ZrCl4-catalysed synthesis of new 4-(2-hydroxyphenyl)pyrazolo[3,4-b]pyridine derivatives

Article abstract of DOI:10.3184/174751915X14296297811712

In the presence of a catalytic amount of zirconium(IV) chloride, an efficient synthesis of new 4-(2-hydroxyphenyl)pyrazolo[3,4-b]pyridines has been developed by the reaction 2-hydroxychalcones with 3-methyl-1-phenyl-1H-pyrazol-5-amine in refluxing ethanol. All these novel compounds have been characterised by ¹H NMR, ¹³C NMR, HRMS, IR spectra and X-ray crystallographic analysis.

Full text of DOI:10.3184/174751915X14296297811712

JOURNAL OF CHEMICAL RESEARCH 2015
VOL. 39 MAY, 263–266
RESEARCH PAPER 263
ZrCl4-catalysed synthesis of new 4-(2-hydroxyphenyl)pyrazolo[3,4-b]pyridine
derivatives
Meilin Liu and Guodong Yin*
Hubei Collaborative Innovation Center for Rare Metal Chemistry, Hubei Key Laboratory of Pollutant Analysis and Reuse Technology, Hubei Normal University,
Huangshi 435002, P.R. China
In the presence of a catalytic amount of zirconium(IV) chloride, an efficient synthesis of new 4-(2-hydroxyphenyl)pyrazolo[3,4-b]pyridines
has been developed by the reaction 2-hydroxychalcones with 3-methyl-1-phenyl-1H-pyrazol-5-amine in refluxing ethanol. All these novel
compounds have been characterised by 1H NMR, 13C NMR, HRMS, IR spectra and X-ray crystallographic analysis.
Keywords: zirconium(IV) chloride, 2-hydroxychalcones, pyrazolo[3,4-b]pyridines, aromatisation
Functionalised pyrazolo[3,4-b]pyridines have attracted ever-
increasing attention as they are widely present in numerous natural
products, anxiolytic targets (such as cartazolate, etazolate and
tracazolate)1,2 and fluorescent dyes.3 Therefore, a variety of methods
have been reported for the preparation of pyrazolo[3,4-b]pyridine
derivatives, most of them involving the multicomponent reactions
of aldehydes, 5-aminopyrazoles and highly active methylene
compounds catalysed by acetic acid,4,5 L-proline6,7 or microwave
irradiation.8 As a mild Lewis acid catalyst, zirconium(IV)
chloride (ZrCl4) has the advantage of low cost and low toxicity,
but it has been rarely utilised in catalytic organic synthesis.9–11
Recently, we have developed an efficient method for the synthesis
of coumarin- and cyclohexandione-fused 2,8-oxazabicyclo[3.3.1]
nonanes by the three-component reaction of 2-hydroxychalcones,
4-hydroxycoumarin/1,3-cyclohexandiones
and
aqueous
ammonia.12–14 On the basis of the possible intermolecular Michael
addition/amination/intramolecular bicyclisation domino reaction
mechanism and excellent nucleophilicity of 5-aminopyrazoles,
we expected to be able to synthesise the pyrazole-fused
2,8-oxazabicyclo[3.3.1]nonane 6a from 2-hydroxychalcone 3a
and 3-methyl-1-phenyl-1H-pyrazol-5-amine 4. However, it was
found that the expected product did not form, and the reaction gave
4-(2-hydroxyphenyl)pyrazolo[3,4-b]pyridine 5a in excellent yield
in the presence of ZrCl4 (Table 1).
