A green and efficient synthesis of furo[3,4-e]pyrazolo[3,4-b]-pyridine derivatives in water under microwave irradiation without catalyst

Article abstract of DOI:10.1002/jhet.5570450425

(Chemical Equation Presented) A series of furo[3,4-e]pyrazolo[3,4-b] pyridine analogues of podophylloxin were synthesized via three-component reactions of aldehydes, 3-methyl-1-phenyl-1H-pyrazol-5-amine and tetronic acid in water under microwave irradiation without catalyst. This efficient synthesis not only offers an economical and green synthetic strategy to this class of significant compounds but also enriches the investigations on microwave-assisted synthesis in water.

Full text of DOI:10.1002/jhet.5570450425

Jul-Aug 2008
1103
A Green and Efficient Synthesis of Furo[3,4-e]pyrazolo[3,4-b]-
pyridine Derivatives in Water under Microwave Irradiation
without Catalyst
Feng Shi,a Qian Wang,b Shujiang Tu,*, a Jianfeng Zhou,c Bo Jiang,a Chunmei Li, a
Dianxiang Zhou, a Qingqing Shao a and Longji Cao a
a. School of Chemistry & Chemical Engineering, Xuzhou Normal University, Key Laboratory of Biotechnology
for Medicinal Plant, Xuzhou, Jiangsu, 221116, P. R. China
b. Xuzhou Medical College, Xuzhou, Jiangsu, 221116, P. R. Chin
c. Department of Chemistry, Huaiyin Teacher’s College, Jiangsu Key Laboratory for Chemistry of Low-
Dimensional Materials, Huai’an, Jiangsu, 223300, P. R. China
Received September 28, 2007
R
O
O
N
MWI
H2O
N
+
+
O
RCHO
O
N
N
N
O
Ph
NH2
Ph
1
2
3
4
A series of furo[3,4-e]pyrazolo[3,4-b]pyridine analogues of podophylloxin were synthesized via three-
component reactions of aldehydes, 3-methyl-1-phenyl-1H-pyrazol-5-amine and tetronic acid in water
under microwave irradiation without catalyst. This efficient synthesis not only offers an economical and
green synthetic strategy to this class of significant compounds but also enriches the investigations on
microwave-assisted synthesis in water.
J. Heterocyclic Chem., 45, 1103 (2008).
INTRODUCTION
hypoglycemic, anti-inflammatory, analgesic and anti-
pyritic activities. It is promising that the modifications on
ring A, changed into pyrazole ring, may bring about great
changes in bioactivities.
Tetronic acid derivatives and their metabolites are
interesting and intriguing because of their antibiotic [1],
anticoagulant [2], antiepileptic [3], antifungal [4],
insecticidal [5], analgesic [6] and anti-inflammatory [7]
activities. Recently, these compounds have also been
Very recently, Magedov and co-workers have reported
the synthesis of dihydropyridopyrazole analogues of
podophyllotoxin via multi-component condensations
using triethylamine as catalyst and ethanol as solvent
under traditional heating condition [11]. Moreover, they
have found promising anticancer activity of this new
scaffold, which will arouse more attentions on the
synthesis and pharmacological activities of these types of
compounds. Although the above method offered a
synthetic approach to this class of important compounds,
it still has some disadvantages such as being less
economical and environmentally unfriendly since the
volatile and flammable or toxic organic reagents,
reported
as
HIV-1
protease
inhibitors
[8].
Podophyllotoxin, one of the derivatives of tetronic acid, is
an antitumor lignan that inhibits microtubule assembly.
Attempts to use it for the treatment of human neoplasia
were mostly unsuccessful and were complicated by side
effects. Extensive structural modifications have been
performed in order to obtain more potent and less toxic
anticancer agents [9]. However, most modifications were
performed on ring B and C (Figure 1), and modification
on ring A has had minimal investigation.
triethylamine and ethanol are used. As
a result,
H
N
O
developing a green and efficient method on the synthesis
of pyridopyrazole analogues of podophyllotoxin is of
great significance.
