Simple and efficient method for synthesis of 3-cyano-6,7-diarylpyrazolo[1, 5-a]pyrimidine from isoflavones

Article abstract of DOI:10.1080/00397911.2010.521902

A series of 3-cyano-6,7-diarylpyrazolo[1,5-a]pyrimidines have been synthesized directly from the 5-amino-4-cyano-1H-pyrazole and isoflavones. The target compound was obtained by a condensation reaction. Structures of compounds were demonstrated by Fourier

Full text of DOI:10.1080/00397911.2010.521902

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Simple and Efficient Method
for Synthesis of 3-Cyano-6,7-
diarylpyrazolo[1,5-a]pyrimidine from
Isoflavones
Yu-Qing Ma a b , Zun-Ting Zhang a b , Qing He a b , Dong Xue a b
Peng-Fei Zhang a b
&
a Key Laboratory of the Ministry of Education for Medicinal
Resources and Natural Pharmaceutical Chemistry, National
Engineering Laboratory for Resource Development of Endangered
Crude Drugs in Northwest China
b School of Chemistry and Materials Science, Shaanxi Normal
University , Xi'an , China
Accepted author version posted online: 24 Aug 2011.Published
online: 16 Dec 2011.
To cite this article: Yu-Qing Ma , Zun-Ting Zhang , Qing He , Dong Xue & Peng-Fei Zhang (2012) Simple
and Efficient Method for Synthesis of 3-Cyano-6,7-diarylpyrazolo[1,5-a]pyrimidine from Isoflavones,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 42:7, 933-941, DOI: 10.1080/00397911.2010.521902
To link to this article: http://dx.doi.org/10.1080/00397911.2010.521902
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Synthetic Communications1, 42: 933–941, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.521902
SIMPLE AND EFFICIENT METHOD FOR SYNTHESIS OF
3-CYANO-6,7-DIARYLPYRAZOLO[1,5-a]PYRIMIDINE
FROM ISOFLAVONES
Yu-Qing Ma, Zun-Ting Zhang, Qing He, Dong Xue, and
Peng-Fei Zhang
Key Laboratory of the Ministry of Education for Medicinal Resources and
Natural Pharmaceutical Chemistry, National Engineering Laboratory for
Resource Development of Endangered Crude Drugs in Northwest China, and
School of Chemistry and Materials Science, Shaanxi Normal University,
Xi’an, China
GRAPHICAL ABSTRACT
Abstract A series of 3-cyano-6,7-diarylpyrazolo[1,5-a]pyrimidines have been synthesized
directly from the 5-amino-4-cyano-1H-pyrazole and isoflavones. The target compound
was obtained by a condensation reaction. Structures of compounds were demonstrated by
Fourier transform infrared, NMR, and elemental analysis. The advantages of this synthetic
route are simple operation, mild reaction conditions, and good yields.
Keywords Condensation; 3-cyano-6,7-diarylpyrazolo[1,5-a]pyrimidine; isoflavones
INTRODUCTION
Pyrazolo[1,5-a]pyrimidines are important pharmaceutical targets (Scheme 1).[1]
They and related fused heterocycles are of interest as potential bioactive molecules.
Pyrazole and pyrimidine derivatives have attracted the attention of organic chemists
because of their biological and chemotherapeutic importance. They are known to
exhibit a wide range of biological activities and act as cSRC kinase inhibitors involved
with ischemic brain pathology,[2] cyclin dependent kinase 1 (CDK1) inhibitors,[3] HIV
reverse transcriptase inhibitors,[4] CCR1 antagonists,[5] protein kinase inhibitors,[6]
Received March 12, 2010.
Address correspondence to Zun-Ting Zhang, School of Chemistry and Materials Science, Shaanxi
Normal University, Xi’an 710062, China. E-mail: zhangzt@snnu.edu.cn
933

934
Y.-Q. MA ET AL.
