Regiospecific synthesis of 6-aryl-3-cyano-5-alkylamino/arylamino-1-p-tolyl- 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones via iminophosphorane-mediated annulation

Article abstract of DOI:10.1016/j.tet.2010.04.114

An efficient and straightforward approach to the synthesis of 6-aryl-3-cyano-5-alkylamino-1-p-tolyl-IH- pyrazolo[4,3-d]pyrimidin-7(6H)-ones 8 has been developed from the readily commercially available starting materials 4-methylaniline and malononitrile i

Full text of DOI:10.1016/j.tet.2010.04.114

Tetrahedron 66 (2010) 5112e5120
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regiospecific synthesis of 6-aryl-3-cyano-5-alkylamino/arylamino-1-p-tolyl-
1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones via iminophosphorane-mediated
annulation
,
b
a
c
d,
Ming-Hu Wu a , Ji-Huan Hu , Dong-Sheng Shen , Paul Brémond , Haibing Guo
*
*
a School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, China
b Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China
c Institut des Sciences Moléculaires de Marseille, Equipe STéRéO, Université Paul Cézanne, Campus Scientifique de St Jérôme, Case 541, Avenue Escadrille Normandie-Niemen,
13397 Marseille Cedex 20, France
d Department of Chemical and Chemical Biology, Harvard University, Cambridge 02138, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and straightforward approach to the synthesis of 6-aryl-3-cyano-5-alkylamino-1-p-tolyl-1H-
pyrazolo[4,3-d]pyrimidin-7(6H)-ones 8 has been developed from the readily commercially available
starting materials 4-methylaniline and malononitrile in five steps. The key to the pyrazolo[4, 3-d]pyr-
imidin-7(6H)-ones relies on an iminophosphorane-mediated annulation, followed by a nucleophilic
addition with amines. The structures of the title compounds are clearly characterized by IR, 1H NMR, MS,
elemental analysis or X-ray diffraction crystallography.
Received 14 March 2010
Received in revised form 25 April 2010
Accepted 26 April 2010
Available online 25 May 2010
Keywords:
Pyrazolo[4,3-d]pyrimidin-7-one
Carbodiimide
Published by Elsevier Ltd.
Iminophosphorane
aza-Wittig reaction
Annulation
Synthesis
1. Introduction
structure have abirritative and hypnotic activities particularly
when they contain a carbonitrile group as, for example, 3-carbon-
Over the past decade, nitrogen-containing heterocyclic mole-
cules have been considered as the privileged synthetic targets in
the pharmaceutical and veterinary industries1 because of the di-
verse biological properties and a wide variety of applications, e.g.,
anticancer, diuretic, anticonvulsant, anti-inflammatory and anti-
hypertensive activities.2 The nitrogen-containing heterocyclic
molecules, particularly with fused heterocyclic, bis-heterocyclic,
multi-heterocyclic structures, have demonstrated a high degree of
binding affinity when they serve as ligands for various biological
receptors.3 The fused-pyrazolo pyrimidinone, a class of pyrazole
derivatives, has been attracted considerable attention for medicinal
chemistry in drug discovery area as nucleosides mimics, such as
cGMP-PDE,4,5 adenosine,6 methionyl t-RNA synthetase,7 DNA pol-
yase,8 release of histamine,9 xanthine oxidase,10 and regulative
CDK2 of cell-division cycle.11 Among the fused-pyrazolo pyr-
imidinones, the molecules bearing pyrazolo[4,3-d]pyrimidin-7-one
itrile-5-methyl-7-substituted pyrazolo[1,5-a]pyridine.12a Also, its
appearance in the structure of zaleplon, which 3-carbonitrile is
probably necessary to maintain the drug’s effect.12b
Several known synthetic approaches to pyrazolo[4,3-d]pyr-
imidin-7-ones have been reported.13,14 The most common and
widely applicable route13 was completed by the cyclization of
4-substituted amido-1H-pyrazole-3-carboxamide under basic
conditions. The other approach involved in a SN2 displacement
of chloride in 5-amino-4,6-dichloropyrimidine with 4-chlor-
oaniline, followed by acylation, cyclocondensation, hydrolysis,
and N-alkylation to form the pyrazolo pyrimidinones.15 How-
ever, the key intermediate 4-substituted amido-1H-pyrazole-
3-carboxamide in these reported methods was synthesized with
tedious synthetic route. In addition, 5-amino substituted
pyrazolo[4,3-d]pyrimidin-7-ones are not easily accessible by
currently existing routes.
Aza-Wittig-mediated annulation has been widely used for the
synthesis of nitrogen-containing heterocyclic compounds15,16, for
example, the synthesis of quinzazolinones via an aza-Wittig reac-
tion.16e,f,m However the synthesis of pyrazolo[4,3-d]pyrimidin-7-
* Corresponding authors. E-mail addresses: minghuwu@hotmail.com (M.-H. Wu),
haibingguojj@yahoo.com (H. Guo).
0040-4020/$ e see front matter Published by Elsevier Ltd.
doi:10.1016/j.tet.2010.04.114

M.-H. Wu et al. / Tetrahedron 66 (2010) 5112e5120
5113
onesbymeans of tandemaza-Wittig reactions of iminophosphorane
annulation with aryl isocyanates and amines has received less at-
tention. In continuationwith ourongoing heterocyclic synthesis and
drug discovery project,17 we have focused on the synthesis of
quinzazolinones and other fused-heterocyclic pyrimidinone.
Herein, we report an efficient approach to the synthesis of a new
series of 6-aryl-3-cyano-5-alkylamino-1-p-tolyl-1H-pyrazolo[4,3-
d]pyrimidin-7(6H)-ones 8 via iminophosphorane-mediated annu-
lation with aromatic isocyanates, followed by nucleophilic addition
with amines. Our convenient synthetic approach begins with an
easy availability of starting material to synthesize functionalized
fused-pyrazolo pyrimidinones. This method is potentially very
useful in medicinal chemistry, as well as in synthetic and
coordination chemistry.
With iminophosphorane 5 in hand, we next turned our at-
tention to the synthesis of final products 6-aryl-3-cyano-5-
alkylamino-1-p-tolyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H) -ones 8
(Scheme 2), which were obtained via aza-Wittig reaction and
subsequent pyrimidinone formation in two steps. Iminophos-
phorane 5 was first treated with aromatic isocyanates to form
carbodiimides 6 by the aza-Wittig reaction in good yields (76%).
The reaction proceeded smoothly in mild conditions (0e5 ꢀC)
and was completed in 12 h. The carbodiimides 6 were then
conveniently converted to 6-aryl-3-cyano-5-alkylamino-1-p-
tolyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H) -ones 8 (see Table 1)
with aliphatic or aryl primary/secondary amines. Specifically,
a nucleophilic addition of amines to the carbodiimide cumulenic
system gave the highly reactive guanidine intermediates 7,
which in turn underwent intramolecular hetero-conjugate an-
nulation to produce the 6-aryl-3-cyano-5-alkylamino-1-p-tolyl-
1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones 8. When primary
amines were used, a small amount of potential regioisomers 9
(less than 5%) were observed as minor products and detected by
LC/MS. Regardless of the presence or absence of EtONa/EtOH, the
annulation could be accomplished smoothly to provide the title
compounds 8 in good to excellent yields (70e97%, see Table 1).
No significant differences in yields of producing the title com-
pounds 8 were observed when a phenyl group at C-6 position
was used for the final cyclization. Switching the phenyl group to
an electronic withdrawing group (4-F-phenyl, 4-Cl-phenyl) or an
electronic donating group (4-CH3ephenyl) resulted in more than
92% yields to compounds 8 in several cases (8j, 8s, 8u, 8K, 8L).
Either primary or sterically hindered secondary amines as nu-
cleophiles in the annulation were not found to make significant
difference for final yields of the synthesis of compounds 8,
whereas the reaction kinetics was significantly affected by the
sterically hindered amines, such as cases 8h, 8m, 8o, 8t, 8D, 8E,
8I, 8J, 8N.
2. Results and discussion
Our strategy to 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones com-
menced with the commercially available starting material p-tolui-
dine (Scheme 1). The dicyanohydrazone 2 was synthesized by
a one-pot protocol, which involved diazotization, followed by
treatment with malononitrile in 99% yield. The hydrazone 2 was
converted into 4-aminopyrazole 3 in 60% yield by an N-alkylation
and in situ cyclization under basic conditions (K2CO3, DMF, 90 ꢀC).
Diazotization of 4-amino-1H-pyrazole-5-carboxylate 3 with HCl/
NaNO2 and subsequent azidation afforded the 4-azido-pyrazole,
which was converted to iminophorane 5 with triphenylphosphine
in a low yield (28% in two steps). To efficiently synthesize imino-
phorane 5, an improved one-step procedure has been developed,
which easily provided the important intermediate iminophorane 5
with a satisfactory yield (76%). Indeed, treatment of 4-amino-1H-
pyrazole-5-carboxylate 3 with triphenylphosphine smoothly gen-
erated iminophosphorane 5 in presence of weakly basic conditions
(Et3N).
CH3
NC
HN
CN
CH3
CH3
CH3
N
NH2
a
b
g
N
f
N
N
CO2Et
N
N
N
N
N
CO2Et
NHAr
N
N
CO2Et
NAr
NC
CO2Et
PPh3
CH3
NC
CH3
NH2
NC
NC
N
C
C
NRR'
1
2
3
5
6
7
e
CH3
CH3
CH3
CH3
O
O
+
Ar
R'R
N
N
N
N
N
N
d
c
N
3
N
R'R
N
N
N
Ar
N
H
N
N
H
CO2Et
PPh3
CN
CN
CO2Et
NC
NC
8
9
N
N3
R, R' = H or alkyl, Ar = C6H5, 4-F-C6H4, 4-Cl-C6H4, 4-CH3-C6H4
4
5
Scheme 1. Synthesis of iminophorane 5. Reagents and conditions: a. NaNO2, MeOH,
HCl/H2O, 0 ꢀC, then NCCH2CN, NaOAc, H2O (99%); b. BrCH2CO2Et, K2CO3, DMF, 90 ꢀC,
6e7 h (60%); c. NaNO2, TFA, 0 ꢀC, then NaN3 (70%); d. Ph3P, CH2Cl2, rt, 6 h (40%); e.
