Versatile synthesis and fungicidal activities of 6-amino-3-alkylthio-1,5- dihydro-1-phenyl-pyrazolo [3,4-d]pyrimidin-4-one derivatives

Article abstract of DOI:10.1080/10426500490474897

A series of new 6-alkylamino-3-alkylthio-1-phenyl-1H-pyrazolo[3,4-d] pyrimidin-4(5H)-one derivatives 5 and 6 have been rapidly synthesized by a novel solution-phase regioselective synthetic method. Treatment of pyrazole o-aminoester 1 with dibromotriphenylphosphorane gave iminophosphorane 2, which underwent a aza-Wittig reaction with phenyl ioscyanate to provide the carbodiimide 3. The latter intermediate reacted with alkylamines and regioselectively provided the 1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one derivatives 5 and 6, some of which exhibited good fungicidal activity.

Full text of DOI:10.1080/10426500490474897

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Phosphorus, Sulfur, and Silicon and the Related
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VERSATILE SYNTHESIS AND FUNGICIDAL ACTIVITIES
OF 6-AMINO-3- ALKYLTHIO-1,5-DIHYDRO-1-PHENYL-
PYRAZOLO [3,4-D]PYRIMIDIN-4-ONE DERIVATIVES
Hong-Qing Wang a , Zhao-Jie Liu a & Ming-Wu Ding a
a Institute of Organic Synthesis, Central China Normal University , Wuhan, P. R. China
b College of Chemistry and Chemical Engineer, NanHua University , Hengyang, P. R. China
Published online: 16 Aug 2010.
To cite this article: Hong-Qing Wang , Zhao-Jie Liu & Ming-Wu Ding (2004) VERSATILE SYNTHESIS AND FUNGICIDAL ACTIVITIES
OF 6-AMINO-3- ALKYLTHIO-1,5-DIHYDRO-1-PHENYL-PYRAZOLO [3,4-D]PYRIMIDIN-4-ONE DERIVATIVES, Phosphorus, Sulfur, and
Silicon and the Related Elements, 179:10, 2039-2050, DOI: 10.1080/10426500490474897
To link to this article: http://dx.doi.org/10.1080/10426500490474897
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Phosphorus, Sulfur, and Silicon, 179:2039–2050, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490474897
VERSATILE SYNTHESIS AND FUNGICIDAL
ACTIVITIES OF 6-AMINO-3-
ALKYLTHIO-1,5-DIHYDRO-1-PHENYL-PYRAZOLO
[3,4-d]PYRIMIDIN-4-ONE DERIVATIVES
Hong-Qing Wang,a,b Zhao-Jie Liu,a and Ming-Wu Dinga
Institute of Organic Synthesis, Central China Normal
University, Wuhan, P. R. China;a and College of Chemistry and
Chemical Engineer, NanHua University, Hengyang,
P. R. Chinab
(Received December 5, 2003; accepted March 16, 2004)
A series of new 6-alkylamino-3-alkylthio-1-phenyl-1H-pyrazolo[3,4-d]
pyrimidin-4(5H)-one derivatives 5 and 6 have been rapidly synthe-
sized by a novel solution-phase regioselective synthetic method. Treat-
ment of pyrazole o-aminoester 1 with dibromotriphenylphosphorane
gave iminophosphorane 2, which underwent a aza-Wittig reaction with
phenyl ioscyanate to provide the carbodiimide 3. The latter interme-
diate reacted with alkylamines and regioselectively provided the 1,5-
dihydro-pyrazolo[3,4-d]pyrimidin-4-one derivatives 5 and 6, some of
which exhibited good fungicidal activity.
Keywords: Aza-Wittig reaction; fungicidal activities; pyrazolo[3,4-
d]pyrimidin-4-one; synthesis
INTRODUCTION
Pyrazolo[3,4-d]pyrimidine derivatives are of considerable chemical and
pharmacological importance as purine analogs.1,2 They exhibit excel-
lent antibacterial, antiphlogistic,3–5 and antiumor6 activities, and they
have been employed in the treatment of erectile dysfunction in male
animals.7–9 In previous reports, various synthetic procedures have
been devised for the conversion of o-aminonitriles and o-aminoesters
We gratefully acknowledge the financial support of this work by the National Nature
Science Foundation (No. 20101001).
Address correspondence to Zhao-Jie Liu, Institute of Organic Synthesis, Central
China Normal University, Wuhan 430079, P. R. China. E-mail: HQWang2001cn@yahoo.
com.cn
2039

