A convenient, rapid, and highly selective method for synthesis of new pyrazolo[1,5-a]pyrimidines via the reaction of enaminones and 5-amino-1H-pyrazoles under microwave irradiation

Article abstract of DOI:10.1002/jhet.5570420526

Twelve new 7-aryl-3-cyanopyrazolo[1,5-a]pyrimidines (3a-f) and ethyl 7-arylpyrazolo[1,5-a]pyrimidine-3-carboxylates (3g-1) have been conveniently synthesized by the reaction of enaminones with 5-amino-1H-pyrazoles in good yields under microwave irradiatio

Full text of DOI:10.1002/jhet.5570420526

Jul-Aug 2005
925
A Convenient, Rapid, and Highly Selective Method for Synthesis of
New Pyrazolo[1,5-a]pyrimidines via the Reaction of Enaminones and
5-Amino-1H-pyrazoles under Microwave Irradiation
1
1
1
2
3
Li Ming *, Wang Shuwen , Wen Lirong , Yang Huazheng , and Zhang Xiuli
1
College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao,
266042, P. R. China
2
State Key Laboratory of Elemental Organic Chemistry, Nankai University, Tianjin, 300071, P. R. China
3
Institute of Marine Drug and Food, Ocean University of China, Qingdao, 266003, P. R. China
Received July 14, 2004
Twelve new 7-aryl-3-cyanopyrazolo[1,5-a]pyrimidines (3a-f) and ethyl 7-arylpyrazolo[1,5-a]pyrimidine-
3-carboxylates (3g-l) have been conveniently synthesized by the reaction of enaminones with 5-amino-1H-
pyrazoles in good yields under microwave irradiation. With one substituded enaminone, only one regioiso-
1
mer was obtained. The structures of new compounds were fully confirmed by elemental analysis, ir, H nmr
and X-ray diffraction (XRD) analysis. A plausible reaction mechanism for the synthesis of title compounds
is presented. The antifungal activities of some compounds are also reported.
J. Heterocyclic Chem., 42, 925 (2005).
Introduction.
substituted enaminones [8-9] in refluxing glacial acetic
acid. More recently, microwave irradiation has broken new
grounds in synthetic organic chemistry [10], not only in
terms of the reduction of reaction time, but also simplicity
of reaction procedures [11]. The combination of
microwave irradiation with inorganic solid support further
extends the application and scope of microwave [12], thus
forming a promising candidate for eco-friendly chemistry.
It shows many advantages such as high efficiency, selec-
tivity and ease of separation and purification [13]. All
these merits are in good accordance with green chemistry’s
initiatives of energy saving, high efficiency and environ-
mentally benign procedures [14-17]. Herein we report the
synthesis of twelve new pyrazolo[1,5-a]pyrimidine deriva-
tives by the reaction 5-amino-1H-pyrazoles with a variety
Many fused heterocyclic compounds have showed
impressive biological activities in recent reports. Triazolo-
[1,5-a]pyrimidines, developed by DOW Company of
America, have been a new-style of acetolactate synthase
(ALS) enzyme inhibitors [1-4]. Later, another series of
ALS enzyme inhibitors 1,2,4-thiadiazolo[1,5-a]pyrim-
idines were developed by Takeda Chemical Industries Ltd.
[5-6]. Inspired by all these satisfactory research results, we
then replaced the triazole or thiadiazole, as described
above, with a pyrazole ring, in an effort to improve the
bioactivities.
The syntheses of the pyrazolo[1,5-a]pyrimidines frame-
work has been mainly based on ring closure reactions of
5-amino-1H-pyrazole derivations with β- diketones [7] or
Scheme 1
Synthetic route for the synthesis of compounds 3a-l.

926
L. Ming, W. Shuwen, W. Lirong, Y. Huazheng, and Z. Xiuli
Vol. 42
of enaminones under microwave irradiation, which has not
been reported before. The antifungal activities of some
compounds have also been determined and reported.
Structure characterizations of 3a-3l were performed on
the basis of ir and H nmr spectroscopy. Furthermore, the
structure of 3j was also determined by X-ray diffraction.
1
Results and Discussion.
Crystallographic Data and Structure Determination of
Compound 3j.
