Multi-component solvent-free versus stepwise solvent mediated reactions: Regiospecific formation of 6-trifluoromethyl and 4-trifluoromethyl-1H- pyrazolo[3,4-b]pyridines

Article abstract of DOI:10.1016/j.jfluchem.2012.04.007

A simple and efficient regiospecific synthesis of 6-trifluoromethyl-1H- pyrazolo[3,4-b]pyridines has been achieved in excellent yields via a three-component reaction between 2-hydrazinobenzothiazoles, α- cyanoacetophenones and trifluoromethyl-β-diketones under solvent-free conditions. This method was found to be more convenient than the classical stepwise solvent mediated process, which furnished not only the opposite regioisomer i.e. 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines (50-60%) but also an undesired amide, 5-acetylamino-1-(benzothiazol-2′-yl)-3-phenyl-1H- pyrazole as a side product. The structure of the two regioisomers was established with certainty on the basis of rigorous analysis of ¹H, ¹³C, ¹⁹F-NMR spectral data and (¹H ¹³C) gs-HMQC, (¹H¹³C) gs-HMBC experiments.

Full text of DOI:10.1016/j.jfluchem.2012.04.007

Journal of Fluorine Chemistry 140 (2012) 31–37
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Multi-component solvent-free versus stepwise solvent mediated
reactions: Regiospecific formation of 6-trifluoromethyl and
4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines
a
a
b
b
Ranjana Aggarwal a, , Virender Kumar , Anshul Bansal , Dionisia Sanz , Rosa M. Claramunt
*
a Department of Chemistry, Kurukshetra University, Kurukshetra 136119, Haryana, India
b
´
´
Departamento de Quı´mica Organica y Bioorganica, Facultad de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain
A R T I C L E I N F O
A B S T R A C T
Article history:
A simple and efficient regiospecific synthesis of 6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines has been
achieved in excellent yields via a three-component reaction between 2-hydrazinobenzothiazoles,
cyanoacetophenones and trifluoromethyl- -diketones under solvent-free conditions. This method was
Received 7 February 2012
Received in revised form 19 March 2012
Accepted 9 April 2012
a-
b
found to be more convenient than the classical stepwise solvent mediated process, which furnished not
only the opposite regioisomer i.e. 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines (50–60%) but also an
undesired amide, 5-acetylamino-1-(benzothiazol-20-yl)-3-phenyl-1H-pyrazole as a side product. The
structure of the two regioisomers was established with certainty on the basis of rigorous analysis of 1H,
13C, 19F-NMR spectral data and (1H–13C) gs-HMQC, (1H–13C) gs-HMBC experiments.
ß 2012 Elsevier B.V. All rights reserved.
Available online 18 April 2012
Keywords:
2-Hydrazinobenzothiazole
a-Cyanoacetophenone
Trifluoromethyl- -diketone
b
Regiospecific reactions
Pyrazolopyridines
1. Introduction
prompted us to undertake the preparation of trifluoromethyl
substituted pyrazolo[3,4-b]pyridines. Generally, the synthesis of
Multicomponent reactions (MCRs) are special type of syntheti-
cally useful organic reactions, in which three or more simple
reactants are consumed in a single chemical step to produce a
product that incorporates substantial portions of all the reactants.
Generally multicomponent reactions, being one-pot process,
afford good yields. They are fundamentally different from two
component stepwise reactions in several ways such as: the
simplicity of one-pot procedure, possible structural variation,
complicated synthesis and large number of accessible compounds.
Organic reactions under solvent-free conditions have gained much
attention due to several advantages over the conventional
methods in terms of enhanced selectivity, cleaner reaction profile,
ease of manipulation and relatively benign conditions [1–6].
Among the condensed heterocyclic systems, pyrazolo[3,4-
b]pyridines are an important class of heterocyclic systems being
part of therapeutically interesting compounds that display
significant activity such as antimicrobial [7], antiviral [8], anti-
inflammatory [9], antitumor agents [10] and as potent PDE4B
such heterocycles is accomplished by two distinct routes. The first
one (Route A, Fig. 1) involves formation of a pyrazole ring on a 3-
acetyl/cyanopyridine bearing a good leaving group in 2-position,
but this method lacks versatility in terms of substitution, as only
pyridines containing, methyl, aryl, hydroxyl and amino groups at
position-3 can be attained.
The second route uses the condensation reaction of 5-amino-
1H-pyrazoles with bifunctional electrophiles to form the pyridine
moiety (Route B, Fig. 1), and offers a great diversity and flexibility
in terms of substitution at pyrazole and pyridine rings. Neverthe-
less, this method is disadvantageous due to multiple step
synthesis, large reaction times and low/moderate yields. Moreover,
formation of different regioisomers has been reported in the
literature i.e. in the reaction of 5-amino-1H-pyrazoles with
trifluoromethyl-
[13,14].
b-diketones under similar reaction conditions
In view of these observations and our ongoing interest to
develop greener protocols for the synthesis of heterocyclic
compounds [15–18], we report here a mild and efficient MCR
inhibitors [11]. In addition, pyrazolo[3,4-b]pyridines with
a
trifluoromethyl group are known to possess multidrug function
with antimalarial activity [12]. The foregoing observations
providing a regiospecific synthesis of 6-trifluoromethyl-1H-
pyrazolo[3,4-b]pyridines under solvent-free conditions. At the
same time, and in order to compare the results obtained by MCR
with those using a multistep solvent mediated process, regioiso-
meric 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines will also be
described.
* Corresponding author. Tel.: +91 1744 238734; fax: +91 1744 238277.
E-mail address: ranjana67in@yahoo.com (R. Aggarwal).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.04.007

32
R. Aggarwal et al. / Journal of Fluorine Chemistry 140 (2012) 31–37
R3
X
nitrogen, displayed fluorine signals at about
respectively [19].
To examine the scope of this new MCR, a series of different
symmetrical and unsymmetrical -diketones 3b-d were selected,
and our results prove that this protocol can be applied to aliphatic,
aryl and heteroaryltrifluoromethyl- -diketones (Scheme 1).