Ph3P, C2Cl6, Et3N, CH3CN, rt, 5 h (76%).
Scheme 2. Synthesis of 6-aryl-3-cyano-5-alkylamino-1-p-tolyl-1H-pyrazolo[4, 3-d]
pyrimidin-7(6H)-ones. Reagents and conditions: f. ArNCO, CH2Cl2, 0e5 ꢀC, 12 h; g.
RR0NH, CH2Cl2, rt, 6e12 h. When primary amine is used, 8 is the major product
(73e96%), whereas when secondary amine is used, 8 is the sole product (70e97%).

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M.-H. Wu et al. / Tetrahedron 66 (2010) 5112e5120
Table 1
Preparation of 6-aryl-3-cyano-5-alkylamino/arylamino-1-p-tolyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones 8a.
Entry
Aryl
R R0
Time (h)
Yield (%)b
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
8p
8q
8r
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-FePh
4-FePh
4-FePh
4-FePh
4-FePh
4-FePh
4-FePh
4-ClePh
4-ClePh
4-ClePh
4-CH3ePh
4-CH3ePh
4-CH3ePh
4-CH3ePh
4-CH3ePh
Ph
n-C3H7NH
n-C4H9NH
Cyclohexylamino
t-C4H9NH
(R)-a-Phenylethylamino
6
6
12
12
6
8
6
12
6
6
86
75
88
82
81
78
80
83
84
93
87
88
79
86
85
78
73
86
92
77
94
96
73
80
83
78
70
75
85
82
79
76
97
95
72
82
81
79
PhNH
PhCH2NH
i-C3H7NH
n-C3H7NH
n-C3H9NH
Cyclohexylamino
t-C4H9NH
(R)-a-Phenylethylamino
PhCH2NH
i-C3H7NH
n-C3H7NH
PhCH2NH
n-C4H9NH
PhCH2NH
i-C3H7NH
n-C3H7NH
Cyclohexylamino
(n-C4H9)2N
(CH2)5N
(n-C3H7)2N
(i-C3H7)2N
(n-C6H13)2N
(n-C4H9)2N
(CH2)5N
(n-C3H7)2N
(i-C3H7)2N
(n-C6H13)2N
(n-C3H7)2N
(n-C4H9)2N
(CH2)5N
6
12
12
6
12
6
8
6
6
12
6
8
8
8
8
12
12
8
8
8
12
12
8
8
8
12
8
8
8s
8t
8u
8v
8A
8B
8C
8D
8E
8F
8G
8H
8I
Ph
Ph
Ph
4-FePh
4-FePh
4-FePh
4-FePh
4-FePh
4-ClePh
4-ClePh
4-ClePh
4-CH3ePh
4-CH3ePh
4-CH3ePh
8J
8K
8L
8M
8N
8O
8P
(n-C5H11)2N
(CH2)5N
(n-C4H9)2N
a
The reactions were carried out according to general experimental procedure.
Isolated yields are based on iminophosphorane 5.
b
As for the regioselectivity of annulation between the
a
- or
Furthermore, single-crystal X-ray analyses of products 8u and 8H
b-ethoxylcarbonyl carbodiimines and amines seems to be con-
allowed us to ascertain the structures (Figs 1 and 2).
troversial, 6-alkylamino substituted heterocycle was reported as
the major or the only products,18,19 whereas the 6-arylamino
substituted heterocycle was produced as the sole product in the
literature.19 The regioselectivity in our approach was similar to
that reported by Liu.16e Finally, the completely pure 6-aryl-3-cy-
ano-5-alkylamino-1-p-tolyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)
-ones 8 were easily obtained after recrystallization in EtOH and
CH2Cl2.
The structures of the title compounds 8 were confirmed by
spectral data: 1H NMR, GC/MS, IR, and X-ray analysis. For example,
the 1H NMR spectra of the compound 8a show the signal of NH at
4.20 ppm as a triplet and NCH2 at 3.41 ppm as a quartet, which
unambiguously demonstrates the existence of NHCH2CH2CH3
group in the compound 8a. The other signals at 7.62e7.21 (m, 9H,
AreH), 2.37 (s, 3H, CH3Ar), 1.51e1.64 (m, 2H, CH2CH3) and 0.86 (t,
3H, J¼7.2 Hz, CH2CH3) ppm are also in agreement with its structure.
The IR spectra of 8a exhibit a strong stretching resonance peak at
1709 cmꢁ1, which indicates the presence of a C]O bond. The MS
spectra of 8a show Mþ at m/z 384 with 94% abundance. The 1H NMR
spectra of 8A show the signals of NCH2 at 3.03 ppm as a triplet, and
the other signals appear at 7.56e7.23 (m, 9H, AreH), 2.38 (s, 3H,
CH3Ar), 1.23e1.12 (m, 8H, 2CH2CH2CH3) and 0.84 (t, 6H, J¼7.2 Hz,
2CH2CH2CH3) ppm. The IR spectra of 8A show the strong stretching
resonance peak of C¼O at 1707 cmꢁ1. It is also confirmed by the MS
spectra of 8A show Mþ at m/z 455 with 45% abundance.
3. Conclusion
In conclusion, a series of 6-aryl-3-cyano-5-alkylamino-1-p-tolyl-
1H-pyrazolo [4,3-d] pyrimidin-7(6H)-ones 8 have been synthesized
by a practical and efficient synthetic approach. The tandem aza-
Wittig reaction of iminophosphorane and the subsequent in-
termolecular nucleophilic annulation with different amines have
been utilized for the formation of pyrimidinone ring. This attractive
synthetic route provides 6-aryl-3-cyano-5-alkylamino-1-p-tolyl-
1H-pyrazolo [4,3-d] pyrimidin-7(6H)-ones 8 in good to excellent
yields (70e97%) at final annulation reaction in presence of primary
amines or sterically hindered secondary amines. The approach is
also amenable to the synthesis of the other functionalized fused-
heterocyclic compounds. Further application of this approach to the
synthesis of other class of pyrazolo pyrimidinones and biological
testing are currently ongoing and will be reported in due course.
4. Experimental section
4.1. General procedures
1H NMR were recorded in CDCl3 on a Varian Mercury 400
spectrometer and resonance are given in ppm (
Mass spectra were obtained on a Finnigan trace MS spectrometer.
d) relative to TMS.

M.-H. Wu et al. / Tetrahedron 66 (2010) 5112e5120
5115
Figure 1. Crystal structure of 8u.
Figure 2. Crystal structure of 8h.
Melting points were recorded on X-4 electrothermal melting point
apparatus and were uncorrected. Elemental analyses were de-
termined on a 2400 PerkineElmer elemental analysis instrument.
this temperature. After cooling to room temperature, the reaction
mixture was poured into ice water, and the resulting reside was
collected, washed with water and dried to afford brick red solid 3
(8.1 g, 30 mmol, yield 60%), mp: 121e122 ꢀC. IR (KBr):
n
¼3440 (NH),
2232 (CN), 1729 (C]O), 1623, 1513, 1291 cmꢁ1. 1H NMR (400 MHz,
CDCl3):
¼7.29e7.25 (m, 4H, AreH), 4.75(s, 2H, NH2), 4.23 (q, 2H,
J¼7.2 Hz, OCH2CH3), 2.42 (s, 3H, CH3Ar), 1.17 (t, 2H, J¼7.2 Hz,
CH2CH3) ppm. 13C NMR (MHz, CDCl3):
4.1.1. Preparation of p-tolylcarbonohydrazonoyl dicyanide 2. Com-
pound 2 was prepared according to the improved method de-
scribed in the literature.20 To a mixture of p-anisidine (10.72 g,
0.1 mol), MeOH (100 mL), water (50 mL), and concd HCl (60 mL),
was added dropwise a solution of NaNO2 (7.60 g, 0.11 mol) in water
(20 mL) at 0 ꢀC. The reaction mixture was stirred for 15 min. Then
to the reaction mixture, a solution of NaOAc (12 g) in water (20 mL)
was added dropwise followed by a solution of malononitrile (6.61 g,
0.1 mol), NaOAc (78 g), and water (130 mL), and the reaction mix-
ture was stirred for additional 30 min. The reaction mixture was
filtered, and the residual was washed with water and dried to afford
the yellow solid, (18.23 g, 99 mmol, yield 99%), mp: 154e155 ꢀC. IR
d
d
¼14.2, 21.4, 60.6, 114.4,
117.7, 123.8, 125.1, 128.6, 129.6, 135.9, 136.8, 160.5 ppm. MS: m/z
(%)¼271 (11, [Mþ1]þ), 270 (100, Mþ), 242 (19), 143(28), 117(88), 91
(50), 65(16). Anal. Calcd for C14H14N4O2 (270.29): C, 62.21; H, 5.22;
N, 20.73. Found: C, 62.35; H, 5.21; N, 20.77.