Scheme 1.
cGMP degradation inhibitors, and herbicides and fungicides.[7] These compounds
can also be used as intermediates in the dyestuff industry.[8] Numerous methods for
the synthesis of pyrazolo[1,5-a]pyrimidines have been reported in the past 20 years,
which involve the reaction between 5-aminopyrazoles and 1,3-bis-electrophilic
compounds, such as b-dicarbonyl, alkoxymethylene-b-dicarbonyl, and b-enaminone
compounds.[9,10] Shipps et al. and Paruch et al. have synthesized 3-cyano-6,7-
diphenylpyrazolo[1,5-a]pyrimidine.[11] Recently, we have reported the high-throughput
synthesis of 3,4-diarylpyrazoles, 4,5-biphenyl-2-pyrimidinyl- guanidine, and 2,3-
diarylpyrimido[1,2-a]benzimidazole by using one-step reactions of hydrazine,[12]
biguanidine,[13] and 2-aminobenzimidazole[14] with isoflavones. Herein, we report a
new strategy for the preparation of a wide variety of 3-cyano-6,7-diarylpyrazolo[1,5-
a]pyrimidines bearing different substituents on the phenyl units from isoflavones.
RESULTS AND DISCUSSION
We designed the cyclocondensations of isoflavone 1, which can generate a 1,3-
dicarbonal equivalent in the presence of alkali, with aminopyrazoles 2 to synthesize
3-cyanodiarylpyrazolo[1,5-a]pyrimidine 3 (Scheme 2). Thus, treatment of ipriflavone
1a with 5-amino-4-cyano-1H-pyrazole 2 (1.1 eq) in refluxed ethanol in the presence
of sodium hydroxide (3 eq) for 12 h afforded 3-cyano-6-phenyl-7-(2-hydroxyl-4-
isopropoxyphenyl)pyrazolo[1,5-a]pyrimidine 3a (22%) (Table 1, entry 1). We then
optimized the conditions of the cyclocondensations between isoflavone 1a and
5-amino-4-cyano-1H-pyrazole 2 (Table 1). When NaOH (5 M) was used as base,
3a was obtained in 22% yield (entry 1). It was also found that Et3N was ineffective
in providing the desired condensation product (entry 2). A comparative reactivity
study of bases in the reaction showed that NaOMe proved to be most effective for
the cyclocondensation (entry 3). Further study with varying NaOMe equivalents
revealed that 3.0 equiv of base is necessary to obtain a good yield of 3a (entries
Scheme 2.

3-CYANO-6,7-DIARYLPYRAZOLO[1,5-a]PYRIMIDINE
935
Table 1. Optimization of cyclocondensation of isoflavone 1a with 5-amino-4-cyano-1H-pyrazole 2a
Entry
Solvent
Base
Molar ratios (eq.) 1a=2=base
3a yield (%)b
1c
2
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
THF
NaOH
Et3N
1=1.1=3
1=1.1=3
1=1.1=2
1=1.1=3
1=1.1=4
1=1.1=5
1=1.1=3
1=1.1=3
1=1.2=3
1=1.3=3
1=1.4=3
1=1.5=3
22
0
3
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
43
49
54
35
20
25
55
60
56
62
4
5
6
7
8d
9
DMF
MeOH
MeOH
MeOH
MeOH
10
11
12
aAll reactions were carried out with isoflavone 1a (2 mmol), 5-amino-4-cyano-1H-pyrazole 2, and
different kinds of bases until the formation in appropriate solvents (20 mL) was completed as monitored
by TLC (24 h, refluxing).
bIsolated yield based on isoflavone.
cReactions with EtOH, MeOH, and THF as solvent were carried out under the boiling point.
dThe reaction with DMF as solvent was carried at 100 ꢀC.
3–6). MeOH was the solvent of choice, because reactions in tetrahydrofuran (THF),
dimethylformamide (DMF), or EtOH gave lesser yields (entries 6–10). Compound
3a was obtained in a good yield when a ratio of 1a=2 (1:1.3) was used (entry 10).
Next, condensations of a variety of structurally divergent isoflavones 1 with 2
were performed to illustrate this concise and general method for the synthesis of 3.
The wide range of isoflavones (1a–1l) reacted efficiently with 2 under the basic con-
ditions to afford the respective products 3 (16–20 h) in moderate to excellent yields
1
(Table 2). All products were characterized by infrared (IR), H NMR, 13C NMR,
and elemental analysis.
The reaction has a general character, and isoflavone 1 with various substituents
on the both aryl rings (alkoxy, benzyoxyl) groups gave 3 in good yields (Table 3).
The yields, however, decrease when the hydroxyl group exists in the aryl rings.