In order to compare the efficiency, synthetic utility, regios-
electivity/regiospecificity and scope of the MCR over the classical
approach, the synthesis of pyrazolo[3,4-b]pyridines was also
attempted in a stepwise manner in solvents i.e. ethanol and acetic
acid (Scheme 2). Initially, the key intermediate, 3-aryl-1-(ben-
zothiazol-20-yl)-5-amino-1H-pyrazole 5a was prepared by cyclo-
d
ꢀ68 and ꢀ62 ppm,
Route A
R
N
R2
N
N
R1
N
b
RNHNH2
b
R
N
Route B
N
R2
R1
H2N
X = Cl, OH
R3 = COAr, COOCH3, COCH3, CN
R, R1, R2 = alkyl, aryl, OH, NH2
condensation of 1a with
ethanol in the presence of a few drops of acetic acid for 5–6 h.
Subsequently, the reaction of 5a with trifluoromethyl- -diketone
a-cyanoacetophenone 2a, in refluxing
b
3a was accomplished by refluxing in acetic acid for 10 h. TLC of the
crude reaction mixture indicated the formation of two products,
none of which matching the previously obtained under solvent-
free conditions, 4a. Finally, both the products were separated by
column chromatography and identified as 1-(benzothiazol-20-yl)-
3-phenyl-6-methyl-4-trifluoromethyl-1H-pyrazolo[3,4-b]pyri-
dine 6a and 5-acetylamino-1-(benzothiazol-20-yl)-3-phenyl-1H-
pyrazole 7 (see Section 4).
Fig. 1. Synthetic routes of pyrazolo[3,4-b]pyridines.
2. Results and discussion
Scheme 1 outlines the general method, we have used to prepare
the title compounds: reaction between 2-hydrazinobenzothiazole
1a,
a
-cyanoacetophenone 2a and 4,4,4-trifluoro-1-phenylbutane-
The synthesis of regioisomers 6b-h was also achieved in a
1,3-dione 3a for 20 min, in the presence of p-toluenesulphonic acid
(PTSA) as a catalyst, resulted in the formation of pyrazolo[3,4-
b]pyridine 4a in 79% yield. Theoretically, this reaction may lead to
two isomeric products having the CF3 group located either at
position 4 or 6 of the pyrazolo[3,4-b]pyridine ring, but only a single
product was isolated which was characterized to be 1-(benzothia-
zol-20-yl)-3-phenyl-4-methyl-6-trifluoromethyl-1H-pyrazolo[3,4-
b]pyridine 4a, by the combined use of multinuclear NMR
spectroscopy. The 1H NMR spectrum of compound 4a displayed
similar manner by applying different
b-ketonitriles 2b-c and
various -diketones 3b-d (Scheme 2). Comparison of the condi-
b
tions and results between the MCR and the stepwise solvent
mediated synthesis are given in Table 1.
Again, unambiguous assignment of the structure to compound
6a was based on multinuclear NMR data. 1H NMR spectrum of 6a
showed, the lack of the signal at
aminopyrazole, and the presence of a singlet at
corresponding to the H-5 proton of the pyrazolo[3,4-b]pyridine
system in 6a. Also, 6a displayed a singlet at 2.93 ppm for the CH3
group, a downfield value compared to that observed at 2.56 ppm
d
5.82 ppm due to the NH2 of 5-
d
7.50 ppm
two sharp singlets at
d
2.56 ppm (3H) and at
d
7.51 ppm (1H)
d
corresponding to methyl and H-5 protons of the pyrazolo[3,4-
d
b]pyridine system. The 13C NMR spectrum of 4a exhibited a quartet
in 4a, in agreement with the deshielding effect of the (–N55C–)
fragment. The 13C NMR spectrum of 6a exhibited a characteristic
quartet at d
132.86 ppm (2JC-F = 35.1 Hz) due to the CF3 group at
carbon C-4 [14]. If the trifluoromethyl group was located at
position 6 the signal would appear at about 147 ppm due to the
deshielding effect of the (–N55C–) fragment. The 19F NMR spectrum
2
due to CF3 group at
d
147.62 ppm with a coupling constant JC-
F = 35.2 Hz indicating the presence of the CF3 group at C-6. Further
support to the presence of the CF3 group at position 6 was obtained
from the 19F NMR spectrum of 4a which exhibited a signal at
d
ꢀ66.75 ppm. It has been reported in the literature that trifluor-
omethyl groups at positions 2 and 4, adjacent to the pyridine
of compound 6a showed a signal at
d
ꢀ60.04 ppm typical of a 4-CF3
O
O
O
N
NHNH2
CN
+
+
R''
CF3
R'
S
R
3
2
1
4
a
b
c
d
e
f
R
R'
R''
1, R = H(a), F(b)
H
H
H
H
H
H
F
C6H5
CH3
CF3
CH3
C6H5
PTSA grinding & heating
20 min.
2, R' = C6H5(a), p-ClC6H4(b),
p-CH3C6H4(c),
C6H5
p-ClC6H4
p-ClC6H4
3, R'' = CH3(a), CF3 (b)
C6H5(c), 2-thienyl (d)
2
N
S
3
p-CH3C6H4 C6H5
p-CH3C6H4 2-thienyl
p-CH3C6H4 CH3
p-CH3C6H4 C6H5
N
1
R'
N
3a
R
R''
7a
g
h
N
7
4
F
6
F3C
5
4
Scheme 1. Multicomponent solvent-free synthesis of 6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines (4).

R. Aggarwal et al. / Journal of Fluorine Chemistry 140 (2012) 31–37
33
N
S
N
N
O
R'
EtOH, reflux
NHNH2
N
+
CN
R'
3 ml AcOH
S
R
R
H2N
2
1
5
1, R =H (a), F (b)
O
O
Acetic acid
reflux 10 h
2, R' = C6H5 (a), p-ClC6H4 (b),
p-CH3C6H4 (c),
R''
CF3
3
3, R'' = CH3,(a), CF3 (b),
C6H5 (c), 2-thienyl (d)
6
a
b
c
d
e
f
R
H
H
H
H
H
H
F
R'
R''
2
2
N
N
3
N
1
R'
4
C6H5
C6H5
CH3
CF3
N
S
1
R'
N
+
N
3a
5
S
3
R
CF3
7a
7
R
p-ClC6H4 CH3
p-ClC6H4 C6H5
p-CH3C6H4 C6H5
5
N
4
NHCOCH3
6
R''
7
6
p-CH3C6H4 2-Thienyl
p-CH3C6H4 CH3
7, R = H, R' = C6H5 (a), R = H, R' = p-ClC6H4 (b),
R = H, R' = p-CH3C6H4 (c), R = F, R' = p-CH3C6H4 (d)
g
h
F
p-CH3C6H4 C6H5
Scheme 2. Stepwise solvent mediated synthesis of 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines (6).
