, CH), 7.23–
7.53 (m, 9H, Ar-H). δC 14.1, 27.0, 98.9, 114.1, 114.5, 115.8,
116.0, 123.3, 126.6, 129.5, 129.8, 129.9, 134.8, 139.3, 145.4,
146.5, 160.5, 162.9. m/z (ESI) 368 [M + Na]+. (Found: C 69.65,
H 4.75, N 20.19. Calc. for C20H16FN5: C 69.55, H 4.67, N
20.28%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(3-nitrophenyl)methyl)malononitrile (3j)
Pale yellow solid. Mp 136–138◦C. δH 1.95 (s, 3H, CH3), 5.26 (d,
1H, J 11.2, CH), 5.61 (br s, 2H, NH2), 5.96 (d, 1H, J 11.2, CH),
7.30 (t, 1H, J 7.6, Ar-H), 7.45 (t, 2H, J 8.0, Ar-H), 7.51 (d, 2H,
J 7.6, Ar-H), 7.74 (t, 1H, J 8.0, Ar-H), 7.88 (d, 1H, J 8.0, Ar-H),
8.20 (d, 1H, J 8.0, Ar-H), 8.31 (s, 1H, Ar-H). δC 14.1, 26.7, 97.9,
113.8, 114.2, 122.6, 123.1, 123.5, 126.8, 129.6, 130.8, 134.6,
139.2, 140.7, 145.7, 146.4, 148.3. m/z (ESI) 395 [M + Na]+.
(Found: C 64.59, H 4.39, N 22.49. Calc. for C20H16N6O2: C
64.51, H 4.33, N 22.57%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(4-chlorophenyl)methyl)malononitrile (3d)
White solid. Mp 180–183◦C. δH 1.92 (s, 3H, CH3), 5.06 (d, 1H, J
10.8, CH), 5.48 (br s, 2H, NH2), 5.76 (d, 1H, J 10.8, CH), 7.30 (t,
1H, J 7.2, Ar-H), 7.42–7.53 (m, 8H, Ar-H). δC 13.7, 26.5, 98.3,
113.7, 114.1, 123.0, 126.3, 128.7, 129.2, 129.4, 132.2, 137.2,
139.0, 145.1, 146.1. m/z (ESI) 384, 386 [M + Na]+. (Found: C
66.45, H 4.54, N 19.29. Calc. for C20H16ClN5: C 66.39, H 4.46,
N 19.36%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(3-fluorophenyl)methyl)malononitrile (3k)
White solid. Mp 110–112◦C. δH 1.92 (s, 3H, CH3), 5.08 (d, 1H,
J 10.0, CH), 5.52 (br s, 2H, NH2), 5.80 (d, 1H, J 10.4, CH), 7.15–
7.29(m, 4H,Ar-H), 7.44–7.51(m, 5H,Ar-H). δC 14.0, 26.7, 98.5,
114.0, 114.4, 114.6, 114.7, 114.8, 114.9, 123.4, 124.1, 126.7,
129.5, 131.1, 131.2, 139.3, 141.3, 141.4, 145.6, 146.5, 161.3,
163.7. m/z (ESI) 368 [M + Na]+. (Found: C 69.59, H 4.73, N
20.21. Calc. for C20H16FN5: C 69.55, H 4.67, N 20.28%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(4-bromophenyl)methyl)malononitrile (3e)
White solid. Mp 161–164◦C. δH 1.91 (s, 3H, CH3), 5.05 (d, 1H,
J 10.8, CH), 5.52 (br s, 2H, NH2), 5.77 (d, 1H, J 10.8, CH),

386
X. Zhang et al.
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(3-chlorophenyl)methyl)malononitrile (3l)
114.4, 123.1, 126.5, 127.2, 128.3, 129.5, 129.6, 130.8, 134.0,
135.0, 139.4, 146.4, 146.7. m/z (ESI) 384, 386 [M + Na]+.
