Facile synthesis of diarylpyrazolo[1,5-a]pyrimidine from isoflavones

Article abstract of DOI:10.1002/jhet.1633

A new facile and straightforward method for synthesis of 2-methyl-6,7-diphenyl- pyrazolo[1,5-a]pyrimidines has been described. The cyclocondensation of isoflavones with 3-amino-5-methylpyrazole in the presence of sodium methoxide gave fused 2-methyl-6,7-diphenylpyrazolo[1,5-a]pyrimidines in moderate to good yields. A series of 20 new compounds were obtained and characterized by FT-IR, NMR, and elemental analysis.

Full text of DOI:10.1002/jhet.1633

24
Facile Synthesis of Diarylpyrazolo[1,5-a]pyrimidine from Isoflavones
Vol 51
*
Junling Yang, Zunting Zhang, and Qing He
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 of China, and School of
Chemistry and Materials Science, Shaanxi Normal University, Xi’an 710062, People’s Republic of China
*
E-mail: zhangzt@snnu.edu.cn
Received September 1, 2011
DOI 10.1002/jhet.1633
Published online 7 October 2013 in Wiley Online Library (wileyonlinelibrary.com).
R7
N
R1
H3C
N
R7
R5
R2
R3
O
O
R6
N
NH2
EtOH,NaOMe
R6
R5
+
OH
R1
H3C
R4
N
N
reflux
H
R4
R3
R2
A new facile and straightforward method for synthesis of 2-methyl-6,7-diphenyl- pyrazolo[1,5-a]
pyrimidines has been described. The cyclocondensation of isoflavones with 3-amino-5-methylpyrazole
in the presence of sodium methoxide gave fused 2-methyl-6,7-diphenylpyrazolo[1,5-a]pyrimidines in
moderate to good yields. A series of 20 new compounds were obtained and characterized by FT-IR,
NMR, and elemental analysis.
J. Heterocyclic Chem., 51, 24 (2014).
INTRODUCTION
donating group, but its electron donating effect is weaker
than hydroxyl located at pyrazole ring. In this paper, in
order to explore forming-fused pyrazolo[3,4-b]-pyridines
or pyrazolo[1,5-a]pyrimidines, the cyclocondensation of
3-amino-5-methylpyrazole with isoflaovens was carried out.
In general, the fused heterocyclic compound, pyrazolo
[1,5-a]pyrimidines are known to possess pharmacological
activity and anxiolytic properties, such as translocator
protein ligands [1,2] (Scheme 1), HIV (human immunodefi-
ciency virus)reverse transcriptase inhibitors [3], estrogen
receptor ligands [4], KDR (kinase insert domain-containing
receptor) kinase inhibitors [5], COX-2-selective inhibitors
[6], and CRF-1 receptor antagonists. [7] They are also used
as intermediates in the dyestuff industry. [8,9] These
interesting activities have stimulated chemists to develop
the chemistry of this class of compounds.
Numerous methods for the synthesis of pyrazolo[1,5-a]
pyrimidines have been reported in the last 20 years, which
involved the reaction between aminopyrazoles and 1,3-
biselectrophilic compounds, including a,b-unsaturated
ketones [10], dithioacetals [11], and enaminone compounds.
[12] It was reported that the chromone fragment of the
isoflavone can generate a 1,3-diketone equivalent in the
present of alkali, which readily reacts with amidine [13],
hydrazine [14], biguanidine [15], and 2-aminobenzimidazole
[16] to form the corresponding pyrimidines and diarylpyra-
zoles. Recently, we have reported the synthesis of diarylpyr-
azolo[3,4-b]pyridines [17] and diphenylpyrazolo[1,5-a]
pyrimidines [18] by using one-step reaction of 3-amino-5-
hydroxypyrazole (X=OH) and 3-aminopyrazole (X=H)
with isoflavones (Scheme 2). The different fused nitrogen
was obtained, because hydroxyl located at pyrazole ring
is donating electron to the ring. [18] For the methyl of
3-amino-5-methylpyrazole, (X=Me) is also an electron
RESULT AND DISCUSSION
Reaction of 7-isopropoxyisoflavone 1a (1.0 equiv) and ]
3-amino-5-methylpyrazole 2 (1.2 equiv) were carried out in
refluxing ethanol in the presence of sodium methoxide as
base to promote the ring-opening of isoflavone. The prog-
ress of the reaction was monitored by thin layer chromatog-
raphy (TLC) until the starting 1a disappeared. The product
that was purified by column chromatography on silica gel,
1
and characterized by IR, H NMR, and 13C NMR, finally
confirmed condensation of 1a and 2 mainly product
2-methyl-6-phenyl-7-(2-hydroxyl-4-isopropoxyphenyl)-
pyrazo[1,5-a]pyrimidine (3a).