4.1.3. Synthesis of the iminophosphorane 5. 4-Aminopyrazole-car-
boxylate 3 (2.70 g, 0.01 mol), triphenylphosphine (7.87 g, 0.03 mol),
and hexachloroethane(7.10 g, 0.03 mol) was dissolved in MeCN
(50 mL). After stirred 15 min, triethylamine (6.07 g, 0.06 mol) was
added dropwise to the reaction mixture and stirred for 5 h at room
temperature. The reaction mixture was poured into an ice water
(500 mL), extracted with CH2Cl2 (3ꢂ200 mL), dried under anhy-
drous CaCl2, and concentrated to afford the crude residue, which
was recrystallized with anhydrous ethanol to give white solid 5
(KBr):
n
¼3448 (NH), 2245 (CN), 1625, 1513, 1291 cmꢁ1
.
1H NMR
(400 MHz, CDCl3):
d
¼9.61 (s, 1H, NH), 7.29e7.19 (m, 4H, AreH), 2.37
(s, 3H, CH3) ppm. 13C NMR (MHz, CDCl3):
d
¼21.4, 84.5, 112.2, 116.4,
129.7, 131.3, 140.4 ppm. MS: m/z (%)¼184 (46, Mþ). Anal. Calcd for
C10H8N4 (184.20): C, 65.21; H, 4.38; N, 30.42. Found: C, 63.31; H,
4.37; N, 30.40.
(4.02 g, 7.6 mmol, yield 76%), mp: 116e117 ꢀC IR (KBr):
(NH), 2232 (CN), 1731 (C]O), 1624, 1557, 1514, 1449, 1411,
1291 cmꢁ1. 1H NMR (400 MHz, CDCl3):
¼7.81e7.15 (m, 19H, AreH),
n
¼3367
4.1.2. Preparation of ethyl 4-amino-3-cyano-1-p-tolyl-1H-pyrazole-
5-carboxylate 3. Compound 3 was prepared according to the im-
proved method described in the literature.19 To a stirring mixture of
2 (9.21 g, 0.05 mol), K2CO3 (6.91 g, 0.05 mol) in DMF (120 mL), was
dropwise added bromoacetate (8.35 g, 0.05 mol) at room temper-
ature. The reaction mixture heated to 90 ꢀC and stirred for 6 h at
d
3.91 (q, 2H, J¼7.2 Hz, OCH2CH3), 2.38 (s, 3H, CH3Ar), 0.99 (t, 3H,
J¼6.8 Hz, OCH2CH3) ppm. 13C NMR (MHz, CDCl3):
¼14.2, 21.4, 60.6,
d
109.1,114.4,125.1,128.6, 128.8,129.6,131.2,132.4,132.6,134.7,135.8,
136.8, 160.5 ppm. MS: m/z (%), 531 (34, [Mþ1]þ), 530 (100, Mþ), 457

5116
M.-H. Wu et al. / Tetrahedron 66 (2010) 5112e5120
(39), 288 (36), 183 (63), 91 (59), 77 (19), 65 (15). Anal. Calcd for
C32H27N4O2P (530.57): C, 72.44; H, 5.13; N, 10.56. Found: C, 72.27;
H, 5.14; N, 10.50.
C23H22N6O (398.47): C, 69.33; H, 5.56; N, 21.09. Found: C, 69.30; H,
5.56; N, 21.08.
4.3.5. (R)-3-Cyano-6-phenyl-5-(a-phenylethylamino)-1-p-tolyl-1H-
4.2. General procedure for synthesis of the carbodiimide 6
pyrazolo[4,3-d] pyrimidin-7(6H)-one (8e). White crystals; mp:
130e132 ꢀC. IR (KBr):
¼3409 (NH), 2242 (CN), 1670 (C]O), 1571,
1531, 1489, 1297 cmꢁ1. 1H NMR (400 MHz, CDCl3):
n
To a solution of iminophosphorane 5 (1.59 g, 3.0 mmol) in an-
hydrous THF (10 mL) was added rapidly aryl isocyanate (3.0 mmol)
at room temperature. The reaction mixture was left unstirred for
6e12 h at 0e5 ꢀC to generate carbodiimides 6, which were used
directly for next step without further purification.
d¼7.63e7.21 (m,
14H, AreH), 5.36 (s, 1H, NCH), 4.42 (s, 1H, HN), 3.37 (s, 3H, CH3Ar),
1.44 (d, 3H, J¼6.4 Hz, CHCH3) ppm. 13C NMR (100 MHz, CDCl3):
d
¼21.3, 22.0, 51.4, 113.2, 118.4, 121.7, 124.5, 126.4, 127.1, 128.1, 128.7,
129.6, 130.5, 131.6, 136.4, 137.8, 139.9, 141.7, 143.5, 148.5, 153.0 ppm.
MS: m/z (%)¼446 (100, Mþ), 342 (42), 341 (77), 120 (16), 105 (52),
103 (16), 77 (21). Anal. Calcd for C27H22N6O (446.19): C, 72.62; H,
4.97; N, 18.83. Found: C, 72.65; H, 4.96; N, 18.85.
4.3. General procedure for synthesis of the title compound 8
To the reaction mixture of 6 (3.0 mmol), was added a little ex-
cessive alkylamine or dialkylamine (3.1 mmol) at room tempera-
ture. The reaction mixture was allowed to stir for 6e12 h,
condensed and the crude residue was recrystallized with EtOH and
CH2Cl2 to give 8 in 70e97% yields.
4.3.6. 3-Cyano-6-phenyl-5-phenylamino-1-p-tolyl-1H-pyrazolo[4,3-
d]pyrimidin-7(6H)-one (8f). White crystals; mp >250 ꢀC (nobody
give this number). IR (KBr):
1601, 1547, 1290 cmꢁ1. 1H NMR (400 MHz, CDCl3):
14H, AreH), 6.06 (s, 1H, HN), 2.39 (s, 3H, CH3Ar) ppm. 13C NMR
(100 MHz, CDCl3):
n
¼3408 (NH), 2233 (CN), 1719 (C]O),
d
¼7.57e7.00 (m,
4.3.1. 3-Cyano-6-phenyl-5-propylamino-1-p-tolyl-1H-pyrazolo[4,3-
d]pyrimidin-7(6H)-one (8a). White crystals; mp: 177e178 ꢀC. IR
d¼21.4, 113.5, 118.4, 121.1, 121.8, 122.3, 124.3,
128.7, 129.1, 129.6, 130.5, 131.5, 136.4, 137.6, 138.3, 139.6, 143.7,
148.8, 153.1 ppm. MS: m/z (%)¼419 (100, [Mþ1]þ), 418 (56, Mþ), 417
(56, [Mþ1]þ), 327 (8), 91 (5), 77 (8). Anal. Calcd for C25H18N6O
(418.46): C, 71.76; H, 4.34; N, 20.08. Found: C, 71.80; H, 4.35; N,
20.09.
(KBr):
n
¼3367 (NH), 2236 (CN), 1709 (C]O), 1568, 1487, 1260 cmꢁ1
.
1H NMR (400 MHz, CDCl3):
d
¼7.62e7.21 (m, 9H, AreH), 4.20 (s, 1H,
HN), 3.41 (q, 2H, J¼6.8 Hz, NCH2), 2.37 (s, 3H, CH3Ar), 1.51e1.64 (m,
2H, CH2CH3), 0.86 (t, 3H, J¼7.2 Hz, CH2CH3) ppm. 13C NMR
(100 MHz, CDCl3):
d
¼11.5, 21.4, 24.6, 44.0, 112.9, 118.3, 121.0, 124.5,
128.7, 129.4, 130.7, 131.7, 134.1, 136.5, 139.3, 143.6, 148.8, 153.3 ppm.
MS: m/z (%)¼384 (94, Mþ), 341 (100), 266 (7), 143 (13), 117 (22), 91
(54), 77 (46), 65 (15). Anal. Calcd for C22H20N6O (384.44): C, 68.73;
H, 5.24; N, 21.86. Found: C, 68.80; H, 5.23; N, 21.85.
4.3.7. 5-Benzylamino-3-cyano-6-phenyl-1-p-tolyl-1H-pyrazolo[4,3-
d]pyrimidin-7(6H)-one (8g). White crystals; mp >250 ꢀC. IR (KBr):
n
¼3403 (NH), 2234 (CN), 1704 (C]O), 1567, 1534, 1460, 1294 cmꢁ1
.
1H NMR (400 MHz, CDCl3):
d
¼7.61e7.22 (m, 14H, AreH), 4.65 (d,
2H, J¼5.6 Hz, NCH2), 4.55 (s, 1H, HN), 2.37 (s, 3H, CH3Ar) ppm. 13
C
4.3.2. 5-Butylamino-3-cyano-6-phenyl-1-p-tolyl-1H-pyrazolo[4,3-d]
pyrimidin-7(6H)-one (8b). White crystals; mp: 186e187 ꢀC. IR
NMR (100 MHz, CDCl3):
d¼21.3, 45.5, 112.7, 118.4, 121.7, 124.5, 126.6,
127.0, 128.1,128.9, 129.5,130.8,131.7,136.4,137.8, 138.3, 139.8, 143.7,
148.6, 153.0 ppm. MS: m/z (%)¼433 (28, [Mþ1]þ), 432 (18, Mþ), 431
(8, [Mꢁ1]þ), 182 (18), 167 (82), 91 (100), 77 (18). Anal. Calcd for
C26H20N6O (432.48): C, 72.21; H, 4.66; N, 19.43. Found: C, 72.33; H,
4.65; N, 19.40.
(KBr):
n
¼3403 (NH), 2242 (CN), 1702 (C]O), 1579, 1488, 1242 cmꢁ1
.
1H NMR (400 MHz, CDCl3):
d
¼7.62e7.21 (m, 9H, AreH), 4.15 (s, 1H,
HN), 3.44 (q, 2H, J¼6.8 Hz, NCH2), 2.37 (s, 3H, CH3Ar), 1.51e1.25 (m,
4H, CH2CH2CH3), 0.903 (t, 3H, J¼7.2 Hz, CH2CH3) ppm. 13C NMR
(100 MHz, CDCl3):
d¼14.0, 20.5, 21.5, 30.1, 42.0, 112.5, 118.6, 121.5,
124.7, 128.7, 129.4, 130.8, 131.7, 136.4, 137.7, 139.6, 143.7, 148.5,
153.0 ppm. MS: m/z (%)¼398 (84, Mþ), 367 (4), 356 (53), 341 (100),
266 (10), 143 (18), 117.2 (23), 106 (23), 91 (65), 77 (37), 65 (15). Anal.