(Found: C 66.31, H 4.39, N 19.30. Calc. for C20H16ClN5: C
66.39, H 4.46, N 19.36%.)
White solid. Mp 116–118◦C. δH 1.93 (s, 3H, CH3), 5.08 (d, 1H, J
10.8, CH), 5.53 (br s, 2H, NH2), 5.82 (d, 1H, J 10.8, CH), 7.28–
7.53 (m, 9H, Ar-H). δC 14.1, 26.6, 98.4, 114.0, 114.4, 123.4,
126.6, 126.7, 127.8, 127.9, 129.5, 131.0, 133.7, 139.3, 141.0,
145.6, 146.4. m/z (ESI) 384, 386 [M + Na]+. (Found: C 66.52,
H 4.56, N 19.31. Calc. for C20H16ClN5: C 66.39, H 4.46, N
19.36%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(2-bromophenyl)methyl)malononitrile (3r)
White solid. Mp 177–179◦C. δH 1.68 (s, 3H, CH3), 5.13 (d, 1H,
J 10.8, CH), 5.53 (br s, 2H, NH2), 5.78 (d, 1H, J 10.8, CH),
7.26–7.31 (m, 2H, Ar-H), 7.42–7.54 (m, 5H, Ar-H), 7.67–7.75
(m, 2H, Ar-H). δC 14.0, 27.0, 96.5, 113.9, 114.4, 123.2, 124.8,
126.5, 127.8, 128.6, 129.5, 129.9, 134.2, 136.4, 139.4, 146.5,
146.7. m/z (ESI) 428, 430 [M + Na]+. (Found: C 59.21, H 4.03,
N 17.16. Calc. for C20H16BrN5: C 59.13, H 3.97, N 17.24%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(3-bromophenyl)methyl)malononitrile (3m)
Pale yellow solid. Mp 80–82◦C. δH 1.93 (s, 3H, CH3), 5.07 (d,
1H, J 11.2, CH), 5.53 (br s, 2H, NH2), 5.82 (d, 1H, J 11.2, CH),
7.29 (t, 1H, J 7.2,Ar-H), 7.36–7.47 (m, 4H,Ar-H), 7.51–7.53 (m,
3H, Ar-H), 7.60 (s, 1H, Ar-H). δC 14.1, 26.6, 98.4, 114.0, 114.4,
122.3, 123.4, 126.7, 126.9, 129.5, 130.6, 130.9, 131.3, 139.2,
141.2, 145.6, 146.4. m/z (ESI) 428, 430 [M + Na]+. (Found: C
59.29, H 3.99, N 17.15. Calc. for C20H16BrN5: C 59.13, H 3.97,
N 17.24%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(2-nitrophenyl)methyl)malononitrile (3s)
Pale yellow solid. Mp 163–165◦C. δH 1.56 (s, 3H, CH3), 5.54
(br s, 2H, NH2), 5.62 (d, 1H, J 9.6, CH), 5.74 (d, 1H, J 9.6,
CH), 7.27–7.31 (m, 1H, Ar-H), 7.42–7.49 (m, 4H, Ar-H), 7.60–
7.64 (m, 1H, Ar-H), 7.85 (d, 2H, J 4.0, Ar-H), 7.91 (d, 1H, J
7.6, Ar-H). δC 13.5, 27.0, 36.2, 96.6, 113.7, 114.3, 123.3, 125.8,
126.7, 128.2, 129.5, 131.1, 133.0, 139.3, 146.3, 146.6, 150.0.
m/z (ESI) 395 [M + Na]+. (Found: C 64.62, H 4.33, N 22.47.