Then we turned our attention to optimize the conditions
to improve yields (Table 1). Under different equivalency
of NaOH and NaOMe, it was found that 3.0 equivalency
of NaOMe gave the best result (Table 1, entry 4). EtOH
was an ideal solvent. The best condition to obtain the max-
imum yield (83%) was using NaOMe (0.5 molÁL-1, 3.0 eq)
as base in ethanol with 1:1.5 as the ratio of 1a/2.
Having the optimized conditions, the scope of the
reaction was examined and summarized in Table 2. All
1
products were characterized by IR, H NMR, 13C NMR
spectra, and elemental analysis.
© 2013 HeteroCorporation

January 2014
Facile Synthesis of Diarylpyrazolo[1,5-a]pyrimidine from Isoflavones
25
Table 1
Scheme 1. Pyrazolo[1,5-a]pyrimidine as a TSPO (translocator protein)
ligand.
Optimization of cyclocondensation of 7-isopropoxyisoflavone 1a with
3-amino-5-methylpyrazole 2.a
Molar ratios 3a yield
1a/2/base
Entry
Solvent b
Base
(%)c
1
2
3
4
5
6
7
8
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
THF
NaOH(s)
1/1.2/2
1/1.2/2
1/1.2/2
1/1.2/3
1/1.2/4
1/1.2/3
1/1.2/3
1/1.2/3
1/1.3/3
1/1.5/3
1/1.7/3
30
45
57
64
58
74
55
58
79
83
82
NaOH(3 molÁL-1)
NaOMe(0.5 molÁL-1)
NaOMe(0.5 molÁL-1)
NaOMe(0.5 molÁL-1)
NaOMe(0.5 molÁL-1)
NaOMe(0.5 molÁL-1)
NaOMe(0.5 molÁL-1)
NaOMe(0.5 molÁL-1)
NaOMe(0.5 molÁL-1)
NaOMe(0.5 molÁL-1)
DMF d
EtOH
EtOH
EtOH
9
10
11
As shown in Table 2, isoflavones containing fluorine
group take reaction easily and give 3 in high yields. The
yields become the lowest when isoflavones with hydroxyl
group. Isoflavones 1o, 1p, and 1q (Table 2, entries15–17),
which contain fluorine group, gave 3 about 85%. Isoflavone
with hydroxyl group 1g, 1h, and 1i (Table 2, entries7–9)
afforded 3 about 50%. The yields of 3 directly depended
on the substituents present on the engaged isoflavones. It
seems possible that strong electronegativity of fluorine might
be beneficial to take reaction. Although the hydroxyl groups
under the basic conditions would become oxyanions, which
possess stronger electron donating ability than alkoxy and
benzyoxyl groups, preventing condensation with 2.
aAll reactions were carried out with 7-isopropoxyisoflavone 1a (2 mmol),
3-amino-5-methylpyrazole 2, and different kinds of bases in indicated
solvents (20 mL) for 24 h.
bReactions with MeOH, EtOH, and THF as solvent were carried out at
reflux.
cIsolated yield on the basis of isoflavone 1a.
dThe reaction with DMF as solvent was carried at 100ꢀC.
with isoflavones formed pyrazolo[3,4-b]pyridine because
of the hydroxyl group that would become an oxyanion in
basic condition, enhancing the nucleophilicity of C4 of
3-amino-5-hydroxypyrazole that attacks the b-carbon of 5
more easily [18]. On the contrast, the electron donating abil-
ity of methyl is weaker than hydroxyl, the C4 of 3-amino-5-
methylpyrazole has poor nucleophilicity, and the proposed
mechanism is similar to the reaction of 3-aminopyrazole with
isoflavones [19], as shown in Scheme 3; the primary amine
group of the 2 first attacks the b-carbon of 5, followed by ring
closure, then pyrazolo[1,5-a]pyrimidine is formed.