Calcd for C23H22N6O (398.47): C, 69.33; H, 5.56; N, 21.09. Found: C,
69.34; H, 5.53; N 21.10.
4.3.8. 3-Cyano-5-isopropylamino-6-phenyl-1-p-tolyl-1H-pyrazolo
[4,3-d]pyrimidin-7(6H)-one (8h). White crystals; mp: 178e179 ꢀC.
IR (KBr):
n
¼3418 (NH), 2234 (CN), 1710 (C]O), 1575, 1525,
1291 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.62e7.22 (m, 9H, AreH),
4.33 (s, 1H, HN), 3.92 (m, 1H, CCHC), 2.36 (s, 3H, CH3Ar), 1.14 (d, 6H,
J¼6.8 Hz, 2(CH3)2C) ppm. 13C NMR (100 MHz, CDCl3):
¼21.2, 23.8,
d
4.3.3. 3-Cyano-5-cyclohexylamino-6-phenyl-1-p-tolyl-1H-pyrazolo
[4,3-d]pyrimidin-7(6H)-one (8c). White crystals; mp: 227e229 ꢀC.
42.9, 112.8, 118.7, 121.7, 124.5, 128.9, 129.5, 130.9, 131.7, 136.5, 137.7,
139.7, 143.8, 148.5, 153.2 ppm. MS: m/z (%)¼384 (53, Mþ), 369 (6),
359 (12), 341 (100), 266 (12), 117 (41), 91 (43), 77 (41). Anal. Calcd
for C22H20N6O (384.44): C, 68.73; H, 5.24; N, 21.86. Found: C, 68.60;
H, 5.23; N, 21.90.
IR (KBr):
1291 cmꢁ1. 1H NMR (400 MHz, CDCl3):
4.01 (s, 1H, HN), 2.35 (s, 3H, CH3Ar), 1.95e1.03 (m, 11H, (CH2)5CH)
ppm. 13C NMR (100 MHz, CDCl3):
n
¼3398 (NH), 2234 (CN), 1712 (C]O), 1567, 1489,
d
¼7.62e7.22 (m, 9H, AreH),
d
¼21.2, 24.8, 25.8, 32.9, 50.8,
112.7, 118.4, 121.7, 124.5, 128.9, 129.5, 130.9, 131.7, 136.5, 137.7, 139.7,
143.8, 148.5, 153.2 ppm. MS: m/z (%)¼425 (82, [Mþ1]þ), 367 (9),
341 (100), 225 (6), 143 (10), 117 (16), 91 (29), 77 (29), 67 (10). Anal.
Calcd for C25H24N6O (424.51): C, 70.72; H, 5.70; N, 19.81. Found: C,
70.76; H, 5.69; N, 19.83.
4.3.9. 3-Cyano-6-(4-fluorophenyl)-5-propylamino-1-p-tolyl-1H-pyr-
azolo[4,3-d]pyrimidin-7(6H)-one
221e222 ꢀC. IR (KBr):
¼3360 (NH), 2241 (CN), 1709 (C]O), 1571,
1435, 1294 cmꢁ1. 1H NMR (400 MHz, CDCl3):
(8i). White
crystals;
mp:
n
d
¼7.55e7.22 (m, 8H,
AreH), 4.19 (s, 1H, HN), 3.42 (q, 2H, J¼7.2 Hz, NCH2), 2.38 (s, 3H,
CH3Ar), 1.59e1.53 (m, 2H, CH2CH3), 0.87 (t, 3H, J¼7.2 Hz, CH2CH3)
4.3.4. 5-tert-Butylamino-3-cyano-6-phenyl-1-p-tolyl-1H-pyrazolo
[4,3-d]pyrimidin-7(6H)-one (8d). White crystals; mp: 219e220 ꢀC.
ppm. 13C NMR (100 MHz, CDCl3):
d
¼11.5, 21.3, 23.8, 42.5, 113.1,
115.5, 118.8, 121.8, 124.7, 129.8, 131.8, 136.4, 137.87, 139.8, 143.8,
148.9, 153.0, 163.2 ppm. MS: m/z (%)¼404 (34, [Mþ2]þ), 402 (100,
Mþ), 373 (5), 361 (23), 359 (69), 344 (6),117 (5), 91 (10), 89 (7). Anal.
Calcd for C22H19FN6O (402.43): C; 65.66; H, 4.76; N, 20.88. Found: C,
65.68; H, 4.75; N, 20.82.
IR (KBr):
1294 cmꢁ1. 1H NMR (400 MHz, CDCl3):
4.05 (s, 1H, HN), 2.37 (s, 3H, CH3Ar), 1.39 (s, 9H, (CH3)3C) ppm. 13
NMR (100 MHz, CDCl3):
128.8, 129.2, 130.8, 131.8, 136.4, 137.5, 139.7, 143.6, 148.5, 153.1 ppm.
MS: m/z (%)¼398 (23, Mþ), 377 (5), 342 (41), 341 (100), 225 (4), 143
(10), 117 (27), 91 (34), 77 (26), 65 (13), 57(16). Anal. Calcd for
n
¼3426 (NH), 2237 (CN), 1709 (C]O), 1567, 1456,
d
¼7.60e7.21 (m, 9H, AreH),
C
d¼21.3, 30.1, 53.6, 112.4, 118.8, 122.0, 124.7,
4.3.10. 5-Butylamino-3-cyano-6-(4-fluorophenyl)-1-p-tolyl-1H-pyr-
azolo [4,3-d]pyrimidin-7(6H)-one (8j). White crystals; mp

M.-H. Wu et al. / Tetrahedron 66 (2010) 5112e5120
5117
206.5e207.5 ꢀC. IR (KBr):
1602, 1579, 1513, 1290 cmꢁ1
¼7.56e7.23 (m, 8H, AreH), 4.11 (s, 1H, HN), 3.45 (q, 2H, J¼7.2 Hz,
n
¼3397 (NH), 2248 (CN), 1699 (C]O),
137.6, 139.7, 143.8, 148.6, 153.0, 163.1 ppm. MS: m/z (%)¼403 (36,
[Mþ1]þ), 402 (100, Mþ), 387 (11), 359 (93), 344 (12), 266 (15), 117
(15), 91 (40). Anal. Calcd for C22H19FN6O (402.43): C, 65.66; H, 4.76;
N, 20.88. Found C, 65.60; H, 4.77; N, 20.82.
.
1H NMR (400 MHz, CDCl3):
d
NCH2), 2.38 (s, 3H, CH3Ar), 1.56e1.26 (m, 4H, CH2CH2C), 0.92 (t, 3H,
J¼7.2 Hz, CH2CH3) ppm. 13C NMR (100 MHz, CDCl3):
¼13.9, 20.2,
d
21.5, 32.6, 42.2, 112.7, 115.4, 118.4, 121.7, 124.5, 130.5, 131.7, 136.3,
137.5, 139.8, 143.7, 148.5, 153.1, 162.9 ppm. MS: m/z (%)¼418 (23,
[Mþ2]þ), 416 (100, Mþ), 387 (14), 374 (49), 360 (83), 344 (11), 225
(4), 250 (5), 195 (5),117 (17) 109 (48), 95 (27), 91 (30), 75 (5), 65(14).
Anal. Calcd for C23H21FN6O (416.46): C, 66.33; H, 5.08; N, 20.18.
Found: C, 66.30; H, 5.09; N, 20.14.
4.3.16. 6-(4-Chlorophenyl)-3-cyano-5-propylamino-1-p-tolyl-1H-
pyrazolo[4,3-d]pyrimidin-7(6H)-one (8p). White crystals; mp:
207.5e208.5 ꢀC. IR (KBr):
n
¼3369 (NH), 2240 (CN), 1708 (C]O),
1575, 1488, 1295 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.59e7.22 (m,
8H, AreH), 4.14 (s, 1H, HN), 3.42 (q, 2H, J¼7.2 Hz, NCH2), 2.38 (s, 3H,
CH3Ar), 1.59e1.53 (m, 2H, CH2CH3), 0.88 (t, 3H, J¼7.6 Hz, CH2CH3)
ppm. 13C NMR (100 MHz, CDCl3):
d¼11.3, 21.5, 23.4, 42.2, 112.9,
4.3.11. 3-Cyano-5-cyclohexylamino-6-(4-fluorophenyl)-1-p-tolyl-
1H-pyrazolo [4,3-d] pyrimidin-7(6H)-one (8k). White crystals; mp:
115.4,118.3,121.0, 124.6,128.9, 130.5, 131.7, 133.3,137.5, 139.8, 145.8,
150.9, 153.3 ppm. MS: m/z (%)¼420 (11, [Mþ2]þ), 419 (21, [Mþ1]þ),
375 (99), 117 (69), 91(100). Anal. Calcd for C22H19ClN6O (418.89): C,
63.08; H, 4.57; N, 20.06. Found: C, 63.13; H, 4.56; N, 20.01.