Calc. for C20H16N6O2: C 64.51, H 4.33, N 22.57%.)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(3-methylphenyl)methyl)malononitrile (3n)
Pale yellow solid. Mp 66–68◦C. δH 1.90 (s, 3H, CH3), 2.30 (s,
3H, CH3), 4.98 (d, 1H, J 11.2, CH), 5.48 (br s, 2H, NH2), 5.73
(d, 1H, J 11.2, CH), 7.11 (d, 1H, J 7.2, Ar-H), 7.18 (s, 1H, Ar-H),
7.21 (d, 1H, J 7.2, Ar-H), 7.28 (t, 2H, J 7.2, Ar-H), 7.44 (t, 2H,
J 7.6, Ar-H), 7.52 (d, 2H, J 7.6, Ar-H). δC 14.1, 21.6, 26.8, 99.2,
114.3, 114.6, 123.2, 124.6, 126.6, 128.5, 128.6, 128.9, 129.5,
138.2, 138.5, 139.4, 145.4, 146.6. m/z (ESI) 364 [M + Na]+.
(Found: C 73.95, H 5.65, N 20.40. Calc. for C21H19N5: C 73.88,
H 5.61, N 20.51%.)
6-Amino-5-cyano-3-methyl-4-(4-nitrophenyl)-1-phenyl-
pyrazolo[3,4-b]pyridine (4a)
Yellow solid. Mp 226–228◦C (lit.[15] 221–223◦C). δH 1.82
(s, 3H, CH3), 7.27 (t, 1H, J 7.6, Ar-H), 7.34 (br s, 2H, NH2),
7.48 (t, 2H, J 7.6, Ar-H), 7.85 (d, 2H, J 8.8, Ar-H), 8.14 (d, 2H, J
7.6, Ar-H), 8.39 (d, 2H, J 8.8, Ar-H). δC 14.3, 87.7, 107.7, 116.1,
120.6, 123.7, 125.7, 129.1, 130.5, 138.8, 140.7, 143.5, 148.4,
150.2, 151.1, 159.2. m/z (ESI) 393 [M + Na]+.
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(pyridin-3-yl)methyl)malononitrile (3o)
White solid. Mp 86–88◦C. δH 1.93 (s, 3H, CH3), 5.13 (d, 1H,
J 11.2, CH), 5.55 (br s, 2H, NH2), 5.85 (d, 1H, J 11.2, CH),
7.30 (t, 1H, J 7.2, Ar-H), 7.43–7.53 (m, 5H, Ar-H), 7.83 (d,
1H, J 7.6, Ar-H), 8.52 (d, 1H, J 4.4, Ar-H), 8.63 (s, 1H, Ar-H).
δC 14.0, 26.6, 38.6, 98.2, 113.9, 114.3, 123.5, 124.1, 126.8,
129.6, 134.3, 135.4, 139.2, 145.6, 146.4, 149.1, 149.2. m/z (ESI)
351 [M + Na]+. (Found: C 69.52, H 4.95, N 25.53. Calc. for
C19H16N6: C 69.50, H 4.91, N 25.59%.)
6-Amino-5-cyano-3-methyl-1,4-diphenyl-pyrazolo
[3,4-b]pyridine (4b)
White solid. Mp 208–209◦C (lit.[12] 208◦C). δH 1.83 (s, 3H,
CH3), 7.21 (br s, 2H, NH2), 7.26 (t, 1H, J 7.2, Ar-H), 7.45–7.56
(m, 7H, Ar-H), 8.15 (d, 2H, J 8.0, Ar-H). δC 14.3, 88.0, 108.1,
116.5, 120.5, 125.6, 128.5, 128.6, 129.0, 129.7, 134.2, 138.9,
143.8, 151.1, 152.6, 159.3. m/z (ESI) 348 [M + Na]+.
