Base-catalyzed one-pot tandem reaction: An effective strategy for the synthesis of pyrazolo[3,4-d]pyrimidinone derivatives

Article abstract of DOI:10.1016/j.tet.2015.07.065

An effective one-pot multicomponent synthesis of pyrazolo[3,4-d]pyrimidinone derivatives through the tandem heterocyclization of hydrazine, methylenemalononitrile and aldehyde has been developed. This highly effective method includes nucleophilic addition

Full text of DOI:10.1016/j.tet.2015.07.065

Accepted Manuscript
Base-catalyzed one-pot tandem reaction: an effective strategy for the synthesis of
pyrazolo[3,4-d]pyrimidinone derivatives
Ming-xing Liu, Jia-rong Li, Kai Zheng, Huan Yao, Qi Zhang, Da-xin Shi
PII:
S0040-4020(15)01142-4
10.1016/j.tet.2015.07.065
TET 27010
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 23 June 2015
Revised Date: 20 July 2015
Accepted Date: 25 July 2015
Please cite this article as: Liu M-x, Li J-r, Zheng K, Yao H, Zhang Q, Shi D-x, Base-catalyzed one-pot
tandem reaction: an effective strategy for the synthesis of pyrazolo[3,4-d]pyrimidinone derivatives,
Tetrahedron (2015), doi: 10.1016/j.tet.2015.07.065.
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Graphical Abstract
Base-catalyzed one-pot tandem reaction: an
effective strategy for the synthesis of
Leave this area blank for abstract info.
pyrazolo[3,4-d]pyrimidinone derivatives
Ming-xing Liu, Jia-rong Li, Kai Zheng, Huan Yao, Qi Zhang, Da-xin Shi
School of Chemical Engineering and Environment, Beijing Institute of Technology, 5 South, Zhongguancun
Street, Beijing, 100081, P. R. China

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Base-catalyzed one-pot tandem reaction: an effective strategy for the synthesis of
pyrazolo[3,4-d]pyrimidinone derivatives
Ming-xing Liua , Jia-rong Lia , Kai Zhenga , Huan Yaoa , Qi Zhanga , Da-xin Shia,
aSchool of Chemical Engineering and Environment, Beijing Institute of Technology, 5 South, Zhongguancun Street, Beijing, 100081, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An effective one-pot multicomponent synthesis of pyrazolo[3,4-d]pyrimidinone derivatives
through the tandem heterocyclization of hydrazine, methylenemalononitrile and aldehyde has
been developed. This highly effective method includes nucleophilic addition, heterocyclization,
substitution, intramolecular Pinner, Dimroth rearrangement and dehydroaromatization.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Pyrazolo[3,4-d]pyrimidinone
one-pot multicomponent heterocyclization
sildenafil
ester18 can be converted to pyrazolopyrimidinones as well. But
there are some drawbacks such as the requirement of oxidant,16
multistep sequences,19 high reaction temperature,16,20 complicated
reagents,21 high pressure12b or long reaction time.18a
1. Introduction
Pyrazolopyrimidine compounds are exist widely in nature and
biologically active compounds. 1 Pyrazolopyrimidinones, as a
subtype, possess a series of biological activities such as anti-
cancer, 2 anti-schistosomal, 3 anti-inflammatory, 4 anti-obesity, 5
adenosine receptors (A3) antagonists,6 herbicide,7 PDE inhibitor.8
Ibrutinib and sildenafil, recently received extensive attention, are
the most representative pyrazolopyrimidine drugs (Figure 1).
O
O
OR2
NH2
N
N
N
carboxylic acid[9]
acyl chloride[10]
orthoester[11]
ester[12]
NH2
N
NH2
R1
R1
R2=H, Me, Et[18]
aldehyde[13]
imine[9b]
amide[14]
O
carboxylic acid[9a,15]
acid anhydride[16]
ketone[17]
CN
NH
R2
N
N
N
N
N
H
NH2
R1
R1
Scheme 1. The general syntheses of pyrazolo[3,4-
d]pyrimidinones
Figure 1. Representative pyrazolopyrimidine drugs
The traditional methods (Scheme 1) for the synthesis of
pyrazolo[3,4-d]pyrimidinones need multiple steps, including the
reaction of 5-aminopyrazole-4-carboxamide hydrolyzed from o-
aminonitrile and carboxylic acid,9 acyl chloride,10 orthoester,11
In our previous studies, the cyclocondensation of ketone and
aromatic o-aminonitrile catalyzed by base afforded pyrimidinone
derivatives.17 And we thought 5-aminopyrazole-4-carbonitrile is
synthesized in the condition of base. So we designed one-pot
multicomponent heterocyclization of methylenemalononitriles,
hydrazines and aldehydes for the synthesis of 4H-pyrazolo[3,4-
d]pyrimidin-4-ones (Scheme 2).
ester,12 aldehyde,13 imine,9b amide14, and the cyclization of 5-
15
aminopyrazole-4-carbonitrile with carboxylic acid,9a,
acid
anhydride,16 ketone.17 Other 5-aminopyrazole carboxylic acid or
———
Corresponding author. Tel.: +86-010-6891-8012; fax: +86-010-6891-8012; e-mail: shidaxin@bit.edu.cn

