An efficient synthesis of new class of pyrazolo[3,4-b]pyridine-6-one derivatives by a novel cascade reaction

Article abstract of DOI:10.1002/jhet.5570440506

(Chemical Equation Presented) A novel cascade reaction of 4-arylidene-2-phenyl-1,3-oxazol-5(4H)-one with 3-methyl-l-phenyl-1H-pyrazol-5- amine was described and a number of new pyrazolo[3,4-b]pyridine-6-one derivatives were synthesized. This new protocol has the advantages of shorter time, higher yields, and lower cost as well as easier operation.

Full text of DOI:10.1002/jhet.5570440506

Sep-Oct 2007
1013
An Efficient Synthesis of New Class of Pyrazolo[3,4-b]pyridine-6-
one Derivatives by A Novel Cascade Reaction
Feng Shi, Junyong Zhang, Shujiang Tu,* Runhong Jia, Yan Zhang, Bo Jiang, Hong Jiang
Department of Chemistry, Xuzhou Normal University, Key Laboratory of Biotechnology for Medicinal Plant,
Xuzhou, Jiangsu, 221116, P. R. China
Received September 28, 2006
H
N
Ph
Ph
N
O
H2N
+
O
N
O
N
N
glycol / HOAc
MWI
N
Ph
O
N
CH3
H
Ph
Ar
CH3
Ar
A novel cascade reaction of 4-arylidene-2-phenyl-1,3-oxazol-5(4H)-one with 3-methyl-1-phenyl-1H-
pyrazol-5-amine was described and a number of new pyrazolo[3,4-b]pyridine-6-one derivatives were
synthesized. This new protocol has the advantages of shorter time, higher yields, and lower cost as well as
easier operation.
J. Heterocyclic Chem., 44, 1013 (2007).
product of one reaction is preprogrammed to be the
starting material for the next one in a domino-like process
[11]. Such methods enable the rapid assembly of complex
molecular architectures from simple starting materials
[12,13]. Unlike stepwise bond formation toward a target
molecule, such process has the advantages of greatly
enhanced synthetic efficiency, while generating less waste
and minimizing the excessive handling. Hence, there is an
ongoing demand for new types of cascade reaction in the
synthesis of natural products and other compounds having
useful properties.
In the context of our interest in the design and
development of useful tactics for the synthesis of
nitrogen–contained heterocycles [14], in this paper, we
wish to report an efficient synthesis of a new series of
N-(4-aryl-4,5,6,7-tetrahydro-3-methyl-6-oxo-1-phenyl-
1H-pyrazolo[3,4-b]pyridin-5-yl)benzamides 3 by a
novel cascade reaction. To the best of our
knowledge, the synthesis of pyrazolo[3,4-b]pyridine-
6-ones substituted by benzamide in 5-position has
seldom been reported.
INTRODUCTION
Pyrazolo[3,4-b]pyridines are attractive targets in
organic synthesis due to their significant biological and
pharmacological properties. For example, a number of
pyrazolo[3,4-b]pyridines display interesting anxiolytic
activity [1] (e.g. tracazolate [2]), are potentially
biologically active compounds as new inhibitors of
xantine oxidases [3]. Besides, they have been proved to be
active against Gram positive and Gram negative bacteria
[4] and as cholesterol formation-inhibiting compounds
[5]. More importantly, they are also promising for the
treatment of cataracts associated with diabetes [6]. In
addition, these compounds also exhibit interesting
agricultural activities [7]. Recent search of literature
reveals that some pyrazolo[3,4-b]pyridines have been
identified as potent, selective CDK inhibitors and as
potent inhibitors of glycogen synthase kinase-3 [8].