Table 1 Optimisation of reaction conditions for the synthesis of 5a
Ph
NH
O
Ph
N
N
e
M
a
6
e
M
reac on
ti
H
O
con ons
ti
di
+
N
H2N
Ph
N
H
O
Ph
Ph
O
N
a
3
4
N
e
M
Ph
N
a
5
Entrya
1
2
3
4
5
6
7
8
Catalystb
InBr3
Solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
MeCN
Temp/oC
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
40
Yield/%c
20
Trace
<5
50
Trace
<5
Trace
89
92
76
35
<5
0
75
85
81
24
20
AcOH
L-proline
H3PO4
AgOTf
In(OTf)3
ZnCl2
I2
ZrCl4
ZrCl4
ZrCl4
ZrCl4
ZrCl4
ZrCl4
ZrCl4
ZrCl4
ZrCl4
ZrCl4
9
10d
11e
12
13
14
15
16
17
18
25
Reflux
Reflux
80
80
80
Toluene
DMSO
DMF
b
aAll reactions were performed with 3a (0.5 mmol), 4 (0.5 mmol) in an appropriate solvent (5 mL) for 10 h. 0.25 equiv. of catalyst was employed in these reactions unless mentioned.
cIsolated yield. d0.2 equiv. of catalyst was employed. e0.1 equiv. of catalyst was employed.
* Correspondent. E-mail: gdyin_hbnu@163.com

264 JOURNAL OF CHEMICAL RESEARCH 2015
R1
H
O
H
O
O
e
O
M
H
O
e
M
r
R2
Z
l
C 4
a
( )
1 N
H
O
R2
N
H2N
re ux
Et H fl
O
,
( )
2 2M H l
C
N
N
O
N
R1
R1
N
R2
Ph
Ph
1
2
4
3
5
1
2
2
1
1
2
=
=
=
-
(5i, 85%)
(5j, 91%)
a
(5a, 92%)
(5b, 85%)
i
j
=
=
=
=
=
=
=
R
R
H R
,
H R
,
2 furyl
-
2
thienyl
R
H R
,
H5
C6
1
2
=
=
=
=
=
=
=
=
-
4
-
b
c
R
H R
,
H R
H
C
H4
3 C6
-
1
2
1
2
2
=
= -
2
pyridyl
=
Me
k
-
4
R
H R
,
=
H R
,
R
R
H
C
H4
3O C6
(5k, 62%)
(5l, 65%)
,
(5c, 91%)
(5d, 60%)
(5e, 85%)
(5f, 83%)
(5g, 80%)
(5h, 81%)
1
2
1
l
-
-
R
d
e
H R
4 H
H4
O C6
,
2
1
2
=
=
=
- -
4 F H4
m R1 H R
n R1
R1
H
H
C C
( )
3 2
C
R2
=
,
R
H R
(5m, 53%)
(5n, 82%)
(5o, 89%)
(5p, 85%)
C6
,
R1 H R
R1 H R
l
H4
H4
2
=
=
=
-
4
e
=
-
4
-
M
O
H5
C6
H5
H5
f
,
C C6
,
l R2
2
-
=
- r-
4 B
o
p
5 C
C6
,
C6
h
,
g
h
1
R2
- r
5 B
,
1
2
=
C6
=
-na
2
R
R
H R
,
p
Scheme 1 Synthesis of pyrazolo[3,4-b]pyridines.
Initially, a reaction of 2-hydroxychalcone, synthesised by the
condensation of salicylaldehyde (1a) with acetophenone (2a)
according to known methods,15 with 4 was carried out under
varied conditions for the attempted preparation of 6a (Table
1 and Scheme 1). It was found that the hydroxy group did not
participate in the cyclisation reaction, and 5a was obtained in
20% yield in refluxing ethanol using InBr3 as the catalyst (entry
1
1). The structure was confirmed by means of H NMR, 13C
NMR, HRMS and IR spectra. Frequently used catalysts (such
as AcOH and L-proline) for the synthesis of pyrazolo[3,4-b]
pyridines were ineffective for this reaction (entries 2 and 3).