CO
O
A
B
O
In recent years, microwave-assisted synthesis in water
as solvent has become a hot topic of investigation since it
combines the two prominent green chemistry principles of
“safer solvents” and “energy efficiency” [12]. Among the
different solvent alternatives in organic chemistry, water
is extremely inexpensive and nontoxic [13]. In addition to
these general advantages, several benefits for the reaction
are expected when using water as reaction medium for
microwave-superheated protocols. First, water is rapidly
H3CO
OCH3
OCH3
Figure 1. Structure of podophyllotoxin analogue.
Pyrazolo[3,4-b]pyridines are attractive targets in
organic synthesis due to there interesting biological and
pharmacological properties [10] such as vasodialotors,

1104
F. Shi, Q. Wang, S. Tu, J. Zhou, B. Jiang, C. Li, D. Zhou, Q. Shao and L. Cao
Vol 45
heated by microwave irradiation to high reaction
temperatures, enabling water to act as a less polar pseudo-
organic solvent. Second, precise control of the reaction
temperature is easily achieved because of the very high
capacity of water. Third, the lack of flammable properties
makes the use of water safe also with pressurized
exothermic reactions [14].
organic reagents, water was preferred as solvent for all
further microwave-assisted reactions.
In order to optimize the reaction temperature, the
reaction of 1c (1 mmol), 2 (1 mmol) and 3 (1 mmol) was
carried out using water (2 mL) as solvent under MWI
(100 W) at temperatures ranging from 70 to 120 °C, with
an increment of 10 °C each time. Similarly, the crude
product was purified by recrystallization from EtOH. The
results are shown in Table 2. The yield of product 4c was
increased and the reaction time was shortened when the
temperature was increased from 70 °C to 100 °C (Entries
1ꢀ4, Table 2), whereas the yield leveled off when the
temperature was further increased to 110 and 120 °C
(Entries 5ꢀ6, Table 2). So, 100 °C is assigned as the most
suitable reaction temperature. Furthermore, we found that
the yield of this reaction was affected by the volume of
water. The synthesis of 4c was tested in different volumes
of water at 100 °C. The outcomes show that 2.0 mL of
water is optimal as solvent since it generates the highest
yield of 4c.
As
a continuation of our efforts on structural
modification of podophyllotoxin analogue with green and
efficient method [15], we herein report the synthesis of
furo[3,4-e]pyrazolo[3,4-b]pyridine derivatives through
three-component reactions of aldehydes 1, 3-methyl-1-
phenyl-1H-pyrazol-5-amine 2 and tetronic acid 3 in water
under microwave irradiation (MWI) without catalyst
(Scheme 1). This efficient synthesis not only offers an
economical and green synthetic strategy to this class of
significant compounds but also enriches the investigations
on microwave-assisted synthesis in water.
Scheme 1
R
O
Table 2
O
N
MWI
H2O
Temperature optimization for the synthesis of 4c.
N
O
RCHO
O
N
N
N
O
Ph
NH2
Entry
T (oC)
70
Time (min)
Yield (%)
Ph
1
2
3
4
1
2
3
4
5
6
12
11
8
80
85
91
95
95
94
80
90
100
110
120
6
RESULTS AND DISCUSSION
6
To demonstrate the superiority of water as solvent, in
spite of its natural property of being harmless to
environment, we compared the synthesis of 4c in water
with other organic solvents including glycol, DMF,
glacial acetic acid and ethanol. The mixture of 4-
bromophenyl aldehyde 1c (1 mmol), 3-methyl-1-phenyl-
1H-pyrazol-5-amine 2 (1 mmol), tetronic acid 3 (1 mmol)
and corresponding solvent (2 mL) was irradiated under
MWI at 80 °C and 100 W for a given time, then the crude
product was purified by recrystallization from EtOH.
