Synthesis of Functionalized Pyrazolo[1,5-a]pyridines: [3+2] Cycloaddition of N-Aminopyridines and α,β-Unsaturated Carbonyl Compounds/Alkenes at Room Temperature

Article abstract of DOI:10.1055/s-0036-1588753

The synthesis of functionalized pyrazolo[1,5-a]pyridines through oxidative [3+2] cycloaddition of N-aminopyridines with α,β-unsaturated carbonyl compounds or electron-withdrawing olefins is described. The reactions proceed in N-methylpyrrolidone as the solvent under metal-free conditions at room temperature.

Full text of DOI:10.1055/s-0036-1588753

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–J
paper
A
C. Ravi et al.
Paper
Synthesis
Synthesis of Functionalized Pyrazolo[1,5-a]pyridines: [3+2] Cyclo-
addition of N-Aminopyridines and α,β-Unsaturated Carbonyl
Compounds/Alkenes at Room Temperature
Chitrakar Ravi
O
R
Supravat Samanta
O
metal-free
NMP/O2
Darapaneni Chandra Mohan
N. Naresh Kumar Reddy
Subbarayappa Adimurthy*
+
31 examples
Ar/
N
R
Het
I
N
N
NH2
up to 95% yield
R = Me, Ar/Het
Academy of Scientific & Innovative Research, CSIR–Central
Salt & Marine Chemicals Research Institute, G. B. Marg,
Bhavnagar–364 002, Gujarat, India
adimurthy@csmcri.res.in
Received: 02.01.2017
Accepted after revision: 23.02.2017
Published online: 14.03.2017
and drug development.2 In particular, pyrazolo[1,5-a]pyri-
dines (Figure 1) exhibit a wide spectrum of biological activ-
ity; examples include 5HT3-adenosine antagonists,3 p38 ki-
nase inhibitors,4 dopamine D3/D4 antagonists, 2,4-antiher-
petic agents,5 and potent treatments for cardiac
arrhythmias.6 Moreover, some pyrazole scaffolds are very
useful moieties in supramolecular and polymer chemistry
as well as in food and pharmaceutical industries.2 The pyra-
zolo[1,5-a]pyridine structure has been proposed as a stable
bioisosteres of the indole nucleus to circumvent problems
arising from the metabolic instability of indoles.7
DOI: 10.1055/s-0036-1588753; Art ID: ss-2017-z0003-op
Abstract The synthesis of functionalized pyrazolo[1,5-a]pyridines
through oxidative [3+2] cycloaddition of N-aminopyridines with α,β-un-
saturated carbonyl compounds or electron-withdrawing olefins is de-
scribed. The reactions proceed in N-methylpyrrolidone as the solvent
under metal-free conditions at room temperature.
Key words N-methylpyrrolidone, chalcones, metal-free, drug inter-
mediates, [3+2] cycloaddition
Due to the importance of these pyrazolo[1,5-a]pyri-
dines, many methods for their synthesis have been devel-
oped from pyridinium ylides8 through 1,3-dipolar cycload-
dition and intramolecular 1,5-cyclization using different
transition-metal catalysts such as copper,9 palladium,10
gold,11 silver,12 etc. In most of these cases, the reactions
involve sequential regioselective [3+2] cycloaddition of N-
Pyridine derivatives play significant roles in the synthe-
sis of fused nitrogen-based heterocycles.1 Heterocycles de-
rived from pyridine including imidazo[1,2-a]pyridines, im-
idazo[1,5-a]pyridines, imidazo[1,2-a]pyrazines, indolizines,
imidazo[2,1-a]isoquinolines and pyrazolo[1,5-a]pyridines
are important intermediates in both medicinal chemistry
H
N
N
O
O
N
N
N
COOH
Ph
F
Ph
HO
N
N
N
N
N
N
HN
adenosine receptor antagonist
diuretic adenosine A1 antagonist
antiherpetic
Cl
N
N
HN
N
O
N
NH
NH2
N
N
F
Ph
N
N
N
N
N
Ph
N
N
OCH2CF3
N
N
5HT3 antagonist
p38 kinase inhibitor
dopamine D4 antagonist
ERK inhibitor FR180204
Figure 1 Biologically active pyrazolo[1,5-a]pyridines
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

B
C. Ravi et al.
Paper
Synthesis
aminopyridine with benzyne intermediates and alkynes
bearing electron-withdrawing groups,13 domino direct
alkynylation,13b,14 direct oxidative annulation of N-iminopy-
ridinium ylides with terminal alkynes,15 nitrene insertion,16
denitrogenation17a rearrangements of pyridine deriva-
tives17b and other methods.18 Therefore, the development of
more facile methods employing mild reaction conditions to
access these molecules is still challenging and deserves fur-
ther investigation.7,19,20
a 35% yield of 3a (Table 1, entries 8–13). Along with NMP,
other solvents such as DMSO, DMF and water were tested;
in these cases, 3a was isolated in 24%, 29% and 51% yield,
Table 1 Optimization of the Conditions for the Synthesis of 3aa
O
O
Within our program on the synthesis of N-heterocy-
cles,21 we have developed a strategy for the synthesis of
functionalized pyrazolo[1,5-a]pyridines under metal-free
conditions from a commercially available N-aminopyridine
and α,β-unsaturated carbonyl compounds (Scheme 1).
Some of these molecules are key intermediates for the syn-
thesis of the ERK inhibitor, FR180204, and an adenosine A1
receptor.22
N
N
N
I
NH2
1a
2a
3a
Entry
Cat. (mol%) Base (mmol)
Solvent
Temp (°C) Yield (%)b
1
2
CuI (10)
FeCl3 (10)
FeCl2 (10)
FeCl2 (10)
I2 (20)
I2 (20)
I2 (20)
–
–
toluene
toluene
toluene
toluene
toluene
DCB
110
110
110
110
110
110
110
110
110
110
110
trace
trace
10
–
3
–
4c
5d
6d
7d
8
–
33
Our previous report
–
42
R
NO2
NMP
–
41
+
N
R
N
–
DMSO
30
N
I
NH2
KOH (0.5)
Cs2CO3 (0.5)
DBU (0.5)
toluene
toluene
toluene
toluene
nr
O
This work
9
–
trace
nr
R
O
10
11
–
NMP
O2
R
+
–
pyrrolidine
(0.5)
nr
N
N
N
I
NH2
R = Me, Ar/Het
12
–
piperidine
(0.5)
toluene
110
nr
Scheme 1 Cyclization of 1-aminopyridinium iodide
13
14
15
16
17
18
19
20
21
22f
23g
24h
25
26
27
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
NMP (0.5)
toluene
DMSO
DMF
H2O
110
110
110
110
110
110
r.t.