The starting enaninones 1 and 5-amino-1H-pyrazoles 2
were prepared according to references [18-19]. These
A light yellow crystal of the title compound 3j with
dimensions of 0.30 mm x 0.26 mm x 0.22 mm was mounted
on a glass fiber in a random orientation. The data were col-
lected by BRUKER SMART 1000 CCD diffractometer with
a graphite monochromated MoKα radiation (λ=0.71073 Å)
by using an ω scan mode in the range of 1.46≤θ≤25.00°at
293(2)K. A total of 7476 reflections were collected with
compounds and 5 mL glacial acetic acid were irradiated in
TM
Smithesynthesized
to give the corresponding pyra-
zolo[1,5-a]pyrimidines 3a-3l which were isolated in good
yields (Scheme 1).
Replacement of the cyano groups in 2 with the less elec-
tron-withdrawing ester group decreased the reaction rate as
expected [20]. Accordingly, cyclization of 5-amino-4-
ethoxycarbonyl-1H- pyrazole with 1 required a higher
temperature (140 °C) relative to those of the 5-amino-4-
cyano-1H-pyrazole (120 °C) with 1.
2577 unique ones (R = 0.0321), of which 1726 with I >
int
2σ(I) were considered as observed and used in the succeed-
ing refinements. The intensity data were corrected for Lp
factors and semi-empirical absorption. The structure was
solved by direct methods and expanded by using Fourier
difference techniques with SHELXS-97 [21]. All of the non-
hydrogen atoms were located with successive difference
Fourier syntheses. The structure was refined by full-matrix
Theoretically, the condensation of 5-amino-1H-pyra-
zoles 2 with enaninones 1 can proceed in two possible
ways, as shown in Scheme 2. As for route 1, the nucle-
ophilic amino group attacks the double bond via a
Michael addition reaction, followed by loss of the
dimethylamino group. The intermediate A then cyclizes
to form A-1 with subsequent dehydration to give 3,
whose aryl group is at the 7-position. As for route 2, the
exocyclic amino group of compound 2 attacks the car-
bonyl group to generate compound 3-1 via intermediate
structures B and B-1, which is the isomer of 3, with the
aryl group located at the 5-position. This regioselectivity
has been unambiguously substantiated through X-ray
crystallographic analysis of the product 3j whose aryl
group is at the 7-position of the pyrazolo[1,5-a]pyrimi-
dine skeleton rather than the 5-position.
2
least-squares method on F with anisotropic thermal para-
meters for all non-hydrogen atoms. The hydrogen atoms
were added according to theoretical models. The final
2
2
refinement gave R = 0.0608, wR = 0.1720 (w = 1/[σ (F ) +
o
2
2
2
(0.0864P) + 0.2072P] where P =(F + 2F )/3), s=1.14,
o
c
3
(∆/σ) = 0.000, (∆ρ)
= 0.44 and (∆ρ) = –0.34e/Å .
max
max
min
A summary of the crystallographic results is listed in Table
1. The final atomic parameters and equivalent isotropic ther-
mal parameters for non-hydrogen atoms are listed in Table
2. The selected bond lengths and bond angles are illustrated
in Table 3 and 4 respectively. Figure 1 shows the molecular
structure of compound 3j.
Scheme 2
The proposed reaction mechanism of cyclocondensation

Jul-Aug 2005
Synthesis of New Pyrazolo[1,5-a]pyrimidines
927
Table 1
In compound 3j, there exist three planes, p1 (pyrazole
ring), p2 (pyrimidine ring), p3 (benzene ring). The dihe-
dral angles between p1 and p2, p1 and p3, p2 and p3 are
1.33, 43.84 and 42.57˚ respectively, which indicates the p1
and p2 are nearly coplanar. In p1 the bond lengths of C
(13)–N (1) and C (11)–N (2) (1.321 and 1.394 Å, respec-
tively) are remarkably shorter than the normal C–N bond
(1.47 Å), but close to C=N bond (1.33 Å)[22-23], reveal-
ing that these two bonds have features of an unsaturated
double bond. In p2, the sum of the C (8)–N (2)–N (1), N
(1)–N (2)–C (11), C (8)–N (2)–C (11) bond angles is
Summary of Crystallographic Results for Compound 3j
Formula
Formula weight
Crystal system
Space group
a / Å
b/ Å
c/ Å
α/º
C H N O
16 15 3 3
297.31
Monoclinic
P2(1)/c
7.479(2)
27.897(8)
7.226(2)
90
104.355(5)
90
1826(2)
4
β/º
γ/º
V/ Å
3
2
Z
360.0º, indicating N (2) atom is of sp hybridization [23].