Due to their diverse biological activities, several groups
have been interested in the synthesis of derivatives of this
structural type. For example, Falcó and co-workers [9]
have reported the synthesis of pyrazolo[3,4-b]pyridine-6-
ones by treatment of hydrazine or alkyl substituted
hydrazine (RNHNH2) with 2-methoxy-6-oxo-1,4,5,6-
tetrahydropyridine-3-carbonitrile, which in advance were
synthesized by the reaction of ꢀ,ꢁ-unsaturated ester with
malononitrile in NaOMe/MeOH. Goda et al [10] have
reported the synthesis of pyrazolo[3,4-b]pyridines through
three steps. However, these synthetic methods have the
disadvantages of involving multi-step reactions, drastic
reaction conditions, longer synthetic route and reaction
time. Therefore, the development of simple and facile
methods for the preparation of pyrazolo[3,4-b]pyridine
derivatives is still strongly desirable.
RESULTS AND DISCUSSION
The desired products 3 were easily obtained by
treatment of 4-arylidene-2-phenyl-1,3-oxazol-5(4H)-ones
1, which in advance were conveniently prepared
following a literature procedure [15], with an equimolar
amount of 3-methyl-1-phenyl-1H-pyrazol-5-amine 2 in
the presence of ethylene glycol and glacial acetic acid
under MWI (Scheme 1).
In order to search for the optimum reaction condition,
different organic solvents such as ethylene glycol, glacial
acetic acid, DMF and mixed solvent of ethylene glycol
with glacial acetic acid were tested in the synthesis of 3a
at 100 °C under MWI. As shown in Table 1, we could see
Cascade reactions are powerful synthetic tools that
involve sequential bond-forming events in which the

1014
F. Shi, J. Zhang, S. Tu, R. Jia, Y. Zhang, B. Jiang, H. Jiang
Vol 44
Table 1
the reaction in the mixed solvent of ethylene glycol with
glacial acetic acid (the preferred volume ratio is 2:1) gave
the best result (Entry 5, Table 1).
Solvent optimization for the synthesis of 3a under MWI
Entry
Solvent
Time/min
Yield/%
Moreover, to further optimize the reaction temperature,
the synthesis of 3a was performed in the mixed solvent of
ethylene glycol with glacial acetic acid (2:1, V/V) at the
temperatures ranging from 100 °C to 160 °C in the
increment of 10 °C each time at 300 W. As illustrated in
Table 2, when the temperature was increased from 100 °C
to 140 °C, the yield of product 3a was obviously
improved. However, no significant increase in the yield of
product 3a was observed as the reaction temperature was
raised from 140 °C to 160 °C. Therefore, the temperature
of 140 °C was chosen for all further microwave-assisted
reactions.
The power of microwave irradiation was optimized by
carrying out the same reaction of synthesizing 3a at the
powers of 50, 100, 150, 200, 250 and 300 W respectively,
using mixed ethylene glycol with glacial acetic acid as
solvent (2:1, V/V) at 140 °C (Table 3). The results
indicated that microwave irradiation at 200 W gave the
highest yield (Entry 4, Table 3). Hence, microwave power
of 200 W was selected as the optimum power.
1
2
3
4
5
6
DMF
8
8
8
7
7
7
37
46
52
61
68
65
HOAc
glycol
glycol/HOAc(3:1)
glycol/HOAc (2:1)
glycol/HOAc (1:1)
Table 2
Temperature optimization for the synthesis of 3a under MWI
Temp / °C
100
110
Time / min
Yield / %
7
6
6
6
5
5
4
68
72
73
78
85
85
84
120
130
140
150
160
Table 3
Power optimization for the synthesis of 3a under MWI
Under these optimized reaction conditions, we synthe-
sized a series of products 3 with this simple reaction
procedure. The results were summarized in Table 4.
Additionally, the synthesis of 3a under conventional
heating and MWI was compared to demonstrate the
specific microwave effect that might be involved in the
reaction. The reaction under conventional heating
conditions remained largely incomplete in very low yields
after a short reaction period (4 min).
Entry
Power/W
Time/min
Yield/%
1
2
3
4
5
6
50
5
5
5
5
5
5
35
56
76
91
87
85
100
150
200
250
300
Instead, the same reaction under MWI exhibited
remarkable advantages over the conventional heating by
not only significantly reducing the reaction time, but also
improving the reaction yield dramatically.