The (1H–13C) gs-HMBC of compound 4a shows cross peaks of
the methyl protons ( 2.56) with C-5 ( 117.26) and with C-3a (d
Table 1
Reaction times and yields of the MCR preparation of 4a-h and the stepwise solvent
mediated synthesis of 6a-h.
d
d
118.10) (see Fig. 2a), thus confirming that the CH3 is at position 4 of
the pyrazolo[3,4-b]pyridine system. Furthermore, the low fluorine
coupling (3JCF = 2.0 Hz) of the CF3 group with C-5 of pyrazolopyr-
idine ring indicates no connectivity of the 6-CF3 with C-5.
The (1H–13C) gs-HMBC spectrum of compound 6a presents
Compounds
Overall yield in
the MCR process
(20 min)
Compounds
Overall yield in the
stepwise solvent
mediated process
(5 h + 10 h)
4a
4b
4c
4d
4e
4f
79
80
86
82
76
74
88
84
6a
6b
6c
6d
6e
6f
52
61
43
22
45
50
47
45
cross peaks of the methyl protons (d 2.93) with C-5 (d 116.68) and
C-6 (161.22), but none cross peak was observed with C-3a (110.0)
(see Fig. 2b), showing that such CH3 group is not adjacent to C-3a,
so being at position 6. In this compound, the fluorine coupling
(3JCF = 5.2 Hz) of the CF3 group with C-5 of pyrazolopyridine is in
agreement with the better connectivity of the 4-CF3 with C-5.
Compounds 7 were identified on the basis of IR, 1H NMR and
their physical data as reported in literature [20]. The IR spectra
presents sharp bands at 3200 cmꢀ1 due to NH stretch in addition to
a strong band at about 1700 cmꢀ1 due to >C55O stretch. The 1H
NMR spectra of compounds 7 show a singlet of three proton
4g
4h
6g
6h
[19]. Detailed 19F NMR data of 4a-h and 6a-h are gathered in Table
2.
Concluding evidence of the structures of compounds 4 and 6
were obtained by recording the 2D NMR (1H–1H) gs-COSY,
(1H–13C) gs-HMQC and (1H–13C) gs-HMBC experiments (see
Supplementary material). All results of the correlations are
presented for compound 4a in Table 3 and for 6a in Table 4.
intensity at d 2.3 ppm due to –COCH3 group, and all other protons
in the aromatic region including the singlet corresponding to H-5
of the pyrazole ring.
As the chemistry for the formation of the 4-trifluoromethyl-
pyrazolo[3,4-b]pyridines (6) is similar to that described in
Table 2
19F NMR data for 4a–h and 6a-h.
Compounds
CF3 position
d
Compounds
CF3 position
d
4a
6
6
6
6
6
6
6
6
ꢀ66.75
ꢀ66.74
ꢀ66.79
ꢀ66.64
ꢀ66.59
ꢀ66.67
ꢀ66.78
ꢀ66.66
6a
4
4
4
4
4
4
4
4
ꢀ60.04
ꢀ59.81
ꢀ59.77
ꢀ59.88
ꢀ59.81
ꢀ60.01
ꢀ59.99
ꢀ60.03
4b = 6b
4c
4b = 6b
6c
4d
6d
4e
6e
4f
6f
4g
6g
4h
6h

34
R. Aggarwal et al. / Journal of Fluorine Chemistry 140 (2012) 31–37
Table 3
NMR data in CDCl3, chemical shifts (d, ppm) and coupling constants (J, Hz), for compound 4a.
Nuclei
d
J
gs-HMQC correlation
gs-HMBC correlation
4-CH3
60-H
2.56 (s, 3H)
7.39 (t, 1H)
20.05
124.83
126.47
117.26
128.41
129.69
129.94
121.26
123.06
2.56
7.51
–
50-H
5-H
7.48–7.55 (m, 5H)
Hm + Hp
Ho
7.72 (m, 2H)
7.92 (td, 1H),
8.11 (dd, 1H)
20.05
70-H
40-H
4-CH3
5-CH
3a-C
70-CH
6-CF3
40-CH
60-CH
50-CH
m-CH
p-CH
o-CH
i-C
3J = 7.9, 4J = 5J = 0.6
3J = 8.1
1J = 128.8, 3J = 4.6
7.50
3
117.26
1J = 163. 8, JCF = 2.0
2.56
118.10
–
2.56, 7.51
7.50
121.26
1J = 164.1, 3J = 7.7
1JCF = 275.0
1J = 164.1, 3J = 7.7
1J = 162.6, 3J = 7.7
1J = 163.1, 3J = 7.7
1J = 159.9
7.92
–
121.43
–
123.06
8.11
7.39
7.50
7.53
7.53
7.72
–
7.39
124.83
8.11
126.47
7.92
128.41
7.53
129.69
1J = 161.0, 3J = 3J = 7.2
1J = 156.4
3J = 3J = 7.8
3J = 6.1; 3J = 9.2
2JCH3 = 6.1
2JCF = 35.2
–
7.72
129.94
7.72, 7.53
7.53
131.66
7a0-C
133.36
–
7.39, 8.11
2.56
4-C
146.86
–
6-C
147.62
–
7.50
7a-C
3a0-C
3-C
149.79
–
–
149.82
–
–
7.92, 7.50
7.72
149.92
–
–
20-C
155.79
–
–
–
Table 4
NMR data in CDCl3. chemical shifts (
d
, ppm) and coupling constants (J, Hz), for compound 6a.