-3
D
µ/ mm
/g.cm
1.352
0.096
(calcd.)
-1
In p3, the phenyl ring does not show any unusual features
and the bond lengths and bond angles are within the nor-
mal range. The length of C (14)–O (2) bond is 1.232 Å,
indicating that it is a normal C=O bond. The dihedral
angles between the planes are listed in Table 5.
Crystal size/mm
Temp. /K
θ ranges/°
0.30x0.26x0.22
293(2)
1.46-25.00
-8,5/-27,33/-8,8
7476
h/k/l
Reflections collected
Independent reflections
Absorption correction
Data / restraints / parameters
Final R indices[I>2Û(I)]
F(000)
2577
Semi-empirical from equivalents
2577/64/238
R =0.0608 wR =0.1433
1
2
624
The crystallographic data for the compound 3j has been
deposited with the Cambridge Crystallographic Data
Center, and the number is 244520.
In conclusion, our results demonstrate that the current
reactions are operative under microwave conditions.
Moreover, the same high region-selectivity is obtained
under microwave conditions as conventional heating.
Figure 1. Molecular structure of 3j
Table 2
Atomic Coordinates (x10 ) and Equivalent Isotropic Displacement Parameters (Å x10 )
4
2
3
Atom
x
y
z
Ueq
Atom
x
y
z
Ueq
N(1)
N(2)
N(3)
N(4)
C(1)
C(2)
C(3)
C(4)
C(5)
356(3)
4874(2)
5241(2)
4407(2)
1074(2)
3665(2)
3226(2)
2020(2)
4263(2)
5571(2)
5726(1)
4939(1)
3472(1)
3941(2)
5573(2)
4712(2)
4292(2)
4302(2)
3287(2)
45(1)
37(1)
46(1)
63(1)
47(1)
46(1)
446(1)
39(1)
48(1)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
2475(3)
1863(3)
1957(3)
2463(4)
2606(4)
2241(4)
1738(4)
1602(3)
2359(4)
6600(2)
6445(2)
7464(2)
7203(2)
8202(2)
9484(2)
9728(2)
8744(2)
10580(2)
3895(2)
4755(1)
5444(1)
6322(2)
6929(2)
6697(2)
5823(2)
5204(2)
7365(2)
43(1)
36(1)
37(1)
44(1)
47(1)
44(1)
45(1)
41(1)
60(1)
1152(3)
1765(3)
-517(4)
-176(54)
251(4)
-183(4)
1112(3)
2399(4)
Ueq is defined as one third of the trace of the orthogonalized Uij tensor.
Table 3
Selected Bond lengths [Å]
Bond
Dist.
Bond
Dist.
1.400(3)
1.385(3)
1.426(3)
1.396(3)
1.373(3)
1.472(3)
1.388(3)
Bond
Dist.