After screening the catalysts H3PO4, AgOTf, In(OTf)3, ZnCl2,
iodine and ZrCl4, the latter proved to be the most efficient
affording 5a in 92% isolated yield (entries 4–8). The amount
of ZrCl4, nature of the solvent (MeOH, MeCN, toluene, DMSO
o
and DMF) and reaction temperature (40 oC and 25 C) were
also examined, and it was shown that 0.25 equiv. of catalyst
in refluxing ethanol was the optimal reaction condition (entries
9–18).
We also attempted the ZrCl4-catalysed reaction of 1a, 2a and 4
in refluxing ethanol in a one-pot procedure, but 5a was obtained
in only 45% yield. The low yield was probably attributed to
the relatively low activity of acetophenone compared with the
reported highly active methylene compounds.4–7 In view of the
facile synthesis of 2-hydroxychalcones, a variety of substituted
derivatives were used to react with 4 under the optimal
conditions, and the results are summarised in Scheme 1. It
was observed that the substrates in which R1 = H and R2 was a
phenyl ring bearing an electron-donating substituent (–CH3 and
–OCH3) afforded the corresponding products 5b and 5c in 85%
and 91% yields respectively. The 4-(hydroxyphenyl) substrate
3d provided 5d in 60% yield. Halogen atom substituted
substrates (–F, –Cl and –Br) also gave the target products 5e–g
in good yields (80–85%). The structures of 5e and 5g were
further confirmed by X-ray crystallographic analysis (Fig. 1).
The crystal data of compound 5e (CCDC 1041603):
C25H18FN3O·C6H12, M = 479.58, crystal system: monoclinic,
space group: P2(1)/c, lattice parameters: a = 11.1099(17) Å, b
= 11.3558(18) Å, c = 21.839(3) Å, α = 90o, β = 104.529(3)o, γ
= 90o, V = 2667.1(7) Å3, Z = 4, Dc = 1.194 g cm-3, F000 = 1016,
final R indices [I > 2sigma(I)]: R1 = 0.0566, wR2 = 0.1520.
The crystal data of compound 5g (CCDC 1041604):
C25H18BrN3O·C6H12, M = 540.49, crystal system: monoclinic,
space group: P2(1)/n, lattice parameters: a = 10.8901(19) Å, b =
11.0738(19) Å, c = 22.857(4) Å, α = 90o, β = 95.749(3)o, γ = 90o,
Fig. 1 X-ray structures of 5e and 5g (solvent n-hexane was
omitted for clarity)
V = 2742.6(8) Å3, Z = 4, Dc = 1.309 g cm-3, F000 = 1120, final R
indices [I > 2sigma(I)]: R1 = 0.0502, wR2 = 0.1290.
This transformation was also suitable for the naphthalene-
linked ring and heterocyclic substrates (furan, thiophene and
pyridine), delivering 5h–k in 62–91% yields. In addition,
the alkyl substrates 3l and 3m were also effective for this
transformation with the isolation of 5l and 5m in 65% and
53% yields respectively. Moreover, 4-methoxy-, 5-chloro- and
5-bromo-substituted (R1) 2-hydroxychalcones also furnished
5n–p in excellent yields (82–89%).
A literature survey indicated that 4,7-dihydro-pyrazolo[3,4-b]
pyridines have been prepared from 5-aminopyrazoles and
chalcones in DMF, which can be subsequently dehydrogenated
to aromatic pyrazolo[3,4-b]pyridines upon treatment with
N-bromosuccinimide.16 This reaction has also been performed
in an ionic liquid, leading to the pyrazolo[3,4-b]pyridines
in good yield.17 However, no 2-hydroxyphenyl-substituted

JOURNAL OF CHEMICAL RESEARCH 2015 265
Hz, 2H), 8.12 (d, J = 8.6 Hz, 2H), 7.62–7.57 (m, 3H), 7.38–7.29 (m,
3H), 7.05–6.90 (m, 4H), 2.19 (s, 3H); 13C NMR (75 MHz, DMSO-d6)
δ 159.2, 156.0, 154.6, 150.8, 143.8, 142.9, 139.5, 130.5, 130.2, 129.2,
128.9, 125.1, 124.4, 120.0, 119.1, 115.7, 115.6, 114.8, 113.9, 13.5; HRMS
(EI): m/z calcd for C25H20N3O2: 394.1550; found: 394.1553 [M + H]+.