215.5e216 ꢀC. IR (KBr):
n
¼3426 (NH), 2235 (CN), 1714 (C]O), 1601,
1567, 1489, 1254 cmꢁ1. 1H NMR (400 MHz, CDCl3):
¼7.56e7.23 (m,
8H, AreH), 3.98 (s, 1H, HN), 2.38 (s, 3H, CH3Ar), 1.97e1.04 (m, 11H,
(CH2)5CH) ppm. 13C NMR (100 MHz, CDCl3):
d
d
¼21.5, 24.9, 25.9, 32.6,
4.3.17. 5-Benzylamino-6-(4-chlorophenyl)-3-cyano-1-p-tolyl-1H-
pyrazolo[4,3-d]pyrimidin-7(6H)-one (8q). White crystals; mp
50.0, 113.0, 115.7, 118.3, 121.6, 124.3, 130.5, 131.5, 136.2, 137.7, 139.7,
143.6, 148.4, 153.0, 163.0 ppm. MS: m/z (%)¼444 (12, [Mþ2]þ), 442
(58, Mþ), 385 (6), 361 (100), 359 (100), 344 (4), 225 (3), 117 (5), 95
(7), 91(9), 65 (5), 55 (9). Anal. Calcd for C25H23FN6O (442.50): C,
67.86; H, 5.24; N, 18.99. Found: C, 67.90; H, 5.24; N, 19.01.
200e202 ꢀC. IR (KBr):
n
¼3378 (NH), 2241 (CN), 1702 (C]O), 1571,
1512, 1254 cmꢁ1. 1H NMR (400 MHz, CDCl3):
¼7.56e7.22 (m, 13H,
AreH), 4.64 (d, 2H, J¼5.6 Hz, NCH2), 4.53 (s, 1H, HN), 2.44 (s, 3H,
CH3Ar) ppm. 13C NMR (100 MHz, CDCl3):
d
d
¼21.3, 46.2, 113.0, 118.8,
121.0, 124.6,126.5,127.0,128.1,128.9, 129.5, 130.5,131.7,133.3,137.5,
138.10, 139.8, 145.8, 150.9, 153.3 ppm. MS: m/z (%)¼468(20,
[Mþ2]þ), 466 (83, M]þ), 216 (21), 201 (69), 165 (12), 106 (13), 91
(100). Anal. Calcd for C26H19ClN6O (466.93): C, 66.88; H, 4.10; N,
18.00. Found: C, 66.85; H, 4.09; N, 17.79.
4.3.12. 5-tert-Butylamino-3-cyano-6-(4-fluorophenyl)-1-p-tolyl-1H-
pyrazolo[4,3-d]pyrimidin-7(6H)-one (8l). White crystals; mp:
211e212 ꢀC. IR (KBr):
1457, 1294 cmꢁ1
AreH), 4.01 (s, 1H, HN), 2.37 (s, 3H, CH3Ar), 1.40 (s, 9H, (CH3)3C)
ppm. 13C NMR (100 MHz, CDCl3):
n
¼3431 (NH), 2238 (CN), 1709 (C]O), 1571,
.
1H NMR (400 MHz, CDCl3):
d
¼7.56e7.22 (m, 8H,
d¼21.3, 30.0, 53.6, 112.6, 115.4,
4.3.18. 5-Butylamino-6-(4-chlorophenyl)-3-cyano-1-p-tolyl-1H-pyr-
118.6,121.8,124.5,130.8,131.8,136.2,137.7,139.8,143.8,148.5,153.0,
163.0 ppm. MS: m/z (%)¼418 (8, [Mþ2]þ), 416 (45, Mþ), 401 (5), 362
(13), 360 (100), 359 (89), 250 (5), 225 (5) 117 (7) 95 (10), 91 (14), 89
(4) 65 (6), 57 (14). Anal. Calcd for C23H21FN6O (416.46): C, 66.33; H,
5.08; N, 20.18. Found: C, 66.32; H, 5.08; N, 20.21.
azolo[4,3-d]pyrimidin-7(6H)-one (8r). White-White crystals; mp:
229e231 ꢀC. IR (KBr):
n
¼3389 (NH), 2244 (CN), 1695 (C]O), 1578,
1489, 1295 cmꢁ1
.
1H NMR (400 MHz, CDCl3): 7.59e7.21 (m, 8H,
AreH), 4.11 (s, 1H, HN), 3.45 (q, 2H, J¼7.2 Hz, NCH2), 2.38 (s, 3H,
CH3Ar), 1.57e1.27 (m, 4H, CH2CH2C), 0.92 (t, 3H, J¼7.6 Hz, CH2CH3)
ppm. 13C NMR (100 MHz, CDCl3):
d
¼14.0, 20.4, 21.5, 30.1, 42.0,112.9,
4.3.13. (R)-3-Cyano-6-(4-fluorophenyl)-5-(
p-tolyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (8m). White crys-
tals; mp 178e179 ꢀC. IR (KBr):
¼3435 (NH), 2239 (CN),1703 (C]O),
1601, 1571, 14,571, 1298 cmꢁ1 1H NMR (400 MHz, CDCl3):
a
-phenylethylamino)-1-
118.3,121.0,124.5,128.9,129.6,130.3,131.8,133.4,137.5,139.7,145.5,
150.9,153.3 ppm. MS: m/z (%)¼434 (57, [Mþ2]þ), 433 (100, [Mþ1]þ),
432 (87, M]þ), 378 (41), 375 (88), 91 (56). Anal. Calcd for C23H21ClN6O
(432.91): C, 63.81; H, 4.89; N,19.41. Found: C, 63.82; H, 4.89; N,19.46.
n
.
d
¼7.54e7.20 (m, 13H, AreH), 5.36 (s,1H, NCH), 4.39 (s, 1H, HN), 2.37
(s, 3H, CH3Ar), 1.47 (d, 3H, J¼6.8 Hz, CHCH3) ppm. 13C NMR
4.3.19. 5-Benzylamino-3-cyano-1, 6-di (p-tolyl)-1H-pyrazolo[4,3-d]
pyrimidin-7(6H)-one (8s). Whitecrystals; mp: 178e180 ꢀC. IR (KBr):
(100 MHz, CDCl3):
d
¼21.3, 22.0, 51.3, 112.7, 115.4, 118.4, 121.7, 126.5,
127.1, 128.6, 130.5, 131.7, 136.4, 137.5, 138.1, 139.7, 141.8, 143.7, 148.6,
153.2, 162.8 ppm. MS: m/z (%)¼465 (73, [Mþ1]þ), 464 (58, Mþ), 361
(19), 358 (16),105 (100), 91 (29), 77 (23). Anal. Calcd for C27H21FN6O
(464.50): C, 69.82; H, 4.56; N,18.09. Found: C, 69.80; H, 4.55; N,18.14.
n
¼3429 (NH), 2236 (CN),1711 (C]O),1570,1512,1491,1292 cmꢁ1.1H
NMR (400 MHz, CDCl3):
d
¼7.58e7.15 (m, 13H, AreH), 4.65 (s, 2H,
NCH2), 4.55 (s, 1H, HN), 2.42(s, 3H, CH3Ar), 2.37 (s, 3H, CH3Ar) ppm.
13C NMR (100 MHz, CDCl3):
d¼21.3, 21.4, 45.5, 112.6, 118.8, 121.5,
124.6,126.5,127.0,128.0,128.8,129.5,130.8,131.7,136.4,137.6,138.0,
139.7, 143.7, 148.6, 153.1 ppm. MS: m/z (%)¼446 (100, Mþ), 354 (10),
196 (38),181 (91),106 (21), 91 (82), 77 (8). Anal. Calcd for C27H22N6O
(446.19): C, 72.63; H, 4.97; N,18.82. Found: C, 72.58; H, 4.98; N,18.77.
4.3.14. 5-Benzylamino-3-cyano-6-(4-fluorophenyl)-1-p-tolyl-1H-
pyrazolo[4,3-d]pyrimidin-7(6H)-one (8n). White crystals; mp:
247e249 ꢀC. IR (KBr):
n
¼3405 (NH), 2237 (CN), 1705 (C]O), 1570,
1474, 1225 cmꢁ1. 1H NMR (400 MHz, CDCl3):
¼7.56e7.22 (m, 13H,
AreH), 4.59 (d, 2H, J¼5.6 Hz, NCH2), 4.43 (s, 1H, HN), 2.39 (s, 3H,
CH3Ar) ppm. CDCl3:
d
4.3.20. 3-Cyano-5-isopropylamino-1, 6-di (p-tolyl)-1H-pyrazolo[4,3-
d]pyrimidin-7(6H)-one (8t). White crystals; mp: 159e160 ꢀC. IR
d
¼21.4, 45.3, 112.9, 115.5, 118.8, 121.8, 126.5,
127.3, 128.7, 130.6, 131.7, 136.5, 137.5, 138.2, 139.7, 141.8, 143.7, 148.6,
153.0, 162.9 ppm. MS: m/z (%)¼451 (13, [Mþ1]þ), 450 (57, Mþ), 449
(30, [Mꢁ1]þ),185 (100),184 (22), 91 (41). Anal. Calcd for C26H19FN6O
(450.47): C, 69.32; H, 4.25; N,18.66. Found:C, 69.30;H, 4.25; N,18.65.
(KBr):
n
¼3377 (NH), 2234 (CN), 1708 (C]O), 1563, 1511, 1488,
1292 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.58e7.12 (m, 8H, AreH),
4.32 (s, 1H, HN), 4.01 (m, 1H, CCHC), 2.45 (s, 3H, CH3Ar), 2.37 (s, 3H,
CH3Ar), 1.14 (d, 6H, J¼6.4 Hz, 2(CH3)2C) ppm. 13C NMR (100 MHz,
CDCl3):
d¼21.3, 21.4, 23.5, 42.8, 112.8, 118.9, 121.6, 124.8, 128.7,
4.3.15. 3-Cyano-6-(4-fluorophenyl)-5-isopropylamino-1-p-tolyl-1H-
pyrazolo [4,3-d] pyrimidin-7(6H)-one (8o). White crystals; mp:
129.5, 130.8, 131.7, 136.5, 137.9, 139.6, 143.9, 148.5, 153.1 ppm. MS:
m/z (%)¼400 (6, Mþþ2), 398 (45, Mþ), 355 (77), 340 (6), 132 (48),
117 (26), 91 (100), 77 (10). Anal. Calcd for C23H22N6O (398.47): C,
69.33; H, 5.56; N, 21.09. Found: C, 69.23; H, 5.47; N, 21.02.