2
Tetrahedron
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Table 2. Three-component one-pot tandem synthesis of 4H-
pyrazolo[3,4-d]pyrimidin-4-onesa
Scheme 2. The retrosynthetic design of reaction.
4c, 89%
4b, 85%
4a, 82%
2. Results and Discussion
The reaction of 2-(ethoxymethylene)malononitrile phenyl-
hydrazine, and benzaldehyde is selected as the model to optimize
the reaction conditions, and the results were summarized in Table
1. No target product was obtained with acid catalyst or no
catalyst (Table 1, entries 1-3), and the catalytic performance of
4e, 85%
4d, 82%
4f, 90%
Table 1. Optimization of reaction conditionsa
O
NH
N
N
N
Et
N
Et
4g, 92%
4i, 81%
4h, 77%
Entry
1
Solvent
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DMSO
Dioxc
Cat (eqiv)
-
Temp (oC)
Yieldb (%)
60
0
2
ZnCl2 (1.0)
TsOH (1.0)
KOBu-t (0.2)
DBU (0.2)
NaOEt (0.2)
KOH (0.2)
NaOH (0.2)
NaOH (0.2)
NaOH (0.2)
NaOH (0.2)
NaOH (0.2)
NaOH (0.1)
NaOH (0.4)
60
0
4j, 83%
4k, 82%
3
60
0
4l, 81%
4
60
28
56
69
69
83
56
14
73
63
35
83
5
60
6
60
4n, 82%
7
60
4m, 85%
8
60
9
60
10
11
12d
13
14
60
4o, 83%
4p, 85%
Toluene
Toluene
Toluene
Toluene
Reflux
25
aReactions conditions: 1a (1.2 mmol), 2a (1 mmol), 3a (1.2 mmol) and
NaOH (0.2 mmol) in toluene (20 ml); R4=Et or Me
60
were listed in Table 2. Aromatic aldehydes possessing
electron-donating groups (EDG) provided the corresponding
target products in good to excellent yields (Table 2, 4a-g). And
the aromatic aldehyde with electron-withdraw groups (EWG)
gave lower yields than that of aldehyde with EDG. The possible
reason is that the EDG increased the nucleophilicity, which
facilitated intramolecular Pinner reaction. To further expand this
one-pot methodology, some 1-substituted and 3-substituted
pyrazolo[3,4-d]pyrimidin-4-ones were synthesized in good yields
(Table 2, 4j-m). And the corresponding product was obtained
from aliphatic hydrazine in good yields (Table 2, 4n). Notably,
reaction between ketones and chain aldehydes afforded the
corresponding compounds in good yields (Table 2, 4o-p). These
results indicated the universality and advantages of one-pot
method.
60
aReactions conditions: 1a (1.2 mmol), 2a (1 mmol), 3a (1.2 mmol) and
catalyst in solvent (20 ml). Isolated yields. Diox = 1,4-dioxane. Reaction
time: 48h.
b
c
d
inorganic bases was higher than that of organic bases (Table 1,
entries 4-8). Toluene was best solvent (Table 1, entries 8-10).
The affect of temperature was also investigated (Table 1, entries
11-12). Although higher temperature facilitated the reaction,
more by-products were obtained, therefore the apposite
temperature was 60oC. The amount of catalyst had influence on
the reaction and the appropriate choice was 0.2 equivalent (Table
1, entries 8, 13, 14).
With the optimum conditions in hand, a range of 4H-
pyrazolo[3,4-d]pyrimidin-4-ones were synthesized and the results