2040
H.-Q. Wang et al.
bearing pyrazole ring to pyrazolopyrimidinones derivatives, which
involved inter alia (1) hydrolysis of aminonitriles, followed by reac-
tion with aliphatic ester,10,11 aromatic aldehydes,12 and carboxylic
acids;12,13 (2) treatment of o-aminoesters with aryl isothiocycanates
and subsequent reaction with hydrazine monohydrate;14,15 or (3)
generated pyrazolooxazine or o-ethoxymethyleneaminoesters which
were reacted with amines.16 Taylor17 also reported the preparation of
6-phenylamino-1,5-dihydro-1-methyl-pyrazolo[3,4-d]pyrimidin-4-one
by utilizing o-phosphoranylideneamino pyrazolyl ester to react with
isocyanates and amines. As a part of an extension of our studies
on tandem aza-Wittig reaction,18–20 we developed a new versatile
solution-phase regioselective annulation process to synthesize novel
6-amino-3-alkylthio-1-phenyl-1,5-dihydro-pyrazolo-[3,4-d]pyrimidin-
4-one derivatives 5 and 6 (Scheme 1) and examined their fungicidal
activities.
SCHEME 1
RESULTS AND DISCUSSION
The iminophosphorance 2, which was prepared from 5-aminopyrazole 1
in the presence of triphenylphosphine and bromine, reacted with phenyl
isocyanate to give carbodiimide 3, which was allowed to react with
alkylamines at room temperature to give intermediate guanidines 4. In

Pyrazolo Pyrimidin-4-one Derivatives
2041
the presence of EtONa/EtOH, the reaction proceeded smoothly at room
temperature to give 5 or 6 in good yields. Whenever R2 was alkyl substi-
tuted with aliphatic group or aromatic group and small (R2 = n-Pr) or
bulky (R2 = iso-Pr), the cyclization was achieved all in good yields with
the same regioselective product 5 obtained separately from the reac-
tion mixture by recrystallization or flash chromatography with a silica
column. But when R2 was hydrogen, 6 was the regioselective product.
It was noteworthy that when Ar possessed a strong electron-drawing
group, whenever R2 was aliphatic or aromatic alkyl substituted, the
cyclic product couldn’t be obtained. Examples are 5k and 5l. The struc-
tures of 1,5-dihydro-1-phenyl-pyrazolo[3,4-d]pyrimidin-4-ones (5 and 6)
1
1
were deduced from their H NMR spectra data. For example, the H
NMR spectra data of 5b showed the signals of NH at δ 4.89 as triplet,
which were not the same as the proton of PhNH, the chemical shift of
which is greater than δ 7.0.17 Its methylene protons displayed a doublet
−
also, which strongly suggested the existence of an NHCH2 group. Also,
6a showed the signal of N-H at δ 9.70 as a broad absorption, which was
the same in the literature.15 It suggested the existence of PhNH group.
It was found that various carbodiimides reacted with nucleophiles in
need of excessive catalytic solid potassium carbonate in our previous
research,18−20 but we carried out the reactions of carbodiimide 3 with
alkylamines in the presence of EtONa. However, in the absence of a
base, the intermediate guanidine 4 did not cyclize completely and was
recovered (see Table I).
TABLE I Preparation of 1,5-Dihydro-pyrazolo[3,4-d]pyrimidin-4-one
Derivatives 5 and 6
Compound
Ar
R1
R2
Conditions Yield (%)∗
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
6a
6b
Ph
Me
p-FPhCH2
3-pyridinemethyl
2-pyridinemethyl
2-(1-ethylpyrrolidine)methyl r.t./3 h
2-thiophenemethyl
n-Pr
r.t./3 h
r.t./2 h
r.t./2 h
83.7
76.0
96.0
74.6
69.6
75.4
66.2
69.5
76.9
92.8
0.0
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
r.t./3 h
r.t./2 h
r.t./5 h
r.t./5 h
r.t./5 h
r.t./2 h
Reflux/6 h
Reflux/6 h
r.t./2 h
PhCH2 3-pyridinomethyl
PhCH2 2-pyridinomethyl
PhCH2 2-thiophenemethy
PhCH2 iso-Pr
p-FPh Me
p-FPh Me
Ph
Ph
3-pyridinemethyl
n-Pr
H
0.0
82.9
90.2
Me
PhCH2
H
r.t./3 h
∗Isolated yields based on iminophosphorance 2.
r.t., Room temperature.