35
24
29
51
47
55
84
81
83
72
62
18
nr
Initially, we focused on the optimization of the reaction
conditions for the annulation reaction of N-aminopyridine
1a and (E)-chalcone (2a) as starting substrates, as both of
these are commercially available. N-Aminopyridine and (E)-
chalcone have not been previously reported for the con-
struction of pyrazolo[1,5-a] pyridines. Firstly, we per-
formed the reaction of 1-aminopyridinium iodide (1a) (0.3
mmol), (E)-chalcone (2a) (0.25 mmol), and CuI (0.025
mmol) as the catalyst at 110 °C in toluene under O2 (bal-
loon), which resulted in the formation of a trace amount of
phenyl(2-phenylpyrazolo[1,5-a]pyridin-3-yl)methanone
(3a) (Table 1, entry 1). The reaction with iron salts such as
FeCl3 and FeCl2 was examined, but only a trace and 10%
yield of 3a were isolated, respectively (Table 1, entries 2 and
3). A further reaction with FeCl2 to which I2 (20 mol%) had
been added resulted in an increased yield (33%) of 3a (Table
1, entry 4). Next, we turned our attention to a system utiliz-
ing I2 (0.05 mmol) and di-tert-butyl peroxide (DTBP) (0.5
mmol), and screened different solvents including toluene,
1,2-dichlorobenzene (DCB) and DMSO; under these condi-
tions, 42%, 41% and 30% yields of 3a, respectively, were ob-
tained (Table 1, entries 5–7). Further, we screened various
inorganic and organic bases such as KOH, Cs2CO3, DBU, pyr-
rolidine, piperidine and N-methylpyrrolidone (NMP), but
only NMP was reactive compared to the other bases, giving
NMP (0.5)
NMP (0.5)
NMP (0.5)
NMP (0.5)
–
NMP (1.25)
–
–
–
–
–
–
–
–
–
–
NMP
NMPe
NMP
NMP
NMP
NMP
DMSO
toluene
DMF
r.t.
60
r.t.
r.t.
r.t.
r.t.
r.t.
nr
r.t.
nr
a Reaction conditions: 1a (0.3 mmol), 2a (0.25 mmol), solvent (1 mL), O2
(balloon), 24 h.
b Yield of isolated product; nr = no reaction.
c I2 (0.05 mmol) was also added.
d Di-tert-butyl peroxide (DTBP) (0.5 mmol) was added.
e NMP (2 mL) was used.
f Reaction time = 12 h.
g Reaction performed open to air.
h Reaction performed under argon (balloon).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Synthesis
respectively (Table 1, entries 14–16). In the reactions with-
out any solvent, but with 0.5 mmol or 1.25 mmol of NMP,
the yield was increased to 47% and 55%, respectively (Table
1, entries 17 and 18). Surprisingly, in the reaction in NMP
(1.0 mL) without any co-solvent at room temperature, the
yield of 3a was increased to 84% (Table 1, entry19). A fur-
ther increase in the amount of NMP to 2 mL, and raising the
temperature to 60 °C led to diminished yields (Table 1, en-
tries 20 and 21). By reducing the reaction time and per-
forming the reaction in air or argon atmospheres, the yield
of 3a was further decreased (Table 1, entries 22–24). When
NMP was replaced with DMSO, toluene or DMF as the sol-
vent (1.0 mL), no reaction was observed (Table 1, entries
25–27). The best yield of the desired product was observed
in NMP as the solvent at room temperature, hence the con-
ditions shown in entry 19 (Table 1) were deemed as opti-
mum.
metal-free conditions. Gratifyingly, good yields of the de-
sired products were obtained using the optimized condi-
tions (Schemes 2 and 3).
Having established the optimized conditions, the reac-
tions of 1-aminopyridinium iodide (1a) with chalcones 2
(containing a substituent on one of either of the two phenyl
groups) were examined (Scheme 2). It was found that the
majority of the reactions proceeded with chalcones 2 pos-
sessing electron-donating (such as methyl, ethyl, methoxy
and thiomethyl) or electron-withdrawing (fluoro and
chloro) substituents on the phenyl rings, and afforded the
corresponding products 3b–g in good yields (60–80%). The
structure of 3g was also confirmed by single crystal XRD
analysis (Figure 2).
In the case of a strong electron-withdrawing (nitro)
chalcone, only a trace amount of the desired product was
observed 3h. The reaction of 1a with (Z)-3-(naphthalen-1-
yl)-1-phenylprop-2-en-1-one gave the desired product 3i
in 81% yield. This reaction indicates the steric hindrance
due to the presence of the naphthalene group did not affect
the outcome. Furthermore, heteroarylated chalcones (such
as 2-pyridyl, 2-thiophene and 1-isoquinoline) were well
Generally, the insertion of acyl/benzoyl groups on aza-
heterocycles is a difficult task and often requires forcible re-
action conditions. To overcome these difficulties, we took
on the challenge to obtain directly acylated/benzoylated
pyrazolo[1,5-a]pyridines from N-aminopyridines under
R2
O
O
R1
R2
NMP
O2, rt
R1
N
+
I
N
NH2
1a
N
2
3
O
O
O
O
O
O
S
N
N
N
N
N
N
N
N
N
N
3a; 84%
3b; 80%
3c; 75%
3d; 60%
3e; 62%
O
O
O
O
O
Cl
F
NO2
N
N
N
N
N
N
N
N
N
N
N
3f; 77%
3g; 75%
3h; trace
3i; 81%
3j; 97%
N
N
O
S
O
O
O
O
N
S
Cl
F
N
N
N
N
N
N
N
N
N
N
3k; 85%
3l; 88%
3m; 91%
3n; 83%
3o; 74%
O
O
O
O
O
O
S
F
N
N
N
N
N
N
N
N
N
N
3p; 50%
3q; 59%
3r; 63%
3s; 42%
3t; 51%
Scheme 2 Substrate scope of benzoylated pyrazolo[1,5-a]pyridines. Reagents and conditions: 1a (0.3 mmol), 2 (0.25 mmol), NMP (1.0 mL), 24 h, r.t.,
O2 (balloon). Yields are those of isolated products.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Synthesis
the total synthesis of various drugs. In particular, 5a is a key
intermediate for the synthesis of the ERK inhibitor,
FR180204.22
Due to their efficacy in the syntheses of a variety of
drugs, further studies were undertaken. The presence of
electron-donating or electron-withdrawing substituents on
the phenyl ring of benzylideneacetones 4 provided the cor-
responding products 5b–g in good to excellent yields (55–
95%). Under the same conditions, a 46% yield of 1-[2-(naph-
thalen-1-yl)pyrazolo[1,5-a]pyridin-3-yl]ethan-1-one (5h)
was isolated from the corresponding naphthalene deriva-
tive 4.