6
Under these optimized reaction conditions (2.0 mL of
water, 100 °C), a series of furo[3,4-b]pyrazolo[4,3-
e]pyridine derivatives 4 were synthesized. The results are
illustrated in Table 3. As shown in Table 3, this protocol
can be applied not only to aromatic aldehydes with either
electron-withdrawing groups (such as nitro or halide
groups) or electron-donating groups (such as alkoxyl
group), but also to heterocyclic and aliphatic aldehydes
with excellent yields under the same conditions.
Therefore, the electronic nature of the substrate has no
significant effect on this reaction.
Table 1
Solvent optimization for the synthesis of 4c.
Entry
Solvent
glycol
water
Time (min)
Yield (%)
Moreover, we also performed the synthesis of 4 in
water at 100 °C under standard heating conditions (SC).
The results (Table 3) reveal that microwave irradiation
efficiently promoted the reactions, resulting in dramatic
reduction of reaction time, from hours to minutes, and
remarkable increase in yields as well.
1
2
3
4
5
12
11
15
16
18
86
85
71
63
60
AcOH
DMF
EtOH
Although the detailed mechanism of the above reaction
remains to be fully clarified, the formation of furo[3,4-b]-
pyrazolo[4,3-e]pyridine derivatives 4 could be explained
The results (Table 1) reveal that water as solvent can
not only improve the yield but also shorten the time of
this reaction. Although the yield of the reaction in glycol
by
a reaction sequence of condensation, addition,
is
a
little higher than that in water, considering
cyclization and dehydration (Scheme 2). First, the
environmental friendliness and avoidance of using toxic
condensation of aldehyde 1 and tetronic acid 3 gave the

Jul-Aug 2008
A Green and Efficient Synthesis of Furo[3,4-e]pyrazolo[3,4-b]pyridine Derivatives in Water
1105
Table 3
Synthesis of 4 in water at 100 °C under MWI and SC.
o
o
Entry
Entry
4
4
1
1
R
R
Time (min)
Time (min)
Yield (%)
Yield (%)
Mp ( C)
Mp ( C)
MWIc
MWIc
2
SCd
SCd
150
MWIc
MWIc
96
SCd
SCd
72
1
4a
1a
4-ClC H
230ꢀ231
1
2
4a
4b
1a
1b
4-ClC66H44
2
2
150
180
96
97
72
73
230ꢀ231
249ꢀ250
4-FC H
2
3
4b
1b
4-FC66H44
4-BrC H
2
1
180
180
180
210
210
180
180
180
180
180
180
210
210
180
180
120
12
210
21
180
18
240
97
95
73
68
249ꢀ250
222ꢀ223
4c
4c
4d
1c
1c
1d
3
4-BrC66H44
C6H5
1
95
68
222ꢀ223
4
3
95
72
216ꢀ218
4
5
4d
1d
C6H5
3
2
95
95
72
74
216ꢀ218
269ꢀ270
4e
1e
3-OCH3-4-OHC6H3
5
4e
4f
1e
1f
3-OCH3-4-OHC6H3
2
95
74
269ꢀ270
6
2,3-(CH3O)2C6H3
2
96
69
243ꢀ244
6
7
4f
1f
2,3-(CH3O)2C6H3
3-NO2C6H4
2
1
96
96
69
71
243ꢀ244
265ꢀ266
4g
1g
7
4g
1g
3-NO2C6H4
1
96
71
265ꢀ266
8
4h
4h
1h
1h
4-NO2C6H4
2
98
70
297ꢀ298
8
4-NO2C6H4
4-OCH3C6H4
4-OCH C H
2,4-Cl C H
4
3
2
3
98
94
70
75
75
77
7
74
297ꢀ298
202ꢀ204
9
4i
4i
1i
1i
9
10
3
94
97
7
202ꢀ204
4j
1j
1
236ꢀ238
3
6
2
6
0
j
k
l
j
k
l
2
Cl C H
1
36 38
250ꢀ251
255ꢀ256
258ꢀ260
126548ꢀ12650
164ꢀ165
11
4k
4l
4m
4nm
4n
1k
1l
1m
1nm
1n
3,4-OCH OC H
2
95
5
2
6
3
2 6
3
3
1
3,4-OCH OC H
4-N(CH ) C H
4-N(CH ) C H
Thiophe3n-2-yl4
CThHi3oCpHheCn-H2-yClH2
CH3CH2CH2CH2
2
4
0
1
12
3
96
72
2
2
6
4
3
6
2
3
4
4
4
6
97
97
97
5
56
13
72
702
70
2
6
143
14
2140
210
2
2
d
c
The time and yields under microwave irradiation conditions. The time and yields under standard heating conditions.