According to the report [19], isoflavone may undergo
ring opening reaction in the presence of alkali to form an
a,b-unsaturated ketone intermediate 5 (Scheme 3) which
at high concentration of base may eliminate HC(OMe)3 to
generate byproduct 6. 3-amino-5-hydroxypyrazole react
Scheme 2. Cyclocondensations of 3-amino-5-hydroxypyrazole and 3-aminopyrazole with isoflavones. [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]
R1
R2
HO
H
N
R3
R7
R6
N
X=OH
N
R4
HO
R1
H
N
R5
R7
R5
MeOH
R2
R3
O
O
NaOMe
3-hydroxy-5,6-diphenylpyrazolo[3,4-b]pyridines
X
N
+
R6
reflux
R7
NH2
N
R4
R6
N
N
X=H
HO
R5
R4
R3
R1
R2
6,7-diphenylpyrazolo[1,5-a]pyrimidines
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

26
J. Yang, Z. Zhang, and H. Qing
Vol 51
Table 2
Synthesis of 6,7-diphenylpyrazolo[1,5-a]pyrimidines 3.a
R7
N
R1
H3C
N
R7
R2
R3
O
O
R6
N
NH2
EtOH,NaOMe
R6
R5
+
H3C
OH
R1
R4
N
N
reflux
H
R4
R5
R3
R2
Entry
Substance
R1
R2
R3
R4
R5
R6
R7
Product
Yield (%)b
Time (h)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
H
H
H
H
H
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
H
i-OPr
OMe
OMe
OMe
OBn
OMe
OH
OMe
OMe
i-OPr
OMe
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
F
H
H
OMe
Me
H
H
H
H
OH
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
i-Pr
H
H
H
H
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
83
80
77
75
77
71
56
60
58
78
76
75
82
81
87
88
86
83
85
82
20
24
24
24
27
24
72
48
56
18
27
30
24
24
18
18
16
18
24
20
OMe
OMe
H
OMe
H
OMe
OH
OMe
H
OMe
H
Me
OMe
H
Me
OMe
H
H
H
H
H
H
H
H
H
H
i-Pr
H
H
H
H
H
H
H
H
H
9
10
11
12
13
14
15
16
17
18
19
20
F
F
Br
Br
H
1s
1t
H
H
Me
F
3t
aIsoflavones 1 (2 mmol), 2 (3.0 mmol), and NaOMe (4 mmol were used for fluorine group and 8 mmol were used for 1 hydroxyl group in 1, respectively)
in ethanol.
bIsolated yield.
disappearance of 1 that was indicative of the reaction being
complete. The reaction mixture was adjusted to neutrality
with the solution of 5% HCl and then poured into water
(30 mL). A yellow precipitate appeared and was filtered.
Finally, the precipitate was recrystallized from absolute ethanol
or purified by column chromatography on silica gel using
petroleum ether-ethyl acetate (4:1) to give the corresponding
pure product 3a–3t.
CONCLUSION
Make the comparison of isoflavones react with 3-amino-
5-hydroxypyrazole, 3-aminopyrazole and 3-amino-5-
methylpyrazole under the basic condition afforded
chemoselectivity fused pyrazolo[3,4-b]pyridines and pyrazolo
[1,5-a]pyrimidines. It is indicative that the electron donating
ability of substituents probably is one of the key factors that
will lead to form different structures. Extended to all the
alkyl-3-aminopyrazole, which react with isoflavones under
the aforementioned conditions will be mainly formed the
structure of pyrazolo[1,5-a]pyrimidines.
Characterizations of products
2-Methyl-6-phenyl-7-(2-hydroxyl-4-isopropoxyphenyl)pyrazolo
[1,5-a]pyrimidine (3a). Mp 223.7–224.1ꢀC. IR (KBr), n (cm-1):
1
3842, 2980, 2926, 1604, 1497, 1271, 1179, 1108, 990, 463. H
NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 1.29 (d, 6H,
J = 5.8Hz), 2.40 (s, 3H), 4.56 (m, 1H), 6.42 (d, 1H, J =8.7 Hz),
6.46 (s, 1H), 6.55 (s, 1H), 6.98 (d, 1H, J = 8.7 Hz), 7.30 (s, 5H),
1
8.55 (s, 1H), 9.78 (s, 1H). H NMR [300 MHz, DMSO-d6 + D2O/
EXPERIMENTAL
TMS, d (ppm)]: 1.29 (d, 6H, J = 5.8 Hz), 2.40 (s, 3H), 4.56
(m, 1H), 6.42 (d, 1H, J = 8.7 Hz), 6.46 (s, 1H), 6.55 (s, 1H), 6.98
(d, 1H, J = 8.7 Hz), 7.30 (s, 5H), 8.55 (s, 1H). 13C NMR [75MHz,
DMSO-d6/TMS, d (ppm)]: 14.9, 22.2, 69.8, 95.9, 103.0, 106.6,
110.8, 121.9, 127.7, 128.9, 129.7, 132.0, 135.9, 142.6, 148.9,
150.6, 154.4, 157.1, 160.1. Anal. Calcd for C22H21N3O2: C,
73.52; H, 5.89; N, 11.69; Found C, 73.48; H, 5.96; N, 11.75.
General procedure for the reaction of isoflavones with 3-
amino-5-methylpyrazole to synthesize pyrazolo[1,5-a]
pyrimidine.
The corresponding isoflavones 1 (2 mmol), 3-
amino-5-methyl-pyrazole 2 (3 mmol), and sodium methoxide
(6 mmol) were refluxed in ethanol (20 mL) for 16–72 h. All
reactions were monitored by usingTLC, which showed the
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2014
Facile Synthesis of Diarylpyrazolo[1,5-a]pyrimidine from Isoflavones
27
Scheme 3. Proposed mechanism for the formation of 3.