2042
H.-Q. Wang et al.
SCHEME 2
The formation of 5 or 6 (Scheme 2) can be rationalized in terms of
geometry of the intermediate 4, which might be Z-form suitable for
arylamino group to cyclize, and conjugative effect of product 5 and 6.
It is estimated that the configurations of carbodiimide 3 are mainly
coplanar due to the resonance effect. When the amines reacted with
3a, Z-4a formed since the amines would attack 3a mainly from the op-
posite direction of COOEt group due to the steric hindrance of COOEt
group. When the amines reacted with 3b, Z-4b formed since the amines
would attack 3b mainly from the opposite direction of phenyl group due
to the steric hindrance of pyrazole ring and phenyl group. Actually, 4a
is equivalent to 4b and 4c through the C N single-bond rotation. How-
ever, 4a is suitable for arylamine group to cyclize, and 4c is suitable for
alkylamine group to cyclize. When R2 is alkyl, the initially formed 4a
cyclizes to give 5 at first rather than mutating to afford 4c because there
is not a notable different steric hindrance to ester group between aryl
group and alkyl, and the compounds 5 are more stable than the com-
pounds 6 because of conjugative effect. However, when R2 is hydrogen
atom, the initially formed 4a mutates into 4c, followed by cyclization to
give 6, since 4c is more stable than 4a because of the steric hindrance
and the cyclized compound from 4c is more stable via its existence of
two interconverting isomers. This is because the isomer 6Aꢀ bearing a
hydroxyl has a completely conjugated ring, but the 5m does not (see
Scheme 3). It demonstrates that 5k and 5l cannot also cyclize.
The structures of 5 and 6 have been fully characterized by 1H NMR,
IR, MS, and elementary analyses. In the IR spectral data of 5, the

Pyrazolo Pyrimidin-4-one Derivatives
2043
SCHEME 3
relatively strong stretching resonance absorption of N-H appears at
3352–3442 cm−1, which is only one peak. The stretching resonance of
C O showed strong absorption at about 1684–1712 cm−1. However,
in the IR spectral data of 6, there were two relatively strong stretch-
ing resonance absorption peaks at about 3432 cm−1 and 3110 cm−1
,
and the absorption of C O was very weak due to 6 interconverting
(see Scheme 3). This demonstrated the identification of 6 also. The MS
spectrum of all compounds prepared showed strong molecule ion peaks.
The structure of 5 was further confirmed by X-ray crystallographic
analysis. The X-ray structural analysis of 5a showed that it was 5-
phenyl-6-(p-fluorobenzylamino)-substituted pyrazolo[3,4-d]-pyrimidin-
4-one (see Figure 1). The single crystal of 5a was orthorhombic, space
˚
˚
group Pbca, unit cell dimensions A = 10.327(4) A, B = 20.307(7) A,
◦
◦
◦
3
˚
˚
C = 21.234(9) A, α = 90 , β = 90 , γ = 90 , V = 4453 (3) A , Mc = 457.52,
FIGURE 1 Crystal structure of 5a.