N(1)-C(1)
N(1)-N(2)
N(2)-C(7)
N(2)-C(4)
N(3)-C(5)
N(3)-C(4)
N(4)-C(3)
1.323(3)
1.371(2)
1.372(3)
1.385(3)
1.314(3)
1.341(3)
1.133(3)
C(1)-C(2)
C(2)-C(4)
C(2)-C(3)
C(5)-C(6)
C(6)-C(7)
C(7)-C(8)
C(8)-C(13)
C(8)-C(9)
C(9)-C(10)
C(10)-C(11)
C(11)-C(12)
C(11)-C(14)
C(12)-C(13)
1.392(3)
1.375(3)
1.389(3)
1.382(3)
1.509(3)
1.375(3)

928
L. Ming, W. Shuwen, W. Lirong, Y. Huazheng, and Z. Xiuli
Vol. 42
Table 4
Selected Bond Angles [º]
Bond
(°)
Bond
(°)
Bond
(°)
C(1)-N(1)-N(2)
N(1)-N(2)-C(7)
N(1)-N(2)-C(4)
C(7)-N(2)-C(4)
C(5)-N(3)-C(4)
N(1)-C(1)-C(2)
C(4)-C(2)-C(1)
C(4)-C(2)-C(3)
C(1)-C(2)-C(3)
N(4)-C(3)-C(2)
103.72(19)
125.87(18)
112.46(18)
121.62(18)
115.1(2)
113.3(2)
105.3(2)
125.2(2)
129.4(2)
N(3)-C(4)-N(2)
N(3)-C(4)-C(2)
N(2)-C(4)-C(2)
N(3)-C(5)-C(6)
C(7)-C(6)-C(5)
N(2)-C(7)-C(6)
N(2)-C(7)-C(8)
C(6)-C(7)-C(8)
C(10)-C(9)-C(8)
C(9)-C(10)-C(11)
123.3(2)
131.4(2)
105.29(19)
124.5(2)
120.6(2)
114.8(2)
121.24(19)
124.0(2)
120.0(2)
121.9(2)
C(12)-C(11)-C(10)
C(12)-C(11)-C(14)
C(10)-C(11)-C(14)
C(13)-C(12)-C(11)
C(12)-C(13)-C(8)
C(13)-C(8)-C(9)
C(13)-C(8)-C(7)
C(9)-C(8)-C(7)
117.5(2)
120.5(2)
122.0(2)
121.5(2)
120.6(2)
118.5(2)
118.9(2)
122.5(2)
178.5(3)
Table 5
The Least-squares Plane Equations and Deviations of the Atoms
Plane 1
7.054 x –6.06 y +0.071 z =-1.250
Atoms
Deviations(Å)
Plane 2
N(1)
-0.004
N(2 )
0.003
C(11)
-0.001
C(12)
-0.001
C(13)
0.003
6.996 x – 6.56 y +0.170 z = -1.483
Atoms
N(2)
N(3)
C(8)
C(9)
C(10)
C(11)
Deviations(Å)
Plane 3
0.003
0.011
0.006
-0.006
-0.002
-0.011
3.369 x –15.64 y+4.057 z =-5.016
Atoms
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
Deviations(Å)
- 0.001
- 0.004
p1-p2
1.33
0.004
0.001
p1-p3
43.84
-0.005
p2-p3
42.57
0.005
Dihedral angle(º)
Table 6
Comparison Between Microwave and Conventional Methods
Compound
Microwave Method
Conventional Method
Isolated yield (%)
Microwave
Method
Conventional
Method
3a
3b
3c
3d
3e
3f
3g
3h
3i
120 °C, 20 minutes
120 °C, 20 minutes
120 °C, 20 minutes
120 °C, 20 minutes
120 °C, 20 minutes
120 °C, 30 minutes
140 °C, 20 minutes
140 °C, 20 minutes
140 °C, 20 minutes
140 °C, 20 minutes
140 °C, 20 minutes
140 °C, 30 minutes
Room temperature, 15 hours
Room temperature, 18 hours
Room temperature, 12 hours
Room temperature, 12 hours
Room temperature, 18 hours
Refluxing, 4 hours
81.82
91.34
85.47
81.91
85.64
81.41
92.63
93.45
85.42
87.81
94.56
82.62
71.2
65.3
62.6
75.1
72.4
73.5
74.4
75.3
69.1
70.2
77.5
73.6
Refluxing, 4 hours
Refluxing, 4 hours
Refluxing, 3 hours
Refluxing, 4 hours
Refluxing, 3.5 hours
Refluxing, 5 hours
3j
3k
3l
Table 6 summarizes the comparison between microwave
method and conventional method. As can be observed, the
yields from the microwave irradiation were slightly
improved by 10-20% and the reaction rates were from 10
to 100 times enhanced.
33.3%, 26.7%, 26.7% at 50 ppm, respectively. Further
studies on other bioactivities are underway.
EXPERIMENTAL
The preliminary biological tests showed that some com-
pounds exhibited inhibiting activity against four fungi,
Gibberrella zeave (3d), Alternaria solani (3b), Phoma
asparagi (3j) and Cercosporsa arachidicola hori (3j), but
not remarkably. The inhibiting rates reached up to 38.5%,
All melting points were determined with a RY-1 apparatus and
were uncorrected. Elemental analyses were carried out by
Yanaco MT-3 instrument. All H nmr chemical shifts were
1
reported in δ (ppm) downfield from TMS in DMSO-d on a
6
Bruker AC-300 spectrometer. The coupling constants were

Jul-Aug 2005
Synthesis of New Pyrazolo[1,5-a]pyrimidines
929
expressed in Hz. Ir spectra were recorded on a Nicolet 510 PF-IR
8.82 (s, 1H, pyrazole-H), 8.99 (d, 1H, J = 4.5, pyrimidine-Ha).