2-Methyl-6-(4-methoxyphenyl)-7-(2-hydroxyl-4-methoxyphenyl)
pyrazolo[1,5-a]pyrimidine (3b). Mp 227.1–228.5ꢀC. IR (KBr), n
(cm-1): 3845, 2948, 1609, 1504, 1416, 1295, 1248, 1093, 1020,
828, 742, 568. 1H NMR [300 MHz, DMSO-d6/TMS, d (ppm)]:
2.36 (s, 3H), 3.73 (s, 6H), 6.40 (d, 1H, J = 8.4Hz), 6.44 (s, 1H),
6.57 (s, 1H), 6.86 (d, 2H, J = 7.9 Hz), 6.98 (d, 1H, J = 8.4 Hz),
7.20 (d, 2H, J = 7.9 Hz), 8.50 (s, 1H), 9.79 (s, 1H). 1H NMR
[300MHz, DMSO-d6 + D2O/TMS, d (ppm)]: 2.35 (s, 3H), 3.72 (s,
6H), 6.39 (d, 2H, J = 8.4 Hz), 6.45 (s, 1H), 6.45 (s, 1H), 6.57 (s,
1H), 6.85 (d, 2H, J = 7.9 Hz), 6.97 (d, 1H, J = 8.4 Hz), 7.19 (d,
2H, J = 7.9 Hz), 8.50 (s, 1H). 13C NMR [75 MHz, DMSO- d6/
TMS, d (ppm)]: 14.9, 55.5, 95.8, 101.6, 105.4, 111.4, 114.2,
121.7, 128.0, 130.5, 132.0, 142.2, 148.8, 150.7, 154.1, 157.0,
159.0, 161.8. Anal. Calcd for C21H19N3O3: C, 69.79; H, 5.30; N,
11.63; Found C, 69.85; H, 5.24; N, 11.67.
DMSO-d6/TMS, d (ppm)]:14.4, 55.0, 69.2, 95.2, 102.1, 105.6,
111.2, 113.7 121.2, 127.5, 127.9, 128.4, 130.4, 131.5, 136.9, 141.7,
148.3, 150.2, 153.5, 156.7, 158.4, 160.4. Anal. Calcd for
C27H23N3O3: C, 74.12; H, 5.30; N, 9.60; FoundC, 74.20; H, 5.25;
N, 9.56.
2-Methyl-6-phenyl-7-(2-hydroxyl-4-methoxyphenyl)pyrazolo
[1,5-a]pyrimidine (3f). Mp 223.4–224.9ꢀC. IR (KBr), n (cm-1):
3431, 3029, 2962, 1606, 1497, 1440, 1338, 1294, 1205, 1160, 695.
1H NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 2.36 (s, 3H), 3.72
(s, 3H), 6.38 (d, 2H, J= 8.1 Hz), 6.43 (s, 1H), 6.58 (s, 1H), 6.97 (d,
2H, J= 8.1 Hz), 7.28 (s, 5H), 8.52 (s, 1H), 9.81 (s, 1H). 13C NMR
[75 MHz, DMSO-d6/TMS, d (ppm)]: 14.4, 55.3, 95.3, 101.2, 104.8,
110.8, 121.4, 127.2, 128.2, 129.2, 131.5, 135.4, 142.1, 148.5,
150.1, 153.7, 156.7, 161.3. Anal. Calcd for C20H17N3O2: C, 72.49;
H, 5.17; N, 12.68; Found C, 72.55; H, 5.12; N, 12.72.
2-Methyl-6-(4-methoxyphenyl)-7-(2,4-dihydroxylphenyl)pyrazolo
[1,5-a]pyrimidine (3g). Mp 273.8–274.6ꢀC. IR (KBr), n (cm-1):
3283, 3134, 3001, 1600, 1514, 1439, 1382, 1318, 1265, 1169, 829,
742, 642, 593. 1H NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 2.36
(3H), 3.72 (3H), 6.22 (d, 1H, J= 8.1 Hz), 6.35 (s, 1H), 6.55 (s, 1H),
6.85 (d, 2H, J= 7.8 Hz), 6.87 (d, 1H, J= 8.1 Hz), 7.19 (d, 2H,
J= 7.8 Hz), 8.48 (s, 1H), 9.57 (s, 1H). 13C NMR [75 MHz, DMSO-
d6/TMS, d (ppm)]: 14.9, 55.5, 95.6, 103.0, 107.1, 109.8, 114.1,
121.6, 128.2, 130.9, 131.9, 142.7, 148.9, 150.7, 153.9, 157.0, 158.9,
160.0. Anal. Calcd for C20H17N3O3: C, 69.15; H, 4.93; N, 12.10;
Found C, 69.22; H, 4.86; N, 12.13.