To examine the efficiency and applicability of the novel
cascade reaction, various aldehydes were tested. Results
indicate that this protocol can be applied to aromatic
aldehydes either with electron-withdrawing groups (such
as nitro group) or with electron-donating groups (such as
Scheme 1
Ph
Ph
H
N
O
H2N
O
N
O
N
N
O
glycol/HOAc
MWI
N
Ph
N
+
Ph
N
H
CH3
CH3
Ar
Ar
1
2
3
Table 4
Physical data of products 3
Entry
1
2
3
4
5
6
7
8
Product
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
Ar
Time / min
Yield / %
91
88
Mp / °C
242-243
255-257
245-247
261-263
265-267
264-266
268-270
255-257
267-269
281-283
279-281
269-270
234-236
4-BrC6H4
4-ClC6H4
4-FC6H4
2,4-Cl2C6H3
3,4-Cl2C6H3
4-CH3OC6H4
C6H4
3-NO2C6H4
4-CH3C6H4
3,4-(OCH2O)C6H3
2-CH3OC6H4
5
4
4
5
5
6
6
5
6
6
6
5
6
90
85
87
82
83
86
81
79
9
10
11
12
13
77
82
3,4,5-(CH3O)3C6H2
3,4-(CH3O)2C6H3
3m
83

Sep-Oct 2007
An Efficient Synthesis of New Class of Pyrazolo[3,4-b]pyridine-6-one Derivatives
1015
alkoxyl group). However, the desired results were not
obtained when aliphatic aldehydes and heterocyclic
aldehydes were employed.
In summary, we have disclosed a novel cascade
reaction that offered a simple and efficient route for the
synthesis of a new type of highly functionalized
pyrazolo[3,4-b]pyridin-6-one derivatives. This method
has the advantages of shorter reaction time, higher yields
as well as convenient operation. Most importantly, we
have successfully introduced a benzamido group in the 5-
position of pyrazolo[3,4-b]pyridine-6-ones. This new
series of pyrazolo[3,4-b]pyridin-6-one derivatives may
prove to be of biological interest and provide new class of
biologically active compounds for biomedical screening.
An extension of this work is currently under investigation.
1
All the products were characterized by IR, H NMR
spectra and elemental analyses. The structure of 3b was
also determined by X-ray crystallography (Figure 1) [16].
Although the detailed mechanism of the reaction has not
been established in experimental manner, the formation of
3 could be explained by a reaction sequence presented in
Scheme 2. The amine attacks the reactive lactone and then
the imidate tautomer of the new amide (an open hetero-
triene system) undergoes a symmetry allowed electrocyclic
ring closure to a cyclic hetero-diene intermediate, which
gives the product after tautomerization.
EXPERIMENTAL
All reactions were performed in a monomodal EmrysTM
Creator from Personal Chemistry, Uppsala, Sweden. Melting
points were determined in open capillaries and are uncorrected.
IR spectra were recorded on a FT-IR-tensor 27 spectrometer. 1H
NMR spectra were measured on a DPX 400 MHz spectrometer
using TMS as an internal standard and DMSO-d6 as solvent.
Elemental analysis was determined by using a Perkin-Elmer
240c elemental analysis instrument.
General Procedure for 4-arylidene-2-phenyl-1,3-oxazol-
5(4H)-one (1). A mixture of aromatic aldehyde (2 mmol),
hippuric acid (2 mmol) and acetic anhydride (0.5 mL) was added
to a 10 mL reaction vessel of the monomodal EmrysTM Creator
microwave synthesizer and allowed to react under microwave
irradiation at 180 W power and 120°C for 4-7 minutes. The
reaction mixture was cooled to room temperature, then poured
into water (50 mL), filtered to give crude product, which was
further purified by recrystallization from EtOH.