2-[6-(4-Fluorophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]
pyridin-4-yl]phenol (5e): White solid; 168 mg, yield 85%; m.p.
198–199 °C. IR (KBr) νmax/cm-1 3446, 1644, 1504, 1445, 1229,
pyrazolo[3,4-b]pyridines have been reported. We now describe
the successful development of a ZrCl4-catalysed reaction for the
synthesis of novel 4-(2-hydroxyphenyl)pyrazolo[3,4-b]pyridine
derivatives from easily available 2-hydroxychalcones and
3-methyl-1-phenyl-1H-pyrazol-5-amine in refluxing ethanol.
All of these hitherto unknown compounds were characterised
by means of their 1H NMR, 13C NMR, HRMS and IR spectra.
In addition, the structures of 5e and 5g were confirmed by
single crystal X-ray diffraction analysis. The main advantages
of this approach are the wide scope of substrates and functional
group tolerances.
1
1157, 1097, 841, 757; H NMR (300 MHz, DMSO-d6) δ 9.81 (s, 1H),
8.38–8.31 (m, 4H), 7.71–7.70 (m, 1H), 7.62–7.56 (m, 2H), 7.39–7.30 (m,
5H), 7.06–6.97 (m, 2H), 2.21 (s, 3H); 13C NMR (75 MHz, DMSO-d6)
1
δ 163.2 (d, JC-F = 245.6 Hz), 154.7, 154.5, 150.6, 144.2, 143.0, 139.3,
134.8 (d, 4J C-F = 2.8 Hz), 130.6, 130.3, 129.6 (d, 3JC-F = 8.4 Hz), 129.1,
125.3, 124.2, 120.2, 119.1, 115.8 (d, 2J C-F = 21.8 Hz), 115.6, 114.6, 13.5;
HRMS (EI): m/z calcd for C25H19FN3O: 396.1507; found: 396.1513 [M
+ H]+.
Experimental
All the chemicals were commercially available and used without
further purification. All the organic solvents were dried and freshly
1
distilled before use. H and 13C NMR spectra were recorded using
2-[6-(4-Chlorophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]
pyridin-4-yl]phenol (5f): White solid; 171 mg, yield 83%; m.p.
210–211 °C. IR (KBr) νmax/cm-1 3442, 1644, 1595, 1499, 1443, 1392,
1343, 1093, 826, 753; 1H NMR (300 MHz, CDCl3) δ 8.37–8.34
(m, 2H), 8.14–8.09 (m, 2H), 7.57–7.49 (m, 4H), 7.47–7.39 (m, 2H),
7.34–7.29 (m, 2H), 7.13–7.04 (m, 2H), 5.12 (s, 1H), 2.28 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 155.8, 152.6, 151.4, 142.9, 141.5, 139.5,
137.3, 135.8, 130.7, 130.3, 129.0, 128.8, 125.6, 123.9, 121.0, 120.9,
116.0, 115.6, 114.5, 13.8; HRMS (EI): m/z calcd for C25H19ClN3O:
412.1211; found: 412.1213 [M + H]+.
Bruker AV 300 MHz spectrometers with CDCl3 or DMSO-d6 as
the solvent. High resolution mass spectra (EI) were recorded using
a Waters GCT Premier. IR spectra were obtained as KBr pellet
samples using a Nicolet 5700 FTIR spectrometer. Melting points
were determined using an uncorrected X-4 apparatus. The X-ray
crystal structure determination was performed using a Bruker Smart
Apex CCD system. 2-Hydroxychalcones 3 were synthesised by the
condensation of salicylaldehyde with acetophenones according to
known methods.15,18,19
2-[6-(4-Bromophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]
pyridin-4-yl]-phenol (5g): White solid; 182 mg, yield 80%; m.p.