Nuclei
d
J
gs-HMQC correlation
gs-HMBC correlation
6-CH3
60-H
2.93(s, 3H)
7.39(t, 1H)
25.15
124.87
126.45
116.68
127.89
129.33
129.76
121.12
123.21
2.93
50-H
5-H
7.48–7.50(m, 5H)
Hm, Hp
Ho
7.62(m, 2H)
7.89(td, 1H,)
8.11 (td, 1H,
25.15
70-H
40-H
6-CH3
3a-C
5-CH
J = 8.0; J = J =0.5
J = 8.2; J = J = 0.4
1J = 129.3
3J = 7.6
7.50
7.50
2.93
110.0
116.68
1J = 167.2
3JCH3 = 4.6
3JCF = 5.2
1J = 164.1
3J = 9.2
7.50
70-CH
CF3
121.12
122.0
7.89
–
7.50
1JCF = 273.9
3J = 4.6
–
40-CH
60-CH
50-CH
m-CH
p-CH
o-CH
123.21
124.87
126.45
127.89
129.33
129.76
1J = 164.1
3J = 7.7
8.11
7.39
7.50
7.50
7.50
7.62
7.39
1J = 161.8
3J = 8.4
8.11
1J = 158.0
3J = 7.7
7.89
1J = 162.0
3J = 7.2
7.50
1J = 161.0
3J = 3J = 7.7
1J = 161.0
3J = 3J = 6.2
3J = 3J = 6.9
2JCF = 35.1
3J = 10.0
3J = 7.0
7.62
7.62, 7.50
7.50
i-C
131.68
132.86
133.17
–
–
–
4-C
7a0-C
8.11, 7.39
3-C
148.46
150.15
151.40
156.47
161.22
–
–
–
–
–
–
7.62
3a0-C
7a-C
20-C
6-C
–
7.89,7.50
–
–
–
–
–
2.93, 7.50

R. Aggarwal et al. / Journal of Fluorine Chemistry 140 (2012) 31–37
35
(ppm)
(ppm)
110.0
112.0
114.0
116.0
118.0
a
b
116.4
116.8
117.2
117.6
118.0
118.4
118.8
C-3a
C-5
C-3a
C-5
(ppm) 7.2
6.4
5.6
4.8
4.0
3.2
(ppm) 7.2 6.4 5.6 4.8 4.0 3.2 2.4
Fig. 2. 1H–13C gs-HMBC of 1-(benzothiazol-2-yl)-4-methyl-3-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridine (4a) in CDCl3(a) and 1-(benzothiazol-2-yl)-6-methyl-3-
phenyl-4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridine (6a) in CDCl3(b).
previous works [14,21], the regiospecificity reversal exhibited in
solvent-free reactions suggests an alternative mechanism without
the intermediacy of the 5-aminopyrazole derivatives 5, most
probably a tandem reaction in which the cyclization of two rings
take place simultaneously giving rise to the regioisomeric 6-
trifluoromethylpyrazolo[3,4-b]pyridines (4). This proposal, based
on the observation that the multi-component solvent-free reaction
(MCR) generates regioisomers 4 in short reaction times (10 min)
meanwhile in the stepwise solvent mediated synthesis the
corresponding 5-aminopyrazoles 5 were obtained after 15 min,
will be further investigated extending the MCR reaction to other
substrates.
1024 ꢁ 256 data set, number of scans 2 (gs-HMQC) or 4 (gs-HMBC)
and relaxation delay 1 s. The FIDs were processed using zero filling
in the F1 domain and a sine-bell window function in both
dimensions was applied prior to Fourier transformation. In the gs-
HMQC experiments GARP modulation of 13C was used for
decoupling.
Trifluoromethyl
Diketones (4c-d) [22],
b
-diketones (4a-b) are available commercially.
-cyanoacetophenones [23] and 2-hydra-
a
zino-6-substitutedbenzothiazoles [24] were prepared according to
the literature procedure.
4.1. General procedure for three-component solvent-free synthesis of
1-(benzothiazol-20-yl)-3-aryl-4-substituted-6-trifluoromethyl-1H-
pyrazolo[3,4-b]pyridines 4a-h
3. Conclusion
Equimolar amounts of appropriate 2-hydrazinobenzothiazole
In a nutshell, a one-step three-component reaction of structur-
1a-b,
in pestle mortar and heated on water bath for 4–5 min and then
equimolar amount of appropriate trifluoromethyl -diketones 3a-d
was added to it and mixed thoroughly. The reaction mixture was
again heated 80–90 8C for 15 min on water bath. The solid was
obtained byaddition of aq. ethanol, filtered and crystallized fromthe
mixture of ethanol and chloroform to give pure 4.
a-cyanoacetophenone 2a-c, and PTSA were mixed thoroughly
ally diverse fluorinated-
b-diketones with 2-hydrazinobenzothia-
zoles and -cyanoacetophenones resulted in the formation of 6-
a
b
trifluoromethyl-1H-pyrazolo[3,4-b]pyridines. This methodology is
not only advantageous in terms of high yield, considerably
reduction in reaction time and cleaner work up, but also induces
regiospecificity. In solvent mediated synthesis, there was forma-
tion of 4-trifluoromethyl isomers along with undesired amides as
side products.
1-(Benzothiazol-20-yl)-4-methyl-3-phenyl-6-trifluoromethyl-1H-
pyrazolo[3,4-b]pyridine 4a: Yield 79%; Mp 236 8C; IR (KBr, cmꢀ1):
1528, 3078 (–C55N); 1H NMR (400 MHz, CDCl3)
d: 2.56 (s, 3H, 4-
4. Experimental
CH3), 7.39 (t, 1H, 60-H), 7.48–7.55 (m, 5H, 50-H, 5-H, Hm, Hp), 7.72
(m, 2H, Ho), 7.92 (td, 1H, 70-H, J = 7.9, 0.6 Hz), 8.11 (dd, 1H, 40-H,
Melting points were determined in open capillaries in electrical
apparatus and are uncorrected. IR spectra were recorded on a Buck
scientific IRM-500 spectrophotometer in KBr pellet (vmax in cmꢀ1).
1H and 13C-NMR spectra were recorded on a Bruker instrument at
300 MHz and 75 Hz respectively. 19F-NMR spectra were performed
on DRX-300 and DPX-400 at 282 and 376 MHz respectively, at SAIF
Lucknow, India.
2D (1H–1H) gs-COSY and inverse proton detected heteronuclear
shift correlation spectra, (1H–13C) gs-HMQC, (1H–13C) and gs-
HMBC, of compounds 4a and 6a, were acquired on a Bruker DRX
400 (9.4 Tesla, 400.13 MHz for 1H and 100.62 MHz for 13C)
spectrometer with a 5-mm inverse-detection H–X probe equipped
with a z-gradient coil, at 300 K and processed using standard
Bruker NMR software and in non-phase-sensitive mode. Gradient
selection was achieved through a 5% sine truncated shaped pulse
gradient of 1 ms.