c The time and yields under microwave irradiation conditions. d The time and yields under standard heating conditions.
intermediate product 5. The addition of 2 to 5 then
furnished the intermediate product 6, which upon
intermolecular cyclization and dehydration gave rise to 4.
Scheme 4
O
O
Cl
O
Scheme 2
3
+
N
not isolated
N
H2N
Ph
N
R
O
O
O
O
O
O
O
N
RCHO
1
1a
2
Ph
H2N
CHR
N
O
2
O
Cl
O
N
NH2
Ph
5
3
6
O
O
R
R
O
O
+
C
Cl
[O]
-H2O
O
H
N
N
N
O
N
O
N
N
N
N
N
H
N
N
Ph
Ph
Ph
Ph
4
7
8
For the aim to support the proposed mechanism, the
compound 5a [16] was firstly prepared from p-chloro-
benzaldehyde 1a and tetronic acid 3. Then 5a reacted with
2 to afford product 4a in a yield similar to that obtained in
the one-pot reaction (Scheme 3).
All the products were characterized by IR, 1H NMR and
elemental analyses. Moreover, the structure of 4a, 4d, 4i
and 4m were also established by X-ray crystallography
(Figure 2-5) [18].
Scheme 3
Cl
O
O
N
C
Cl
+
N
N
O
O
H
Ph
H2N
N
N
O
Ph
2
5a
4a
However, p-chlorobenzaldehyde 1a was first condensed
with 2 followed by reaction with tetronic acid 3 failed to
give the target compound 4a. Instead, compounds 8 {Mp
250~251°C (249~251°C) [17]} was obtained (Scheme 4).
Figure 2. ORTEP diagram of 4a.

1106
F. Shi, Q. Wang, S. Tu, J. Zhou, B. Jiang, C. Li, D. Zhou, Q. Shao and L. Cao
Vol 45
hand, this reaction supplies a good example of efficient
microwave-assisted synthesis in water as solvent. In
addition, this method may provide a shortcut for further
investigations on the pharmacological activities of these
types of compounds as important and novel podophyl-
lotoxin analogues.
EXPERIMENTAL
Microwave irradiation was carried out in a monomodal
EmrysTM Creator from Personal Chemistry, Uppsala, Sweden.
Melting points were determined in XT5 apparatus and are
uncorrected. IR spectra were recorded on a FT-IR-Tensor 27
1
spectrometer. H NMR spectra were measured on a DPX 400
spectrometer operating at 400 MHz, using DMSO-d6 as solvent
Figure 3. ORTEP diagram of 4d
and TMS as internal standard.
Elemental analysis was
determined by using a Perkin-Elmer 240c elemental analysis
instrument.ꢀX-Ray crystallographic analysis was performed with
a Siemens SMART CCD and a Semens P4 diffractometer.
General Procedure for the syntheses of compounds 4 with
microwave irradiation. Typically, in a 10 mL EmrysTM reaction
vial, aldehyde 1 (1 mmol), 5-amino-3-methyl-1-phenylpyrazol 2
(1 mmol), tetronic acid 3 (1 mmol) and water (2 mL) were
mixed and then capped. The mixture was irradiated at 150 W
and at 100 °C for a given time. The reaction mixture was cooled
to room temperature and poured into water (50 mL), filtered to
give the crude product, which was further purified by
recrystallization from EtOH.