Figure 2 ORTEP diagram of 3g (CCDC 1496245)
Gram-scale reactions were also performed with N-ami-
nopyridine 1a and α,β-unsaturated carbonyl compounds 2a
and 4a for the synthesis of intermediates 3a and 5a under
the optimized conditions (Scheme 4). The reaction of 1a
(1.332 g, 6 mmol) and 2a (1.04 g, 5 mmol) gave the desired
product 3a in 63% yield (0.934 g) (Scheme 4, eq 1) (with pe-
riodic bubbling of O2). Similarly, the reaction of 1-aminopy-
ridinium iodide (1a) (1.864 g, 8.4 mmol) and benzylidene-
acetone 4a (1.022 g, 7 mmol) gave the key intermediate 5a
(used in the synthesis of the ERK inhibitor, FR180204) in
46% yield (0.754 g) (Scheme 4, eq 2). These experiments in-
dicate the practical applicability of the present methodolo-
gy for the synthesis of desirable key intermediates, which
are required for drug design and synthesis.
tolerated under these metal-free conditions and gave excel-
lent yields (74–97%) of the corresponding heteroarylated
pyrazolo[1,5-a]pyridines 3j–o. These heteropyrazolo[1,5-
a]pyridines are known to exhibit better biological activities
than those of simple pyrazolo[1,5-a]pyridines.4 Also, the 2-
furylchalcone derivative gave a moderate yield (50%) of the
desired product 3p. We also subjected a substituted amino-
pyridinium iodide (1-amino-2-methylpyridin-1-ium io-
dide) to this reaction with different chalcones, and ob-
tained the corresponding products 3q–t in moderate to
good yields.
To expand the scope of the methodology, a variety of
benzylideneacetones 4 were reacted with 1-aminopyridini-
um iodide (1a) to afford the acylated pyrazolo[1,5-a]pyri-
dines 5 (Scheme 3). The reaction of 1a with 4a under the
optimized conditions gave the desired acylated pyrazo-
lo[1,5-a]pyridine derivative 5a in 74% yield. These acylated
pyrazolo[1,5-a]pyridines are highly useful intermediates in
Finally, we extended this strategy for the synthesis of
functionally designed pyrazolo[1,5-a]pyridines (Scheme 5).
Under the optimized conditions, acrylonitrile (6a) was re-
acted with 1a to afford 7a in a moderate 41% yield. Further,
the regiochemistry of the product 7a23 was also confirmed
by single crystal XRD analysis (Figure 3). Under the same
conditions, the reaction of 1a with substrates 6b–d (ethyl
acrylate, diethyl but-2-ynedioate, ethyl cinnamate) pro-
O
O
NMP
R1
R1
N
+
NH2
O2, rt
I
N
N
1a
4
5
O
O
O
O
O
F
N
N
N
N
N
N
N
N
5a; 74%
5b; 55%
5c; 68%
5d; 91%
O
O
O
O
NO2
NO2
Cl
N
N
N
N
N
N
N
N
5e; 69%
5f; 95%
5g; 85%
5h; 46%
Scheme 3 Substrate scope of acylated pyrazolo[1,5-a]pyridines. Reagents and conditions: 1a (0.3 mmol), 4 (0.25 mmol), NMP (1.0 mL), 24 h, r.t., O2
(balloon). Yields are those of isolated products.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

E
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Synthesis
Based on our present observations and previous re-
ports,13 a plausible reaction mechanism has been proposed
(Scheme 6). Initially, the [3+2] cycloaddition of 1a and 2a in
NMP generates the intermediate A. In the presence of O2, A
is transformed into intermediate B. Finally, oxidation of in-
termediate B followed by aromatization yields the desired
product 3a.
O
O
+
(1)
NMP (20 mL)
O2
N
I
N
NH2
N
1a
2a
3a
(6 mmol,1.332 g) (5 mmol,1.040 g)
(63%, 0.934 g)
O
O
+
O
NMP (20 mL)
O2
O
N
Ph
(2)
Ph
I
N
NH2
H
N
Ph
2a
Ph
1a
4a
5a
(46 %, 0.754 g)
N
I
N
N
H
NMP
[3+2] cycloaddition
1a
(8.4 mmol, 1.864 g) (7 mmol, 1.022 g)
NH2
H
A
Scheme 4 Gram-scale syntheses of key intermediates 3a and 5a
O
+
NMP
O2
Ph
[O]
Ph
2a
ceeded smoothly and provided the corresponding function-
alized products 7b–d in 84%, 75% and 20% yields, respec-
tively. However, simple styrene (6e) and stilbene (6f) did
not give the desired products under the present conditions,
indicating that an olefin bearing an electron-withdrawing
group is necessary for the reaction to proceed.
O
O
Ph
[O]
Ph
Ph
N
Ph
N
3a
N
N
H
B
Scheme 6 A plausible reaction mechanism
In summary, we have developed a new protocol for the
synthesis of functionalized (acylated/benzoylated) pyrazo-
lo[1,5-a]pyridines including the key intermediate for the
ERK inhibitor, FR180204, through the selective [3+2] cyc-
loaddition of N-aminopyridines with α,β-unsaturated car-
bonyl compounds under metal-free conditions at room
temperature. This methodology is also applicable for elec-
tron-withdrawing olefins, which afford good to excellent
yields of the corresponding pyrazolo[1,5-a]pyridines under
mild reaction conditions. The feasibility of the method for
scale-up studies has been demonstrated by the synthesis of
the two key drug intermediates, 3a and 5a.