6-Amino-5-cyano-4-(4-fluorophenyl)-3-methyl-1-phenyl-
pyrazolo[3,4-b]pyridine (4c)
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(2-fluorophenyl)methyl)malononitrile (3p)
White solid. Mp 212–214◦C (lit.[15] 216–218◦C). δH 1.85 (s, 3H,
CH3), 7.23–7.28 (m, 3H, Ar-H, NH2), 7.40 (t, 2H, J 8.8, Ar-H),
7.47 (t, 2H, J 8.0, Ar-H), 7.57–7.61 (m, 2H, Ar-H), 8.14 (d, 2H,
J 8.0, Ar-H). δC 14.3, 88.2, 108.2, 115.5, 115.7, 116.4, 120.5,
125.6, 129.0, 130.5, 131.1, 131.2, 138.9, 143.8, 151.1, 151.6,
159.3, 161.7, 164.1. m/z (ESI) 366 [M + Na]+.
White solid. Mp 158–160◦C. δH 1.83 (s, 3H, CH3), 5.27 (d, 1H,
J 11.6, CH), 5.52 (br s, 2H, NH2), 5.80 (d, 1H, J 11.6, CH),
7.21–7.31 (m, 3H, Ar-H), 7.36–7.46 (m, 3H, Ar-H), 7.52 (d, 2H,
J 8.0, Ar-H), 7.65 (t, 1H, J 7.6, Ar-H). δC 13.8, 26.4, 34.7, 97.2,
113.9, 114.4, 116.3, 116.5, 123.2, 124.6, 125.0, 125.2, 126.6,
128.4, 129.5, 130.0, 130.1, 139.3, 145.7, 146.6, 159.0, 161.5.
m/z (ESI) 368 [M + Na]+. (Found: C 69.61, H 4.73, N 20.21.
Calc. for C20H16FN5: C 69.55, H 4.67, N 20.28%.)
6-Amino-4-(4-chlorophenyl)-5-cyano-3-methyl-1-phenyl-
pyrazolo[3,4-b]pyridine (4d)
White solid. Mp 194–196◦C (lit.[12] 195◦C). δH 1.86 (s, 3H,
CH3), 7.25–7.28 (m, 3H, Ar-H, NH2), 7.47 (t, 2H, J 8.0, Ar-H),
7.56 (d, 2H, J 8.4, Ar-H), 7.63 (d, 2H, J 8.4, Ar-H), 8.14 (d, 2H,
J 7.6, Ar-H). δC 14.4, 88.0, 108.0, 116.4, 120.5, 125.7, 128.7,
129.1, 130.7, 133.0, 134.6, 138.9, 143.7, 151.2, 151.3, 159.3.
m/z (ESI) 382, 384 [M + Na]+.
2-((5-Amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)
(2-chlorophenyl)methyl)malononitrile (3q)
White solid. Mp 179–181◦C. δH 1.71 (s, 3H, CH3), 5.22 (d, 1H,
J 11.2, CH), 5.55 (br s, 2H, NH2), 5.81 (d, 1H, J 11.2, CH), 7.28
(t, 1H, J 7.2, Ar-H), 7.37 (t, 1H, J 7.6, Ar-H), 7.42–7.53 (m, 6H,
Ar-H), 7.74 (d, 1H, J 7.6, Ar-H). δC 13.9, 26.8, 38.3, 96.5, 113.9,

Multi-Component Reactions in Ionic Liquid
387
6-Amino-4-(4-bromophenyl)-5-cyano-3-methyl-1-phenyl-
pyrazolo[3,4-b]pyridine (4e)
6-Amino-5-cyano-4-(3-fluorophenyl)-3-methyl-
1-phenylpyrazolo[3,4-b]pyridine (4k)
White solid. Mp 210–213◦C (lit.[15] 222–223◦C). δH 1.87 (s, 3H,
CH3), 7.26–7.28 (m, 3H, Ar-H, NH2), 7.46–7.50 (m, 4H, Ar-H),
7.77 (d, 2H, J 8.0, Ar-H), 8.14 (d, 2H, J 7.6, Ar-H). δC 14.4,
87.9, 107.9, 116.4, 120.6, 123.3, 125.7, 129.1, 130.9, 131.6,
133.4, 138.9, 143.7, 151.2, 151.3, 159.3. m/z (ESI) 426, 428
[M + Na]+.