Scheme 2
Ar
Ar
O
N
O
N
O
+ H+
Ph
Ph
HO
+
Ar
Ar
H3C
N
H3C
N
O
N
O
Ph
N
Ph
..
+
N
N
N
NH2
HO
OH
H2
Ph
+
Ph
Ar
Ar
Ph
H3C
N
H3C
N
N
NHCOPh
O
- H+
O
OH
..
N
N
N
N
H
H
Ph
Ph
General Procedure for N-(4-aryl-4,5,6,7-tetrahydro-3-
methyl-6-oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)ben-
zamide (3). The reactions were performed in a 10 mL EmrysTM
reaction vial, a 4-arylidine-2-phenyl-1,3-oxazol-5(4H)-ones 1 (1
mmol), 3-methyl-1-phenyl-1H-pyrazol-5-amine 2 (1 mmol),
ethylene glycol and glacial acetic acid (2 mL) (2:1, V/V) were
mixed and then capped. The mixture was irradiated at 200 W at
140 °C for a given time. The reaction mixture was cooled to
room temperature and poured into water (50 mL), filtered to
Ar
H3C
NHCOPh
OH
electrocyclization
N
N
N
Ph
Ar
Ar
H3C
H3C
NHCOPh
OH
NHCOPh
O
N
N
N
N
N
N
H
give the crude product, which was further
purified by
Ph
Ph
recrystallization from EtOH (3a-3m). All the products were
characterized by IR, 1H NMR spectral data.
N-(4-(4-bromophenyl)-4,5,6,7-tetrahydro-3-methyl-6-oxo-1-
phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3a). This
compound was obtained according to above general procedure;
ir (potassium bromide): 3369, 3145, 3069, 2923, 1706, 1642,
1577, 1541, 813, 761, 690; 1H nmr (DMSO-d6) (ꢀ, ppm): 11.10
(s, 1H, NH), 7.94 (d, 1H, NH, J = 6.8 Hz), 7.78 (d, 2H, ArH, J =
7.2 Hz), 7.62-7.37 (m, 10H, ArH), 6.94 (d, 2H, ArH, J = 8.0
Hz), 5.30 (m, 1H, CH), 4.58 (d, 1H, CH, J = 7.6 Hz), 2.03 (s,
3H, CH3). Anal calcd. for C26H21BrN4O2, C, 62.28; H, 4.22; N,
11.17. Found: C, 62.41; H, 4.05; N, 11.28
N-(4-(4-chlorophenyl)-4,5,6,7-tetrahydro-3-methyl-6-oxo-1-
phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3b). This
compound was obtained according to above general procedure;
ir (potassium bromide): 3369, 3146, 3068, 2924, 1707, 1642,
1
1578, 1517, 817, 762, 691; H nmr (DMSO-d6) (ꢀ, ppm): 11.08
(s, 1H, NH), 7.89 (d, 1H, NH, J = 6.8 Hz), 7.79 (d, 2H, ArH, J =
Figure 1 ORTEP diagram of 3b

1016
F. Shi, J. Zhang, S. Tu, R. Jia, Y. Zhang, B. Jiang, H. Jiang
Vol 44
1
7.2 Hz), 7.62 (d, 2H, ArH, J = 7.6 Hz), 7.58-7.33 (m, 8H, ArH),
7.01(d, 2H, ArH, J = 8.4 Hz), 5.31 (m, 1H, CH), 4.60 (d, 1H,
CH, J = 7.6 Hz), 2.03 (s, 3H, CH3). Anal calcd. for
C26H21ClN4O2, C, 68.34; H, 4.63; N, 12.26. Found: C, 68.51; H,
4.43; N, 12.42.