Figure 3 ORTEP diagram of 7a (CCDC 1498880)
R
R
NMP
O2, rt
+
N
N
N
I
NH2
1a
6
7
CN
6a
CO2Et
Ph
CO2Et
6
7
EtO2C
CO2Et
6b
6f
Ph
6e
6c
CO2Et
6d
Ph
Ph
CO2Et
CN
CO2Et
Ph
Ph
CO2Et
N
Ph
7f; trace
Ph
7d; 20%
N
N
N
N
N
N
N
N
N
N
N
7a; 41%
7b; 84%
7c; 75%
7e; nr
Scheme 5 Synthesis of functionalized pyrazolo[1,5-a]pyridines. Reagents and conditions: 1a (0.3 mmol), 6 (0.25 mmol), NMP (1.0 mL), 24 h, r.t., O2
(balloon). Yields are those of isolated products.
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Synthesis
All commercially available chemicals and reagents were used without
any further purification unless otherwise indicated. The progress of
the reactions was monitored by thin-layer chromatography (TLC) us-
ing Merck TLC silica gel 60 F254 plates. All products were purified
through column chromatography using SDFCL silica gel (100–200
mesh size) and 20% EtOAc/hexane as the eluent. Melting points were
recorded using a Mettler Toledo Mel-Temp melting point apparatus.
1H and 13C NMR spectra were recorded at 500 MHz and 125 MHz, re-
spectively using a Bruker Avance II 500 spectrometer, and at 600 MHz
and 125 MHz, respectively, using a Jeol Resonance EC 600R spectrom-
eter. The spectra were recorded in CDCl3 as the solvent. The multiplic-
ities are indicated as follows: s (singlet); d (doublet); t (triplet); q
(quartet); m (multiplet), and coupling constants (J) are given in Hz.
Chemical shifts are reported in ppm relative to TMS as an internal
13C NMR (125 MHz, CDCl3): δ = 190.8, 156.1, 148.5, 142.7, 136.5,
132.3, 129.5, 128.5, 128.2, 127.8, 127.2, 127.1, 119.0, 114.0, 109.5,
28.7, 15.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H19N2O: 327.1497; found:
327.1512.
[2-(4-Methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl](phenyl)meth-
anone (3d)
Yield: 49.6 mg (60%); white solid; mp 144.7 °C.
1H NMR (500 MHz, CDCl3): δ = 8.56 (d, J = 7.0 Hz, 1 H), 7.98 (d, J = 8.5
Hz, 1 H), 7.60 (d, J = 7.5 Hz, 2 H), 7.40–7.32 (m, 4 H), 7.19 (t, J = 7.5 Hz,
2 H), 6.97 (t, J = 7.0 Hz, 1 H), 6.72 (d, J = 7.5 Hz, 2 H), 3.74 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 191.1, 159.7, 156.0, 143.0, 139.0,
131.6, 130.9, 129.3, 128.5, 127.7, 127.3, 124.6, 119.0, 114.0, 113.4,
109.1, 55.1.
standard. The signals around δ values of 7.2 (1H NMR) and 77.0 (13
C
NMR) correspond to the residual non-deuterated solvent. Mass spec-
tra were obtained using a Micromass Q-TOF, Waters 2487 spectrome-
ter and applying the electron impact (EI) ionization method.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H17N2O2: 329.1290; found:
329.1291.
Phenyl(2-phenylpyrazolo[1,5-a]pyridin-3-yl)methanone (3a);
Typical Procedure
{2-[4-(Methylthio)phenyl]pyrazolo[1,5-a]pyridin-3-yl}(phe-
nyl)methanone (3e)
A clean, washed boiling tube equipped with a magnetic stir bar was
charged with 1-aminopyridinium iodide (1a) (0.0665 g, 0.3 mmol),
(E)-chalcone (2a) (0.0520 g, 0.25 mmol) and NMP (1 mL). The mixture
was stirred for 24 h at r.t. under O2 (balloon). After completion of the
reaction, the mixture was poured into hypo solution (10 mL). The
mixture was extracted with EtOAc (3 × 10 mL), dried over anhydrous
Na2SO4 and the solvent removed under reduced pressure. The residue
was purified through column chromatography using silica gel (20%
EtOAc/hexane) to afford 3a.
Yield: 53.1 mg (62%); white solid; mp 122 °C.
1H NMR (500 MHz, CDCl3): δ = 8.57 (d, J = 7.0 Hz, 1 H), 7.97 (d, J = 9.0
Hz, 1 H), 7.60 (d, J = 7.0 Hz, 2 H), 7.39 (q, J = 8.5 Hz, 4 H), 7.22 (t, J = 8.0
Hz, 2 H), 7.07 (d, J = 8.5 Hz, 2 H), 6.98 (t, J = 7.0 Hz, 1 H), 2.42 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 190.9, 155.6, 142.9, 139.2, 139.0,
131.7, 129.5, 129.2, 128.8, 128.5, 127.8, 127.3, 125.6, 119.0, 114.1,
109.2, 15.4.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H17N2OS: 345.1062; found:
345.1057.
Yield: 62.5 mg (84%); white solid; mp 103 °C.
1H NMR (500 MHz, CDCl3): δ = 8.48 (d, J = 7.0 Hz, 1 H), 7.94 (d, J = 8.5
Hz, 1 H), 7.49 (d, J = 7.0 Hz, 2 H), 7.34 (t, J = 6.0 Hz, 3 H), 7.30 (t, J = 7.0
Hz, 1 H), 7.22 (t, J = 7.5 Hz, 1 H), 7.12–7.04 (m, 4 H), 6.89 (q, J = 7.0 Hz,
1 H).
13C NMR (125 MHz, CDCl3): δ = 191.1, 156.3, 143.0, 139.0, 132.2,
131.6, 129.6, 129.3, 128.6, 128.3, 127.7, 127.4, 119.2, 114.2, 109.4.
[2-(4-Fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl](phenyl)meth-
anone (3f)
Yield: 60.5 mg (77%); white solid; mp 142 °C.