219–220 °C. IR (KBr) νmax/cm-1 3439, 1633, 1590, 1500, 1445, 1399,
1349, 1069, 865, 755; 1H NMR (300 MHz, DMSO-d6) δ 9.81 (s,
1H), 8.36–8.33 (m, 2H), 8.22 (d, J = 8.6 Hz, 2H), 7.75–7.72 (m, 3H),
7.62–7.57 (m, 2H), 7.40–7.31 (m, 3H), 7.06–6.97 (m, 2H), 2.22 (s,
3H); 13C NMR (75 MHz, DMSO-d6) δ 155.1, 155.0, 151.1, 144.9,
143.5, 139.7, 138.1, 132.4, 131.1, 130.8, 129.9, 129.7, 125.9, 124.6,
123.9, 120.8, 119.7, 116.2, 116.1, 115.4, 14.0; HRMS (EI): m/z calcd for
C25H19BrN3O: 456.0706; found: 456.0706 [M + H]+.
Synthesis of 1H-pyrazolo[3,4-b]pyridines 5; general procedure
A mixture of the 2-hydroxychalcone derivatives (3, 0.5 mmol) and
3-methyl-1-phenyl-1H-pyrazol-5-amine (4, 0.5 mmol) and ZrCl4
(29 mg, 0.125 mmol) was heated under reflux in anhydrous ethanol
(5 mL). When the reactant disappeared (10 h, monitored by TLC),
the mixture was cooled to room temperature and purified by column
chromatography using petroleum ether–ethyl acetate as the eluent to
deliver compounds 5. Characterisation data of all new compounds are
as follows.
2-(1,6-Diphenyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)phenol
2-[(3-Methyl-6-naphthalen-2-yl)-1-phenyl-1H-pyrazolo[3,4-b]
pyridin-4-yl]phenol (5h): White solid; 173 mg, yield 81%; m.p.
220–222 °C. IR (KBr) νmax/cm-1 3438, 1737, 1596, 1496, 1444, 1369,
(5a): White solid; 174 mg, yield 92%; m.p. 218–220 °C. IR (KBr) νmax
/
cm-1 3445, 1596, 1499, 1279, 1156, 1098, 1037, 862, 755; 1H NMR (300
MHz, DMSO-d6) δ 9.81 (s, 1H), 8.38 (d, J = 8.3 Hz, 2H), 8.28–8.25 (m,
2H), 7.71 (s, 1H), 7.63–7.48 (m, 5H), 7.39–7.31 (m, 3H), 7.06–6.97 (m,
2H), 2.22 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 155.8, 154.6, 150.7,
144.2, 143.0, 139.3, 138.4, 130.6, 130.3, 129.7, 129.2, 128.9, 127.4,
125.3, 124.2, 120.2, 119.2, 115.8, 115.6, 114.7, 13.5; HRMS (EI): m/z
calcd for C25H20N3O: 378.1601; found: 378.1602 [M + H]+.
1
1283, 859, 750, 699; H NMR (300 MHz, DMSO-d6) δ 9.90 (s, 1H),
8.92 (s, 1H), 8.54–8.47 (m, 3H), 8.18–8.13 (m, 2H), 8.06–8.03 (m,
1H), 7.98 (s, 1H), 7.72–7.62 (m, 4H), 7.47–7.39 (m, 3H), 7.14–7.05
(m, 2H), 2.30 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 155.7, 154.6,
150.7, 144.2, 143.0, 139.4, 135.7, 133.5, 133.1, 130.6, 130.3, 129.2,
128.8, 128.5, 127.6, 127.1, 127.0, 126.5, 125.3, 124.7, 124.3, 120.2,
119.2, 116.0, 115.6, 114.7, 13.5; HRMS (EI): m/z calcd for C29H22N3O:
428.1757; found: 428.1757 [M + H]+.