Anal. Calcd. for C H N Cl : C 54.01, H 2.09, N 19.38.
Found: C 53.87, H 2.08, N 19.42.
spectrometer as KBr pellets. Microwave irradiation was per-
13
6
4
2
TM
formed on a Smithesynthesized
.
General Procedure for Microwave Assisted Aynthesis of 7-Aryl-
General Procedure for Microwave Assisted Synthesis of Ethyl 7-
3-cyanopyrazolo[1,5-a]pyrimidines (3a-3f).
Arylpyrazolo[1,5-a]pyrimidine-3-carboxylate (3g-3l).
To the solution of glacial acetic acid (5 mL) were added 5-
amino-4-cyano-1H-pyrazole (0.108 g, 1 mmol) and enaminones
(1 mmol). The mixture was sealed in a 10 mL glass tube with a
To the solution of glacial acetic acid (5 mL) were added a
5-amino-4-ethoxycarbonyl-1H-pyrazole (0.155 g, 1 mmol)
and enaminones (1 mmol). The mixture was sealed in a 10
TM
magnetic stirring bar and irradiated in a Smithesynthesized at
mL glass tube with a magnetic stirring bar and irradiated in a
TM
120 °C for 20 min under adjustable microwave power range 0-25
W. Completion of the reaction was checked by TLC and the
yields were determined by isolation.
Smithesynthesized
at 140 °C for 20 min under adjustable
microwave power range 14-44 W. Completion of the reaction
was checked by TLC and the yields were determined by
isolation.
3-Cyano-7-phenylpyrazolo[1,5-a]pyrimidine (3a).
Ethyl 7-Phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate (3g).
Reaction time was 20 min to give yellow needles, yield
81.82%, mp 235-236 °C; ir: 2231, 1616, 1548, 1494, 755, 890
Reaction time was 20 min to give yellow needles, yield
92.63%, mp 133-134 °C; ir: 1694, 1614, 1549, 1496, 771,
-1
1
cm
; H nmr: δ 7.58 (d, 1H, J = 4.5, pyrimidine-Hb),
-1
1
7.62~8.10(m, 5H, Ph-H), 8.86 (s, 1H, pyrazole-H), 8.91 (d, 1H, J
= 4.5, pyrimidine-Ha).
701cm ; H nmr: δ 1.33 (t, 3H, J = 6.6, CH CH ), 4.34 (q, 2H, J
2 3
= 6.6, CH CH ), 7.49 (d, 1H, J = 4.5, pyrimidine-Hb), 7.62~8.10
2
3
Anal. Calcd. for C H N : C 70.90, H 3.66, N 25.44. Found: C
70.82, H 3.65, N 25.53.
(m, 5H, Ph-H), 8.67 (s, 1H, pyrazole-H), 8.89 (d, 1H, J = 4.5,
pyrimidine-Ha).
13
8 4
Anal. Calcd. for C
Found: C 67.23, H 4.91, N 15.75.
H N O : C 67.41, H 4.90, N 15.72.
15 13 3 2
3-Cyano-7-[4-chlorophenyl]pyrazolo[1,5-a]pyrimidine (3b).
Reaction time was 20 min to give a yellow solid, yield 91.34%,
Ethyl 7-[4-Chlorophenyl] pyrazolo[1,5-a]pyrimidine-3-
carboxylate (3h).
-1
1
mp 256-258 °C; ir: 2237, 1614, 1593, 1551, 1495 cm ; H nmr:
δ 7.60 (d, 1H, J = 4.5, pyrimidine-Hb), 7.62~8.16 (m, 4H, Ph-H),
8.87 (s, 1H, pyrazole-H), 8.92 (d, 1H, J = 4.5, pyrimidine-Ha).
Reaction time was 20 min to give a white solid, yield 93.45%,
Anal. Calcd. for C H N Cl: C 61.31, H 2.77, N 22.00.
mp 158.5-160 °C CH CH ), 7.51 (d, 1H, J = 4.5, pyrimidine-Hb),
13
7
4
2 3
Found: C 61.45, H 2.76, N 21.94.