1H NMR (500 MHz, CDCl3): δ = 8.57 (d, J = 7.0 Hz, 1 H), 8.00 (d, J = 9.0
Hz, 1 H), 7.58 (d, J = 7.0 Hz, 2 H), 7.45–7.34 (m, 4 H), 7.20 (t, J = 7.5 Hz,
2 H), 7.00 (t, J = 7.0 Hz, 1 H), 6.88 (t, J = 9.0 Hz, 2 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H15N2O: 299.1184; found:
299.1196.
13C NMR (125 MHz, CDCl3): δ = 190.9, 163.8, 161.8, 155.3, 143.0,
139.0, 131.8 (d, J = 44.0 Hz), 131.4, 129.3, 128.6 (d, J = 22.8 Hz), 127.8,
127.5, 119.2, 115.0 (d, J = 21.6 Hz), 114.3, 109.4.
(2-Phenylpyrazolo[1,5-a]pyridin-3-yl)(p-tolyl)methanone (3b)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H14N2OF: 317.1090; found:
Yield: 62.5 mg (80%); white solid; mp 109 °C.
1H NMR (500 MHz, CDCl3): δ = 8.56 (d, J = 7.0 Hz, 1 H), 7.94 (d, J = 8.5
Hz, 1 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.47 (t, J = 6.0 Hz, 2 H), 7.34 (t, J = 7.5
Hz, 1 H), 7.21 (t, J = 6.0 Hz, 3 H), 6.99–6.93 (m, 3 H), 2.27 (s, 3 H).
317.1094.
[2-(4-Chlorophenyl)pyrazolo[1,5-a]pyridin-3-yl](phenyl)meth-
13C NMR (125 MHz, CDCl3): δ = 190.7, 156.0, 142.8, 142.3, 136.3,
132.3, 129.5, 128.5, 128.4, 128.2, 127.8, 127.0, 119.0, 114.0, 109.5,
21.4.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H17N2O: 313.1341; found:
313.1333.
anone (3g)
Yield: 62.2 mg (75%); white solid; mp 146 °C.
1H NMR (500 MHz, CDCl3): δ = 8.56 (d, J = 6.5 Hz, 1 H), 7.97 (d, J = 9.0
Hz, 1 H), 7.59 (d, J = 7.0 Hz, 2 H), 7.41–7.36 (m, 4 H), 7.21 (t, J = 8.0 Hz,
2 H), 7.17 (d, J = 8.5 Hz, 2 H), 7.00 (t, J = 7.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 190.8, 155.0, 142.9, 139.0, 134.5,
131.9, 130.8, 129.3, 128.6, 128.1, 127.9, 127.5, 119.2, 114.4, 109.4.
[2-(4-Ethylphenyl)pyrazolo[1,5-a]pyridin-3-yl](phenyl)meth-
anone (3c)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H14ClN2O: 333.0795;
found: 333.0800.
Yield: 61.4 mg (75%); colorless liquid.
1H NMR (500 MHz, CDCl3): δ = 8.57 (d, J = 7.0 Hz, 1 H), 8.00 (d, J = 9.0
Hz, 1 H), 7.53 (d, J = 8.0 Hz, 2 H), 7.45 (d, J = 7.5 Hz, 2 H), 7.36 (t, J = 7.5
Hz, 1 H), 7.20 (q, J = 6.0 Hz, 3 H), 7.00–6.95 (m, 3 H), 2.58 (q, J = 7.5 Hz,
2 H), 1.14 (t, J = 7.5 Hz, 3 H).
[2-(Naphthalen-1-yl)pyrazolo[1,5-a]pyridin-3-yl](phenyl)meth-
anone (3i)
Yield: 70.7 mg (81%); white solid; mp 116 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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1H NMR (500 MHz, CDCl3): δ = 8.64 (d, J = 6.5 Hz, 1 H), 8.31 (d, J = 8.5
Hz, 1 H), 7.95 (t, J = 5.5 Hz, 1 H), 7.70–7.64 (m, 2 H), 7.47 (t, J = 8.0 Hz,
1 H), 7.40–7.36 (m, 3 H), 7.28 (q, J = 6.5 Hz, 3 H), 7.03 (t, J = 7.0 Hz, 1
H), 6.98 (t, J = 7.5 Hz, 1 H), 6.75 (t, J = 7.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 191.4, 155.3, 142.6, 139.0, 133.1,
131.9, 130.8, 130.1, 129.0, 128.8, 128.7, 128.1, 127.9, 127.8, 126.7,
126.3, 125.5, 125.3, 124.5, 119.4, 114.5, 111.6.
13C NMR (125 MHz, CDCl3): δ = 190.5, 149.8, 142.7, 139.2, 133.5,
132.1, 129.8, 129.2, 128.5, 128.1, 127.3, 127.2, 127.0, 118.7, 114.1,
108.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H13N2OS: 305.0749; found:
305.0755.
(2-Phenylpyrazolo[1,5-a]pyridin-3-yl)(thiophen-2-yl)methanone
(3n)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H17N2O: 349.1341; found:
349.1342.
Yield: 63.0 mg (83%); white solid; mp 133 °C.
1H NMR (500 MHz, CDCl3): δ = 8.56 (d, J = 7.0 Hz, 1 H), 7.99 (d, J = 9.0
Hz, 1 H), 7.61 (q, J = 3.0 Hz, 2 H), 7.48 (d, J = 4.0 Hz, 1 H), 7.37 (t, J = 8.0
Hz, 1 H), 7.28 (t, J = 3.0 Hz, 3 H), 7.16 (d, J = 2.5 Hz, 1 H), 6.95 (t, J = 7.0
Hz, 1 H), 6.76 (t, J = 4.0 Hz, 1 H).
Phenyl[2-(pyridin-2-yl)pyrazolo[1,5-a]pyridin-3-yl]methanone
(3j)
Yield: 72.1 mg (97%); white solid; mp 118 °C.