pyrazolo[3,4-d]pyrimidin-4-ones was developed. This is the first
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time to construct pyrazolo[3,4-d]pyrimidinones from hydrazines,
methylenemalononitriles and aldehydes. This method avoids
expensive catalyst, high reaction temperature and long reaction
time. All products were easy to isolate and have a convenient
application for the construction of pyrazolopyrimidinone
skeleton.
4. Experimental section
General Methods: The raw materials including hydrazines,
2-(ethoxymethylene)malononitrile and aldehydes are commer-
cially available. 2-(1-Ethoxyethylidene)malononitrile and 2-(1-
methoxy-butylidene)malononitrile were synthesized from ortho-
ester using the method reported by Markwalder.[ 26 ] Melting
points were determined using XT4 microscope melting point
apparatus (uncorrected). Infrared (IR) spectra were recorded on a
1
Perkin Elmer FT-IR spectrophotometer with KBr pellets. H and
13C NMR spectra were recorded at a Bruker 400 MHz spectro-
meter with TMS as the internal standard. Mass spectra were
obtained with ESI ionization using a Bruker APEX IV and ZAB-
HS mass spectrometer.
Scheme 3. Proposed mechanism of the formation of 4.
In order to rationalize the process of reaction, a possible
reaction mechanism is depicted in Scheme 3. Methylenemalono-
nitrile 2 undergoes nucleophilic addition with hydrazine 1, and
then followed by cyclisation, aromatization to obtain the
intermediate 5-aminopyrazole-4-carbonitrile 5. The amino group
of 5 attacks aldehyde to afford 6 with the catalysis of base. Then
6 undergoes intramolecular nucleophilic addition and 3,1-oxazine
7 is formed, and then rearranges to dihydro pyrazolo[3,4-d]pyri-
midin-4-ones 9 (Dimroth rearrangement22). At last, 9 transforms
to the target product 4 by air oxidant.23
General Procedure for the Synthesis of 4: Hydrazine (1, 1.2
mmol) and methylenemalononitrile (2, 1.0 mmol) were mixed in
toluene, then NaOH (0.2 mmol) and aldehyde (3, 1.2 mmol) was
added at 60oC. At the end of the reaction (TLC monitoring), the
reaction mixture was extracted with EtOAc (3×20 mL). Then
the organic layer was evaporated under reduced pressure. The
crude product was washed by ethanol and then filtered. The filter
cake was dried and purified by crystallization from ethanol to
afford pure 4.
1,6-Diphenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-
one (4a): White solid; m.p. > 300oC; IR (KBr, v, cm-1): 3077,
1
1684; H NMR (400 MHz, DMSO-d6) (δ, ppm): 12.65 (s, 1H),
8.37 (s, 1H), 8.20-8.15 (m, 4H), 7.64-7.57 (m, 5H), 7.44-7.40 (m,
1H); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 158.7, 156.5,
152.7, 138.9, 136.5, 132.5, 132.5, 129.8, 129.2, 128.7, 127.5,
122.1, 106.5; HRMS (ESI): calcd. For C17H12N4OH [M+H]+
289.1084; found 289.1091.
Scheme 4. The synthesis of 4a by the reaction of 5a with 3a
.
To further demonstrate this mechanism, the key intermediates,
5-amino-1-phenyl-1H-pyrazole-4-carbonitrile 5a24, was separated
and reacted with benzaldehyde 3a in the catalyst of NaOH to
give the targeted product, 1,6-diphenyl-1,5-dihydro-4H-pyrazolo-
[3,4-d]pyrimidin-4-one 4a in 85% yield (Scheme 4).
6-(4-Ethylphenyl)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-
d]pyrimidin-4-one (4b): White solid; m.p. 253-255oC; IR (KBr,
1
v, cm-1): 3078, 2966, 1686; H NMR (400 MHz, DMSO-d6) (δ,
ppm): 12.53 (s, 1H), 8.34 (s, 1H), 8.17-8.11 (m, 4H), 7.62-7.58
(m, 2H), 7.43-7.40 (m, 3H), 2.71 (q, J = 8.0 Hz, 2H), 1.23 (t, J =
8.0 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 158.7,
156.5, 152.8, 148.8, 138.9, 136.5, 130.0, 129.8, 128.8, 127.4,
122.0, 106.3, 28.6, 15.7; HRMS (ESI): calcd. For C19H16N4OH
[M+H]+ 317.1397; found 317.1397.
1
All products were characterized by IR, H-NMR, 13C-NMR
and ESI spectra. And the structure of 4n was further confirmed
by X-ray diffraction (Figure 2).25
1-Phenyl-6-(p-tolyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyri-
midin-4-one (4c)27: White solid; m.p. 295-297oC; IR (KBr, v,
1
cm-1): 3078, 2971, 1684; H NMR (400 MHz, DMSO-d6) (δ,
ppm): 12.58 (s, 1H), 8.35 (s, 1H), 8.17-8.09 (m, 4H), 7.62-7.58
(m, 2H), 7.43-7.37 (m, 3H), 2.40 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) (δ, ppm): 159.0, 156.6, 152.9, 142.6, 139.0, 136.5,
129.8, 128.6, 127.4, 122.0, 106.3, 21.5; ESI-MS (m/z) = 303
([M+H]+).
1-Phenyl-6-(3,4,5-trimethoxyphenyl)-1,5-dihydro-4H-pyr-
azolo[3,4-d]pyrimidin-4-one (4d): White solid; m.p. > 300oC;
IR (KBr, v, cm-1): 3103, 2939, 1685; 1H NMR (400 MHz,
DMSO-d6) (δ, ppm): 12.65 (s, 1H), 8.36 (s, 1H), 8.19-8.17 (m,
2H), 7.63-7.59 (m, 4H), 7.43-7.39 (m, 1H), 3.90 (s, 6H), 3.76 (s,
3H); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 158.8, 155.8,
153.3, 152.6, 141.1, 138.9, 136.6, 129.7, 127.4, 127.3, 121.9,
Figure 2. Molecular structure of compound 4n.
3. Conclusions
In summary, an effective method for combining two well-
known reactions into one-pot tandem reaction for synthesis of