2-(3-Methyl-1-phenyl-6-p-tolyl-1H-pyrazolo[3,4-b]pyridin-4-yl)
phenol (5b): White solid; 167 mg, yield 85%; m.p. 210–212 °C. IR
(KBr) νmax/cm-1 3432, 1580, 1501, 1446, 1346, 1280, 1155, 1035, 863,
753; 1H NMR (300 MHz, CDCl3) δ 8.34 (d, J = 8.2 Hz, 2H), 8.03 (d, J =
8.2 Hz, 2H), 7.53–7.48 (m, 3H), 7.40–7.34 (m, 1H), 7.30–7.25 (m, 4H),
7.07–7.00 (m, 2H), 5.61 (s, 1H), 2.41 (s, 3H), 2.22 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 157.2, 152.8, 151.4, 142.9, 141.2, 139.8, 139.5,
136.0, 130.5, 130.3, 129.5, 128.9, 127.5, 125.4, 124.2, 121.0, 120.7,
116.0, 115.6, 114.1, 21.3, 13.7; HRMS (EI): m/z calcd for C26H22N3O:
392.1757; found: 392.1758 [M + H]+.
2-(6-Furan-2-yl-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-4-
yl)phenol (5i): White solid; 156 mg, yield 85%; m.p. 225–228 °C. IR
(KBr) νmax/cm-1 3441, 1598, 1497, 1442, 1387, 1293, 1156, 868, 750;
1H NMR (300 MHz, DMSO-d6) δ 9.82 (s, 1H), 8.38–8.35 (m, 2H),
7.94–7.93(m, 1H), 7.60–7.52 (m, 3H), 7.41–7.29 (m, 4H), 7.06–6.96 (m,
2H), 6.73–6.72 (m, 1H), 2.19 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ
154.5, 152.8, 150.5, 147.7, 145.1, 144.1, 143.1, 139.3, 130.5, 130.4, 129.2,
125.3, 123.9, 120.0, 119.2, 115.6, 114.5, 114.1, 112.6, 111.0, 13.5; HRMS
(EI): m/z calcd for C23H18N3O2: 368.1394; found: 368.1400 [M + H]+.
2-(3-Methyl-1-phenyl-6-thiophen-2-yl-1H-pyrazolo[3,4-b]pyridin-
4-yl)phenol (5j): Yellow solid; 175 mg, yield 91%; m.p. 225–227 °C.
IR (KBr) νmax/cm-1 3437, 1644, 1582, 1440, 1356, 1291, 1155, 1094, 859,
754; 1H NMR (300 MHz, CDCl3) δ 8.35 (d, J = 8.0 Hz, 2H), 7.68–7.66
(m, 1H), 7.53–7.25 (m, 7H), 7.13–7.02 (m, 3H), 5.50 (s, 1H), 2.20 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 152.7, 152.1, 150.9, 144.8, 143.1,
141.4, 139.4, 130.6, 130.3, 128.9, 128.7, 128.2, 126.2, 125.4, 123.9,
120.72, 120.68, 116.1, 114.4, 114.2, 13.7; HRMS (EI): m/z calcd for
C23H18N3OS: 384.1165; found: 384.1166 [M + H]+.
2-[6-(4-Methoxyphenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]
pyridin-4-yl]phenol (5c): White solid; 186 mg, yield 91%; m.p.