2044
H.-Q. Wang et al.
TABLE II Selected Bond Lengths (A) of 5a
˚
Bond
Dist.
Bond
Dist.
S(1) C(5)
F(1) C(16)
N(1) C(1)
N(2) C(2)
N(3) C(3)
N(3) C(19)
N(5) C(2)
O(1) C(1)
C(3) C(4)
C(12) C(13)
1.733(3)
1.363(4)
1.421(3)
1.302(3)
1.349(3)
1.415(3)
1.333(3)
1.213(3)
1.373(4)
1.495(4)
S(1) C(25)
N(1) C(2)
N(1) C(6)
N(2) C(3)
N(3) N(4)
N(4) C(5)
N(5) C(12)
C(1) C(4)
C(4) C(5)
1.786(3)
1.383(3)
1.443(3)
1.348(3)
1.388(3)
1.314(3)
1.440(3)
1.409(4)
1.409(4)
Z = 8, Dc = 1.365 g/cm3, µ = 0.182 mm−1, F (000) = 1904, R = 0.0600,
Rw = 0.0932. The selected bond distances and angles are listed in
Tables II and III.
In this compound, the bond lengths of N (2) C (2) and N (4) C (5)
˚
are 1.302 (3) and 1.314 (3) A, slightly shorter than the normal C N
21
22
˚
˚
bond distance (1.33 A) and close to 1.312 A as reported by Chen.
The N (1) C (3), N (1) C (6), N (2) C (3), N (3) C (3), N (3) C (19),
N (5) C (2), and C (3) = C (4) bond distances are 1.421(3), 1.383(3),
˚
1.443(3), 1.348(3), 1.349(3), 1.415(3), 1.333(3), and 1.373(4) A, respec-
tively, between the classical single- and double-bond lengths. This is
because the rough plane defined by S (1), C (1), C (2), C (3), C (4), C (5),
TABLE III Selected Bond Angles (◦) of 5a
Angle
(◦)
Angle
(◦)
C(5) S(1) C(25)
C(2) N(1) C(6)
C(2) N(2) C(3)
C(3) N(3) C(19)
C(5) N(4) N(3)
O(1) C(1) C(4)
C(4) C(1) N(1)
N(2) C(2) N(1)
N(2) C(3) N(3)
N(3) C(3) C(4)
C(3) C(4) C(5)
N(4) C(5) C(4)
C(4) C(5) S(1)
C(11) C(6) N(1)
C(14) C(13) C(12)
C(17) C(16) F(1)
C(20) C(19) N(3)
100.50(15)
120.6(2)
113.8(2)
130.3(2)
105.0(2)
128.2(3)
112.5(2)
124.7(2)
125.6(2)
107.4(2)
105.1(2)
111.7(2)
126.0(2)
119.7(2)
118.4(3)
118.6(4)
120.9(3)
C(2) N(1) C(1)
C(1) N(1) C(6)
C(3) N(3) N(4)
N(4) N(3) C(19)
C(2) N(5) C(12)
O(1) C(1) N(1)
N(2) C(2) N(5)
N(5) C(2) N(1)
N(2) C(3) C(4)
C(3) C(4) C(1)
C(1) C(4) C(5)
N(4) C(5) S(1)
C(7) C(6) N(1)
N(5) C(12) C(13)
C(18) C(13) C(12)
C(15) C(16) F(1)
C(24) C(19) N(3)
122.2(2)
117.2(2)
110.9(2)
118.7(2)
121.6(2)
119.3(3)
118.2(2)
117.0(2)
127.0(2)
119.6(2)
135.3(3)
122.3(2)
119.6(3)
115.3(2)
123.5(3)
118.8(4)
119.0(3)

Pyrazolo Pyrimidin-4-one Derivatives
2045
TABLE IV The Fungicidal Activities of Compounds 5 (50 mg/l, Inhibitory
Rate %)
Compound
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
Pellicularia sasakii
Cercospora beticola
70.0 40.0 66.0 66.0 84.0 76.0 34.3 48.6 28.8 80.6
66.7 61.1 44.4 61.1 72.2 61.1 18.8 56.2 28.1 15.6
Physalospora piricola 58.3 75.0 33.3 16.7 33.3 75.0 30.3 81.8 36.4 12.1
N (1), N (2), N (3), N (4), O (1), and N (5) atoms is coplanar within the
˚
average deviation of 0.0207 A to form a fully delocalized system. The
six-member ring of C (1), C (2), C (3), C (4), N (1), and N (2) formed a π67
configuration in which the N (1) atom is sp2 hydrobrid, which results in
the formation of the trigonal configurations of the N (1) nitrogen. The
sum of the C (2)-N (1)-C (1), C (2)-N (1)-C (6), and C (1)-N (1)-C (6) bond
angle is 360◦.
The preliminary fungicidal activities of some compounds 5 were mea-
sured in a concentration of 50 mg/l according to the reported method.23
The results of biological assay are given in Table IV. The results showed
that they exhibited good fungicidal activities, especially against Pellic-
ularia sasakii. For example, 5e showed 84.0% inhibitory rate of Pellic-
ularia sasakii at the dosage of 50 mg/l.
EXPERIMENTAL
Melting points were determined with a WRS-1B Digital melting point
apparatus and were uncorrected. EI-MS were measured on a Finnigen-
Trace Mass 2000 Spectrometer, and LC-MS spectra were measured on
API 2000. IR spectra were recorded on an Avatar 360 Spectrometer.
1H NMR spectra were taken on a Varian XL-300 Spectrometer with
TMS as the internal and with CDCl3 or DMSO-d6 as the solvents. Ele-
mentary analyses were recorded on a Vario EL III elementary analysis
instrument. All of the solvents and materials were reagent grade and
purified as required.
5-Aminopyrazole 1 was prepared according to the literature
procedures,24 R1 = Me, yield, 92.6%, m.p. 102.2–103.6◦C; R1 = PhCH2,
yield, 85.6%, m.p. 85.7–86.5◦C.
General Procedure for the Preparation
of Iminophosphoranes 225
For example, when R1 is CH3, a solution of triphenylphosphine (13.1 g,
50 mmol) in dichloromethane (120 ml) at 0◦C was treated with bromine
(8.0 g, 50 mmol). The resulting reaction mixture was stirred at 0◦C for