202e203 ꢀC. IR (KBr):
n
¼3378 (NH), 1708 (C]O), 1575, 1525,
12,890 cmꢁ1
.
1H NMR (400 MHz, CDCl3):
d
¼7.55e7.23 (m, 8H,
AreH), 4.32 (s, 1H, HN), 3.90 (m, 1H, CCHC), 2.38 (s, 3H, CH3Ar), 1.16
(d, 6H, J¼6.8 Hz, 2(CH3)2C) ppm. 13C NMR (100 MHz, CDCl3):
4.3.21. 3-Cyano-5-propylamino-1, 6-di (p-tolyl)-1H-pyrazolo[4,3-d]
pyrimidin-7(6H)-one (8u). White-White crystals; mp: 164e165 ꢀC.
d¼21.4, 23.6, 42.8, 112.7, 115.4, 118.4, 121.8, 124.5, 130.6, 131.7, 136.4,

5118
M.-H. Wu et al. / Tetrahedron 66 (2010) 5112e5120
IR (KBr):
n
¼3427 (NH), 2242 (CN), 1700 (C]O), 1580, 1490,
118.5, 121.5, 124.7, 128.7, 129.4, 130.6, 131.7, 136.6, 137.9, 139.6, 143.8,
1297 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d¼7.58e7.13 (m, 8H, AreH),
148.7, 153.2 ppm. MS m/z (%)¼427 (14, [Mþ1]þ), 383 (100), 370
(17), 326 (23), 307 (3), 116 (19), 91 (28), 77 (28). Anal. Calcd for
C25H26N6O (426.52): C, 70.40; H, 6.14; N, 19.70. Found: C, 70.51; H,
6.14; N, 19.71.
4.25 (s, 1H, HN), 3.40 (q, 2H, J¼6.8 Hz, NCH2), 2.44 (s, 3H, CH3Ar),
2.37 (s, 3H, CH3Ar), 1.60e1.52 (m, 2H, CH2C), 0.87 (t, 3H, J¼7.2 Hz,
CH3) ppm. 13C NMR (100 MHz, CDCl3):
d¼11.3, 21.3, 21.5, 23.5, 42.3,
112.5, 118.6, 121.5, 124.7, 128.7, 129.5, 130.8, 131.6, 136.3, 137.8, 139.6,
143.7, 148.6, 153.2 ppm. MS: m/z (%)¼398 (77, Mþ), 355 (100), 314
(41), 117 (17), 91 (53). Anal. Calcd for C23H22N6O (398.47): C, 69.33;
H, 5.56; N, 21.09. Found: C, 69.40; H, 5.56; N, 21.11.
4.3.27. 3-Cyano-5-dihexylamino-6-phenyl-1-p-tolyl-1H-pyrazolo[4,
3-d]pyrimidin-7(6H)-one (8E). White crystals; mp: 74e75 ꢀC. IR
(KBr):
n
¼2235 (CN), 1715 (C]O), 1593, 1558, 1467, 1290 cmꢁ1
.
1H
NMR (400 MHz, CDCl3):
d
¼7.55e7.23 (m, 9H, AreH), 3.03 (t, 4H,
4.3.22. 3-Cyano-5-cyclohexylamino-1, 6-di (p-tolyl)-1H-pyrazolo
[4,3-d]pyrimidin-7(6H)-one (8v). White crystals; mp: 210e211 ꢀC.
J¼7.6 Hz, CH2NCH2), 2.38 (s, 3H, CH3Ar), 1.29e1.23 (m, 16H,
2CH2CH2CH2CH2C), 0.87 (t, 6H, J¼7.2 Hz, 2CCCH3) ppm. 13C NMR
IR (KBr):
n
¼3424 (NH), 2236 (CN), 1707 (C]O), 1567, 1489,
(100 MHz, CDCl3):
d¼21.5, 25.2, 25.9, 30.4, 59.1, 112.8, 118.9, 121.6,
1291 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.58e7.12 (m, 8H, AreH),
124.5, 128.6, 129.6, 130.7, 131.8, 136.5, 137.8, 139.6, 143.8, 148.5,
153.0 ppm. MS: m/z (%)¼511 (48, [Mþ1]þ), 453 (24), 439 (30), 426
(100), 355 (47), 341 (49), 326 (27), 279 (23), 91 (47), 77(27). Anal.
Calcd for C31H38N6O (510.68): C, 72.91; H, 7.50; N, 16.46. Found: C,
72.88; H, 7.51; N, 16.42.
4.08 (d, 1H, J¼21.2, HN), 2.44 (s, 3H, CH3Ar), 2.37 (s, 3H, CH3Ar),
1.96e1.03 (m, 11H, (CH2)5CH) ppm. 13C NMR (100 MHz, CDCl3):
d
¼21.3, 21.5, 24.8, 25.8, 33.0, 50.4, 112.7, 118.7, 121.6, 124.7, 128.8,
129.5, 130.8, 131.7, 136.4, 137.8, 139.6, 143.7, 148.4, 153.1 ppm. MS:
m/z (%)¼438 (77, Mþ), 385 (6), 355 (100), 340 (6), 225 (7), 117 (18),
91 (31), 65 (7), 55 (7). Anal. Calcd for C26H26N6O (438.53): C, 71.21;
H, 5.98; N, 19.16. Found: C, 71.34; H, 5.99; N, 19.20.
4.3.28. 3-Cyano-5-dibutylamino-6-(4-fluorophenyl)-1-p-tolyl-1H-
pyrazolo[4,3-d]pyrimidin-7(6H)-one (8F). White crystals; mp:
167.5e169 ꢀC. IR (KBr):
n
¼2233 (CN), 1706 (C]O), 1561, 1467,
4.3.23. 3-Cyano-5-dibutylamino-6-phenyl-1-p-tolyl-1H-pyrazolo
1291 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.54e7.17 (m, 8H, AreH),
[4,3-d]pyrimidin-7(6H)-one (8A). Crystals; mp: 124e125 ꢀC. IR
3.04 (t, 4H, J¼7.2 Hz, CH2NCH2), 2.38 (s, 3H, CH3Ar), 1.25e1.16 (m,
(KBr):
(400 MHz, CDCl3):
n
¼2237 (CN), 1707 (C]O), 1593, 1490, 1288 cmꢁ1
.
1H NMR
8H, 2CH2CH2CH3), 0.86 (t, 6H, J¼7.2 Hz, 2CH2CH3) ppm. 13C NMR
d¼7.56e7.23 (m, 9H, AreH), 3.03 (t, 4H, J¼7.6 Hz,
(100 MHz, CDCl3):
d
¼13.9, 20.1, 21.3, 30.2, 49.5, 112.5, 115.7, 118.6,
CH2NCH2), 2.38 (s, 3H, CH3Ar),1.23e1.12 (m, 8H, 2CH2CH2CH3), 0.84
121.5, 124.7, 128.7, 130.8, 131.7, 136.4, 139.6, 143.7, 148.5, 153.0,
162.8 ppm. MS: m/z (%)¼473 (29, [Mþ1]þ), 472 (73, Mþ), 443 (26),
415 (100), 387 (35), 373 (95), 360 (26), 344 (28), 279 (32), 109 (31),
91 (25). Anal. Calcd for C27H29FN6O (472.57): C, 68.62; H, 6.19; N,
17.78. Found: C, 68.75; H, 6.19; N, 17.72.
(t, 6H, J¼7.2 Hz, 2CH2CH3) ppm. 13C NMR (100 MHz, CDCl3):
¼14.0,
d
20.5, 21.5, 30.1, 48.5, 112.8, 118.6, 121.5, 124.7, 128.7, 129.4, 130.8,
131.7, 136.4, 137.7, 139.6, 143.7, 148.5, 153.1 ppm. MS: m/z (%)¼456
(9, [Mþ2]þ), 455 (45, [Mþ1]þ), 453 (87, [Mꢁ1]þ), 425 (29), 412 (36),
399 (33), 356 (85), 321 (42), 91(100). Anal. Calcd for C27H30N6O
(454.57): C, 71.34; H, 6.65; N, 18.49. Found: C, 71.36; H, 6.64; N,
18.48.