186–188 °C. IR (KBr) νmax/cm-1 3447, 1602, 1426, 1240, 1182, 1038,
1
830, 749; H NMR (300 MHz, DMSO-d6) δ 9.79 (s, 1H), 8.38 (d, J =
8.8 Hz, 2H), 8.24 (d, J = 8.9 Hz, 2H), 7.65–7.57 (m, 3H), 7.39–7.30
(m, 3H), 7.11–6.97 (m, 4H), 3.84 (s, 3H), 2.20 (s, 3H); 13C NMR (75
MHz, DMSO-d6) δ 160.7, 155.6, 154.6, 150.7, 144.0, 143.0, 139.4,
130.8, 130.6, 130.2, 129.2, 128.8, 125.2, 124.4, 120.1, 119.2, 115.6,
115.1, 114.3, 114.2, 55.3, 13.5; HRMS (EI): m/z calcd for C26H22N3O2:
408.1707; found: 408.1708 [M + H]+.
2-(6-(4-Hydroxyphenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]
pyridin-4-yl)phenol (5d): White solid; 118 mg, yield 60%; m.p.
194–196 °C. IR (KBr) νmax/cm-1 3442, 1643, 1383, 1163, 756; 1H NMR
(300 MHz, DMSO-d6) δ 10.00 (br, 1H), 9.85 (br, 1H), 8.38 (d, J = 7.9
2-(3-Methyl-1-phenyl-6-pyridin-2-yl-1H-pyrazolo[3,4-b]pyridin-4-
yl)phenol (5k): Yellow solid; 117 mg, yield 62%; m.p. 238–239 °C. IR
(KBr) νmax/cm-1 3438, 1590, 1498, 1277, 1147, 1099, 1036, 749; 1H NMR

266 JOURNAL OF CHEMICAL RESEARCH 2015
(300 MHz, CDCl3) δ 8.43 (d, J = 8.7 Hz, 2H), 8.28 (d, J = 7.7 Hz, 2H),
8.09 (s, 1H), 7.71–7.49 (m, 4H), 7.37–7.28 (m, 2H), 7.19–7.17 (m, 2H),
7.07–6.96 (m, 2H), 2.27 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 155.3,
154.7, 153.3, 150.8, 148.5, 143.2, 142.1, 139.5, 137.1, 130.4, 128.9, 125.4,
124.2, 124.1, 121.9, 120.8, 120.4, 116.5, 116.4, 115.8, 13.8; HRMS (EI):
m/z calcd for C24H19N4O: 379.1553; found: 379.1550 [M + H]+.
IR (KBr) νmax/cm-1 3434, 1644, 1589, 1496, 1151, 1114, 876, 805, 760;
1H NMR (300 MHz, CDCl3) δ 8.29–8.26 (m, 2H), 8.11–8.08 (m, 2H),
7.52–7.27 (m, 9H), 6.68 (d, J = 8.7 Hz, 1H), 6.07 (s, 1H), 2.21 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 157.3, 152.0, 151.4, 142.6, 139.6, 139.4,
138.6, 133.3, 132.7, 129.8, 129.0, 128.9, 127.6, 126.1, 121.0, 117.9, 115.7,
113.9, 112.7, 13.8; HRMS (EI): m/z calcd for C25H19BrN3O: 456.0706;
found: 456.0704 [M + H]+.
2-(3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)phenol
(5l): White solid; 103 mg, yield 65%; m.p. 209–211 °C. IR (KBr) νmax
/
cm-1 3427, 1597, 1343, 1222, 1150, 1089, 1023, 906, 858, 752; 1H NMR
(300 MHz, CDCl3) δ 8.19 (d, J = 7.6 Hz, 2H), 7.51–7.45 (m, 2H),
7.38–7.32 (m, 1H), 7.27–7.16 (m, 2H), 7.04–6.99 (m, 2H), 6.86 (s, 1H),
5.81 (s, 1H), 2.63 (s, 3H), 2.18 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
159.2, 152.8, 150.9, 142.9, 140.9, 139.2, 130.4, 130.1, 128.9, 125.6,
123.9, 121.3, 120.5, 118.7, 116.2, 113.4, 24.8, 13.6; HRMS (EI): m/z
calcd for C20H18N3O: 316.1444; found: 316.1439 [M + H]+.