For example, isoflavones 1f and 1l (entries 6 and 12), which contain hydroxyl group,
gave 3 in about 42% and 45% yields. Other isoflavones, which do not contain
hydroxyl groups, afforded 3 in about 50–60% yields. Isoflavone with two or three
free hydroxyl groups such as daidzein (40,7-dihydroxyisoflavone) and genistein
(40,5,7-trihydroxyisoflavone) with 2 failed to produce product 3. The yields of 3
are directly dependent on the number of free hydroxyl groups present on the engaged
isoflavone. Because the hydroxyls at isoflavones 1 under the basic conditions would

936
Y.-Q. MA ET AL.
Table 2. Synthesis of 3-cyano-6,7-diphenylpyrazolo[1,5-a]pyrimidines 3 by the cyclocondensations of
amino-pyrazoles 2 with isoflavones 1
Entry Substrate R1
R2
R3
R4
R5
R6
R7 Time (h) Product Yield (%)
1
2
1a
1b
1c
1d
1e
1f
H
H
H
H
i-OPr
OMe
OMe
OMe
H
H
H
H
H
H
H
H
H
H
16
16
16
16
18
20
16
17
20
16
16
16
3a
3b
3c
3d
3e
3f
60
59
58
62
58
45
55
63
52
56
54
42
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
3
OMe
OMe
H
4
OMe
H
5
Br i-OPr
6
H
H
H
H
H
H
H
OMe
OMe
H
OH
7
1g
1h
1i
H
i-Pr OMe i-Pr
3g
3h
3i
8
OMe OMe OMe
H
Br
H
H
H
OMe
OMe Br
H
9
OMe
OBn
OBn
OBn
H
H
H
H
H
H
H
H
10
11
12
1j
OMe
OBn
OH
H
H
H
3j
1k
1l
3k
3l
aReaction conditions: 1 (2 mmol), 2 (2.6 mmol), NaOCH3 (6 mmol), 70 ꢀC.
bIsolated yield after silica-gel chromatography.
be oxyanions, which possess stronger electron-donating ability than alkoxy and
benzyoxyl groups, they might prevent condensation of the reaction.
CONCLUSION
An efficient, concise, one-step synthesis of the functionalized 3-cyano-6,7-
diphenyl pyrazolo[1,5-a]pyrimidines is described. This method employs moderate
heating of isoflavones with 5-amino-4-cyano-1H-pyrazole in basic conditions and
afforded regionselectively the fused 3-cyano-6,7-diphenylpyrazolo[1,5-a]pyrimidines.
It is worth mentioning that the goodness and simplicity of this process are due to the
fact that these new compounds are isolated in good yields as stable yellow solids and
are easily purified by recrystallization from ethanol.
EXPERIMENTAL
Melting points were measured on an X-5 micro-melting-point apparatus and
are uncorrected. IR spectra were recorded on a Fourier transform (FT)–IR spec-
trometer. The 1H NMR spectra were recorded at 300.00 MHz on a Bruker
DRX-300 Advance spectrometer; chemical shifts (d scale) are reported in parts per
million (ppm) downfield from Me4Si, which was used as the internal standard for
1
all NMR spectra. H NMR spectra are reported in this order: multiplicity and

3-CYANO-6,7-DIARYLPYRAZOLO[1,5-a]PYRIMIDINE
937
approximate coupling constant (J value) in hertz (Hz), and number of protons.
Signals were characterized as s (singlet), d (doublet), t (triplet), m (multiplet), and
br s (broad signal). The 13C NMR spectra were recorded at 75.00 MHz; chemical
shifts (d scale) are reported in parts per million (ppm). The elemental analyses were
performed with an Elementar Analysensyteme GmbH Vario EL III. All the products
1
are new compounds, which were characterized by IR, H NMR, and 13C NMR
spectra. Thin-layer chromatography (TLC) used silica gel 60 GF254 plate; and the
eluant of column chromatography is the mixture of petroleum ether and ethyl acetate
at a volume ratio of 3:1.
General Procedure for the Synthesis of 3-Cyano-6,7-
diphenylpyrazolo[1,5-a]pyrimidines 3
The isoflavones 1a–1l (2 mmol), 5-amino-4-cyano-1H-pyrazole 2 (2.6 mmol),
and sodium methoxide 6 mmol were refluxed in methanol (40 mL) for 14–20 h. All
reactions were monitored by TLC, which showed the disappearances of the starting
materials. The reaction mixture was then concentrated to 10 mL by using a rotary
evaporator. The condensate was poured into water (15 mL) and neutralized with a
solution of 10% HCl, and a light yellow precipitate formed. This precipitate was
collected by filtration and washed with distilled water. Finally, the precipitate was
recrystallized from absolute ethanol or purified on silica gel column chromatography
(petroleum=ethyl acetate ¼ 6:1), and 3 was obtained.