1578, 1529, 808, 754, 693; H nmr (DMSO-d6) (ꢀ, ppm): 10.89
(s, 1H, NH), 8.73 (d, 1H, NH, J = 8.8 Hz), 8.28 (s, 1H, ArH),
8.14 (d, 1H, ArH, J = 8.0 Hz), 7.88 (d, 1H, ArH, J = 7.2 Hz),
7.72-7.39 (m, 11H, ArH), 5.11 (m, 1H, CH), 4.57 (d, 1H, CH, J
= 7.2 Hz), 1.50 (s, 3H, CH3). Anal calcd. for C26H21N5O4, C,
66.80; H, 4.53; N, 14.98. Found: C, 66.71; H, 4.64; N, 14.77.
N-(4,5,6,7-tetrahydro-3-methyl-6-oxo-1-phenyl-4-p-tolyl-1H-
pyrazolo[3,4-b]pyridin-5-yl)benzamide (3i). This compound
was obtained according to above general procedure; ir
(potassium bromide): 3372, 3137, 3059, 2922, 1703, 1639,
N-(4-(4-fluorophenyl)-4,5,6,7-tetrahydro-3-methyl-6-oxo-1-
phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3c). This
compound was obtained according to above general procedure;
ir (potassium bromide): 3374, 3148, 3070, 2925, 1706, 1642,
1
1578, 1507, 814, 763, 692; H nmr (DMSO-d6) (ꢀ, ppm): 11.10
1
(s, 1H, NH), 7.83 (d, 1H, NH, J = 6.8 Hz), 7.77 (d, 2H, ArH, J =
7.2 Hz), 7.61 (d, 2H, ArH, J = 7.6 Hz), 7.56-7.37 (m, 6H, ArH),
7.14-6.70 (m, 4H, ArH), 5.29 (m, 1H, CH), 4.60 (d, 1H, CH, J =
7.6 Hz), 2.03 (s, 3H, CH3). Anal calcd. for C26H21FN4O2, C,
70.90; H, 4.81; N, 12.72. Found: C, 70.75; H, 4.69; N, 12.53
N-(4-(2,4-dichlorophenyl)-4,5,6,7-tetrahydro-3-methyl-6-oxo-
1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3d).
This compound was obtained according to above general
procedure; ir (potassium bromide): 3382, 3125, 3068, 2921,
1577, 1542, 813, 756, 690; H nmr (DMSO-d6) (ꢀ, ppm): 10.80
(s, 1H, NH), 8.68 (d, 1H, NH, J = 8.8 Hz), 7.75 (d, 2H, ArH, J =
6.8 Hz), 7.57 (d, 2H, ArH, J = 7.2 Hz), 7.54-7.38 (m, 6H, ArH),
7.25 (d, 2H, ArH, J =8.0 Hz), 7.14 (d, 2H, ArH, J = 8.0 Hz),
5.01 (m, 1H, CH), 4.40 (d, 1H, CH, J = 8.0 Hz), 2.27 (s, 3H,
CH3), 1.48 (s, 3H, CH3). Anal calcd. for C27H24N4O2, C, 74.29;
H, 5.54; N, 12.84. Found: C, 74.42; H, 5.34; N, 12.67.
N-(4-(benzo[d][1,3]dioxol-5-yl)-4,5,6,7-tetrahydro-3-methyl-
6-oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide
(3j). This compound was obtained according to above general
procedure; ir (potassium bromide): 3297, 3162, 3066, 2921,
1702, 1638, 1601, 1545, 810, 758, 692; 1H nmr (DMSO-d6) (ꢀ,
ppm): 10.78 (s, 1H, NH), 8.66 (d, 1H, NH, J = 8.8 Hz), 7.76 (d,
2H, ArH, J = 7.2 Hz), 7.57-7.35 (m, 8H, ArH), 6.94 (s, 1H,
ArH), 6.85-6.82 (m, 2H, ArH), 5.99 (s, 2H, OCH2O), 5.01 (m,
1H, CH), 4.32 (d, 1H, CH, J = 7.6 Hz), 1.55 (s, 3H, CH3). Anal
calcd. for C27H22N4O4, C, 69.52; H, 4.75; N, 12.01. Found: C,
69.38; H, 4.92; N, 11.92.