Whitesolid. Mp171–173◦C. δH 1.88(s, 3H, CH3), 7.27–7.30(m,
3H, Ar-H, NH2), 7.37–7.52 (m, 5H, Ar-H), 7.60–7.66 (m, 1H,
Ar-H), 8.16 (d, 2H, J 8.0, Ar-H). δC 14.6, 88.3, 108.3, 116.1,
116.3, 116.7, 116.9, 117.1, 120.8, 125.4, 126.0, 129.4, 131.1,
131.2, 136.6, 136.7, 139.2, 144.0, 151.3, 151.4, 159.6, 160.9,
163.4. m/z (ESI) 366 [M + Na]+. (Found: C 69.91, H 4.16,
N 20.35. Calc. for C20H14FN5: C 69.96, H 4.11, N 20.40%.)
6-Amino-5-cyano-3-methyl-4-(4-methylphenyl)-1-phenyl-
pyrazolo[3,4-b]pyridine (4f)
6-Amino-4-(3-chlorophenyl)-5-cyano-3-methyl-
1-phenylpyrazolo[3,4-b]pyridine (4l)
White solid. Mp 199–202◦C. δH 1.86 (s, 3H, CH3), 2.40 (s, 3H,
CH3), 7.16 (br s, 2H, NH2), 7.26 (t, 1H, J 7.2, Ar-H), 7.34–7.40
(m, 4H, Ar-H), 7.47 (t, 2H, J 8.0, Ar-H), 8.15 (d, 2H, J 8.0,
Ar-H). δC 14.4, 21.0, 88.1, 108.1, 116.6, 120.5, 125.6, 128.6,
129.0, 131.3, 139.0, 139.3, 143.9, 151.2, 152.8, 159.3. m/z (ESI)
362 [M + Na]+. (Found: C 74.38, H 5.08, N 20.54. Calc. for
C21H17N5: C 74.32, H 5.05, N 20.63%.)
Whitesolid. Mp168–170◦C. δH 1.88(s, 3H, CH3), 7.27–7.30(m,
3H, Ar-H, NH2), 7.48–7.53 (m, 3H, Ar-H), 7.59–7.69 (m, 3H,
Ar-H), 8.16 (d, 2H, J 8.0, Ar-H). δC 14.7, 88.3, 108.3,
116.7, 120.8, 126.0, 127.9, 128.8, 129.4, 130.1, 130.9, 133.6,
136.5, 139.2, 144.0, 151.2, 151.5, 159.6. m/z (ESI) 382, 384
[M + Na]+. (Found: C 66.79, H 3.99, N 19.35. Calc. for
C20H14ClN5: C 66.76, H 3.92, N 19.46%.)
6-Amino-5-cyano-4-(4-methoxyphenyl)-3-methyl-
1-phenylpyrazolo[3,4-b]pyridine (4g)
6-Amino-4-(3-bromophenyl)-5-cyano-3-methyl-
1-phenylpyrazolo[3,4-b]pyridine (4m)
White solid. Mp 188–190◦C (lit.[12] 197◦C). δH 1.90 (s, 3H,
CH3), 3.83 (s, 3H, OCH3), 7.10 (d, 2H, J 8.4, Ar-H), 7.15 (br
s, 2H, NH2), 7.26 (t, 1H, J 7.2, Ar-H), 7.44–7.49 (m, 4H, Ar-
H), 8.15 (d, 2H, J 8.0, Ar-H). δC 14.6, 55.4, 88.1, 108.3, 113.9,
116.8, 120.5, 125.6, 126.1, 129.0, 130.3, 139.0, 143.9, 151.2,
152.6, 159.4, 160.3. m/z (ESI) 378 [M + Na]+.