Data for Compounds 3a–3l
3-Cyano-6-phenyl-7-(2-hydroxyl-4-isopropoxyphenyl)pyrazolo[1,5-a]
pyrimidine(3a). Mp 102.0–106.2 ꢀC; IR (KBr), n (cmꢁ1): 3991, 3948, 3853, 3791,
3498, 3464, 3255, 2977, 2928, 2231, 1610, 1499, 1465, 1379, 1283, 1191, 1115, 840,
1
700; H NMR [300 MHz, DMSO-d6=TMS, d (ppm)]: 1.25–1.27 (d, 6H), 4.53 (m,
1H), 6.37 (d, J ¼ 8.4 Hz, 1H), 6.40 (s, 1H), 7.01 (d, J ¼ 8.4 Hz, 1H), 7.33 (s, 5H),
8.74 (s, 1H), 8.92 (s, 1H), 9.88 (s, 1H);13C NMR [75 MHz, DMSO-d6=TMS, d
(ppm)]: 21.8, 69.3, 80.9, 102.5, 106.4, 108.8, 133.4, 125.1, 127.9, 128.3, 129.3,
131.7, 134.1, 144.7, 147.2, 149.3, 154.7, 160.0, 160.3. Anal. calcd. for C22H18N4O2:
C, 71.34; H, 4.90; N, 15.13. Found C, 71.40; H, 5.00; N, 15.17.
3-Cyano-6-phenyl-7-(2-hydroxyl-4-methoxy-6-methyphenyl)pyrazolo[1,
5-a]pyrimidine (3b). Mp 215.2–216.1 ꢀC; IR (KBr), n (cmꢁ1): 3884, 3447, 3441,
3227, 2959, 2229, 1611, 1529, 1441, 1338, 1270, 1195, 1156, 1077, 825, 703, 645;
1H NMR [300 MHz, DMSO-d6=TMS, d (ppm)]: 1.72 (s, 3H), 3.71 (s, 3H), 6. 30
(s, 2H), 7.36 (s, 5H), 8.75 (s, 1H), 9.00 (s, 1H), 9.88 (s, 1H); 13C NMR [75 MHz,
DMSO-d6=TMS, d (ppm)]: 19.6, 55.4, 81.6, 99.2, 106.9, 109.9, 113.7, 126.2, 128.7,
128.9, 129.3, 134.4, 138.8, 144.6, 147.9, 149.8, 155.2, 157.2, 162.0. Anal. calcd. for
C21H16N4O2: C, 70.77; H, 4.53; N, 15.72. Found C, 71.02; H, 4.57; N, 15.77.
3-Cyano-6-(4-methoxyphenyl)-7-(2-hydroxyl-4-methoxyphenyl)pyrazolo
[1,5-a]pyrimidine (3c). Mp 130.8–133.8 ꢀC; IR (KBr), n (cmꢁ1): 3725, 3554, 3459,
3351, 2933, 2837, 2223, 1610, 1499, 1456, 1256, 1178, 1067, 1024, 828; H NMR
1
[300 MHz, DMSO-d6=TMS, d (ppm)]: 3.74 (s, 6H), 6.41 (s, 1H), 6.45 (s, 1H), 6.92

938
Y.-Q. MA ET AL.
(d, J ¼ 8.4 Hz, 2H), 7.03 (s, 1H), 7.06 (s, 1H), 7.25 (d, J ¼ 8.4 Hz, 2H), 8.71 (s, 1H),
8.90 (s, 1H), 9.92 (s, 1H); 13C NMR [75 MHz, DMSO-d6=TMS, d (ppm)]: 55.6,
56.5, 81.3, 101.0, 101.7, 105.7, 109.9, 113.9, 114.4, 115.1, 115.5, 125.4, 126.6, 127.4,
129.7, 131.0, 132.1, 144.8, 149.6, 153.5, 155.3, 157.4, 157.7, 159.5, 162.4. Anal. calcd.
for C21H16N4O3: C,67.73; H, 4.33; N, 15.05. Found C, 67.69; H, 4.01; N, 14.97.