1
1704, 1650, 1576, 1546, 823, 759, 691; H nmr (DMSO-d6) (ꢀ,
ppm): 11.08 (s, 1H, NH), 7.89 (d, 1H, NH, J = 6.8 Hz), 7.79 (d,
1H, ArH, J = 7.2 Hz), 7.62 (d, 2H, ArH, J = 7.6 Hz), 7.58-7.33
(m, 8H, ArH), 7.01(d, 2H, ArH, J = 8.4 Hz), 5.31 (m, 1H, CH),
4.60 (d, 1H, CH, J = 7.6 Hz), 2.00 (s, 3H, CH3). Anal calcd. for
C26H20Cl2N4O2, C, 63.55; H, 4.10; N, 11.40. Found: C, 63.38;
H, 4.22; N, 11.21.
N-(4-(3,4-dichlorophenyl)-4,5,6,7-tetrahydro-3-methyl-6-oxo-
1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3e).
This compound was obtained according to above general
procedure; ir (potassium bromide): 3328, 3165, 3062, 2938,
1699, 1635, 1599, 1538, 892, 731, 692; 1H nmr (DMSO-d6) (ꢀ,
ppm): 10.84 (s, 1H, NH), 8.71 (d, 1H, NH, J = 8.4 Hz), 7.75 (d,
2H, ArH, J = 6.4 Hz), 7.67 (s, 1H, ArH), 7.63-7.52 (m, 6H,
ArH), 7.47 (d, 2H, ArH, J = 7.6 Hz), 7.40 (d, 2H, ArH, J = 6.8
Hz), 5.03 (m, 1H, CH), 4.44 (d, 1H, CH, J = 8.0 Hz), 1.54 (s,
3H, CH3). Anal calcd. for C26H20Cl2N4O2, C, 63.55; H, 4.10; N,
11.40. Found: C, 63.71; H, 4.21; N, 11.25.
N-(4,5,6,7-tetrahydro-4-(2-methoxyphenyl)-3-methyl-6-oxo-
1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3k).
This compound was obtained according to above general
procedure; ir (potassium bromide): 3354, 3136, 3028, 2918,
1
1697, 1643, 1599, 1514, 846, 761, 655; H nmr (DMSO-d6) (ꢀ,
ppm): 10.89 (s, 1H, NH), 8.56 (s, 1H, NH), 7.60 (d, 2H, ArH, J
= 7.2 Hz), 7.58-735 (m, 8H, ArH), 7.23-7.19 (m, 2H, ArH),
7.01-6.81 (m, 2H, ArH), 5.21 (m, 1H, CH), 4.88 (d, 1H, CH, J =
8.0 Hz), 3.54 (s, 3H, OCH3), 1.99 (s, 3H, CH3). Anal calcd. for
C27H24N4O3, C, 71.67; H, 5.35; N, 12.38. Found: C, 71.53; H,
5.50; N, 12.19.
N-(4,5,6,7-tetrahydro-4-(3,4,5-trimethoxyphenyl)-3-methyl-6-
oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3l).
This compound was obtained according to above general
procedure; ir (potassium bromide): 3328, 3130, 3064, 2998,
N-(4-(4-methoxyphenyl)-4,5,6,7-tetrahydro-3-methyl-6-oxo-
1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3f).
This compound was obtained according to above general
procedure; ir (potassium bromide):: 3318, 3162, 3052, 2933,
1
1696, 1643, 1550,1521, 824, 797, 695; H nmr (DMSO-d6)
(ꢀ, ppm): 10.04 (s, 1H, NH), 8.04 (d, 1H, NH, J = 8.0 Hz),
7.64-7.52 (m, 8H, ArH), 7.38-7.25 (m, 4H, ArH), 6.95 (d,
2H, ArH, J = 8.8 Hz), 5.12 (m, 1H, CH), 4.62 (d, 1H, CH, J =
7.2 Hz), 3.76 (s, 3H, OCH3), 2.24 (s, 3H, CH3). Anal calcd.
for C27H24N4O3, C, 71.67; H, 5.35; N, 12.38. Found: C,
71.81; H, 5.23; N, 12.19.