2046
H.-Q. Wang et al.
30 min and then treated with triethylamine (10.1 g, 100 mmol) followed
immediately by the addition of 5-aminopyrazole 1 (13.9 g, 50 mmol).
After 1 was added, the cooling bath was removed, and the reaction
mixture was allowed to stir at 25◦C for 26 h. The reaction mixture
was washed with water and then dried. After removing the solvent,
the residues were recrystallized with benzene/n-hexane to give 22.63 g
(26.85 g theoretical, 84.28%) of 2 as a pale yellow crystal, m.p. 192.1–
1
193.8◦C. H NMR δ (CDCl3, TMS, 300 MHz): 7.16–7.70 (m, 20H, Ph),
3.61 (q, 2H, J = 7.2Hz), 2.51 (s, 3H), 1.44 (t, 3H, J = 7.2Hz); R1 is PhCH2,
yield, 80.2%, m.p. 162.0–163.2◦C.
General Procedure for the Preparation
of 6-Amino-3-alkylthio-1-phenyl-1,5-dihydro-pyrazolo
[3,4-d]pyrimidin-4-one Derivatives 5 and 6
Phenyl isocyanate (0.36 g, 3 mmol) was added into a solution of
iminophosphorane 2 (1.61 g, 3 mmol) in dry methylene dichloride
(20 ml) under nitrogen at room temperature. After the reaction mix-
ture was stirred for 1.5 h, alkylamine was added to the reaction so-
lution, which was then stirred for 30 min. Then the solvent was re-
moved under reduced pressure, and 25 ml of anhydrous ethanol and
1.5 ml 3 mol/l sodium ethoxide were added to the mixture. After
stirring for 2–5 h at room temperature, the solution was condensed
under reduced pressure. The mixture was cooled and filtered to af-
ford a white solid. Recrystallization from dichloromethane/petroleum
ether or via a silica gel column gave pure 6-alkylamino-3-alkylthio-1,5-
diphenyl-1,5dihydro-pyrazolo[3,4-d]pyrimidin-4-one 5, and recrystal-
lization from acetone/ethanol to give pure 6-phenylamino-3-alkylthio-
1-phenyl-1,5dihydro-pyrazolo-[3,4-d]pyrimidin-4-one 6.
6-( p-Fluorobenzylamino)-3-methylthio-1,5-
diphenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 5a
White crystals, m.p. 201.3–201.6◦C, 1H NMR (CDCl3, 300 MHz) δ 8.00
(d, 2H, J = 7.5 Hz, Ph or p-FC6H4), 7.56 (d, 2H, J= 7.2 Hz, Ph or p-
FC6H4), 7.40 (t, 2H, J= 7.5 Hz, Ph or p-FC6H4), 7.19–7.30 (m, 6H, Ph
or p-FC6H4), 6.98 (t, 2H, J= 8.4 Hz, Ph or p-FC6H4), 4.75 (s, 1H, NH),
4.52 (d, 2H, J= 4.5 Hz, CH2), 2.65 (s, 3H, SCH3); IR (KBr) υ (cm−1):
3425 (N H), 2919 (C H), 1707 (C O), 1597, 1553, 1503 (Ph); MS (70
eV, m/z) (relative intensity %): 458 (M+1, 39), 457 (M+, 79), 424 (22),
272 (42), 185 (89), 109 (100), 91 (19), 77 (73). Elemental Anal. Calcd.
for C25H20FN5OS: C, 65.63; H, 4.41; N, 15.31. Found: C, 65.58; H, 4.38;
N, 15.31.