3-Cyano-6-(4-methoxyphenyl)-7-(2-hydroxyl-4,6-dimethoxyphenyl)pyr-
azolo[1,5-a]pyrimidine (3d). Mp 208.8–210.6 ꢀC; IR (KBr), n (cmꢁ1): 3881, 3519,
3421, 2938, 2841, 2229, 1610, 1507, 1463, 1425, 1370, 1250, 1108, 1155, 1104, 1032,
828, 646; 1H NMR [300 MHz, DMSO-d6=TMS, d (ppm)]: 3.51 (s, 3H), 3.67 (s, 3H),
3.74 (s, 3H), 6. 10 (s, 1H), 6. 14 (s, 1H), 6.91 (d, J ¼ 8.1 Hz, 2H), 7.27 (d, J ¼ 8.1 Hz,
2H), 8.69 (s, 1H), 8.87 (s, 1H), 9.93 (s, 1H); 13C NMR [75 MHz, DMSO-d6=TMS, d
(ppm)]: 55.4, 56.1, 81.3, 90.5, 94.2, 99.4, 113.8, 114.3, 126.6, 126.8, 130.4, 142.6,
147.5, 149.5, 155.0, 157.3, 159.3, 159.6, 163.3. Anal. calcd. for C22H18N4O4:
C,65.66; H, 4.51; N, 13.92. Found C, 65.69; H, 4.56; N, 13.97.
3-Cyano-6-phenyl-7-(2-hydroxyl-3-bromo-4-isopropoxyphenyl)pyrazolo
[1,5-a]pyrimidine (3e). Mp 206.6–207.3 ꢀC; IR (KBr), n (cmꢁ1): 3922, 3850, 3720,
3460, 2927, 2230, 1608, 1492, 1403, 1271, 1199, 1106, 1024, 670; 1H NMR [300 MHz,
DMSO-d6=TMS, d (ppm)]: 1.31 (s, 6H), 4.58 (m, 1H), 6.57 (s, 1H), 7.36 (s, 1H), 7.41
(s, 6H), 8.76 (s, 1H), 8.93 (s, 1H), 10.21 (s, 1H); 13C NMR [75 MHz, DMSO-d6=
TMS, d (ppm)]: 22.0, 22.3, 71.8, 81.6, 101.0, 102.8, 110.8, 113.8, 125.9, 128.6,
129.8, 134.4, 134.6, 143.5, 147.7, 150.0, 155.2, 156.5, 166.8. Anal. calcd. for
C22H18N4O4: C, 65.66; H, 4.51; N, 13.92. Found C, 65.69; H, 4.56; N, 13.97.
3-Cyano-6-(4-hydroxylphenyl)-7-(2-hydroxyl-4-methoxyphenyl)pyrazolo
[1,5-a]pyrimidine (3f). Mp 198.2–201.3 ꢀC; IR (KBr), n (cmꢁ1): 3955, 3922, 3865,
3460, 2232, 1611, 1506, 1438, 1374, 1272, 1170, 835; 1H NMR [300 MHz, DMSO-d6-
=TMS, d (ppm)]: 3.74 (s, 3H), 6.45 (s, 1H), 6.70 (s, 1H), 6.73 (d, J ¼ 8.1 Hz, 1H), 7.00
(s, 1H), 7.03 (s, 1H), 7.10 (d, J ¼ 8.1 Hz, 1H), 7.13 (s, 1H), 8.71 (s, 1H), 8.88 (s, 1H),
9.66 (s, 1H), 9.93 (s, 1H); 13C NMR [75 MHz, DMSO-d6=TMS, d (ppm)]: 55.6, 81.2,
101.6, 105.6, 110.0, 113.9, 115.7, 115.8, 124.9, 125.7, 130.9, 131.1, 132.1, 144.6, 147.4,
149.5, 155.3, 157.4, 157.7, 162.3. Anal. calcd for C22H18N4O4: C,65.66; H, 4.51; N,