4
Tetrahedron
106.2 106.1, 60.7, 56.5; HRMS (ESI): calcd. For C2 H18N4O4H
127.0, 121.8, 104.1, 30.04, 21.88, 14.18; HRMS (ESI): calcd. For
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0
[M+H]+ 379.1401; found 379.1402.
C20H18N4OH [M+H]+ 331.1553; found 331.1546.
6-(4-Methoxyphenyl)-1-phenyl-1,5-dihydro-4H-pyrazolo
[3,4-d]pyrimidin-4-one (4e)28: Yellow solid; m.p. > 300oC; IR
(KBr, v, cm-1): 3111, 2971, 1673; 1H NMR (400 MHz, DMSO-d6)
(δ, ppm): 12.49 (s, 1H), 8.34 (s, 1H), 8.22-8.15 (m, 4H), 7.63-
7.59 (m, 2H), 7.44-7.40 (m, 1H), 7.14-7.12 (m, 2H), 3.86 (s, 3H);
13C NMR (100 MHz, DMSO-d6) (δ, ppm): 162.8, 158.8, 156.1,
152.9, 139.0, 136.5, 130.5, 130.0, 127.4, 124.5, 122.0, 114.7,
106.0, 56.0; ESI-MS (m/z) = 319 ([M+H]+).
1-(4-Chlorophenyl)-6-phenyl-1,5-dihydro-4H-pyrazolo
[3,4-d]pyrimidin-4-one (4l): White solid; m.p. > 300oC; IR (KBr,
1
v, cm-1): 3078, 1683; H NMR (400 MHz, DMSO-d6) (δ, ppm):
12.70 (s, 1H), 8.40 (s, 1H), 8.22-8.19 (m, 4H), 7.69-7.57 (m, 5H);
13C NMR (100 MHz, DMSO-d6) (δ, ppm): 158.6, 156.8, 152.8,
137.7, 136.9, 132.6, 131.6, 129.8, 129.3, 128.8, 123.5, 106.6;
HRMS (ESI): calcd. For C17H11ClN4OH [M+H]+ 323.0694;
found 323.0695.
6-(2-Ethoxyphenyl)-1-phenyl-1,5-dihydro-4H-pyrazolo
[3,4-d]pyrimidin-4-one (4f)29: Yellow solid; m.p. 210-212oC; IR
(KBr, v, cm-1): 3078, 2973, 1685; 1H NMR (400 MHz, DMSO-d6)
(δ, ppm): 12.17 (s, 1H), 8.37 (s, 1H), 8.37-8.10 (m, 2H), 7.83-
7.80 (m, 1H), 7.59-7.53 (m, 3H), 7.42-7.38 (m, 1H), 7.22-7.20
(m, 1H), 7.14-7.10 (m, 1H), 4.18 (q, J = 8.0 Hz, 2H), 1.36 (t, J =
8.0 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 157.8,
157.3, 156.0, 136.5, 133.4, 131.1, 129.7, 127.4, 122.2, 121.1,
113.5, 106.3, 64.7, 14.9; ESI-MS (m/z) = 333 ([M+H]+).
1-(3,5-Dimethylphenyl)-6-phenyl-1,5-dihydro-4H-pyrazo-
lo[3,4-d]pyrimidin-4-one (4m): White solid; m.p. 280-282oC; IR
(KBr, v, cm-1): 3073, 2969, 1683; 1H NMR (400 MHz, DMSO-d6)
(δ, ppm): 12.63 (s, 1H), 8.33 (s, 1H), 8.18-8.16 (m, 2H), 7.76 (s,
2H), 7.63-7.59 (m, 3H), 7.06 (s, 1H), 2.39 (s, 6H); 13C NMR (100
MHz, DMSO-d6) (δ, ppm): 158.7, 156.4, 152.6, 139.0, 136.3,
132.5, 132.5, 129.3, 128.9, 128.6, 119.9, 106.4, 21.6; HRMS
(ESI): calcd. For C19H16ClN4OH [M+H]+ 317.1397; found
317.1398.
6-(4-(Diethylamino)phenyl)-1-phenyl-1,5-dihydro-4H-
pyrazolo[3,4-d]pyrimidin-4-one (4g): Yellow solid; m.p. 284-
286oC; IR (KBr, v, cm-1): 3079, 2969, 1689; 1H NMR (400 MHz,
DMSO-d6) (δ, ppm): 12.17 (s, 1H), 8.28 (s, 1H), 8.19 (d, J = 8.0