Pyrazolo Pyrimidin-4-one Derivatives
2047
6-(3-Pyridinemethylamino)-3-methylthio-1,5-diphenyl-
1,5-dihydropyrazolo[3,4-d] pyrimidin-4-one 5b
White crystals, m.p. 222.6–223.8◦C, 1H NMR (CDCl3, 300 MHz) δ 8.49
(d, 2H, J= 4.2 Hz, pyridine), 7.92 (d, 2H, J =7.8 Hz, Ph), 7.22–7.60
(m, 10H, Ph and pyridine), 4.89 (t, 1H, J= 5.4 Hz, NH), 4.57 (d, 2H,
J= 5.4 Hz, NCH2), 2.64 (s, 3H, SCH3); IR (KBr) υ (cm−1): 3430 (N H),
2924(C H), 1698 (C O), 1646, 1598, 1544 (Ph and pyridine); MS (70
eV, m/z) (relative intensity %): 441 (M+1,4), 440 (M+, 34), 333 (2), 107
(16), 92 (100), 77 (52), 65 (46). Elemental Anal. Calcd. for C24H20N6OS:
C, 65.44; H, 4.58; N, 19.08. Found: C, 65.56; H, 4.73; N, 19.29.
6-(2-Pyridinemethylamino)-3-methylthio-1,5-diphenyl-
1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 5c
White crystals, m.p. 227.1–228.4◦C, 1H NMR (CDCl3, 300 MHz) δ 8.34
(d, 1H, J= 2.4 Hz, pyridine), 8.10 (d, 2H, J = 6.9 Hz, Ph), 7.13–7.62 (m,
10H, Ph and pyridine), 5.94 (s, 1H, NH), 4.65 (d, 2H, J= 3.9 Hz, CH2),
2.66 (s, 3H, SCH3); IR (KBr) υ (cm−1): 3441 (N H), 2919 (C H), 1697
(C O), 1598, 1548, 1539 (Ph and pyridine); MS (70 eV, m/z) (relative
intensity %): 441 (M+1, 7), 440 (M+, 26), 349 (12), 168 (12), 93 (13),
92 (12), 77 (100). Elemental Anal. Calcd. for C24H20N6OS: C, 65.44; H,
4.58; N, 19.08. Found: C, 65.33; H, 4.56; N, 18.87.
6-(2-(1-Ethylpyrrolidine)methylamino)-3-methylthio-1,5-
diphenyl-1,5-dihydro-pyrazolo [3,4-d]pyrimidin-4-one 5d
White crystals, m.p. 161.2–162.5◦C, 1H NMR (CDCl3, 300 MHz) δ 8.17
(d, 2H, J= 8.1 Hz, Ph), 7.19–7.56 (m, 8H, Ph), 5.44 (d, 1H, J= 6.0 Hz,
NH), 3.47–3.54 (m, 1H, HNCH2), 3.20–3.26 (m, 1H, HNCH2), 2.77–2.82
(m, 1H, CHN), 2.66 (s, 3H, SCH3), 2.50–2.60 (m, 2H, NCH2CH3), 1.95–
2.08 (m, 2H, CH2), 1.57–1.62 (m, 2H, CH2), 1.30–1.43 (m, 2H, CH2), 0.81
(t, 3H, J= 6.9 Hz, CH3); IR (KBr) υ (cm−1): 3435 (N H), 2967 (C H),
1697 (C O), 1598, 1568, 1554 (Ph); MS (70 eV, m/z) (relative intensity
%): 461 (M+1, 5), 460 (M+, 24), 262 (20), 183 (20), 112 (23), 111 (80),
99 (50), 98 (100), 77 (54). Elemental Anal. Calcd. for C25H28N6OS: C,
65.19; H, 6.13; N, 18.25. Found: C, 64.95; H, 6.01; N, 18.02.
6-(2-Thiophenemethylamino)-3-methylthio-1,5-
diphenyl-1,5-dihydro-pyrazolo[3,4-d] pyrimidin-4-one 5e
White crystals, m.p. 161.6–162.8◦C, 1H NMR (CDCl3, 300 MHz) δ 8.12
(d, 2H, J= 8.1 Hz, Ph), 7.17–7.57 (m, 9H, Ph and thiophene), 6.90