J = 8.1 Hz); 13C NMR (75 MHz, CDCl3)
d: 20.05 (4-CH3), 117.26 (q,
1
3JC-F = 2.0 Hz), 118.10, 121.26, 121.43 (q, JC-F = 275 Hz), 123.06,
124.83, 126.47, 128.41, 129.69, 129.94, 131.66, 133.36, 146.86,
147.62 (q, 2JC-F = 35.2 Hz), 149.79, 149.82, 149.92, 155.79; 19F NMR
(282 MHz, CDCl3)
Elemental analysis calcd. for C21H13F3N4S: C, 61.46; H, 3.19; N,
13.65. Found: C, 61.38; H, 3.16; N, 13.62.
d
: ꢀ66.75 (6-CF3); MS (EI) m/z: 411 [M+1]+;
1-(Benzothiazol-2-yl)-3-phenyl-4,6-bistrifluoromethyl-1H-pyra-
zolo[3,4-b]pyridine 4b: Yield 80%; Mp 247 8C; IR (KBr, cmꢀ1): 1528,
3078(–C55N); 1H-NMR (300 MHz, CDCl3)
d: 7.41–7.65 (m, 7H, C6H5,
50, 60-H), 7.97 (d, 1H, 70-H, J = 8.1 Hz), 8.01 (s, 1H, 5-H), 8.16 (d, 1H, 40-
H, J = 8.7 Hz,); 13C NMR (75 MHz, CDCl3)
d
: 111.60, 112.85, 119.71 (q,
1
1JC-F = 274 Hz), 120.00 (q, JC-F = 273 Hz), 120.33, 122.39, 124.37,
2
125.76, 127.08, 128.78, 128.82, 129.60, 132.31, 134.48(q, JC-
2
F = 36 Hz), 147.32 (q, JC-F = 37 Hz), 147.54, 147.62, 149.11, 154.08;
Selected parameters for (1H–1H) gs-COSY were spectral width
3600 and 600 Hz, the acquisition data size was 1024 points and one
transient was accumulated per increment, with a 1 s relaxation
delay, for a total of 256 experiments, data processing using zero
filling in the F1 domain and shifted sine-bell apodization of factor 0
in both dimensions.
19F NMR (282 MHz, CDCl3)
d
: ꢀ59.81 (4-CF3), ꢀ66.74 (6-CF3); MS (EI)
m/z: 465 [M+1]+; Elemental analysis calcd. for C21H10F6N4S: C, 54.31;
H, 2.17; N, 12.06. Found: C, 54.28; H, 2.15; N, 12.02.
1-(Benzothiazol-20-yl)-3-(p-chlorophenyl)-4-methyl-6-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 4c: Mp 198 8C; IR (KBr, cmꢀ1):
1528, 3063 (–C55N); 1H NMR (300 MHz, CDCl3)
d: 2.60 (s, 3H, 4-
Selected parameters for(1H–13C)gs-HMQC and gs-HMBC spec-
tra were spectral width 3500 Hz for 1H and 20.5 kHz for 13C,
CH3), 7.43 (t, 1H, 60-H), 7.59 (m, 4H, C6H4, 50, 5-H), 7.69 (d, 2H, C6H4,
J = 7.2 Hz), 7.95 (d, 1H, 70-H, J = 8.1 Hz) 8.15 (d, 1H, 40-H, J = 7.8 Hz);

36
R. Aggarwal et al. / Journal of Fluorine Chemistry 140 (2012) 31–37
13C NMR (75 MHz, CDCl3)
121.36 (q, JC-F = 273 Hz),123.07, 124.96, 126.56, 128.78, 130.12,
131.28, 133.35, 136.05,146.68, 147.74 (q, JC-F = 35 Hz), 148.71,
149.65, 149.73, 155.58; 19F NMR (282 MHz, CDCl3)
CF3); MS (EI) m/z: 445/447 (3:1) [M+1]+/[M+1+2]+; Elemental
analysis calcd. for C21H12ClF3N4S: C, 56.70; H, 2.72; N, 12.59.
Found: C, 56.67; H, 2.70; N, 12.56.
d
: 20.18 (4-CH3), 117.39, 117.65, 121.29,
Elemental analysis calcd. for C27H16F4N4S: C, 64.28; H, 3.20; N,
11.11. Found: C, 64.24; H, 3.16; N, 11.06.
1
2
d
: ꢀ66.79 (6-
4.2. General procedure for the synthesis of 3-phenyl-1-(benzothiazol-
20-yl)-5-aminopyrazole 5a
A mixture of 2-hydrazinobenzothiazole 1a (0.825 g, 5 mmol)
1-(Benzothiazol-20-yl)-3-(p-chlorophenyl)-4-phenyl-6-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 4d: Mp 228 8C; IR (KBr, cmꢀ1):
and a-cyanoacetophenone 2a (0.73 g, 5 mmol) was refluxed in
ethanol containing acetic acid (3ml) for 5–6 h. Excess solvent was
removed by distillation. The crude product so obtained was
recrystallized from ethanol to give 5a (1.09 g, 75%), Mp 201 8C (lit.
[20], 202 8C). Other compounds (5b-d) of this type were prepared
similarly.
1512, 3024(–C55N); 1HNMR (300 MHz, CDCl3)
d: 7.13–7.58(m, 11H,
C6H4, Ph, 50, 60-H), 7.76 (s, 1H, 5-H), 7.97 (d, 1H, 70-H, J = 8.1 Hz,), 8.18
(d, 1H, 40-H, J = 7.8 Hz); 13C NMR (75 MHz, CDCl3)
121.51(q, JC-F = 273 Hz), 122.39, 122.88, 125.66, 126.66, 126.87,
d
: 116.84, 117.03,
1
127.99, 128.63, 129.17, 129.33, 129.66, 129.97, 135.17, 136.45,
5-amino-1-(benzothiazol-20-yl)-3-phenyl-1-H-pyrazole 5a: Mp
147.44 (q, 2JC-F = 35 Hz), 146.83, 148.69, 150.45, 150.55, 156.28; 19
F
200 8C (lit. [20] 202 8C).
NMR (282 MHz, CDCl3)
d
:ꢀ66.64(6-CF3);MS(EI)m/z: 507/509(3:1)
5-amino-1-(benzothiazol-20-yl)-3-(p-chlorophenyl)-1-H-pyrazole
5b: Mp 226 8C (lit. [20] 227 8C).
[M+1]+/[M+1+2]+; Elemental analysis calcd. for C26H14ClF3N4S: C,
61.60; H, 2.78; N, 11.05. Found: C, 61.58; H, 2.75; N, 11.02.