Whitesolid. Mp167–169◦C. δH 1.88(s, 3H, CH3), 7.27–7.31(m,
3H, Ar-H, NH2), 7.48–7.58 (m, 4H, Ar-H), 7.78–7.82 (m, 2H,
Ar-H), 8.16 (d, 2H, J 7.6, Ar-H). δC 14.7, 88.3, 108.3,
116.7, 120.9, 122.0, 126.1, 128.3, 129.5, 131.1, 131.6, 133.0,
136.7, 139.2, 144.0, 151.1, 151.5, 159.6. m/z (ESI) 426, 428
[M + Na]+. (Found: C 59.51, H 3.53, N 17.25. Calc. for
C20H14BrN5: C 59.42, H 3.49, N 17.32%.)
6-Amino-5-cyano-3-methyl-4-(4-dimethylaminophenyl)-
1-phenylpyrazolo[3,4-b]pyridine (4h)
6-Amino-5-cyano-3-methyl-4-(3-methylphenyl)-
1-phenylpyrazolo[3,4-b]pyridine (4n)
Yellow solid. Mp 197–198◦C (lit.[15,31] 189–190◦C). δH 2.00 (s,
3H, CH3), 3.00 (s, 6H, N(CH3)2), 6.84 (d, 2H, J 8.8, Ar-H),
7.14 (br s, 2H, NH2), 7.27 (t, 1H, J 7.2, Ar-H), 7.36 (d, 2H, J
8.8, Ar-H), 7.49 (t, 2H, J 8.0, Ar-H), 8.18 (d, 2H, J 8.0, Ar-H).
δC 15.4, 88.0, 108.5, 111.6, 117.6, 120.8, 120.9, 125.9, 129.4,
130.5, 139.4, 144.4, 151.4, 151.7, 153.8, 159.9. m/z (ESI) 391
[M + Na]+.
White solid. Mp 151–153◦C. δH 1.86 (s, 3H, CH3), 2.40 (s, 3H,
CH3), 7.23 (br s, 2H, NH2), 7.26–7.33 (m, 3H, Ar-H), 7.38 (d,
1H, J 8.0, Ar-H), 7.44–7.51 (m, 3H, Ar-H), 8.17 (d, 2H, J 7.6,
Ar-H). δC 14.7, 21.4, 88.3, 108.4, 116.9, 120.8, 126.0, 126.1,
128.8, 129.4, 130.7, 134.4, 138.2, 139.3, 144.2, 151.5, 153.2,
159.7. m/z (ESI) 362 [M + Na]+. (Found: C 74.42, H 5.01, N
20.57. Calc. for C21H17N5: C 74.32, H 5.05, N 20.63%.)
6-Amino-5-cyano-3-methyl-4-(pyridin-4-yl)-
1-phenylpyrazolo[3,4-b]pyridine (4i)
6-Amino-5-cyano-3-methyl-4-(pyridin-3-yl)-
1-phenylpyrazolo[3,4-b]pyridine (4o)
Pale yellow solid. Mp 295–296◦C. δH 1.86 (s, 3H, CH3), 7.29
(t, 1H, J 7.2, Ar-H), 7.40 (br s, 2H, NH2), 7.50 (t, 2H, J 8.0,
Ar-H), 7.61 (d, 2H, J 5.6, C5H4N), 8.15 (d, 2H, J 8.0,Ar-H), 8.80
(d, 2H, J 5.6, C5H4N). δC 14.6, 87.8, 107.7, 116.4, 120.9, 123.8,
126.2, 129.5, 139.1, 142.4, 143.9, 150.0, 150.3, 151.5, 159.5.
m/z (ESI) 349 [M + Na]+. (Found: C 69.98, H 4.35, N 25.66.
Calc. for C19H14N6: C 69.92, H 4.32, N 25.75%.)