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H.-Q. Wang et al.
(d, 2H, J= 3.6 Hz, thiophene), 4.73–4.76 (m, 3H, NH and CH2), 2.66 (s,
3H, SCH3); IR (KBr) υ (cm−1): 3400 (N H), 2924 (C H), 1698 (C O),
1593, 1548 (Ph); MS (70 eV, m/z) (relative intensity %): 446 (M+1, 47),
445 (M+, 76), 412 (28), 333 (26), 272 (28), 181 (40), 173 (95), 169 (39),
112 (40), 97 (100), 77 (82). Elemental Anal. Calcd. for C25H19N5OS2: C,
62.00; H, 4.30; N, 15.7. Found: C, 61.91; H, 4.25; N, 15.42.
6-(n-Propanylamino)-3-methylthio-1,5-diphenyl-1,5-
dihydro-pyrazolo[3,4-d]pyrimidin-4-one 5f
White crystals, m.p. 205.7–206.5◦C, 1H NMR (CDCl3, 300 MHz) δ
7.20–8.18(10H, m, Ph); 4.342 (1H, s, NH); 3.36 (2H, q, NCH2-, J= 6.3
Hz); 2.66 (3H, s, SCH3); 1.54–1.61 (2H, m, CH2CH2CH3); 0.87 (3H, t,
CH2CH3, J= 7.5 Hz); IR (KBr) υ (cm−1): 3433 (N H), 1702 (C O), 1649,
1598 (Ph); MS (70 eV, m/z) (relative intensity %): 391(M+, 94%), 358
(72), 169 (31), 119 (94), 91 (40), 77 (100); Elemental Anal. Calcd. for
C21H21N5OS: C, 64.43; H, 5.41; N, 17.89. Found: C, 64.56; H, 5.38; N,
17.96.
6-(3-Pyridinemethylamino)-3-benzylthio-1,5-
diphenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 5g
White crystals, m.p. 200.0–203.0◦C, 1H NMR (CDCl3, 300 MHz) δ 8.197
(s, 2H, pyridine), 7.91 (d, 2H, J= 7.8 Hz, Ph), 7.18–7.57 (m, 15H, Ph
and pyridine), 4.82 (t, 1H, J= 5.4 Hz, NH), 4.55 (d, 2H, J= 5.7 Hz, 3-
pyridino-CH2N), 4.45 (s, 2H, PhCH2); IR (KBr) υ (cm−1): 3393 (N H),
1712 (C O), 1596, 1547 (Ph and pyridine); MS (70 eV, m/z) (relative in-
tensity %): 517(M+1, 11), 516 (M+, 28), 483 (68), 426 (12), 3169 (11), 168
(23), 92 (80), 91 (100), 77 (47); Elemental Anal. Calcd. for C30H24N6OS:
C, 69.75; H, 4.68; N, 16.27. Found: C, 69.56; H, 4.61; N, 16.33.
6-(2-Pyridinemethylamino)-3-benzylthio-1,5-
diphenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 5h
White crystals, m.p. 199.0–200.0◦C, 1H NMR (CDCl3, 300 MHz) δ 8.34
(d, 1H, J= 3.9 Hz, pyridine), 8.08 (d, 2H, ph, J= 7.5 Hz), 7.11–7.63
(m, 16H, Ph and pyridine), 5.92 (s, 1H, CH2NH), 4.64 (d, 2H, J= 4.2
Hz, 2-pyridino-CH2N), 4.47 (s, 2H, PhCH2); IR (KBr) υ (cm−1): 3442
(N H), 1684 (C O), 1596, 1542 (Ph and pyridine); MS (70 eV, m/z)
(relative intensity %): 517 (M+1, 23), 516 (M+, 32), 483 (42), 426 (19),
210 (24), 169 (24), 168 (28), 92 (100), 77 (40). Elemental Anal. Calcd.
for C30H24N6OS: C, 69.75; H, 4.68; N, 16.27. Found: C, 69.87; H, 4.61;
N, 16.32.