13.92. Found C, 65.69; H, 4.56; N, 13.97.
3-Cyano-6-(3,5-diisopropyl-4-methoxylphenyl)-7-(2-hydroxy-4-methoxy-
phenyl)pyrazolo[1,5-a]pyrimidine (3g). Mp 223.2–225.3 ꢀC; IR (KBr), n (cmꢁ1):
3976, 3885, 3693, 3541, 3493, 2954, 2231, 1735, 1611, 1504, 1463, 1314, 1199,
1166, 1028, 836; 1H NMR [300 MHz, DMSO-d6=TMS, d (ppm)]: 1.02–1.09 (m,
12H), 3.65 (s, 3H), 3.68 (s, 3H), 6.45 (s, 1H), 6.49 (s, 1H), 7.09 (t, 3H), 8.72 (s,
1H), 9.00 (s, 1H), 9.92 (s, 1H); 13C NMR [75 MHz, DMSO-d6=TMS, d (ppm)]:
55.6, 62.4, 81.3, 101.7, 105.7, 110.2, 113.9, 125.5, 125.8, 130.1, 131.8, 141.6, 144.9,
147.6, 149.6, 154.4, 155.2, 157.5, 162.5. Anal. calcd. for C22H18N4O4: C, 65.66; H,
4.51; N, 13.92. Found C, 65.69; H, 4.56; N, 13.97.
3-Cyano-6-(4-methoxyphenyl)-7-(2-hydroxyl-4,5,6-trimethoxyphenyl)
pyrazolo[1,5-a]pyrimi-dine (3h). Mp 205.3–208.2 ꢀC; IR (KBr), n (cmꢁ1): 3974,
3888, 3264, 2941, 2840, 2231, 1607, 1499, 1465, 1412, 1248, 1193, 1101, 1025, 833;
1H NMR [300 MHz, DMSO-d6=TMS, d (ppm)]: 3.42 (s, 3H), 3.62 (s, 3H), 3.75 (s,

3-CYANO-6,7-DIARYLPYRAZOLO[1,5-a]PYRIMIDINE
939
3H), 3.78 (s, 3H), 6.30 (s, 1H), 6.95 (d, J ¼ 8.4 Hz, 2H), 7.31 (d, J ¼ 8.4 Hz, 2H), 8.73
(s, 1H), 8.95 (s, 1H), 9.73 (s, 1H); 13C NMR [75 MHz, DMSO-d6=TMS, d (ppm)]:
55.6, 56.1, 60.8, 61.0, 81.4, 96.0, 103.2, 113.8, 114.4, 126.3, 126.5, 130.6, 134.3,
142.0, 147.6, 149.5, 151.5, 152.2, 155.2, 156.1, 159.8. Anal. calcd. for C23H20N4O5:
C, 63.88; H, 4.66; N, 12.96. Found C, 63.91; H, 4.71; N, 13.01.
3-Cyano-6-(3,5-dibromo-4-methoxyphenyl)-7-(2-hydroxyl-4-methoxy-
phenyl)pyrazolo[1,5-a]pyrimidine (3i). Mp 200.5–205.8 ꢀC; IR (KBr), n (cmꢁ1):
3288, 2923, 2366, 2240, 1609, 1505, 1454, 1378, 1296, 1242, 1169, 1008, 824, 739,
1
694; H NMR [300 MHz, DMSO-d6=TMS, d (ppm)]: 3.74 (s, 3H), 3.83 (s, 3H),
6.57 (s, 1H), 7.10 (d, J ¼ 8.1 Hz, 1H), 7.26 (d, J ¼ 8.1 Hz, 1H), 7.52 (s, 1H), 7.58
(s, 1H), 8.75 (s, 1H), 8.93 (s, 1H), 10.29 (s, 1H); 13C NMR [75 MHz, DMSO-d6=
TMS, d (ppm)]: 55.6, 56.6, 81.6, 99.8, 100.8, 110.3, 110.9, 112.9, 113.8, 114.5,
124.4, 127.9, 130.5, 130.8, 131.0, 134.0, 134.6, 143.2, 147.8, 149.8, 155.3, 155.7,
156.8, 158.1. Anal. calcd. for C21H14Br2N4O3: C, 45.57; H, 2.66; N, 10.57. Found
C, 45.69; H, 2.686; N, 10.67.