1H NMR (500 MHz, CDCl3): δ = 8.62 (d, J = 7.0 Hz, 1 H), 8.43 (d, J = 9.5
Hz, 1 H), 8.07 (d, J = 9.0 Hz, 1 H), 7.61 (d, J = 7.0 Hz, 2 H), 7.50 (d, J = 5.0
Hz, 2 H), 7.41 (t, J = 8.5 Hz, 1 H), 7.32 (q, J = 7.5 Hz, 1 H), 7.17 (t, J = 7.5
Hz, 2 H), 7.09–7.07 (m, 1 H), 7.02 (t, J = 7.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 190.9, 154.8, 151.7, 149.2, 142.6,
139.6, 135.6, 131.4, 129.0, 128.8, 127.7, 127.4, 124.6, 122.7, 119.3,
114.5, 110.0.
13C NMR (125 MHz, CDCl3): δ = 182.4, 155.0, 144.5, 142.5, 133.9,
132.8, 132.3, 129.4, 128.5, 128.1, 127.2, 126.9, 118.7, 114.0, 109.4.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H13N2OS: 305.0749; found:
305.0765.
[2-(Isoquinolin-1-yl)pyrazolo[1,5-a]pyridin-3-yl](phenyl)meth-
anone (3o)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H14N3O: 300.1137; found:
Yield: 64.4 mg (74%); white solid; mp 160 °C.
300.1133.
1H NMR (500 MHz, CDCl3): δ = 8.64 (d, J = 6.5 Hz, 1 H), 8.10 (d, J = 8.5
Hz, 1 H), 7.96 (d, J = 8.5 Hz, 1 H), 7.86 (d, J = 8.5 Hz, 1 H), 7.69–7.65 (m,
4 H), 7.58 (t, J = 7.0 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 1 H), 7.40 (t, J = 9.0 Hz,
1 H), 7.12 (t, J = 7.0 Hz, 1 H), 7.05–6.99 (m, 3 H).
[2-(4-Fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl](pyridin-2-
yl)methanone (3k)
Yield: 67.3 mg (85%); white solid; mp 152.6 °C.
13C NMR (125 MHz, CDCl3): δ = 191.2, 154.6, 151.0, 147.5, 142.6,
139.9, 135.6, 131.2, 129.4, 129.2, 128.8, 127.6, 127.3, 127.1, 126.9,
126.7, 121.5, 119.2, 114.5, 110.4.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H16N3O: 350.1293; found:
350.1299.
1H NMR (500 MHz, CDCl3): δ = 8.56 (d, J = 7.0 Hz, 1 H), 8.20 (d, J = 4.5
Hz, 1 H), 8.16 (d, J = 9.0 Hz, 1 H), 7.84 (d, J = 7.5 Hz, 1 H), 7.72 (t, J = 7.5
Hz, 1 H), 7.47 (t, J = 8.0 Hz, 1 H), 7.40 (q, J = 5.5 Hz, 2 H), 7.21 (t, J = 5.5
Hz, 1 H), 7.03 (t, J = 7.0 Hz, 1 H), 6.86 (t, J = 8.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 189.4, 163.5, 161.5, 156.5, 155.5,
148.2, 143.2, 136.4, 131.1 (d, J = 8.0 Hz), 129.3 (d, J = 78.3 Hz), 128.1,
125.5, 123.5, 119.4, 114.8, 114.7 (d, J = 10.8 Hz), 109.0.
Furan-2-yl(2-phenylpyrazolo[1,5-a]pyridin-3-yl)methanone (3p)
Yield: 36.2 mg (50%); white solid; mp 98 °C.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H13FN3O: 318.1043; found:
318.1030.
1H NMR (500 MHz, CDCl3): δ = 8.58 (d, J = 7.0 Hz, 1 H), 7.73 (d, J = 7.5
Hz, 2 H), 7.58 (d, J = 9.0 Hz, 1 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.38 (t, J = 9.0
Hz, 3 H), 7.29 (t, J = 8.0 Hz, 1 H), 6.97–6.93 (m, 2 H), 6.39 (q, J = 2.0 Hz,
1 H).
13C NMR (125 MHz, CDCl3): δ = 190.3, 146.3, 146.2, 143.4, 142.4,
139.7, 132.0, 128.9, 128.7, 128.2, 127.1, 118.8, 114.2, 112.7, 111.4,
108.6.
[2-(4-Chlorophenyl)pyrazolo[1,5-a]pyridin-3-yl](pyridin-2-
yl)methanone (3l)
Yield: 72.9 mg (88%); white solid; mp 151.9 °C.
1H NMR (500 MHz, CDCl3): δ = 8.57 (d, J = 7.0 Hz, 1 H), 8.18 (d, J = 5.0
Hz, 1 H), 8.14 (d, J = 8.5 Hz, 1 H), 7.85 (d, J = 7.5 Hz, 1 H), 7.74–7.71 (m,
1 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.24 (q, J = 5.0 Hz,
1 H), 7.14 (d, J = 8.5 Hz, 2 H), 7.02 (t, J = 7.0 Hz, 1 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H13N2O2: 289.0977; found:
289.0973.
13C NMR (125 MHz, CDCl3): δ = 189.3, 156.3, 155.6, 148.2, 143.2,
136.5, 134.1, 131.8, 130.5, 128.7, 128.1, 127.9, 125.6, 123.5, 119.4,
114.5, 109.0.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H13N3OCl: 334.0747;
found: 334.0741.
(4-Methyl-2-phenylpyrazolo[1,5-a]pyridin-3-yl)(phenyl)meth-
anone (3q)
Yield: 46.2 mg (59%); white solid; mp 110–113 °C.
1H NMR (600 MHz, CDCl3): δ = 7.97 (d, J = 8.4 Hz, 1 H), 7.58 (q, J = 7.2
Hz, 2 H), 7.46 (t, J = 6.6 Hz, 2 H), 7.45 (t, J = 8.4 Hz, 1 H), 7.31 (t, J = 7.2
Hz, 1 H), 7.20–7.14 (m, 5 H), 6.88 (d, J = 8.4 Hz, 1 H), 2.87 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 191.4, 155.9, 138.8, 132.7, 131.5,
129.8, 129.4, 128.3, 127.9, 127.7, 127.6, 116.7, 113.7, 109.6, 17.9.
Phenyl[2-(thiophen-2-yl)pyrazolo[1,5-a]pyridin-3-yl]methanone
(3m)
Yield: 69.5 mg (91%); yellow solid; mp 138.8 °C.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H16N2ONa: 335.1160;
found: 335.1175.