General Procedure for the syntheses of compounds 4 with
conventional heating. A mixture containing aldehyde 1 (1
mmol), 5-amino-3-methyl-1-phenylpyrazol 2 (1 mmol), tetronic
acid 3 (1 mmol) and water (2.0 mL) was introduced into a 10
mL EmrysTM reaction vial, capped and then stirred at 100 °C (oil
bath temperature) for a given time. The subsequent work-up
procedure was the same as in the microwave irradiation
reactions.
Figure 4. ORTEP diagram of 4i.
4-(4-Chlorophenyl)-3-methyl-1-phenyl-1,7-dihydro-5H-
furo[3,4-b]pyrazolo[4,3-e]pyridine-5-one (4a). This compound
was obtained according to above general procedure; ir (KBr): ꢀ
1
1761, 1582, 1506, 816cm-1; H nmr: ꢀ 8.19 (d, 2H, J=8.0 Hz,
ArH), 7.67 (d, 2H, J=8.0 Hz, ArH), 7.60-7.40 (m, 5H, ArH),
5.50 (s, 2H, CH2), 2.13 (s, 3H, CH3). Anal. calcd for
C21H14ClN3O2: C, 67.12; H, 3.75; N, 11.18; found C, 67.33; H,
3.66; N, 11.38.
4-(4-Fluorophenyl)-3-methyl-1-phenyl-1,7-dihydro-5H-
furo[3,4-b]pyrazolo[4,3-e]pyridine-5-one (4b). This compound
was obtained according to above general procedure; ir (KBr): ꢀ
1756, 1597, 1578, 1512, 830 cm-1; 1H nmr: ꢀ 8.19 (d, 2H, J=7.6
Hz, ArH), 7.66 (d, 2H, J=7.6 Hz, ArH), 7.58-7.39 (m, 5H, ArH),
5.49 (s, 2H, CH2), 2.12 (s, 3H, CH3). Anal. calcd for
C21H14FN3O2: C, 70.19; H, 3.93; N, 11.69; found C, 70.02; H,
3.76; N, 11.85.
Figure 5. ORTEP diagram of 4m.
4-(4-Bromophenyl)-3-methyl-1-phenyl-1,7-dihydro-5H-
furo[3,4-b]pyrazolo[4,3-e]pyridine-5-one (4c). This compound
was obtained according to above general procedure; ir (KBr): ꢀ
In conclusion, we have developed a green and efficient
method on the synthesis of furo[3,4-b]pyrazolo[4,3-
e]pyridine derivatives in water under MWI without
catalyst. This method has the notable advantages over the
existing ones owing to its features of environmental
friendliness, short reaction time, high yield, wide
applicability, low-cost and easy operation. On the other
1
1770, 1577, 1506, 818 cm-1; H nmr: ꢀ 8.18 (d, 2H, J=8.0 Hz,
ArH), 7.78 (d, 2H, J=8.0 Hz, ArH), 7.61 (dd, 2H, J=7.6, 8.4 Hz,
ArH), 7.55 (d, 2H, J=8.4 Hz, ArH), 7.41 (t, 1H, J=7.6 Hz, ArH),
5.49 (s, 2H, CH2), 2.12 (s, 3H, CH3). Anal. calcd for
C21H14BrN3O2: C, 60.02; H, 3.36; N, 10.00; found C, 60.21; H,
3.12; N, 10.13.

Jul-Aug 2008
A Green and Efficient Synthesis of Furo[3,4-e]pyrazolo[3,4-b]pyridine Derivatives in Water
1107
1
4-(4-Phenyl)-3-methyl-1-phenyl-1,7-dihydro-5H-furo[3,4-
b]pyrazolo[4,3-e]pyridine-5-one (4d). This compound was
obtained according to above general procedure; ir (KBr): ꢀ
cm-1; H nmr: ꢀ 8.19 (d, 2H, J=7.6 Hz, ArH), 7.61 (t, 2H, J=7.6
Hz, ArH), 7.40 (t, 1H, J=7.6 Hz, ArH), 7.18 (s, 1H, ArH), 7.13-
7.03 (m, 2H, ArH), 6.18 (s, 2H, CH2), 5.47 (s, 2H, CH2), 2.19 (s,
3H, CH3). Anal. calcd for C22H15N3O4: C, 68.57; H, 3.92; N,
10.90; found C, 68.76; H, 3.78; N, 10.69.