Hz, 2H), 8.12 (d, J = 8.0 Hz, 2H), 7.62-7.58 (m, 2H), 7.42-7.38
(m, 1H), 6.78-6.76 (m, 2H), 3.43 (q, J = 8.0 Hz, 4H), 1.13 (t, J =
8.0 Hz, 6H); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 158.9,
156.4, 153.4, 150.7, 139.2, 136.5, 130.2, 129.7, 127.1, 121.7,
117.2, 111.2, 105.4, 44.3, 12.9; HRMS (ESI): calcd. For
C21H21N5OH [M+H]+ 360.1819; found 360.1810.
1-(Tert-butyl)-6-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]
pyrimidin-4-one (4n): White solid; m.p. > 300oC; IR (KBr, v,
1
cm-1): 3027, 2968, 1674; H NMR (400 MHz, DMSO-d6) (δ,
ppm): 12.39 (s, 1H), 8.17-8.15 (m, 2H), 8.03 (s, 1H), 7.62-7.56
(m, 3H), 1.76 (s, 9H); 13C NMR (100 MHz, DMSO-d6) (δ, ppm):
158.9, 154.0, 152.2, 133.0, 132.8, 132.2, 129.2, 128.4, 106.1,
60.6, 29.6; HRMS (ESI): calcd. For C15H16N4OH [M+H]+
269.1397; found 269.1400.
1-Phenyl-6-propyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyri-
midin-4-one (4o)28: White solid; m.p. 253-255oC; IR (KBr, v,
1
6-(4-Bromophenyl)-1-phenyl-1,5-dihydro-4H-pyrazolo
cm-1): 3077, 2962, 1675; H NMR (400 MHz, DMSO-d6) (δ,
[3,4-d]pyrimidin-4-one (4h)27: White solid; m.p. > 300oC; IR
ppm): 12.29 (s, 1H), 8.26 (s, 1H), 8.09-8.07 (m, 2H), 7.58-7.54
(m, 2H), 7.41-7.37 (m, 1H), 2.65 (t, J = 8.0 Hz, 2H), 1.81-1.72
(m, 2H), 0.95 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, DMSO-d6)
(δ, ppm): 162.1, 158.4, 152.9, 139.0, 136.3, 129.7, 127.3, 121.9,
106.2, 36.6, 20.7, 13.9; ESI-MS (m/z) = 255 ([M+H]+).
1
(KBr, v, cm-1): 3049, 1690; H NMR (400 MHz, DMSO-d6) (δ,
ppm): 12.78 (s, 1H), 8.38 (s, 1H), 8.13-8.10 (m, 4H), 7.81-7.79
(m, 2H), 7.62-7.58 (m, 2H), 7.45-7.41 (m, 1H); 13C NMR (100
MHz, DMSO-d6) (δ, ppm): 158.6, 155.7, 152.5, 138.8, 136.6,
132.3, 131.7, 130.7, 129.8, 127.6, 126.4, 122.2, 106.5; ESI-MS
(m/z) = 367 ([M+H]+).
1'-Phenyl-1',7'-dihydrospiro[cyclohexane-1,6'-pyrazolo
[3,4-d]pyrimidin]-4'(5'H)-one (4p)30 : White solid; m.p. 182-
184oC; IR (KBr, v, cm-1): 3196, 2931, 1651; 1H NMR (400 MHz,
DMSO-d6) (δ, ppm): 7.76 (s, 1H), 7.73 (s, 1H), 7.56-7.52 (m,
2H), 7.47 (s, 1H), 7.38-7.35 (m, 1H), 6.62 (s, 1H), 1.89-1.86(m,
2H), 1.68-1.62 (m, 2H) 1.56-1.51 (m, 4H), 1.46-1.42 (m, 1H),
1.31-1.26 (m, 1H); 13C NMR (100 MHz, DMSO-d6) (δ, ppm):
161.7, 148.3, 139.0, 138.3, 129.8, 127.1, 121.9, 102.4, 71.0, 36.5,
25.2, 22.0; ESI-MS (m/z) = 283 ([M+H]+).
6-(5-Bromo-2-methoxyphenyl)-1-phenyl-1,5-dihydro-4H-
pyrazolo[3,4-d]pyrimidin-4-one (4i): Green solid; m.p. 288-