Pyrazolo Pyrimidin-4-one Derivatives
2049
6-(2-Thiophenemethylamino)-3-benzylthio-1,5-
diphenyl-1,5-dihydro-pyrazolo[3,4-d] pyrimidin-4-one 5i
White crystals, m.p. 213.0–214.0◦C, 1H NMR (CDCl3, 300 MHz) δ 8.11
(d, 2H, J= 7.8 Hz, Ph), 7.16–7.57 (m, 14H, Ph and Thiophene), 6.90 (d,
2H, J= 3.9 Hz, Thiophene), 4.74 (s, 2H, 2-thiophene-CH2N), 4.47 (s, 2H,
PhCH2); IR (KBr) υ (cm−1): 3352 (N H), 2936 (C H), 1695 (C O), 1593,
1539 (Ph); MS (70 eV, m/z) (relative intensity %): 522 (M+1, 19), 521
(M+, 51), 489 (32), 488(100), 392 (22), 319(5), 97(93), 91(92), 77(35).
Elemental Anal. Calcd. for C29H23N5OS2: C, 66.77; H, 4.44; N, 13.43.
Found: C, 66.81; H, 4.46; N, 13.53.
6-(Iso-propanylylamino)-3-benzylthio-1,5-diphenyl-1,5-
dihydro-pyrazolo[3,4-d]pyrimidin-4-one 5j
White crystals, m.p. 169.1–171.7◦C; 1HNMR (CDCl3, 300 MHz) δ: 8.15
(d, 2H, J= 8.1 Hz, Ph), 7.20–7.57 (m, 13H, Ph), 4.47 (s, 2H, PhCH2),
4.16–4.22 (m, 1H, Me2CH), 4.08 (d, 1H, J= 6.6 Hz, NH), 1.16 (d, 6H,
J= 6.6 Hz, Me2); IR (KBr) υ (cm−1): 3429 (N H), 1696 (C O), 1596,
1541 (Ph); MS (70 eV, m/z) (relative intensity %): 469 (M+2, 17), 468
(M+1,50), 467 (M+, 83), 435 (59), 434 (100), 390 (26), 377 (25), 246
(33), 169 (22), 161 (19), 119 (84), 91 (97), 77 (84); Anal. Calcd. for
C27H25N5OS: C, 69.35; H, 5.39; N, 14.98. Found: C, 69.59; H, 5.45; N,
14.72.
3-Methylthio-6-phenylamino-1-phenyl-1,5-dihydro-
pyrazolo[3,4-d]pyrimidin-4-one 6a
1
White crystals, m.p. 344.6–346.2◦C, H NMR (DMSO-d6, 300 MHz) δ
9.70 (br s, 1H, NH), 8.25 (d, 2H, J= 8.0 Hz, Ph), 7.88 (d, 2H, J = 8.0 Hz,
Ph), 750 (t, 2H, J= 8.0 Hz, Ph), 7.29 (t, 2H, J= 7.6 Hz, Ph), 7.22
(t, 1H, J= 7.6 Hz, Ph), 6.91 (t, 1H, J= 7.6 Hz, Ph), 2.595 (s, 3H,
SCH3); IR(cm−1): 3432, 3110 (N H or O H), 1685 (C O, w), 1599,
1551, 1505 (Ph); LC-MS (m/z) (relative intensity %): 350 (M+1, 12),
349 (M, 32), 348 (M-1, 100), 109 (40), 108 (11). Elemental Anal. Calcd.
for C18H15N5OS: C, 61.87; H, 4.33; N, 20.04. Found: C, 61.99; H, 4.38; N,
19.92.
3-Benzylthio-6-phenylamino-1-phenyl-1,5-dihydro-
pyrazolo[3,4-d]pyrimidin-4-one 6b
White crystals, m.p. 247.6–249.2◦C, 1H NMR (DMSO-d6, 300 MHz)
δ 9.96 (br s, 1H, NH), 8.24 (d, 2H, J= 7.6 Hz , Ph), 7.88 (d, 2H,
J= 7.6 Hz, Ph), 7.48–7.52 (m, 4H, Ph), 7.22–7.34 (m, 6H, Ph), 6.91 (t,
1H, J= 7.6 Hz, Ph), 4.54 (s, 2H, SCH2Ph), IR(cm−1): 3403, 3123 (N H

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H.-Q. Wang et al.
or O H), 1687 (C O, w), 1597, 1560, 1506 (Ph); LC-MS (m/z) (relative
intensity %): 426 (M+1, 15), 425 (M, 43), 424 (M-1, 100). Elemental Anal.
Calcd. for C24H19N5OS: C, 67.74; H, 4.50; N, 16.46. Found: C, 67.58; H,
4.56; N, 16.62.
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