1-(Benzothiazol-20-yl)-4-phenyl-3-(p-tolyl)-6-trifluoromethyl-
1H-pyrazolo[3,4-b]pyridine 4e: Mp 200 8C; IR (KBr, cmꢀ1): 1528,
5-amino-1-(benzothiazol-20-yl)-3-(p-tolyl)-1-H-pyrazole 5c: Mp
2278C (lit. [20] 228 8C).
5-amino-1-(60-fluorobenzothiꢀa1zol-20-yl)-3-(p-tolyl)-1-H-pyrazole
3063(–C55N); 1H NMR (300 MHz, CDCl3) : 2.33 (s, 3H, 400-CH3),
d
5d: Mp 213 8C; IR (KBr, cm ): 3201, 3317 (NH); 1H NMR
6.95 (d, 2H, C6H4, J = 7.8 Hz), 7.18 (d, 2H, C6H4, J = 8.1 Hz), 7.24–
(300 MHz, CDCl3)
50, 70, 4-H); MS (EI) m/z: 325 [M+1]+; Elemental analysis calcd. for
17H13FN4S: C, 62.95; H, 4.04; N, 17.27. Found: C, 62.91; H, 4.01; N,
d
: 2.42 (3H, s, 400-CH3), 7.24–7.84 (m, 8H, C6H4, 40,
7.59 (m, 7H, Ph, 50, 60-H), 7.75 (s, 1H, 5-H), 7.97 (d, 1H, 70-H,
J = 7.8 Hz), 8.21 (d, 1H, 40-H, J = 8.1 Hz,); 13C NMR (75 MHz, CDCl3)
C
1
d
: 21.36 (400-CH3), 115.80, 116.77, 121.41 (q, JC-F = 273 Hz),
17.24.
122.67, 125.20, 126.22, 126.54, 126.90, 128.35, 128.46, 128.73,
2
129.43, 129.65, 132.60, 139.17, 135.20, 147.46 (q, JC-F = 35 Hz),
4.3. General procedure for synthesis of 1-(benzothiazole-20-yl)-3-
aryl-6-substituted-4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines
6a-h and 5-acetylamino-1-(benzothiazol-20-yl)-3-substituted-1-H-
pyrazoles 7a-d
148.43, 149.59, 150.37, 150.53, 156.18; 19F NMR (282 MHz, CDCl3)
d
: ꢀ66.59 (6-CF3); MS (EI) m/z: 487 [M+1]+; Elemental analysis
calcd. for C27H17F3N4S: C, 66.66; H, 3.52; N, 11.52. Found: C, 66.62;
H, 3.48; N, 11.48.
1-(Benzothiazol-20-yl)-4-(2000-thienyl)-3-(p-tolyl)-6-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 4f: Mp 210 8C; IR (KBr, cmꢀ1):
3-aryl-1-(benzothiazol-20-yl)-5-aminopyrazole 5 (5 mmol) was
dissolved in acetic acid (20 ml) and equimolar amount of
appropriate trifluoromethyl-b-diketones 3 was added to it. The
1528, 3063 (–C55N); 1H NMR (300 MHz, CDCl3)
d
: 2.48 (s, 3H, 400-
CH3), 6.82 (m, 1H, C4H3S), 7.11 (m, 1H, C4H3S), 7.32–7.65 (m, 7H,
reaction mixture was heated to reflux at about 10 h. After
completion of reaction, the reaction mixture was poured in excess
of water and filtered. The crude products thus obtained were
separated by column chromatography using silica gel (100–200
mesh) with petroleum ether/ethyl acetate (99.5/0.5) as an eluent
afforded 6 and further elution of column with petroleum ether/
ethyl acetate (99: 1) furnished 7.
C6H4, C4H3S, 50, 60-H), 7.77 (s, 1H, 5-H), 7.96 (d, 1H, 70-H, J = 7.8), 8.18
(d, 1H, 40-H, J = 8.1 Hz); 13C NMR (75 MHz, CDCl3)
115.75, 117.14, 121.24, 121.34 (q, JC-F = 273 Hz), 122.37, 125.57,
d
: 21.34 (400-CH3),
1
126.43, 127.54, 128.56, 128.73, 129.02, 129.22, 129.43, 132.22,
2
135.39, 135.80, 147.52 (q, JC-F = 35 Hz), 147.76, 148.14, 150.13,
150.44, 156.24; 19F NMR (282 MHz, CDCl3)
d
: ꢀ66.67 (6-CF3); MS
(EI) m/z: 493 [M+1]+; Elemental analysis calcd. for C25H15F3N4S2: C,
60.96; H, 3.07; N, 11.38. Found: C, 60.92; H, 3.02; N, 11.34.
1-(60-Fluorobenzothiazol-20-yl)-4-methyl-3-(p-tolyl)-6-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 4g: Mp 236 8C; IR (KBr, cmꢀ1):
1-(Benzothiazol-20-yl)-6-methyl-3-phenyl-4-trifluoromethyl-1H-
pyrazolo[3,4-b]pyridine 6a: Mp 256 8C; IR (KBr, cmꢀ1): 1528, 3078
(–C55N); 1H NMR (400 MHz, CDCl3)
d: 2.93 (s, 3H, 6-CH3), 7.39 (t,
1H, 60-H) 7.42–7.50 (m, 5H, Hm, Hp, 50, 5-H), 7.62 (m, 2H, Ho), 7.89
1535, 3063 (–C55N); 1H NMR (300 MHz, CDCl3)
d
: 2.49 (s, 3H, 400-
(dd, 1H, 70-H, J = 8.0, 0.5 Hz), 8.11 (td, 1H, 40-H, J = 8.2, 0.4 Hz); 13C
3
CH3), 2.60 (s. 3H, 4-CH3), 7.34–7.37 (m, 3H, C6H4, 50-H), 7.53 (s, 1H,
5-H), 7.60–7.63 (m, 3H, C6H4,70-H), 8.05–8.10 (m, 1H, 40-H); 13C
NMR (75 MHz, CDCl3)
d
: 25.15 (6-CH3), 110.0, 116.68 (q, JC-
1
F = 5.2 Hz), 121.12, 122.0 (q, JC-F = 273.9 Hz), 123.21, 124.87,
126.45, 127.89, 129.33, 129.76, 131.68, 132.86 (q, 2JC-F = 35.1 Hz),
133.17, 148.46, 150.15, 151.40, 156.47, 161.22; 19F NMR
NMR (75 MHz, CDCl3)
116.40, 118.76 (q, JC-F = 273 Hz), 122.10, 123.14, 126.55 (d, JC-
d
: 20.16 (4-CH3), 21.36 (400-CH3), 115.60,
1
2
2
F = 24 Hz), 128.16, 129.06, 129.87, 132.63, 135.34, 147.56 (q, JC-
F = 35 Hz), 147.92, 148.39, 150.21, 150.31, 155.99, 157.16; 19F NMR
(282 MHz, CDCl3)
d
: ꢀ60.04 (4-CF3); MS (EI) m/z: 411 [M+1]+;
Elemental analysis calcd. for C21H13F3N4S: C, 61.46; H, 3.19; N,
13.65. Found: C, 61.38; H, 3.16; N, 13.62.1-(Benzothiazol-20-yl)-3-
phenyl-4,6-bistrifluoromethyl-1H-pyrazolo[3,4-b]pyridine 6b: Char-
acterisation data of 6b is similar to that of 4b.