3-Cyano-6-(4-methoxyphenyl)-7-(2-hydroxyl-4-benzyloxyphenyl)pyra-
zolo[1,5-a]pyrimidine (3j). Mp 242.4–243.6 ꢀC; IR (KBr), n (cmꢁ1): 3305, 2925,
2235, 1610, 1099, 1451, 1375, 1176, 1029, 884, 745; H NMR [300 MHz, DMSO-d6-
1
=TMS, d (ppm)]: 3.73 (s, 3H), 5.12 (s, 2H), 6.51 (s, 1H), 6.90 (d, J ¼ 7.8 Hz, 1H), 7.02
(s, 1H), 7.05 (s, 1H), 7.23 (d, J ¼ 7.8 Hz, 1H), 7.37 (s, 1H), 7.39 (s, 1H), 7.43 (s, 5H),
8.71 (s, 1H), 8.89 (s, 1H), 9.97 (s, 1H); 13C NMR [75 MHz, DMSO-d6=TMS, d
(ppm)]: 55.6, 70.0, 81.3, 102.5, 106.3, 108.4, 110.0, 114.0, 114.4, 125.4, 126.6,
128.3, 128.4, 128.9, 131.1, 132.1, 133.6, 137.2, 144.7, 147.5, 149.6, 155.4, 157.4,
159.4, 161.5, 164.9. Anal. calcd. for C27H20N4O3: C, 72.31; H, 4.49; N, 12.49. Found
C, 72.35; H, 4.47; N, 12.46.
3-Cyano-6-(4-benzyloxyphenyl)-7-(2-hydroxyl-4-benzyloxyphenyl)pyra-
zolo[1,5-a]pyrimidine (3k). Mp 222.4–223.6 ꢀC; IR (KBr), n (cmꢁ1): 3294, 2917,
2857, 2360, 2233, 1733, 1609, 1502, 1451, 1378, 1299, 1249, 1169, 1008, 837, 742,
1
691; H NMR [300 MHz, DMSO-d6=TMS, d (ppm)]: 5.01 (s, 2H), 5.18 (s, 2H),
6.41 (s, 1H), 6.51 (s, 1H), 6.69 (d, J ¼ 6.6 Hz, 1H), 7.00 (d, 1H), 7.03 (s, 1H), 7.06
(s, 1H), 7.24 (d, J ¼ 6.6 Hz, 1H), 7.43 (s, 10H), 8.71 (s, 1H), 8.90 (s, 1H), 9.97 (s,
1H); 13C NMR [75 MHz, DMSO-d6=TMS, d (ppm)]: 69.7, 70.1, 81.3, 102.5, 106.4,
108.4, 110.0, 113.9, 115.2, 125.4, 126.8, 128.4, 128.9, 130.9, 131.1, 132.2, 137.2,
137.3, 144.7, 147.6, 149.6, 155.4, 157.4, 158.6, 161.5, 165.2. Anal. calcd. for
C33H24N4O3: C, 75.56; H, 4.61; N, 10.68. Found C, 75.53; H, 4.59; N, 10.63.
3-Cyano-6-(4-hydroxyl)-7-(2-hydroxyl-4-benzyloxyphenyl)pyrazolo[1,5-a]
pyrimidine (3l). Mp 246.3–251.1 ꢀC; IR (KBr), n (cmꢁ1): 3550, 3350, 3277, 2874,
2233, 1613, 1502, 1454, 1287, 1166, 1135, 1062, 1104, 837, 739, 698; 1H NMR
[300 MHz, DMSO-d6=TMS, d (ppm)]: 5.01 (s, 2H), 6.48 (s, 1H), 6.51 (s, 1H), 6.70
(d, J ¼ 7.5 Hz, 2H), 7.01 (d, 1H), 7.11 (d, J ¼ 7.5 Hz, 2H), 7.39 (s, 5H), 8.70 (s,
1H), 8.88 (s, 1H), 9.65 (s, 1H), 9.94 (s, 1H); 13C NMR [75 MHz, DMSO-d6=TMS,
d (ppm)]: 69.7, 81.2, 102.4, 106.3, 110.2, 114.0, 115.8, 124.9, 125.7, 128.4, 128.8,
131.1, 132.1, 137.2, 144.5, 147.5, 149.5, 155.4, 157.4, 157.7, 161.4. Anal. calcd. for
C26H18N4O3: C, 71.88; H, 4.18; N, 12.90. Found C, 71.92; H, 4.19; N, 12.93.

940
Y.-Q. MA ET AL.
ACKNOWLEDGMENTS
This research was supported by the National Natural Science Foundation of
China (No: 20772076) and Science and Innovation Funds of Graduate Programs
of Shaanxi Normal University (No. 2008CXS029).
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