4.3.29. 3-Cyano-6-(4-fluorophenyl)-5-(piperidin-1-yl)-1-p-tolyl-1H-
pyrazolo [4,3-d] pyrimidin-7(6H)-one (8G). White crystals; mp:
218e219 ꢀC. IR (KBr):
n
¼2236 (CN), 1705 (C]O), 1558, 1470,
1295 cmꢁ1. 1H NMR (400 MHz, CDCl3):
¼7.53e7.17 (m, 8H, AreH),
3.12 (t, 4H, J¼5.6 Hz, CH2NCH2), 2.38 (s, 3H, CH3Ar), 1.46e1.29 (m,
6H, C(CH2)3C) ppm. 13C NMR (100 MHz, CDCl3):
4.3.24. 3-Cyano-6-phenyl-5-(piperidin-1-yl)-1-p-tolyl-1H-pyrazolo
[4,3-d]pyrimidin-7(6H)-one (8B). White crystals; mp 211e212 ꢀC.
d
IR (KBr):
n
¼2237 (CN), 1709 (C]O), 1592, 1555, 1469, 1295 cmꢁ1. 1H
d
¼21.4, 24.2, 25.9,
NMR (400 MHz, CDCl3):
d¼7.55e7.23 (m, 9H, AreH), 3.14 (t, 4H,
49.0, 113.0, 115.7, 118.3, 121.6, 124.3, 130.5, 131.5, 136.2, 137.7, 139.7,
143.6, 148.4, 153.0, 163.0 ppm. MS: m/z (%)¼430 (20, [Mþ2]þ), 429
(100, [Mþ1]þ), 427 (65, [Mꢁ1]þ), 400 (56), 291 (21), 178 (52), 147
(5), 91 (8). Anal. Calcd for C24H21FN6O (429.48): C, 67.12; H, 5.16; N,
19.57. Found: C, 67.15; H, 5.16; N, 19.58.
J¼5.6 Hz, CH2NCH2), 2.38 (s, 3H, CH3Ar), 1.44e1.25 (m, 6H, C
(CH2)3C) ppm. 13C NMR (100 MHz, CDCl3):
d¼21.3, 24.3, 25.7, 49.5,
112.5, 118.6, 121.5, 124.7, 128.7, 129.5, 130.8, 131.7, 136.5, 137.8, 139.6,
143.7, 148.5, 153.0 ppm. MS: m/z (%)¼411 (40, Mþ), 410 (56,
[Mꢁ1]þ), 382 (18), 291(14), 160 (100), 91 (11), 77 (22). Anal. Calcd
for C24H23N6O (411.49): C, 70.05; H, 5.63; N, 20.42. Found: C, 70.14;
H, 5.64; N, 20.40.
4.3.30. 3-Cyano-5-dipropylamino-6-(4-fluorophenyl)-1-p-tolyl-1H-
pyrazolo[4,3-d]pyrimidin-7(6H)-one (8H). White crystals; mp:
141e142 ꢀC. IR (KBr):
n
¼2238 (CN), 1701 (C]O), 1602, 1555, 1463,
4.3.25. 3-Cyano-5-dipropylamino-6-phenyl-1-p-tolyl-1H-pyrazolo
[4,3-d]pyrimidin-7(6H)-one (8C). White crystals; mp: 105e106 ꢀC.
1292 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.54e7.17 (m, 8H, AreH),
3.02 (t, 4H, J¼7.6 Hz, CH2NCH2), 2.39 (s, 3H, CH3Ar), 1.31e1.29 (m,
IR (KBr):
n
¼2237 (CN), 1705 (C]O), 1593, 1558, 1490, 1298 cmꢁ1
.
4H, 2CH2CH3), 0.77 (t, 6H, J¼7.2 Hz, 2CH2CH3) ppm. 13C NMR
1H NMR (400 MHz, CDCl3):
d¼7.55e7.23 (m, 9H, AreH), 3.02 (t,
(100 MHz, CDCl3):
d
¼11.6, 21.1, 21.5, 50.0, 113.4, 115.8, 118.5, 121.7,
4H, J¼5.6 Hz, CH2NCH2), 2.38 (s, 3H, CH3Ar), 1.29e1.23 (m, 4H,
124.8, 130.5, 131.6, 136.2, 137.8, 139.8, 143.4, 148.7, 153.2, 163.0 ppm.
MS: m/z (%)¼446 (6, [Mþ2]þ), 445 (25, [Mþ1]þ), 444 (100, Mþ), 416
(37), 401 (98), 373 (53), 344 (23), 308 (30), 279 (19), 91 (17). Anal.
Calcd for C25H25FN6O (444.51): C, 67.55; H, 5.67; N, 18.91. Found: C,
67.50; H, 5.66; N, 18.87.
2CH2CH3), 0.74 (t, 6H, J¼7.6 Hz, 2CH2CH3) ppm. 13C NMR
(100 MHz, CDCl3):
d
¼11.7, 21.2, 21.5, 50.1, 112.8, 118.5, 121.6, 124.8,
128.7, 129.6, 130.9, 131.8, 136.5, 137.7, 139.6, 143.7, 148.6,
153.0 ppm. MS: m/z (%)¼427 (70, [Mþ1]þ), 397 (44), 384 (100),
356 (24), 355 (47), 308 (30), 279 (77), 91 (84), 77 (71). Anal. Calcd
for C25H26N6O (426.52): C, 70.40; H, 6.14; N, 19.70. Found: C,
70.35; H, 6.15; N, 19.68.
4.3.31. 3-Cyano-5-diisopropylamino-6-(4-fluorophenyl)-1-p-tolyl-
1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (8I). White crystals; mp
140e141 ꢀC. IR (KBr):
n
¼2236 (CN), 1707 (C]O), 1656, 1561, 1460,
1292 cmꢁ1. 1H NMR (400 MHz, CDCl3):
¼7.54e7.15 (m, 8H, AreH),
3.53 (m, 2H, 2CCHC), 2.38 (s, 3H, CH3Ar), 1.13 (d, 12H, J¼3.2 Hz, 2
(CH3)2C) ppm. 13C NMR (100 MHz, CDCl3):
4.3.26. 3-Cyano-5-diisopropylamino-6-phenyl-1-p-tolyl-1H-pyr-
d
azolo[4,3-d]pyrimidin-7(6H)-one
134e135 ꢀC. IR (KBr):
¼2238 (CN), 1705 (C]O), 1592, 1563, 1488,
1290 cmꢁ1. 1H NMR (400 MHz, CDCl3):
¼7.56e7.23 (m, 9H, AreH),
3.55 (m, 2H, 2CCHC), 2.37 (s, 3H, CH3Ar), 0.74 (d, 12H, J¼6.8 Hz, 2
(CH3)2C) ppm. 13C NMR (100 MHz, CDCl3):
¼21.3, 21.6, 51.9, 112.5,
(8D). White
crystals;
mp:
n
d
¼21.5, 21.9, 52.0, 113.2,
d
115.8,118.4,121.6, 124.5, 130.5, 131.6, 136.2, 137.5, 139.7,143.6, 148.6,
153.0, 163.1 ppm. MS: m/z (%)¼446 (3, [Mþ2]þ), 445 (13, [Mþ1]þ),
444 (8, Mþ), 402 (100), 401 (38), 400 (54), 387 (20), 91 (5). Anal.
d

M.-H. Wu et al. / Tetrahedron 66 (2010) 5112e5120
5119
Calcd for C25H25FN6O (444.51): C, 67.55; H, 5.67; N, 18.91. Found: C,
67.51; H, 5.68; N, 18.89.
(11), 91 (28). Anal. Calcd for C30H36N6O (496.66): C, 72.55; H, 7.31;
N, 16.92. Found: C, 72.47; H, 7.30; N, 16.98.
4.3.32. 3-Cyano-5-dihexylamino-6-(4-fluorophenyl)-1-p-tolyl-1H-
pyrazolo[4,3-d]pyrimidin-7(6H)-one (8J). White crystals; mp:
4.3.37. 3-Cyano-5-(piperidin-1-yl)-1, 6-di (p-tolyl)-1H-pyrazolo[4,3-
d]pyrimidin-7(6H)-one (8O). White crystals; mp: 223.5e224.5 ꢀC.
75e76 ꢀC. IR (KBr):
n
¼2237 (CN), 1708 (C]O), 1603, 1560, 1460,
IR (KBr):
NMR (400 MHz, CDCl3):
n
¼2236 (CN), 1706 (C]O), 1585, 1558, 1467, 1271 cmꢁ1. 1H
1293 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.55e7.14 (m, 8H, AreH),
d
¼7.55e7.17 (m, 8H, AreH), 3.14 (t, 4H,
3.03 (t, 4H, J¼7.6 Hz, CH2NCH2), 2.39 (s, 3H, CH3Ar), 1.29e1.12 (m,
J¼5.6 Hz, CH2NCH2), 2.40 (s, 3H, CH3Ar), 2.38 (s, 3H, CH3Ar),
16H, 2CH2CH2CH2CH2C), 0.88 (t, 6H, J¼6.8 Hz, 2CCCH3) ppm. 13C
1.59e1.25 (m, 6H, C(CH2)3C) ppm. 13C NMR (100 MHz, CDCl3):
NMR (100 MHz, CDCl3):
d¼21.3, 25.2, 25.8, 30.3, 59.8, 113.7, 115.9,
d
¼21.3, 21.4, 24.3, 25.8, 46.5, 112.5, 118.7, 121.6, 124.7, 128.8, 129.5,
118.6, 121.7, 124.6,130.6, 131.5,136.3, 137.5,139.8, 143.7,148.5,153.0,
163.0 ppm. MS: m/z (%)¼528 (31, Mþ), 472 (6), 471 (7), 444 (16), 388
(41), 374 (100), 372 (47), 279 (26), 109 (74), 91 (24). Anal. Calcd for
C31H37FN6O (528.67): C, 70.43; H, 7.05; N, 15.90. Found: C, 70.40; H,
7.05; N, 15.88.
130.7, 131.6, 136.4, 137.8, 139.5, 143.7, 148.7, 153.0 ppm. MS: m/z
(%)¼425 (21, [Mþ1]þ), 424 (30, Mþ), 395 (43), 381 (18), 319 (18),
291 (24), 174 (100), 91 (40). Anal. Calcd for C25H24N6O (424.5): C,
70.73; H, 5.70; N, 19.80. Found: C, 70.65; H, 5.73; N, 19.82.
4.3.38. 5-Dibutylamino-3-cyano-1, 6-di (p-tolyl)-1H-pyrazolo[4,3-d]
4.3.33. 6-(4-Chlorophenyl)-3-cyano-5-dipropylamino-1-p-tolyl-1H-
pyrazolo [4,3-d] pyrimidin-7(6H)-one (8K). White crystals; mp
pyrimidin-7(6H)-one (8P). White crystals; mp: 158e159 ꢀC. IR
(KBr):
n
¼2237 (CN), 1705 (C]O), 1588, 1558, 1486, 1288 cmꢁ1
.