4-[4-(Dimethylamino)phenyl]-3-methyl-1-phenyl-1,7-dihy-
dro-5H-furo[3,4-b]pyrazolo[4,3-e]pyridin-5-one (4l). This
compound was obtained according to above general procedure;
ir (KBr): ꢀ 1760, 1572, 1515, 813 cm-1; H nmr: ꢀ 8.20 (d, 2H,
1
1752, 1584, 1516, 765, 709 cm-1; H nmr: ꢀ 8.19 (d, 2H, J=7.6
Hz, ArH), 7.63-7.41 (m, 8H, ArH), 5.48 (s, 2H, CH2), 2.08 (s,
3H, CH3). Anal. calcd for C21H15N3O2: C, 73.89; H, 4.43; N,
12.31; found C, 74.04.; H, 4.56; N, 12.22.
4-(3-Methoxyl-4-hydroxylphenyl)-3-methyl-1-phenyl-1,7-
dihydro-5H-furo[3,4-b]pyrazolo[4,3-e]pyridine-5-one (4e).
This compound was obtained according to above general
procedure; ir (KBr): ꢀ 3404, 1767, 1653, 1576, 1512, 821, 801,
1
J=8.0 Hz, ArH), 7.60 (d, 2H, J=8.0 Hz, ArH), 7.44-7.37 (m, 3H,
ArH), 6.86 (d, 2H, J=8.8 Hz, ArH), 5.42 (s, 2H, CH2), 3.05 (s,
6H, 2CH3), 2.23 (s, 3H, CH3). Anal. calcd for C23H20N4O2: C,
71.86; H, 5.24; N, 14.57 found C, 71.99; H, 5.13; N, 14.34.
4-(2-Thienyl)-3-methyl-1-phenyl-1,7-dihydro-5H-furo[3,4-b]-
pyrazolo[4,3-e]pyridin-5-one (4m). This compound was
obtained according to above general procedure; ir (KBr): ꢀ
1
703, 709 cm-1; H nmr: ꢀ 9.55 (s, 1H, OH), 8.18 (d, 2H, J=7.6
Hz, ArH), 7.62-6.96 (m, 6H, ArH), 5.45 (s, 2H, CH2), 3.80 (s,
3H, OCH3), 2.20 (s, 3H, CH3). Anal. calcd for C22H17N3O4: C,
68.21; H, 4.42; N, 10.85; found C, 68.08; H, 4.31; N, 110.73.
4-(2,3-Dimethoxyphenyl)-3-methyl-1-phenyl-1,7-dihydro-
5H-furo[3,4-b]pyrazolo[4,3-e]pyridine-5-one (4f). This
compound was obtained according to above general procedure;
ir (KBr): ꢀ 1767, 1586, 1512, 817, 762, 699 cm-1; 1H nmr: ꢀ 8.18
(d, 2H, J=8.0 Hz, ArH), 7.63-7.59 (m, 2H, ArH), 7.41 (t, 1H,
J=8.0 Hz, ArH), 7.29-7.22 (m, 2H, ArH), 6.93-6.91(m, 1H,
ArH), 5.59-5.47(m, 2H, CH2), 3.92 (s, 3H, OCH3), 3.51 (s, 3H,
OCH3), 2.07 (s, 3H, CH3). Anal. calcd for C23H19N3O4: C, 68.82;
H, 4.77; N, 10.47; found C, 68.96; H, 4.76; N, 10.61.
1761, 1579, 1515, 794, 762, 716 cm-1; H nmr: ꢀ 8.18 (d, 2H,
1
J=8.4 Hz, ArH), 7.96 (d, 1H, J=8.4 Hz, ArH), 7.62 (t, 2H, J=8.0
Hz, ArH), 7.46-7.31 (m, 3H, ArH), 5.48 (s, 2H, CH2), 2.23 (s,
3H, CH3). Anal. calcd for C19H15N3O2S: C, 65.31; H, 4.33; N,
12.03 found C, 65.22; H, 4.20; N, 12.14.