290oC; IR (KBr, v, cm-1): 3095, 2947, 1717; 1H NMR (400 MHz,
DMSO-d6) (δ, ppm): 12.39 (s, 1H), 8.38 (s, 1H), 8.06-8.03 (m,
2H), 7.83-7.82 (m, 1H), 7.75-7.72 (m, 1H), 7.60-7.56 (m, 2H),
7.43-7.39 (m, 1H), 7.21-7.19 (m, 1H), 3.86 (m, 3H); 13C NMR
(100 MHz, DMSO-d6) (δ, ppm): 157.9, 157.0, 154.7, 152.5,
138.7, 136.5, 135.4, 133.0, 129.8, 127.6, 124.8, 122.4, 114.9,
112.1, 106.6, 56.8; HRMS (ESI): calcd. For C18H13BrN4O2H
[M+H]+ 397.0295; found 397.0287.
Acknowledgments
This work was supported by the Basic Research Foundation of
Beijing Institute of Technology (20131042006) and International
cooperation in science and Technology (2012DFR40240). We
are grateful for analytical help of The Chinese Academy of
Agricultural Sciences, Peking University and Beijing University
of Chemical Technology.
3-Methyl-1,6-diphenyl-1,5-dihydro-4H-pyrazolo[3,4-d]
pyrimidin-4-one (4j)27: White solid; m.p. > 300oC; IR (KBr, v,
1
cm-1): 3076, 2967, 1679; H NMR (400 MHz, DMSO-d6) (δ,
ppm): 12.53 (s, 1H), 8.19-8.13 (m, 4H), 7.67-7.52 (m, 6H), 2.57
(s, 3H); 13C NMR (100 MHz, DMSO-d6) (δ, ppm): 159.7, 157.3,
155.6, 153.7, 150.3, 139.8, 132.4, 129.7, 129.2, 128.7, 127.0,
121.8, 100.0, 31.2; ESI-MS (m/z) = 303 ([M+H]+).
References and notes
1,6-Diphenyl-3-propyl-1,5-dihydro-4H-pyrazolo[3,4-d]
pyrimidin-4-one (4k): White solid; m.p. 285-287oC; IR (KBr, v,
1
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156.5, 153.2, 150.6, 138.9, 132.6, 132.4, 129.7, 129.2, 128.7,

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Supporting Information
For
Base-Catalyzed One-Pot Tandem Reaction: An Effective Strategy for the
Synthesis of Pyrazolo[3,4-d]pyrimidinone Derivatives
Ming-xing Liu, Jia-rong Li, Kai Zheng, Huan Yao, Qi Zhang, Da-xin Shi*
School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing, 100081,
China
Fax: (+86)-010-68918012; E-mail: shidaxin@bit.edu.cn

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1H and 13C NMR spectra of 4

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O
NH
N
N
OMe
N
OMe
OMe
4d
O
N
NH
N
N
OMe
OMe
OMe
4d

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O
NH
N
N
N
Cl
4l
O
NH
N
N
N
Cl
4l

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HRMS spectra of 4

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O
NH
N
OMe
OMe
N
N
OMe
4d

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O
NH
N
N
N
Cl
4l

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