White solid. Mp 194–196◦C. δH 1.88 (s, 3H, CH3), 7.30 (t, 1H, J
7.2, Ar-H), 7.38 (br s, 2H, NH2), 7.51 (t, 2H, J 7.6, Ar-H), 7.62–
7.65 (m, 1H, C5H4N), 8.06 (d, 1H, J 7.6, C5H4N), 8.17 (d, J 8.0,
2H, Ar-H), 8.78–8.79 (m, 2H, C5H4N). δC 14.8, 88.7, 108.5,
116.7, 120.9, 123.8, 126.1, 129.5, 130.6, 137.0, 139.2, 144.1,
149.1, 149.5, 151.2, 151.5, 159.6. m/z (ESI) 349 [M + Na]+.
(Found: C 69.96, H 4.38, N 25.66. Calc. for C19H14N6: C 69.92,
H 4.32, N 25.75%.)
6-Amino-5-cyano-3-methyl-4-(3-nitrophenyl)-1-phenyl-
pyrazolo[3,4-b]pyridine (4j)
6-Amino-5-cyano-4-(2-fluorophenyl)-3-methyl-
Pale yellow solid. Mp 151–153◦C. δH 1.84 (s, 3H, CH3), 7.28
(t, 1H, J 7.6, Ar-H), 7.31 (br s, 2H, NH2), 7.49 (t, 2H, J 8.0,
Ar-H), 7.88 (t, 1H, J 8.0, Ar-H), 8.04 (d, 1H, J 7.2, Ar-H),
8.15 (d, 2H, J 8.0, Ar-H), 8.41–8.43 (m, 2H, Ar-H). δC 14.4,
88.1, 108.0, 116.2, 120.6, 123.7, 124.6, 125.7, 129.1, 130.4,
135.4, 135.7, 138.8, 143.5, 147.7, 149.9, 151.2, 159.2. m/z (ESI)
393 [M + Na]+. (Found: C 64.91, H 3.86, N 22.60. Calc. for
C20H14N6O2: C 64.86, H 3.81, N 22.69%.)
1-phenylpyrazolo[3,4-b]pyridine (4p)
Pale yellow solid. Mp 158–160◦C. δH 1.87 (s, 3H, CH3), 7.27 (t,
1H, J 7.6,Ar-H), 7.31 (br s, 2H, NH2), 7.39–7.50 (m, 4H,Ar-H),
7.56–7.65 (m, 2H,Ar-H), 8.14 (d, 2H, J 8.0,Ar-H). δC 13.3, 88.8,
108.2, 115.9, 116.0, 116.1, 120.6, 121.6, 121.7, 124.9, 125.8,
129.1, 131.1, 132.4, 132.5, 138.8, 143.5, 146.1, 151.1, 157.3,
159.2, 159.7. m/z (ESI)366[M + Na]+. (Found:C70.01, H4.12,
N 20.32. Calc. for C20H14FN5: C 69.96, H 4.11, N 20.40%.)

388
X. Zhang et al.
6-Amino-4-(2-chlorophenyl)-5-cyano-3-methyl-
1-phenylpyrazolo[3,4-b]pyridine (4q)
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C. A. Ramsden) 1996, Vol. 7, p. 283 (Pergamon: Oxford).
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doi:10.1055/S-1994-22729
[12] J. Quiroga, M.Alvarado, B. Insuasty, R. Moreno, E. Ravina, I. Estevez,
R. H. de Almedia, J. Heterocycl. Chem. 1999, 36, 1311.
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[15] S. Zhu, S. Tu, T. Li, X. Zhang, S. Ji, Y. Zhang, Chin. J. Org. Chem.
2005, 25, 987 (in Chinese).
Pale yellow solid. Mp 191–193◦C (lit.[15] 198–199◦C). δH 1.78
(s, 3H, CH3), 7.27 (t, 1H, J 7.2, Ar-H), 7.33 (br s, 2H, NH2),
7.48 (t, 2H, J 8.0, Ar-H), 7.52–7.62 (m, 3H, Ar-H), 7.70 (d, 1H,
J 7.6, Ar-H), 8.15 (d, 2H, J 8.0, Ar-H). δC 13.0, 88.4, 108.0,
115.8, 120.5, 125.7, 127.7, 129.1, 129.7, 130.5, 131.4, 131.6,
133.1, 138.9, 143.5, 149.4, 151.1, 159.3. m/z (ESI) 382, 384
[M + Na]+.