2-Methyl-6-(4-methoxyphenyl)-7-(2-hydroxyl-4,6-dimethoxyphenyl)
pyrazolo[1,5-a]pyrimidine (3c). Mp 227.7–118.9ꢀC. IR (KBr), n (cm-
1): 3482, 3136, 2803, 1597, 1506, 1462, 1354, 1289, 1108, 1034, 816,
1
571. H NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 2.35 (s, 3H),
3.51 (s, 3H), 3.73 (s, 6H), 6.06 (s, 1H), 6.10 (s, 1H), 6.53 (s, 1H), 6.86
(d, 2H, J= 7.9 Hz), 7.20 (d, 2H, J= 7.9 Hz), 8.46 (s, 1H), 9.69 (s, 1H).
13C NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 14.4, 55.0, 55.5, 89.9,
93.6, 95.0, 101.6, 113.5, 123.0, 126.2, 129.8, 143.6, 148.1, 149.8,
154.0, 156.7, 158.6, 158.9, 162.0. Anal. Calcd for C22H21N3O4: C,
67.51; H, 5.41; N, 10.74; Found C, 67.46; H, 5.49; N, 10.68.
2-Methyl-6-phenyl-7-(2-hydroxyl-4-methoxy-6-methylphenyl)
pyrazolo[1,5-a]pyrimidine (3d). Mp 222.3–223.0ꢀC. IR (KBr),
n (cm-1): 3478, 3013, 2802, 1517, 1269, 1145, 1058, 995, 832,
2-Methyl-6-(4-hydroxylphenyl)-7-(2-hydroxyl-4-methoxyphenyl)
pyrazolo[1,5-a]pyrimidine (3h). Mp 263.0–264.5ꢀC. IR (KBr), n
(cm-1): 3263, 3110, 3003, 1598, 1504, 1439, 1382, 1318,
1
789, 694, 535. H NMR [300 MHz, DMSO-d6/TMS, d (ppm)]:
1
1265,1169, 829, 742, 642, 593. H NMR [300 MHz, DMSO-d6/
1.71 (s, 3H), 2.36 (s, 3H), 3.70 (s, 3H), 6.28 (s, 2H), 6.59 (s,
1H), 7.30 (s, 5H), 8.53 (s, 1H), 9.70 (s, 1H). 13C NMR [75 MHz,
DMSO-d6/TMS, d (ppm)]: 14.9, 19.6, 55.3, 95.8, 99.1, 106.6,
111.4, 122.4, 127.9, 128.7, 129.9, 135.8, 138.5, 141.9, 148.9,
150.4, 154.4, 157.0, 161.3. Anal. Calcd for C21H19N3O2: C,
73.03; H, 5.54; N, 12.17; Found C, 73.10; H, 5.46; N, 12.24.
2-Methyl-6-(4-methoxyphenyl)-7-(2-hydroxyl-4-benzyloxyphenyl)
pyrazolo[1,5-a]pyrimidine (3e). Mp 228.2–229.6ꢀC. IR (KBr), n
(cm-1): 3487, 3096, 3025, 2963, 1609, 1503, 1447, 1293, 1243,
1181, 1032, 828,739. 1H NMR [300 MHz, DMSO-d6/TMS, d
(ppm)]: 2.38 (s, 3H), 3.76 (s, 3H), 5.09 (s, 2H), 6.47–6.59 (m,3H),
6.87 (d, 2H, J= 8.1 Hz), 6.99 (m, 1H), 7.21 (d, 2H, J=8.1Hz),
7.37–7.47 (m, 5H), 8.52 (s, 1H), 9.85 (s, 1H). 13C NMR [75MHz,
TMS, d (ppm)]: 2.34 (s, 3H), 3.73 (s, 3H), 6.38 (d, 1H,
J = 8.1 Hz), 6.43 (s, 1H), 6.58 (s, 1H), 6.66 (d, 2H, J = 8.4 Hz),
6.95 (d, 1H, J = 8.1 Hz), 7.06 (d, 2H, J = 8.4Hz), 8.47 (s, 1H),
9.62 (s, 1H), 9.85 (s, 1H). 13C NMR [75 MHz, DMSO-d6/TMS, d
(ppm)]: 14.9, 55.5, 95.6, 101.6, 105.2, 111.6, 115.5, 122.0, 126.3,
130.9, 131.9, 142.1, 148.7, 150.8, 153.8, 157.1, 157.2, 161.7.
Anal. Calcd for C20H17N3O3: C, 69.15; H, 4.93; N, 12.10; Found
C, 69.09; H, 4.97; N, 12.14.
2-Methyl-6-(4-methoxyphenyl)-7-(2,6-dihydroxyl-4-methoxyphenyl)
pyrazolo[1,5-a]pyrimidine (3i). Mp 267.6–277.4ꢀC. IR (KBr), n
(cm-1): 3256, 3001, 1602, 1502, 1439, 1233, 827, 741, 642, 589.