1H
165.5e166.5 ꢀC. IR (KBr):
n
¼2237 (CN), 1708 (C]O), 1558, 1493,
NMR (400 MHz, CDCl3):
d
¼7.56e7.11 (m, 8H, AreH), 3.05 (t, 4H,
1298 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.54e7.20 (m, 8H, AreH),
J¼6.8 Hz, CH2NCH2), 2.40 (s, 3H, CH3Ar), 2.38 (s, 3H, CH3Ar),
3.02 (t, 4H, J¼7.6 Hz, CH2NCH2), 2.39 (s, 3H, CH3Ar), 1.33e1.31 (m,
1.21e1.12 (m, 8H, 2CH2CH2C), 0.84 (t, 6H, J¼7.2 Hz, 2CH2CH3) ppm.
4H, 2CH2CH3), 0.77 (t, 6H, J¼7.2 Hz, 2CH2CH3) ppm. 13C NMR
13C NMR (100 MHz, CDCl3):
d¼13.9, 20.0, 21.3, 21.4, 30.5, 50.0, 112.8,
(100 MHz, CDCl3):
d
¼11.6, 21.0, 21.3, 50.0, 112.8, 118.2, 121.6, 124.6,
118.5,121.6,124.7,128.5,129.5,130.9,131.8,136.6, 137.8,139.8, 143.7,
148.5, 153.2 ppm. MS: m/z (%)¼469 (21, [Mþ1]þ), 468 (60, Mþ), 439
(16), 425 (37), 411 (100), 369 (67), 321 (24), 279 (19), 91(47). Anal.
Calcd for C28H32N6O (468.60): C, 71.77; H, 6.88; N, 17.93. Found: C,
71.71; H, 6.88; N, 17.92.
128.8, 129.5, 130.6, 131.8, 133.3, 137.6, 139.8, 145.8, 150.6, 153.2 ppm.
MS: m/z (%)¼463 (15, [Mþ3]þ), 462 (21, [Mþ2]þ), 461 (52, [Mþ1]þ),
459 (33), 417 (100), 389 (99), 377 (39), 309 (42), 279 (78), 91 (7).
Anal. Calcd for C25H25ClN6O (460.97): C, 65.14; H, 5.47; N, 18.23.
Found: C, 65.10; H, 5.48; N, 18.21.
4.3.34. 6-(4-Chlorophenyl)-3-cyano-5-dibutylamino-1-p-tolyl-1H-
4.4. X-ray crystal structure analysis for compound 8u
pyrazolo[4,3-d]pyrimidin-7(6H)-one (8L). White crystals; mp
180e181 ꢀC. IR (KBr):
n
¼2233 (CN), 1708 (C]O), 1558, 1489,
C23H22N6O, M¼398.47, colorless crystal, 0.30ꢂ0.20ꢂ0.20 mm,
1289 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
¼7.54e7.19 (m, 8H, AreH),
a¼11.722(2) Å,
b¼9.411(2) Å,
c¼19.868(4) Å,
b¼92.873(3),
3.04 (t, 4H, J¼7.6 Hz, CH2NCH2), 2.39 (s, 3H, CH3Ar), 1.25e116 (m,
V¼2188.9(8) Å3,
r
calcd¼1.209 g cmꢁ3
,
m
¼0.078 mmꢁ1, empirical
8H, 2CH2CH2C), 0.86 (t, 6H, J¼7.2 Hz, 2CH2CH3) ppm. 13C NMR
absorption correction (0.9838ꢃTꢃ0.9597), Z¼4, monoclinic, space
(100 MHz, CDCl3):
d
¼14.0, 20.2, 21.3, 30.4, 49.2, 112.9, 118.4, 121.0,
group P2(1)/c,
flections collected (ꢄh, ꢄk, ꢄl), 5768 independent (Rint¼0.0199)
and 3822 observed reflections [I>2 (I)], 275 refined parameters,
l
¼0.71073 Å, T¼293 K,
u and 4 scans, 15,041 re-
124.6, 128.9, 129.6, 130.5, 131.7, 133.3, 137.6, 139.6, 145.7, 150.8,
153.2 ppm. MS: m/z (%)¼491 (37, [Mþ3]þ), 490 (10, [Mþ2]þ), 488
(100, Mþ), 459 (21), 446 (13), 431 (62), 378 (40), 321 (19), 279 (9),
91 (14). Anal. Calcd for C27H29ClN6O (489.02): C, 66.32; H, 5.99; N,
17.19. Found: C, 66.45; H, 5.99; N, 17.21.
s
R¼0.0463, wR2¼0.1277, max. residual electron density 0.227
(e0.179) e Åꢁ3 and hydrogen atoms were calculated and refined as
riding atoms.
4.3.35. 6-(4-Chlorophenyl)-3-cyano-5-(piperidin-1-yl)-1-p-tolyl-
1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (8M). White crystals; mp:
4.5. X-ray crystal structure analysis for compound 8H
212e213 ꢀC. IR (KBr):
n
¼2236 (CN), 1709 (C]O), 1585, 1513, 1490,
1269 cmꢁ1
.
1H NMR (400 MHz, CDCl3):
d
¼7.53e7.24 (m, 8H,
C25H25FN6O, M¼444.51, colorless crystal, 0.20ꢂ0.10ꢂ0.10 mm,
AreH), 3.13 (t, 4H, J¼5.6 Hz, CH2NCH2), 2.39 (s, 3H, CH3Ar),
a¼7.929 (1) Å, b¼11.708 (2) Å, c¼12.962 (1) Å,
a
¼78.524 (1),
1.47e1.30 (m, 6H, C(CH2)3C) ppm. 13C NMR (100 MHz, CDCl3):
b¼ 82.170 (1),
g
¼85.592 (1), V¼1166.8 (1) Å3,
r
calcd¼1.265 g cmꢁ3
,
m
¼0.087 mmꢁ1, empirical absorptioncorrection(0.9914ꢃTꢃ0.9829),
d
¼21.5, 24.6, 25.8, 46.2, 112.7, 118.4, 121.2, 124.7, 128.8, 129.7, 130.6,
131.5, 133.4, 137.5, 139.8, 145.8, 150.7, 153.0 ppm. MS: m/z (%)¼447
(25, [Mþ3]þ), 446 (30, [Mþ2]þ), 444 (100, Mþ), 415 (29), 401 (8),
291 (5), 194 (25), 111 (23), 91 (62). Anal. Calcd for C24H21ClN6O
(444.92): C, 64.84; H, 4.77; N, 18.92. Found: C, 65.20; H, 4.78; N,
18.89.
Z¼2, triclinic, space group P-1,
l
¼0.71073 Å, T¼295 K,
u and 4 scans,
7486 reflections collected (ꢄh, ꢄk, ꢄl), 4509 independent
(Rint¼0.0456) and 3052 observed reflections [I>2
s
(I)], 301 refined
parameters, R¼0.0567, wR2¼0.1294, max. residual electron density
0.233 (ꢁ0.273) e Åꢁ3 and hydrogen atoms were calculated and re-
fined as riding atoms.
4.3.36. 3-Cyano-5-dipentylamino-1, 6-di (p-tolyl)-1H-pyrazolo[4,3-
d]pyrimidin-7(6H)-one (8N). White crystals; mp: 105e106 ꢀC. IR
(KBr):
(400 MHz, CDCl3):
n
¼2232 (CN), 1705 (C]O), 1562, 1513, 1278 cmꢁ1
.
1H NMR
4.6. Supplementary data
d
¼7.56e7.11 (m, 8H, AreH), 3.02 (t, 4H, J¼5.6 Hz,
CH2NCH2), 2.38 (s, 6H, 2CH3Ar), 1.63e0.86 (m, 12H,
Supplementary data (see footnote on the first page of this arti-
cle): CCDC-740004 and CCDC-740005 contain the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_-
request@ccdc.cam.ac.uk, or by contacting The Cambridge
2CCH2CH2CH2C), 0.83 (t, 6H, J¼7.2 Hz, 2CCCH3) ppm. 13C NMR
(100 MHz, CDCl3):
d¼14.3, 21.3, 21.4, 22.0, 22.5, 30.1, 49.3, 112.7,
118.8, 121.5, 124.8, 128.6, 129.5, 130.8, 131.7, 136.3, 137.8, 139.6,
143.8, 148.6, 153.0 ppm. MS: m/z (%)¼497 (15, [Mþ1]þ), 496 (52,
Mþ), 439 (85), 425 (100), 383 (30), 369 (68), 355 (53), 340 (17), 279

5120
M.-H. Wu et al. / Tetrahedron 66 (2010) 5112e5120
8. Hamilton, H. W.; Ortwme, D. F.; Worth, D. F.; Bristol, J. A. J. Med. Chem. 1987, 30,
91.
9. Ali, A.; Taylor, G. E.; Graham, D. W. Chem. Abstr. 2001, 134, 311225u.
10. Quintela, J. M.; Peinado, Y. C.; Moreira, M. J.; Alfonso, A.; Botana, L. M.; Riguera,
R. Eur. J. Med. Chem. 2001, 36, 321.
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; fax: þ44 1223 336033.
Acknowledgements
11. Bendieh, A.; Russell, P. J.; Fox, J. J. J. Am. Chem. Soc. 1954, 76, 6073.
12. (a) Toque, H. A. F.; Priviero, F. B. M.; Teixeira, C. E.; Perissutti, E.; Fiorino, F.;
Severino, B.; Frecentese, F.; Lorenzetti, R.; Baracat, J. S.; Santagada, V.; Caliendo,
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The authors would like to thank Open Fund of Key Laboratory
for the Synthesis and Application of Organic Functional Molecules,
Ministry of Education (grant No. 2006-KL-013) and Natural Science
Foundation of Hubei Province (grant No.2009CDB317) for financial
support.
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