6-Amino-4-(2-bromophenyl)-5-cyano-3-methyl-
1-phenylpyrazolo[3,4-b]pyridine (4r)
Pale yellow solid. Mp 188–191◦C. δH 1.77 (s, 3H, CH3), 7.27
(t, 1H, J 7.2, Ar-H), 7.33 (br s, 2H, NH2), 7.46–7.60 (m, 5H,
Ar-H), 7.85 (d, 1H, J 8.0, Ar-H), 8.15 (d, 2H, J 8.0, Ar-H). δC
13.0, 88.3, 107.9, 115.8, 120.5, 121.3, 125.7, 128.2, 129.1, 130.3,
131.6, 132.7, 135.2, 138.9, 143.5, 151.0, 151.1, 159.3. m/z (ESI)
426, 428 [M + Na]+. (Found: C 59.49, H 3.54, N 17.25. Calc.
for C20H14BrN5: C 59.42, H 3.49, N 17.32%.)
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J. Heterocycl. Chem. 2007, 44, 811.
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doi:10.1080/00397910801929804
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1098-1128(200007)20:4<304::AID-MED3>3.0.CO;2-8
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[20] R. V. A. Orru, M. Greef, Synthesis 2003, 1471. doi:10.1055/
S-2003-40507
[21] A. Domling, I. Ugi, Angew. Chem. Int. Ed. 2000, 39, 3168.
doi:10.1002/1521-3773(20000915)39:18<3168::AID-ANIE3168>
3.0.CO;2-U
6-Amino-5-cyano-3-methyl-4-(2-nitrophenyl)-
1-phenylpyrazolo[3,4-b]pyridine (4s)
Pale yellow solid. Mp 196–198◦C. δH 1.76 (s, 3H, CH3), 7.30 (t,
1H, J 6.8, Ar-H), 7.38 (br s, 2H, NH2), 7.51 (t, 2H, J 8.0, Ar-H),
7.75 (d, 1H, J 7.2,Ar-H), 7.88–8.01 (m, 2H,Ar-H), 8.17 (d, 2H, J
7.6, Ar-H), 8.36 (d, 1H, J 8.0, Ar-H). δC 13.5, 87.9, 108.0, 116.1,
120.9, 125.5, 126.2, 129.2, 129.5, 131.8, 132.0, 135.0, 139.2,
143.6, 147.6, 149.4, 151.5, 159.4. m/z (ESI) 393 [M + Na]+.
(Found: C 64.93, H 3.84, N 22.61. Calc. for C20H14N6O2: C
64.86, H 3.81, N 22.69%.)
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doi:10.1071/CH04060
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doi:10.1139/V04-155
[24] X. Fan,Y. Li, X. Zhang, G. Qu, J. Wang, Can. J. Chem. 2006, 84, 794.
doi:10.1139/V06-070
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2006, 17, 382. doi:10.1002/HC.20221
[26] X. Zhang, X. Fan, H. Niu, J. Wang, Green Chem. 2003, 5, 267.
doi:10.1039/B212155G
[27] J. Wang, X. Fan, X. Zhang, L. Han, Can. J. Chem. 2004, 82, 1192.
doi:10.1139/V04-066
[28] X. Zhang, X. Li, X. Wang, X. Fan, G. Qu, Acta Crystallogr. 2008,
E64, o689.
[29] X. Zhang, X. Li, X. Wang, D. Li, X. Fan, Acta Crystallogr. 2008, E64,
o908.
Acknowledgements
This work was financially supported by the National Natural Science Foun-
dation of China (No. 20772025 and No. 20873036) and Program for
Science & Technology Innovation Talents in Universities of Henan Province
(No. 2008HASTIT006).
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