4-Butyl-3-methyl-1-phenyl-1,7-dihydro-5H-furo[3,4-b]pyr-
azolo[4,3-e]pyridine-5-one (4n). This compound was obtained
according to above general procedure; ir (KBr): ꢀ 1758, 1592,
1514, 764, 691 cm-1; H nmr: ꢀ 7.68 (d, 2H, J=8.4 Hz, ArH),
7.61-7.57 (m, 2H, ArH), 7.41-7.38 (m, 1H, ArH), 5.43 (s, 2H,
CH2), 3.46 (t, 2H, J=8.0 Hz, CH2), 2.79 (s, 3H, CH3), 1.69-
1.67(m, 2H, CH2), 1.51-1.49 (m, 2H, CH2), 0.97 (t, 3H, J=7.4
Hz, CH3). Anal. calcd for C19H19N3O2: C, 71.01; H, 5.96; N,
13.08; found C, 71.23; H, 5.75; N, 13.01.
1
4-(3-Nitropheny)-3-methyl-1-phenyl-1,7-dihydro-5H-furo-
[3,4-b]pyrazolo[4,3-e]pyridine-5-one (4g). This compound was
obtained according to above general procedure; ir (KBr): ꢀ
1
1773, 1589, 1535, 800, 702 cm-1; H nmr: ꢀ 8.49 (s, 1H, ArH),
8.46 (t, 1H, J=7.6 Hz, ArH), 8.19 (d, 2H, J=7.6 Hz, ArH), 8.08
(d, 1H, J=8.0 Hz, ArH), 7.90 (t, 1H, J=8.0 Hz, ArH), 7.62 (t,
2H, J=8.0 Hz, ArH), 7.42 (t, 1H, J=8.0 Hz, ArH), 5.52 (s, 2H,
CH2), 2.12 (s, 3H, CH3). Anal. calcd for C21H14N4O4: C, 65.28;
H, 3.65; N, 14.50; found C, 65.44; H, 3.76; N, 14.42.
Acknowledgement. We thank the National Natural Science
Foundation of China (No.20672090), the Key Item of Natural
Science Foundation of Xuzhou Normal University (No.
07XLA04) and Xuzhou Medical College (No. 07KJ45) for
financial supports.
4-(4-Nitropheny)-3-methyl-1-phenyl-1,7-dihydro-5H-furo-
[3,4-b]pyrazolo[4,3-e]pyridine-5-one (4h). This compound was
obtained according to above general procedure; ir (KBr): ꢀ
1
1764, 1580, 1517, 837 cm-1; H nmr: ꢀ 8.44 (d, 2H, J=8.0 Hz,
ArH), 8.20 (d, 2H, J=8.0 Hz, ArH), 7.90 (d, 2H, J=8.0 Hz,
ArH), 7.62 (t, 2H, J=8.0 Hz, ArH), 7.42 (t, 1H, J=8.0 Hz, ArH),
5.54 (s, 2H, CH2), 2.11 (s, 3H, CH3). Anal. calcd for
C21H14N4O4: C, 65.28; H, 3.65; N, 14.50; found C, 65.45; H,
3.77; N, 14.30.
4-(4-Methoxyphenyl)-3-methyl-1-phenyl-1,7-dihydro-5H-
furo[3,4-b]pyrazolo[4,3-e]pyridine-5-one (4i). This compound
was obtained according to above general procedure; ir (KBr): ꢀ
1766, 1608, 1580, 1509, 824 cm-1; 1H nmr: ꢀ 8.20 (d, 2H, J=8.4
Hz, ArH), 7.61 (t, 2H, J=8.0 Hz, ArH), 7.53 (d, 2H, J=8.4 Hz,
ArH), 7.40 (t, 1H, J=8.0 Hz, ArH), 7.13 (d, 2H, J=8.0 Hz, ArH),
5.47 (s, 2H, CH2), 3.89 (s, 3H, OCH3), 2.16 (s, 3H, CH3). Anal.
calcd for C22H17N3O3: C, 71.15; H, 4.61; N, 11.31; found C,
71.30; H, 4.46; N, 11.12.