7.70~8.15 (m, 4H, Ph-H), 8.67 (s, 1H, pyrazole-H), 8.89 (d, 1H, J
= 4.5, pyrimidine-Ha).
3-Cyano-7-[4-methylphenyl]pyrazolo[1,5-a]pyrimidine (3c).
Reaction time was 20 min to give yellow prisms, yield
Anal. Calcd. for C H N O Cl: C 59.71, H 4.01, N 13.93.
15 12
3 2
Found: C 59.57, H 4.02, N 13.97.
-1
1
85.47%, mp 224-225 °C; ir: 2224, 1610, 1545, 1505 cm ; H
Ethyl 7-[4-Methylphenyl]pyrazolo[1,5-a]pyrimidine-3-carbox-
ylate (3i).
nmr: δ 2.50 (s, 3H, CH ), 7.45 (d, 1H, J = 4.5, pyrimidine-Hb),
3
7.56~8.88 (m, 4H, Ph-H), 8.04 (d, 1H, J = 4.5, pyrimidine-Ha),
8.86 (s, 1H, pyrazole-H).
Reaction time was 20 min to give a yellow solid, yield 85.42%,
-1
1
Anal. Calcd. for C H N : C 71.78, H 4.30, N 23.92. Found:
mp 112-114 °C; ir: 1689, 1609, 1548, 1511cm ; H nmr: δ 1.33
(t, 3H, J = 6.6, CH CH ), 4.34 (q, 2H, J = 6.6, CH CH ), 2.51 (s,
14 10
4
C 71.68, H 4.31, N 24.01.
2
3
2
3
3H, CH ), 7.47 (d, 1H, J = 4.5, pyrimidine-Hb), 7.42~8.02 (m,
4H, Ph-H), 8.66 (s, 1H, pyrazole-H), 8.86 (d, 1H, J = 4.5, pyrim-
idine-Ha).
3
3-Cyano-7-[4-methoxyphenyl]pyrazolo[1,5-a]pyrimidine (3d).
Reaction time was 20 min to give yellow needles, yield
-1
1
81.91%, mp 214-215 °C; ir: 2229, 1613, 1552, 1511 cm ; H
Anal. Calcd. for C
H N O : C 68.31, H 5.37, N 14.94.
16 15 3 2
nmr: δ 3.89 (s, 3H, OCH ), 7.18 (d, 1H, J = 4.5, pyrimidine-Hb),
Found: C 68.12, H 5.38, N 14.98.
3
7.56~8.85 (m, 4H, Ph-H), 8.17 (d, 1H, J = 4.5, pyrimidine-Ha),
8.86 (s, 1H, pyrazole-H).
Ethyl 7-[4-Methoxyphenyl]pyrazolo[1,5-a]pyrimidine-3-car-
boxylate (3j).
Anal. Calcd. for C
H N O: C 67.19, H 4.03, N, 22.39.
14 10 4
Found: C 67.03, H 4.04, N 22.43.
Reaction time was 20 min to give yellow prisms, yield
-1
1
87.81%, mp 131-133 °C; ir: 1691, 1612, 1551, 1514cm ; H
nmr: _ 1.33 (t, 3H, J = 6.6, CH CH ), 4.33 (q, 2H, J = 6.6,
3-Cyano-7-[4-fluorophenyl]pyrazolo[1,5-a]pyrimidine (3e).
Reaction time was 20 min to give a yellow solid, yield 85.64%,
2
3
CH CH ), 3.88 (s, 3H, OCH ), 7.46 (d, 1H, J = 4.5, pyrimidine-
2
3
3
-1
1
mp 266-268 °C; ir: 2234, 1613, 1550, 1509 cm ; H nmr: δ 7.60
(d, 1H, J = 4.5, pyrimidine-Hb), 7.47~8.22 (m, 4H, Ph-H), 8.87
(s, 1H, pyrazole-H), 8.90 (d, 1H, J = 4.5, pyrimidine-Ha).
Anal. Calcd. for C H N F: C 65.54, H 2.96, N, 23.52. Found:
Hb), 7.16~8.17 (m, 4H, Ph-H), 8.67 (s, 1H, pyrazole-H), 8.83 (d,
1H, J = 4.5, pyrimidine-Ha).