1H NMR [300MHz, DMSO-d6/TMS, d (ppm)]: 2.35 (s, 3H), 3.62
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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J. Yang, Z. Zhang, and H. Qing
Vol 51
(s, 3H), 3.72 (s, 3H), 5.84 (s, 2H), 6.43 (s, 1H), 6.83 (d, 2H,
J = 5.5Hz), 7.23 (d, 2H, J = 5.5Hz), 8.80 (s, 1H), 9.22 (s, 2H).
13C NMR [75MHz, DMSO-d6/TMS, d (ppm)]: 14.7, 55.1, 55.5,
92.8, 94.9, 113.8, 124.4, 128.8, 130.3, 132.9, 148.1, 154.5, 155.6,
156.8, 159.0, 160.8. Anal. Calcd for C21H19N3O4: C, 66.83; H,
5.07; N, 11.13; Found C, 66.90; H, 5.04; N, 11.08.
2-Methyl-6-phenyl-7-(2-hydroxyl-3-bromo-4-isopropoxyphenyl)
pyrazolo[1,5-a]pyrimidine (3j). Mp 223.3–223.9ꢀC. IR (KBr), n
(cm-1): 3483, 2977, 1600, 1487, 1403, 1331, 1260, 1201, 1103,
1031, 889, 751, 697. 1H NMR [300 MHz, DMSO-d6/TMS,
d (ppm)]: 1.32 (d, 6H, J= 5.8 Hz), 2.38 (s, 3H), 4.56 (m, 1H), 6.58
(s, 1H), 6.60 (s, 1H), 7.31 (s, 6H), 8.52 (s, 1H), 10.04 (s, 1H). 13C
NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 14.9, 22.3, 71.7, 96.0,
101.0, 102.9, 112.3 122.2, 127.9, 128.7, 129.8, 134.5, 135.6, 140.9,
148.9, 150.6,154.4, 155.9, 156.7. Anal. Calcd for C22H20BrN3O2:
C, 60.28; H, 4.60; Br, 18.23; N, 9.59; Found C, 60.34; H, 4.58; Br,
18.31; N, 9.51.
2-Methyl-6-(3,5-diisopropyl-4-methoxyphenyl)-7-(2-hydroxyl-
4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine (3k). Mp 229.4–
231.0ꢀC. IR (KBr), n (cm-1): 3478,3083, 2960, 1607, 1499,
1298, 1202, 1114, 1009, 789. 1H NMR [300 MHz, DMSO-d6/
TMS, d (ppm)]: 1.02–1.09 (m,12H), 2.36 (s, 3H), 3.16 (m, 2H),
3.63 (s, 3H), 3.71 (s, 3H), 6.42 (d, 1H, J = 8.4 Hz), 6.49 (s, 1H),
6.57 (s, 1H), 6.92 (d, 1H, J = 8.4 Hz), 7.04 (s, 2H), 8.59 (s, 1H),
9.83 (s, 1H). 13C NMR [75 MHz, DMSO-d6/TMS, d (ppm)]:
14.4, 23.6, 25.8, 55.1, 61.8, 95.2, 101.3, 104.9, 111.2, 121.3,
125.1, 130.9, 131.1, 140.7, 141.8, 148.3, 150.1, 153.2, 153.6,
156.8, 161.4. Anal. Calcd for C27H31N3O3: C, 72.78; H, 7.01; N,
9.43; Found C, 72.85; H, 7.03; N, 9.36.
2-Methyl-6-phenyl-7-(2-hydroxylphenyl)pyrazolo[1,5-a]pyrimidine
(3l). Mp 260.2–261.4ꢀC. IR (KBr), n (cm-1): 3475, 3039,
2967, 1603, 1527, 1451, 1352, 1284, 1231, 844, 752, 697.
1H NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 2.36 (s, 3H),
6.60 (s, 1H), 6.77 (m, 2H), 6.93 (d, 1H, J = 7.6 Hz), 7.04 (d,
1H, J = 7.6 Hz), 7.27 (s, 5H), 8.55 (s, 1H), 9.88 (s, 1H). 13C
NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 14.9, 95.9, 116.2,
118.6, 119.2, 121.8, 127.8, 128.6, 129.8, 131.1, 131.3,
135.6, 142.6, 148.9, 150.6, 154.4, 156.1. Anal. Calcd for
C19H15N3O: C, 75.73; H, 5.02; N, 13.94; Found C, 75.77;
H, 5.05; N, 13.87.
C20H17N3O2: C, 72.49; H, 5.17; N, 12.68; Found C, 72.54;
H, 5.13; N, 12.72.
2-Methyl-6-phenyl-7-(2-hydroxyl-5-fluorophenyl)pyrazolo[1,5-
a]pyrimidine (3o).
Mp 25 8.6–259.2ꢀC. IR (KBr), n (cm-1):
3439, 2983, 2721, 1604, 1511, 1438, 1271, 1235, 1183, 759, 462.