1H NMR (500 MHz, CDCl3): δ = 8.53 (d, J = 7.0 Hz, 1 H), 7.72 (d, J = 7.0
Hz, 2 H), 7.59 (d, J = 9.0 Hz, 1 H), 7.46 (t, J = 7.0 Hz, 1 H), 7.34–7.25 (m,
5 H), 6.93 (t, J = 6.0 Hz, 1 H), 6.88 (t, J = 4.0 Hz, 1 H).
[2-(4-Fluorophenyl)-4-methylpyrazolo[1,5-a]pyridin-3-yl](phe-
nyl)methanone (3r)
Yield: 52.1 mg (63%); white solid; mp 111–114 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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1H NMR (600 MHz, CDCl3): δ = 7.93 (t, J = 8.4 Hz, 1 H), 7.57 (q, J = 6.6
Hz, 2 H), 7.46 (t, J = 5.4 Hz, 2 H), 7.36 (q, J = 7.2 Hz, 2 H), 7.20 (q, J = 7.8
Hz, 2 H), 6.89–6.86 (m, 3 H), 2.86 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 191.3, 154.9, 139.2, 138.8, 131.7,
131.6, 131.5, 129.3, 127.8, 127.7, 116.7, 115.0, 114.8, 113.8, 109.6,
17.9.
1-[2-(4-Methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (5c)
Yield: 45.2 mg (68%); white solid; mp 173.5 °C.
1H NMR (500 MHz, CDCl3): δ = 8.43 (d, J = 7.0 Hz, 1 H), 8.34 (d, J = 8.5
Hz, 1 H), 7.45 (d, J = 9.0 Hz, 2 H), 7.39 (d, J = 7.5 Hz, 1 H), 6.96 (q, J = 8.5
Hz, 3 H), 3.80 (s, 3 H), 2.09 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 193.7, 160.3, 156.6, 142.0, 131.0,
128.4, 128.2, 125.5, 120.1, 114.5, 113.8, 111.5, 55.3, 30.0.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H15N2OFNa: 353.1066;
found: 353.1055.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H15N2O2: 267.1134; found:
267.1146.
[4-Methyl-2-(naphthalen-1-yl)pyrazolo[1,5-a]pyridin-3-yl](phe-
nyl)methanone (3s)
1-[2-(4-Fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (5d)
Yield: 38.2 mg (42%); white solid; mp 121–125 °C.
Yield: 58.0 mg (91%); white solid; mp 153.5 °C.
1H NMR (600 MHz, CDCl3): δ = 8.24 (t, J = 8.4 Hz, 1 H), 7.97 (t, J = 4.2
Hz, 1 H), 7.70–7.69 (m, 1 H), 7.66 (d, J = 8.4 Hz, 1 H), 7.49 (q, J = 6.6 Hz,
1 H), 7.42–7.37 (m, 3 H), 7.28 (t, J = 8.4 Hz, 2 H), 7.29 (d, J = 1.8 Hz, 1
H), 6.99–6.95 (m, 2 H), 6.77–6.74 (m, 2 H), 2.89 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 191.8, 154.9, 130.7, 129.2, 128.8,
128.2, 126.8, 126.3, 125.5, 124.6, 117.1, 114.0, 111.8, 18.0.
1H NMR (500 MHz, CDCl3): δ = 8.43 (d, J = 6.5 Hz, 1 H), 8.33 (d, J = 9.0
Hz, 1 H), 7.51–7.48 (m, 2 H), 7.40 (t, J = 8.5 Hz, 1 H), 7.11 (d, J = 8.5 Hz,
2 H), 6.94 (t, J = 9.0 Hz, 1 H), 2.08 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 164.3, 162.3, 155.6, 141.9, 131.6 (d, J =
8.1 Hz), 129.3, 128.4 (d, J = 7.0 Hz), 120.1, 115.5 (d, J = 21.5 Hz), 114.7,
111.5, 30.1.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H18N2ONa: 385.1317;
found: 385.1335.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H12N2OF: 255.0934; found:
255.0934.
{4-Methyl-2-[4-(methylthio)phenyl]pyrazolo[1,5-a]pyridin-3-
yl}(phenyl)methanone (3t)
1-[2-(4-Chlorophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (5e)
Yield: 46.5 mg (69%); white solid; mp 143.2 °C.
Yield: 45.3 mg (51%); white solid; mp 109–112 °C.
1H NMR (500 MHz, CDCl3): δ = 8.52 (d, J = 7.0 Hz, 1 H), 8.42 (d, J = 9.0
Hz, 1 H), 7.55 (d, J = 8.5 Hz, 2 H), 7.49 (t, J = 8.5 Hz, 3 H), 7.04 (t, J = 7.0
Hz, 1 H), 2.18 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 193.0, 155.4, 141.9, 135.4, 131.8,
131.0, 128.6, 128.5, 128.4, 120.1, 114.7, 111.6, 30.2.
1H NMR (600 MHz, CDCl3): δ = 7.89 (q, J = 8.4 Hz, 1 H), 7.60 (q, J = 6.6
Hz, 2 H), 7.41 (d, J = 9.0 Hz, 2 H), 7.35 (d, J = 7.2 Hz, 2 H), 7.21 (t, J = 7.8
Hz, 2 H), 7.07 (d, J = 8.4 Hz, 2 H), 6.86 (q, J = 6.0 Hz, 1 H), 2.85 (s, 3 H),
2.42 (s, 3 H).
13C NMR (150 MHz, CDCl3): δ = 191.3, 155.3, 143.4, 139.0, 138.6,
131.6, 130.1, 129.4, 127.8, 127.5, 125.9, 116.6, 113.6, 109.5, 17.9, 15.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H12N2OCl: 271.0638;
found: 271.0632.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H19N2OS: 359.1218; found:
359.1225.
1-[2-(4-Nitrophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (5f)
Yield: 66.4 mg (95%); white solid; mp 204.1 °C.