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1
1772, 1578, 1512, 828, 760 cm-1; H nmr: ꢀ 8.19 (d, 2H, J=8.4
Hz, ArH), 7.77 (s, 1H, ArH), 7.71-7.43 (m, 5H, ArH), 5.56 (s,
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release date: 24-Apr-2007, DOI: 10.1021/Cr0509410.
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[18] The single-crystal growth was carried out in ethanol and
DMF at room temperature. X-ray crystallographic analysis was
performed with
a Siemens SMART CCD and a Semens P4
diffractometer (graphite monochromator, MoKa radiation ꢀ = 0.71073
Å). Crystal data for 4a: Empirical formula C21H14ClN3O2, yellow, crystal
dimension 0.47 x 0.36 x 0.05 mm, monoclinic, space group P2(1)/n, a =
8.599(16) Å, b = 21.95(4) Å, c = 9.900(18) Å, ꢁ = 90°, ꢂ = 109.38(3) °,
ꢃ = 90°, V = 1763(6) Å3, Mr = 375.80, Z = 4, Dc = 1.416 Mg/m3 , ꢀ =
0.71073 Å, μ (MOKꢁ) = 0.239 mm-1, F(000) = 776, S = 0.998, R1 =
0.0743, wR2
C21H15N3O2, yellow, crystal dimension 0.42
=
0.1051. Crystal data for 4d: Empirical formula
x
0.21 x 0.10 mm,
monoclinic, space group p2(1)/c, a = 7.067(4) Å, b = 22.439(12) Å, c =
10.871(6) Å, ꢁ = 90°, ꢂ = 104.909(9) °, ꢃ = 90°, V = 1763(6) Å3, Mr =
341.36, Z = 4, Dc = 1.361 Mg/m3 , ꢀ = 0.71073 Å, μ (MOKꢁ) = 0.090
mm-1, F(000) = 712, S =1.003, R1 = 0.0687, wR2 = 0.1334. Crystal data
for 4i: Empirical formula C22H17N3O3, yellow, crystal dimension 0.27 x
0.15 x 0.09 mm, monoclinic, space group P2(1)/c, a = 11.480(4)Å, b =
20.913(7) Å, c = 7.524(3)Å, ꢁ = 90°, ꢂ = 99.862(6) °, ꢃ = 90°, V =
1779.6(11) Å3, Mr = 371.39, Z = 4, Dc = 1.386 Mg/m3, ꢀ = 0.71073 Å, μ
(MOKꢁ) = 0.094 mm-1, F(000) = 776, S = 1.007, R1 = 0.0579, wR2 =
0.1109.Crystal data for 4m: Empirical formula C19H13N3O2S, yellow,
crystal dimension 0.46 x 0.44 x 0.16 mm, monoclinic, space group
P2(1)/c, a = 10.878(5) Å, b = 7.356(3) Å, c = 20.498(9)Å, ꢁ = 90°, ꢂ =
97.448(9) °, ꢃ = 90°, V = 1626.4(12) Å3, Mr = 347.38, Z = 4, Dc = 1.419
Mg/m3, ꢀ = 0.71073 Å, μ (MOKꢁ) = 0.217 mm-1, F(000) = 720, S
=1.004, R1 = 0.0582, wR2 = 0.0844.
[11] Magedov, I. V.; Manpadi, M.; Rozhkova, E.; Przhevalꢀskii,
N. M.; Rogelj, S.; Shors, S. T.; Steelant, W. F. A.; Van slambrouck S.;
Kornienko, A.; Bioorg. Med. Chem. Lett. 2007, 17, 1381.
[12] Dallinger, D.; Kappe, C. O. Chem. Rev., 2007, ASAP web