(282 MHz, CDCl3)
d
: ꢀ66.78 (6-CF3), ꢀ116.16 (60-F); MS (EI) m/z:
443 [M+1]+; Elemental analysis calcd. for C22H14F4N4S: C, 59.72; H,
3.19; N, 12.66. Found: C, 59.68; H, 3.15; N, 12.64.
1-(60-Fluorobenzothiazol-2-yl)-4-phenyl-3-(p-tolyl)-6-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 4h: Mp 218 8C; IR (KBr, cmꢀ1):
1-(Benzothiazol-20-yl)-3-(p-chlorophenyl)-6-methyl-4-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 6c: Mp 198 8C; IR (KBr, cmꢀ1):
1528, 3078 (–C55N); 1H NMR (300 MHz, CDCl3)
d
: 2.33 (s, 3H, 400-
1528, 3078 (–C55N); 1H NMR (300 MHz, CDCl3)
d: 2.96(s, 3H, 6-CH3),
CH3), 6.95 (d, 2H, C6H4,J = 7.8 Hz), 7.16 (d, 2H, C6H4, J = 7.8 Hz),
7.24–7.40 (m, 6H, Ph, 50-H), 7.63 (d, 1H, 70-H, J = 8.1 Hz), 7.74 (s, 1H,
7.39–7.59 (m, 5H, C6H4, 50, 60, 5-H), 7.87–7.94 (m, 3H, C6H4, 70-H),
8.15 (d, 1H, 40-H, J = 7.8 Hz); 13C NMR (75 MHz, CDCl3)
CH3), 95.19, 116.77, 121.15, 122.01 (q, JC-F = 272 Hz), 123.21,
124.99, 126.54, 127.47, 128.86, 129.06, 130.15, 132.69 (q, JC-
F = 35 Hz), 133.20, 147.25, 150.24, 151.46, 156.76, 161.45; 19F NMR
d
: 25.12 (6-
5-H), 8.01–8.12 (m, 1H, 40-H); 13C NMR (75 MHz, CDCl3)
d
: 21.35
1
(400-CH3), 115.74, 116.72, 121.42 (q, 1JC-F = 273 Hz), 122.57, 123.16,
2
2
126.18 (d, JC-F = 24 Hz), 126.56, 126.98, 128.13,128.76, 129.56,
2
129.86, 129.88, 132.77, 135.16, 147.68 (q, JC-F = 35 Hz), 147.82,
(282 MHz, CDCl3)
d
: ꢀ59.77 (4-CF3); MS (EI) m/z: 445/447 (3:1)
148.34, 150.34, 150.47, 156.11, 157.28; 19F-NMR (282 MHz, CDCl3)
[M+1]+/[M+1+2]+; Elemental analysis calcd. for C21H12ClF3N4S: C,
56.70; H, 2.72; N, 12.59. Found: C, 56.67; H, 2.70; N, 12.56.
d
: ꢀ66.66 (6-CF3), ꢀ116.03 (60-F); MS (EI) m/z: 505 [M+1]+;

R. Aggarwal et al. / Journal of Fluorine Chemistry 140 (2012) 31–37
37
1-(Benzothiazol-20-yl)-3-(p-chlorophenyl)-6-phenyl-4-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 6d: Mp 224 8C; IR (KBr, cmꢀ1):
1535, 3047(–C55N); 1H NMR (300 MHz, CDCl3)
: 7.46–7.66 (m, 8H,
C6H4, C6H5, 60-H), 8.01 (m, 1H, 50-H) 8.15 (d, 1H, 70-H, J = 8.4 Hz)
8.18 (s, 1H, 5-H), 8.36 (m, 1H, 40-H), 8.48 (d, 2H, C6H4, J = 6.9 Hz);
13C NMR (75 MHz, CDCl3) : 110.17, 115.56, 121.27, 121.84 (q, 1JC-
d
5-acetylamino-1-(benzothiazol-20-yl)-3-(p-chlorophenyl)-1H-
pyrazole 7b: Mp 206 8C (lit. [20] 208 8C).
d
5-acetylamino-1-(benzothiazol-20-yl)-3-(p-tolyl)-1H-pyrazole 7c:
Mp 238 8C (lit. [20] 240 8C).
5-acetylamino-1-(60-fluorobenzothiazol-20-yl)-3-(p-tolyl)-1H-
pyrazole 7d: Mp 190 8C; IR (KBr, cmꢀ1): 3200 (NH),1698 (CO); 1H
F = 272 Hz), 121.36, 123.24, 124.33, 126.68, 126.66, 128.29, 128.33,
NMR (300 MHz, CDCl3) d
: 2.38 (3H, s, COCH3), 2.42 (3H, s, 400-CH3),
2
129.55, 131.03, 132.38 (q, JC-F = 36 Hz), 132.46, 136.37, 138.22,
7.24–7.84 (m, 8H, C6H4, 40, 50, 70, 4-H); MS (EI) m/z: 367 [M+1]+;
Elemental analysis calcd. for C19H15FN4OS: C, 62.28; H, 4.13; N,
15.29. Found: C, 62.24; H, 4.09; N, 15.26.
146.38, 148.41, 150.91, 154.76, 158.36; 19F NMR (282 MHz, CDCl3)
d
: ꢀ59.88 (4-CF3); MS (EI) m/z: 507/509 (3:1) [M+1]+/[M+1+2]+;
Elemental analysis calcd. for C26H14ClF3N4S: C, 61.60; H, 2.78; N,
11.05. Found: C, 61.58; H, 2.75; N, 11.02.
Acknowledgements
1-(Benzothiazol-20-yl)-6-phenyl-3-(p-tolyl)-4-trifluoromethyl-
1H-pyrazolo[3,4-b]pyridine 6e: Mp 214 8C; IR (KBr, cmꢀ1): 1528,
We are thankful to Council of Scientific and Industrial Research
(CSIR), New Delhi, India and to MICINN of Spain (Grant CTQ2010-
16122) for providing financial assistance and SRF to Virender
Kumar and Anshul Bansal. Thanks are also due to SAIF, CDRI,
Lucknow for providing 19F NMR spectra.