1-(2-Phenylpyrazolo[1,5-a]pyridin-3-yl)ethanone (5a)
1H NMR (500 MHz, CDCl3): δ = 8.56 (d, J = 7.0 Hz, 1 H), 8.38 (q, J = 9.0
Hz, 3 H), 7.84 (d, J = 9.0 Hz, 2 H), 7.54 (t, J = 8.0 Hz, 1 H), 7.09 (t, J = 7.0
Hz, 1 H), 2.25 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 192.2, 154.1, 148.2, 141.9, 140.0,
130.9, 127.9, 123.4, 120.0, 115.0, 111.7, 30.4.
Yield: 43.7 mg (74%); white solid; mp 98 °C.
1H NMR (500 MHz, CDCl3): δ = 8.53 (d, J = 7.0 Hz, 1 H), 8.45 (d, J = 9.0
Hz, 1 H), 7.60 (q, J = 3.5 Hz, 2 H), 7.50 (q, J = 3.5 Hz, 4 H), 7.03 (t, J = 7.0
Hz, 1 H), 2.14 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 193.3, 156.2, 141.6, 131.1, 129.4,
129.2, 129.1, 128.8, 128.6, 128.2, 128.1, 119.9, 114.3, 111.3, 29.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H12N3O3: 282.0879; found:
282.0866.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H13N2O: 237.1028; found:
237.1019.
1-[2-(3-Nitrophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (5g)
Yield: 60.0 mg (85%); white solid; mp 190.3 °C.
1-[2-(3,4-Dimethylphenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone
(5b)
1H NMR (500 MHz, CDCl3): δ = 8.56 (d, J = 7.0 Hz, 2 H), 8.37 (t, J = 9.0
Hz, 2 H), 7.99 (d, J = 7.5 Hz, 1 H), 7.70 (t, J = 8.0 Hz, 1 H), 7.54 (t, J = 8.0
Hz, 1 H), 7.09 (t, J = 7.0 Hz, 1 H), 2.26 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 192.1, 154.0, 148.0, 142.0, 135.8,
135.1, 129.3, 128.7, 124.9, 123.9, 120.0, 115.0, 111.5, 30.4.
Yield: 36.2 mg (55%); white solid; mp 124 °C.
1H NMR (500 MHz, CDCl3): δ = 8.51 (d, J = 7.0 Hz, 1 H), 8.43 (d, J = 9.0
Hz, 1 H), 7.46 (t, J = 7.5 Hz, 1 H), 7.36 (s, 1 H), 7.31 (d, J = 7.5 Hz, 1 H),
7.25 (t, J = 7.5 Hz, 1 H), 7.00 (t, J = 7.0 Hz, 1 H), 2.34 (d, J = 3.0 Hz, 6 H),
2.17 (s, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H12N3O3: 282.0879; found:
13C NMR (125 MHz, CDCl3): δ = 193.8, 157.0, 141.9, 137.6, 136.6,
130.7, 130.6, 129.5, 128.4, 128.2, 127.2, 120.1, 114.4, 111.5, 30.0, 19.7,
19.6.
282.0890.
1-[2-(Naphthalen-1-yl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (5h)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H17N2O: 265.1341; found:
Yield: 32.9 mg (46%); white solid; mp 142.3 °C.
1H NMR (500 MHz, CDCl3): δ = 8.56 (t, J = 6.5 Hz, 2 H), 8.00 (d, J = 8.0
Hz, 1 H), 7.93 (d, J = 8.0 Hz, 1 H), 7.65–7.57 (m, 3 H), 7.55–7.49 (m, 2
H), 7.43 (t, J = 7.0 Hz, 1 H), 7.05 (t, J = 6.5 Hz, 1 H), 1.80 (s, 3 H).
265.1335.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Synthesis
13C NMR (125 MHz, CDCl3): δ = 193.4, 155.2, 141.8, 133.3, 132.5,
131.0, 129.5, 128.5, 128.2, 127.9, 126.8, 126.1, 125.3, 125.0, 120.3,
114.7, 113.1, 29.1.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H15N2O: 287.1184; found:
287.1189.
References
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Pyrazolo[1,5-a]pyridine-3-carbonitrile (7a)23
Yield: 14.7 mg (41%); white solid; mp 73–76 °C.
1H NMR (500 MHz, CDCl3): δ = 8.59 (d, J = 7.0 Hz, 1 H), 8.25 (s, 1 H),
7.80 (d, J = 8.5 Hz, 1 H), 7.48 (t, J = 7.5 Hz, 1 H), 7.05 (t, J = 7.0 Hz, 1 H).
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114.4, 113.7, 82.3.
Ethyl Pyrazolo[1,5-a]pyridine-3-carboxylate (7b)
Yield: 40.0 mg (84%); light yellow liquid.
1H NMR (500 MHz, CDCl3): δ = 8.44 (d, J = 7.0 Hz, 1 H), 8.32 (s, 1 H),
8.08 (d, J = 9.0 Hz, 1 H), 7.31 (t, J = 8.0 Hz, 1 H), 6.85 (t, J = 6.5 Hz, 1 H),
4.32 (q, J = 7.0 Hz, 2 H), 1.33 (t, J = 7.0 Hz, 3 H).
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HRMS (ESI-TOF): m/z [M + H]+ calcd for C10H11N2O2: 191.0821; found:
191.0817.
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Diethyl Pyrazolo[1,5-a]pyridine-2,3-dicarboxylate (7c)
Yield: 49.2 mg (75%); colorless liquid.
1H NMR (500 MHz, CDCl3): δ = 8.44 (d, J = 7.0 Hz, 1 H), 8.08 (d, J = 9.0
Hz, 1 H), 7.36 (t, J = 8.0 Hz, 1 H), 6.94 (t, J = 7.0 Hz, 1 H), 4.44 (q, J = 7.0
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13C NMR (125 MHz, CDCl3): δ = 163.1, 162.1, 147.8, 141.2, 129.1,
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Yield: 13.4 mg (20%); white solid; mp 69–73 °C.
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Acknowledgment
CSIR-CSMCRI Communication No.048/2016. C.R., S.S. and N.N.K.R. are
thankful to AcSIR for their Ph.D. enrolment and the ‘Analytical Disci-
pline and Centralized Instrumental Facilities’ for providing instru-
mentation facilities. S.S. is also thankful to CSIR, New Delhi for his
Senior Research Fellowship. We thank the DST, Government of India
(EMR/2016/000010) and CSIR-CSMCRI (OLP-0087) for financial sup-
port.
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588753.
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