Anal. Calcd. for C
H N O : C 64.64, H 5.09, N 14.13.
16 15 3 3
Found: C 64.48, H 5.10, N 14.16.
13
7 4
C 65.38, H 2.97, N 23.61.
Ethyl 7-[4-Fluorophenyl] pyrazolo[1,5-a]pyrimidine-3-carbox-
ylate (3k).
3-Cyano-7-[2,4-dichlorophenyl]pyrazolo[1,5-a]pyrimidine (3f).
Reaction time was 30 min to give a yellow solid, yield 81.41%,
mp 168-170 °C; ir: 2232, 1619, 1590, 1555, 1481 cm ; H nmr:
δ 7.56 (d, 1H, J = 4.5, pyrimidine-Hb), 7.70~7.96 (m, 3H, Ph-H),
Reaction time was 20 min to give yellow needle, yield 94.56%,
-1
1
-1
1
mp 172-174 °C; ir: 1716, 1616, 1552, 1506cm ; H nmr: δ 1.33
(t, 3H, J = 6.6, CH CH ), 4.34 (q, 2H, J = 6.6, CH CH ), 8.17 (d,
2
3
2
3

930
L. Ming, W. Shuwen, W. Lirong, Y. Huazheng, and Z. Xiuli
Vol. 42
[4] W. A. Kleschick, C. M. Carson, M. J. Castales, J. J. Doney, B.
C. Gerwick, J. B. Hdtwick, R. W. Meikle, W. T. Monte, J. C. Little, N. R.
Pearson, S.W. Snider, M. V Subramanian., J.C. VanHeertum and A. P.
Vinogradoff, Synthesis and Chemistry of Agrochemicals III, York, PA:
Maple Press, 15-25 (1992)
1H, J = 4.5, pyrimidine-Hb), 7.45~8.21 (m,4H, Ph-H), 8.67 (s,
1H, pyrazole-H), 8.89 (d, 1H, J = 4.5, pyrimidine-Ha).
Anal. Calcd. for C H N O F: C 63.15, H 4.24, N 14.73.
15 12
3 2
Found: C 62.98, H 4.25, N 14.70.
Ethyl 7-[2,4-Dichlorophenyl] pyrazolo[1,5-a]pyrimidine-3-car-
boxylate (3l).
[5] N. Okajima, I. Aoki, T. Kuragano and Y. Okada, Pestic. Sci.,
32, 91-104 (1991).
[6] N. Okajima, I. Aoki and Y. Okada, Pestic. Sci., 32, 265
(1991).
[7] G. Tenant in "Heterocyclic Chemistry", Vol 40, P. N. Preston,
John Wiley and Sons, Inc., New York, NY, p 257 (1980).
[8] S. S. Tseng, J. W. Epstein, H. J. Brabander and G. Francisco,
J. Heterocyclic Chem., 24, 837 (1987).
[9] C. Mustazza, M. R. D. Giudice, A. Borioni and F. Gatta, J.
Heterocyclic Chem., 38, 1119-1129 (2001).
Reaction time was 30 min to give a yellow solid, yield 82.62%,
-1
1
mp 130-131 °C; ir: 1711, 1619, 1553, 1485cm ; H nmr: _1.33
(t, 3H, J = 6.6, CH CH ), 4.34 (q, 2H, J = 6.6, CH CH ), 7.45 (d,
2
3
2
3
1H, J = 4.5, pyrimidine-Hb), 7.71~7.94 (m, 3H, Ph-H), 8.62 (s,
1H, pyrazole-H), 8.96 (d, 1H, J = 4.5, pyrimidine-Ha).
Anal. Calcd. for C H N O Cl : C 53.59, H 3.30, N 12.50.
15 11
3
2
2
Found: C 53.77, H 3.29, N 12.46.
[10] S. A. Galema, Chem. Soc. Rev., 26, 233 (1997).
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Meng, Synth. Commun., 30, 829 (2000).
Acknowledements.
The authors are very grateful to the Natural Science
Foundation of Shandong Province (No. Y2003B01) and the
National Science Foundation of China (No. 20172031) for finan-
cial support.
Also the authors are very grateful to the Key Laboratory of
Pesticide & Chemical Biology, Ministry of Education; College of
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*
Correspondence: Li Ming, College of Chemistry and
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