Electronic Supplementary Information
Copies of the 1H and 13C NMR spectra of 5a–p and full details
of the X-ray bond lengths and bond angles for 5e and 5g are
available through stl.publisher.ingentaconnect.com/content/stl/
jcr/supp-data.
We gratefully acknowledge support from the Educational
Commission of Hubei Province (D20142501).
2-[3-Methyl-6-(2-methylpropenyl)-1-phenyl-1H-pyrazolo[3,4-b]
pyridin-4-yl]phenol (5m): White solid; 94 mg, yield 53%; m.p.
146–148 °C. IR (KBr) νmax/cm-1 3436, 1644, 1567, 1496, 1431, 1387,
Received 12 January 2015; accepted 11 April 2015
Paper 1503137 doi: 10.3184/174751915X14296297811712
Published online: 08 May 2015
1
1151, 878, 754; H NMR (300 MHz, CDCl3) δ 8.28–8.25 (m, 2H),
7.51–7.45 (m, 2H), 7.39–7.34 (m, 1H), 7.28–7.21 (m, 2H), 7.06–7.00
(m, 2H), 6.92 (d, J = 1.2 Hz, 1H), 6.42 (d, J = 1.2 Hz, 1H), 5.45–5.31
(m, 1H), 2.31 (s, 3H), 2.21 (s, 3H), 2.01 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 157.2, 152.7, 151.1, 143.9, 142.8, 140.2, 139.4, 130.4, 130.2,
128.8, 125.4, 124.4, 124.0, 121.1, 120.6, 119.8, 116.0, 112.9, 28.1, 20.6,
13.7; HRMS (EI): m/z calcd for C23H22N3O: 356.1757; found: 356.1757
[M + H]+.
5-Methoxy-2-(1,6-diphenyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-
yl)phenol (5n): Yellow solid; 167 mg, yield 82%; m.p. 222–223 °C. IR
(KBr) νmax/cm-1 3446, 1626, 1507, 1397, 1304, 1260, 1156, 1030, 811,
756; 1H NMR (300 MHz, CDCl3) δ 8.36 (d, J = 7.8 Hz, 2H), 8.14 (d, J =
6.9 Hz, 2H), 7.54–7.45 (m, 6H), 7.30–7.28 (m, 1H), 7.20–7.17 (m, 1H),
6.64–6.60 (m, 2H), 5.56 (s, 1H), 3.85 (s, 3H), 2.29 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 161.7, 157.1, 153.8, 151.5, 143.0, 141.2, 139.5, 138.9,
131.0, 129.6, 129.0, 128.8, 127.6, 125.5, 121.0, 116.6, 116.1, 114.6, 106.9,
101.5, 55.4, 13.9; HRMS (EI): m/z calcd for C26H22N3O2: 408.1707;
found: 408.1706 [M + H]+.
4-Chloro-2-(1,6-diphenyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-
4-yl)phenol (5o): Yellow solid; 183 mg, yield 89%; m.p. 218–220
°C. IR (KBr) νmax/cm-1 3438, 1648, 1569, 1496, 1151, 1020, 875, 759;
1H NMR (300 MHz, DMSO-d6) δ 10.14(s, 1H), 8.38–8.28 (m, 4H),
7.76(s, 1H), 7.63–7.51 (m, 5H), 7.46–7.41 (m, 2H), 7.36–7.31 (m, 1H),
7.06 (d, J = 8.6 Hz, 1H), 2.25 (s, 3H); 13C NMR (75 MHz, DMSO-d6)
δ 156.0, 153.7, 150.6, 142.8, 142.4, 139.3, 138.2, 129.94, 129.90, 129.7,
129.2, 128.9, 127.4, 126.0, 125.4, 122.7, 120.2, 117.2, 115.8, 114.4, 13.5;
HRMS (EI): m/z calcd for C25H19ClN3O: 412.1211; found: 412.1214 [M
+ H]+.
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4-Bromo-2-(1,6-diphenyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-
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