N-(4,5,6,7-tetrahydro-3-methyl-6-oxo-1,4-diphenyl-1H-pyra-
zolo[3,4-b]pyridin-5-yl)benzamide (3g). This compound was
obtained according to above general procedure; ir (potassium
bromide): 3342, 3163, 3061, 2946, 1697, 1643, 1578, 1547, 818,
754, 693; 1H nmr (DMSO-d6) (ꢀ, ppm): 10.83 (s, 1H, NH), 8.70
(d, 1H, NH, J = 8.8 Hz), 7.74 (d, 2H, ArH, J = 6.8 Hz), 7.59-
7.50 (m, 9H, ArH), 7.46-7.24 (m, 4H, ArH), 5.05 (m, 1H, CH),
4.40 (d, 1H, CH, J = 7.2 Hz), 1.46 (s, 3H, CH3). Anal calcd. for
C26H22N4O2, C, 73.92; H, 5.25; N, 13.26. Found: C, 73.76; H,
5.38; N, 13.12.
1
1716, 1636, 1574, 1531, 825, 762, 634; H nmr (DMSO-d6) (ꢀ,
ppm): 10.79 (s, 1H, NH), 8.66 (d, 1H, NH, J = 8.8 Hz), 7.75 (d,
2H, ArH, J = 7.6 Hz), 759-7.35 (m, 8H, ArH), 6.68 (s, 2H, ArH),
5.01(m, 1H, CH), 4.35 (d, 1H, CH, J = 7.6 Hz), 3.71 (s, 6H,
2OCH3), 3.62 (s, 3H, OCH3), 1.60 (s, 3H, CH3). Anal calcd. for
C29H28N4O5, C, 67.96; H, 5.51; N, 10.93. Found: C, 68.06; H,
5.72; N, 11.13.
N-(4,5,6,7-tetrahydro-4-(3,4-dimethoxyphenyl)-3-methyl-6-
oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide
(3m). This compound was obtained according to above general
procedure; ir (potassium bromide): 3345, 3132, 3018, 2991,
1699, 1643, 1559, 1511, 820, 768, 685; 1H nmr (DMSO-d6) (ꢀ,
ppm): 11.03 (s, 1H, NH), 8ꢀ59 (d, 1H, NH, J = 7.6 Hz), 7.78 (d,
2H, ArH, J = 7.2 Hz), 7.70 (d, 1H, ArH, J = 6.4 Hz), 7.64-7.38
(m, 7H, ArH), 6.83 (d, 1H, ArH, J = 8.4 Hz), 6.58 (s, 1H, ArH),
6.46 (d, 1H, ArH, J = 6.8 Hz), 5.23 (m, 1H, CH), 4.46 (d, 1H,
CH J = 7.2 Hz), 3.69 (s, 3H, OCH3), 3.50 (s, 3H, OCH3), 2.05 (s,
3H, CH3). Anal calcd. for C28H26N4O4, C, 69.70; H, 5.43; N,
11.61. Found: C, 69.88; H, 5.21; N, 11.45.
N-(4,5,6,7-tetrahydro-3-methyl-4-(3-nitrophenyl)-6-oxo-1-
phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (3h). This
compound was obtained according to above general procedure;
ir (potassium bromide): 3362, 3149, 3066, 2977, 1709, 1647,

Sep-Oct 2007
An Efficient Synthesis of New Class of Pyrazolo[3,4-b]pyridine-6-one Derivatives
1017
Bioorg. Med. Chem. Lett. 2004, 12, 1845-1852.
Acknowledgement. We thank the National Natural Science
Foundation of China (No. 20372057, 20672090), the Nature
Science Foundation of the Jiangsu Province (No. BK2006033)
and the Key Item of Natural Science Foundation of Xuzhou
Normal University (No. 05XLA06) for financial supports.
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