1H NMR [300MHz, DMSO-d6/TMS, d (ppm)]: 2.37 (s, 3H), 6.62
(s, 1H), 6.87 (s, 1H), 6.06 (m, 2H), 7.30 (s, 5H), 8.56 (s, 1H),
9.80 (s, 1H). 13C NMR [75MHz, DMSO-d6/TMS, d (ppm)]: 14.9,
96.0, 117.1, 117.3, 117.6, 117.8, 118.1, 119.3, 121.8, 128.0,
128.7, 129.8, 135.3, 141.0, 148.9, 150.6, 152.4, 153.7, 154.6,
156.8. Anal. Calcd for C19H14FN3O: C, 71.46; H, 4.42; F, 5.95;
N, 13.16; Found C, 71.52; H, 4.39; F, 5.99; N, 13.12.
2-Methyl-6-(4-methylphenyl)-7-(2-hydroxyl-5-fluorophenyl)pyrazolo
[1,5-a]pyrimidine (3p). Mp 237.1–237.6ꢀC. IR (KBr), n (cm-1):
3420, 3182, 1606, 1507, 1429, 1253, 1183, 824, 786. 1H
NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 2.26 (s, 3H),
2.36 (s, 3H), 6.61 (s, 1H), 6.87 (m, 2H), 7.02 (s, 1H), 7.11
(d, 2H, J = 7.5 Hz), 7.18 (d, 2H, J = 7.5 Hz), 8.53 (s, 1H),
9.78 (s, 1H). 13C NMR [75 MHz, DMSO-d6/TMS,
d
(ppm)]:14.9, 21.1, 96.0, 117.1, 117.3, 117.7, 118.0, 119.3,
121.8, 129.3, 129.6, 132.3, 137.3, 140.8, 148.8, 150.7,
152.2, 153.8, 154.4, 156.9. Anal. Calcd for C20H16FN3O: C,
72.06; H, 4.84; F, 5.70; N, 12.61; Found C, 72.12; H, 4.80;
F, 5.74; N, 12.57.
2-Methyl-6-(4-methoxyphenyl)-7-(2-hydroxyl-5-fluorophenyl)
pyrazolo[1,5-a]pyrimidine (3q). Mp 222.7–223.3ꢀC. IR (KBr),
n (cm-1): 3406, 3058, 1599, 1488, 1330, 1268, 1223, 1185, 1135,
781. 1H NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 2.36(s, 3H),
3.72 (s, 3H), 6.60 (s, 1H), 6.87 (d, 2H, J = 8.4 Hz), 7.05 (m, 2H),
7.09 (s, 1H), 7.22 (d, 2H, J = 8.4 Hz), 8.53 (s, 1H), 9.76 (s, 1H).
13C NMR [75 MHz, DMSO-d6/TMS, d (ppm)]: 13.9, 54.6, 95.0,
113.3, 116.2, 116.3, 116.4, 116.7, 117.1, 118.6, 120.6, 126.4,
130.0, 139.7, 147.8, 149.9, 151.4, 152.8, 153.4, 155.9, 158.2.
Anal. Calcd for C20H16FN3O2: C, 68.76; H, 4.62; F, 5.44; N,
12.03; Found C, 68.82; H, 4.60; F, 5.50; N, 12.07.
2-Methyl-6-phenyl-7-(2-hydroxyl-5-bromophenyl)pyrazolo[1,5-
a]pyrimidine (3r). Mp 259.4–260.9ꢀC. IR (KBr), n (cm-1):
3470, 3031, 2943, 2706, 2602, 1602, 1525, 1488, 1413,
1280, 1227, 741, 692. 1H NMR [300 MHz, DMSO-d6/TMS,
d
(ppm)]: 2.37 (s, 3H), 6.62 (s, 1H), 6.86 (d, 1H,
2-Methyl-6-(4-methylphenyl)-7-(2-hydroxylphenyl)pyrazolo[1,5-a]
pyrimidine (3m).
J = 8.7 Hz), 7.30 (s, 6H), 7.42 (d, 1H, J = 8.7 Hz), 8.55 (s,
1H), 10.07 (s, 1H). 13C NMR [75 MHz, DMSO-d6/TMS, d
(ppm)]: 14.9, 96.1, 110.0, 118.3, 120.8, 122.0, 128.0, 128.7,
129.7, 133.2, 134.0, 135.3, 140.7, 148.8, 150.6, 154.6,
155.5. Anal. Calcd for C20H16FN3O: C, 72.06; H, 4.84; F,
5.70; N, 12.61; Found C, 72.13; H, 4.80; F, 5.76; N, 12.68.