3078(–C55N); 1H NMR (300 MHz, CDCl3) : 2.48 (s, 3H, 400-CH3),
d
7.30–7.68 (m, 9H, C6H4, Ph, 50, 60-H), 7.98 (d, 1H, 70-H, J = 8.1 Hz),
8.12 (s, 1H, 5-H), 8.16 (d, 1H, 40-H, J = 8.1 Hz) 8.37 (d, 2H, C6H4,
J = 7.2 Hz); 13C NMR (75 MHz, CDCl3)
d
: 21.49 (400-CH3), 110.59,
1
113.19, 123.04 (q, JC-F = 275 Hz), 123.16, 126.12, 126.56, 127.93,
127.97, 128.07, 128.62, 129.30, 129.69, 131.03, 133.32, 133.77
(q,2JC-F = 35 Hz), 136.94, 139.30, 148.94, 149.78, 151.65, 155.37,
Appendix A. Supplementary data
158.36; 19F NMR (282 MHz, CDCl3)
d
: ꢀ59.81 (4-CF3); MS (EI) m/z:
487 [M+1]+; Elemental analysis calcd. for C27H17F3N4S: C, 66.66; H,
Supplementary data associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.jfluchem.2012.04.007.
3.52; N, 11.52. Found: C, 66.62; H, 3.48; N, 11.48.
1-(Benzothiazol-20-yl)-6-(200-thienyl)-3-(p-tolyl)-4-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 6f: Mp 227 8C; IR (KBr, cmꢀ1):
References
1535, 3063 (–C55N); 1H NMR (300 MHz, CDCl3) : 2.48 (s, 3H, 400-
d
CH3), 7.25–7.67 (m, 8H, C6H4, C4H3S, 50, 60-H), 7.95 (m, 2H, C4H3S,
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4971.
5-H), 7.98 (d, 1H, 70-H, J = 8.1 Hz), 8.15 (d, 1H, 40-H, J = 8.4 Hz,);13C
NMR (75 MHz, CDCl3) d
: 21.48 (400-CH3), 109.25, 112.47, 121.07 (q,
1JC-F = 274 Hz), 121.22, 123.14, 123.87, 126.54, 127.68, 128.24,
2
128.78, 129.13, 129.68, 130.90, 133.36 (q, JC-F = 36 Hz), 133.47,
136.20, 139.29,142.82, 149.73, 150.29, 153.23, 158.16; 19F NMR
(282 MHz, CDCl3)
Elemental analysis calcd. for C25H15F3N4S2: C, 60.96; H, 3.07; N,
d
: ꢀ60.01 (4-CF3); MS (EI) m/z: 493 [M+1]+;
11.38. Found: C, 60.92; H, 3.02; N, 11.34.
1-(60-Fluorobenzothiazol-20-yl)-6-methyl-3-(p-tolyl)-4-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 6g: Mp 208 8C; IR (KBr, cmꢀ1):
1531, 3068 (–C55N); 1H NMR (300 MHz, CDCl3) : 2.47 (s, 3H, 400-
d
CH3), 2.95 (s, 3H, 6-CH3), 7.21–7.52 (m, 5H, C6H4, 5-H), 7.58 (m, 1H,
50-H, J = 8.1 Hz), 7.82 (d, 1H, 70-H, J = 7.8 Hz), 8.16 (dd, 1H, 40-H,
J = 4.8, 9.0, 9.0 Hz); 13C NMR (75 MHz, CDCl3)
d
: 21.46 (400-CH3),
1
25.13(6-CH3), 107.70, 114.76, 120.27 (q, JC-F = 274 Hz), 122.65,
2
124.09, 124.21, 126.18 (d, JC-F = 24 Hz), 128.64, 129.40, 129.58,
2
134.21 (q, JC-F = 36 Hz), 146.79, 139.34, 149.14, 151.39, 154.39,
157.70, 161.26; 19F NMR (282 MHz, CDCl3)
d
: ꢀ59.99 (4-CF3),
ꢀ116.06 (60-F); MS (EI) m/z: 443 [M+1]+; Elemental analysis calcd.
for C22H14F4N4S: C, 59.72; H, 3.19; N, 12.66. Found: C, 59.68; H,
3.15; N, 12.64.
1-(60-Fluorobenzothiazol-2-yl)-6-phenyl-3-(p-tolyl)-4-trifluoro-
methyl-1H-pyrazolo[3,4-b]pyridine 6h: Mp 241 8C; IR (KBr, cmꢀ1):
1543, 3070 (–C55N); 1H NMR (300 MHz, CDCl3) : 2.48 (s, 3H, 400-
d
CH3), 7.30–7.66 (m, 9H, C6H4, Ph, 70, 50-H), 8.07 (d, 1H, 40-H,
J = 5.1 Hz), 8.12 (s, 1H, 5-H), 8.36 (d, 2H, J = 6.9 Hz, C6H4); 13C NMR
1
(75 MHz, CDCl3)
d
:
21.49 (400-CH3), 107.41, 111.19 (q, JC-
2
F = 271 Hz), 113.34, 123.91, 124.02, 124.14, 127.90 (d, JC-
F = 24 Hz), 128.64, 129.33, 129.65, 131.10, 133.84 (q, JC-
2
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734.
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F = 35 Hz), 134.23, 134.37, 136.84, 139.38, 146.28, 149.06,
151.57, 154.88, 158.53, 161.78; 19F NMR (282 MHz, CDCl3)
d:
ꢀ60.03 (4-CF3), ꢀ116.09 (60-F); MS (EI) m/z: 505 [M+1]+; Elemental
analysis calcd. for C27H16F4N4S: C, 64.28; H, 3.20; N, 11.11. Found:
C, 64.24; H, 3.16; N, 11.06.
5-acetylamino-1-(benzothiazol-20-yl)-3-phenyl-1H-pyrazole 7a:
Mp 191 8C (lit. [20] 192 8C).