2-Methyl-6-(4-methylphenyl)-7-(2-hydroxyl-5-bromophenyl)pyrazolo
[1,5-a]pyrimidine (3s). Mp 242.5–244.0ꢀC. IR (KBr), n (cm-1):
Mp 256.6–256.9ꢀC. IR (KBr), n (cm-1):
3461, 3047, 2736, 1602, 1508, 1453, 1350, 1279, 1224,
932, 816, 753, 679. 1H NMR [300 MHz, DMSO-d6/TMS, d
(ppm)]: 2.24 (s, 3H), 2.35 (s, 3H), 6.59 (s, 1H), 6.77 (m,
2H), 6.93 (d, 1H, J = 7.8 Hz), 7.07 (d, 2H, J = 8.4 Hz), 7.16
(d, 2H, J = 8.4 Hz), 7.25 (d, 1H, J = 7.8 Hz), 8.52 (s, 1H),
9.90 (s, 1H). 13C NMR [75 MHz, DMSO-d6/TMS, d (ppm)]:
14.4, 20.6, 95.3, 115.7, 118.2, 118.7, 121.1, 128.8, 129.1,
130.6, 130.8, 132.1, 136.6, 141.9, 148.6, 150.2, 153.8,
155.6. Anal. Calcd for C20H17N3O: C, 76.17; H, 5.43; N,
13.32; Found C, 76.25; H, 5.40; N, 13.28.
2-Methyl-6-(4-methoxyphenyl)-7-(2-hydroxylphenyl)pyrazolo
[1,5-a]pyrimidine (3n). Mp 239.3–240.2ꢀC. IR (KBr), n (cm-1):
3469, 3189, 1821, 1601, 1506, 1453, 1356, 1241, 1172, 1089,
835, 757. 1H NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 2.35
(s, 3H), 3.71 (s, 3H), 6.58 (s, 1H), 6.83 (d, 2H, J= 8.4 Hz), 6.90
(m, 2H), 7.05 (d, 1H, J= 6.3 Hz), 7.19 (d, 2H, J= 8.4 Hz), 7.26
(d, 1H, J= 6.3 Hz), 8.52 (s, 1H), 9.77 (s, 1H). 13C NMR
[75 MHz, DMSO-d6/TMS, d (ppm)]: 14.9, 55.5, 95.8, 114.2,
116.2, 118.8, 119.3, 121.4, 127.7, 130.9, 131.1, 131.3,
142.2, 148.8, 150.8, 154.2, 155.9, 159.0. Anal. Calcd for
1
3478, 3046, 1603, 1514, 1404, 1278, 1225, 815, 741, 587. H
NMR [300 MHz, DMSO-d6/TMS, d (ppm)]: 2.27 (s, 3H), 2.36
(s, 3H), 6.61 (s, 1H) 6.85 (d, 1H, J = 8.7 Hz), 7.12 (d, 2H,
J = 7.5 Hz), 7.18 (d, 2H, J = 7.5 Hz), 7.32 (s, 1H), 7.41 (d,
1H, J = 8.7 Hz), 8.52 (s, 1H), 10.12 (s, 1H). 13C NMR
[75 MHz, DMSO-d6/TMS, d (ppm)]: 14.9, 21.1, 96.0, 110.0,
118.4, 121.0, 121.8, 129.4, 129.6, 132.3, 133.2, 134.0,
137.4, 140.5, 148.8, 150.7, 154.4, 155.5. Anal. Calcd for
C20H16BrN3O: C, 60.93; H, 4.09; Br, 20.27; N, 10.66;
Found C, 60.98; H, 4.13; Br, 20.34; N, 10.59.
2-Methyl-6-(4-fluorophenyl)-7-(2-hydroxylphenyl)pyrazolo[1,5-a]
pyrimidine (3t). Mp 237.1–238.5ꢀC. IR (KBr), n (cm-1): 3481,
3050, 2737, 1604, 1509, 1457, 1279, 1229, 837, 752, 590, 530.
1H NMR [300MHz, DMSO-d6/TMS, d (ppm)]: 2.36 (s, 3H), 6.61
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2014
Facile Synthesis of Diarylpyrazolo[1,5-a]pyrimidine from Isoflavones
29
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(s,1H), 6.81 (d, 1H, J = 7.5Hz), 6,89 (d, 1H, J = 7.5 Hz), 7.11 (m,
3H), 7.29 (m, 3H), 8.54 (s, 1H), 9.80 (s, 1H) . 13C NMR
[75 MHz, DMSO-d6/TMS, d (ppm)]: 14.9, 95.9, 115.4, 116.1,
116.2, 118.4, 119.4, 120.8, 131.1, 131.5, 131.8, 131.9, 132.0,
142.5, 148.9, 150.5, 154.5, 155.7, 160.4, 163.6. Anal. Calcd for
C19H14FN3O: C, 71.46; H, 4.42; F, 5.95; N, 13.16; Found C,
71.54; H, 4.40; F, 6.03; N, 13.20.
Acknowledgments. This research was supported by the National
Natural Science Foundation of China (No: 20772076) and the
Fundamental Funds Research for the Central Universities (No.
Gk200901010).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet