α-aminoazoles in synthesis of heterocycles: III. 4- trifluoromethylpyrazolo[3,4-b]pyridines: Synthesis and structure

Article abstract of DOI:10.1007/s11178-008-2011-x

Cyclocondensation of N-substituted 5-aminopyrazoles with fluorinated 1,3-diketones yielded 4-trifluoromethyl-substituted pyrazolo[3,4-b]pyridines as the only reaction products. The regiostructure of compounds obtained was proved by ¹H and ¹³C NMR homo- and heteronuclear correlation spectroscopy. Characteristic chemical shifts in the ¹³C NMR spectra of regioisomeric pyrazolo[3,4-b]pyridines were established.

Full text of DOI:10.1007/s11178-008-2011-x

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 2, pp. 251−256. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © E.E. Emelina, A.A. Petrov, S.I. Selivanov, D.V. Filyukov, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 2,
pp. 259−263.
α-Aminoazoles in Synthesis of Heterocycles:
III.* 4-Trifluoromethylpyrazolo[3,4-b]pyridines: Synthesis and
Structure
E. E. Emelina, A. A. Petrov, S. I. Selivanov, and D. V. Filyukov
St. Petersburg State University, St. Petersburg, 198504 Russia
e-mail: emelina@hotmail.ru
Received May 15, 2007
Abstract—Cyclocondensation of N-substituted 5-aminopyrazoles with fluorinated 1,3-diketones yielded 4-
trifluoromethyl-substituted pyrazolo[3,4-b]pyridines as the only reaction products. The regiostructure of compounds
1
obtained was proved by H and 13C NMR homo- and heteronuclear correlation spectroscopy. Characteristic
chemical shifts in the 13C NMR spectra of regioisomeric pyrazolo[3,4-b]pyridines were established.
DOI: 10.1134/S1070428008020115
Cyclocondensations of aminopyrazoles with 1,3-di-
electrophiles are extensively used for preparation of
bicyclic nitrogen heterocycles that are biologically active
substances possessing antioxidant, enzymatic, fungicidal,
antibacterial, antiphlogistic, and sedative-hypnotic
actions [2–7], some among them have found application
in pharmacology [8]. The problem of regiodirection of
the reaction is still urgent for the molecules of 3(5)-amino-
pyrazoles and 1,3-dielectrophiles contain nonequivalent
reaction sites.
It is known that in the reaction of N1-substituted
5-aminopyrazoles with 1,3-dielectrophiles formed sub-
stituted pyrazolo[3,4-b]pyridines; as bifunctional reagents
1,3-ketoesters [9, 10], symmetric 1,3-diketones, among
them hexafluoroacetylacetone [10–12] were employed.
However the application of unsymmetrical 1,3-diketones
to the synthesis of pyrazolopyridines is poorly document-
ed evidently because two regioisomeric products may
form in the reaction. In this connection a special interest
can be attracted by pyrazolopyridines containing a tri-
fluoromethyl group capable of modifying the chemical
reactivity and biological action of the heterocycle [13].
The target of this study was the investigation of the
direction of reaction between N-substituted amino-
pyrazoles and trifluoromethyl-containing 1,3-diketones
and establishing characteristic spectral distinctions of
individual regioisomers.
We studied the reactions of N1-substituted 5-amino-
pyrazoles Ia–Il with trifluoromethyl-containing 1,3-di-
ketones IIa–IIf. It was established that the reactions
proceeded regiospecifically giving 4-trifluoromethyl-
containing pyrazolo[3,4-b]pyridines notwithstanding the
character of substituents at the atoms N1 (CH2Ph, Ph)
and C3 of aminopyrazole (R2 = Me, Ar), and the sub-
stituent in diketone (R3 = Me, t-Bu, Ar, Ht). Reaction
was performed by melting or boiling in acetic acid and
resulted in over 90% yield.
The structure of pyrazolo[3,4-b]pyridines obtained
III–VI was proved by means of 1H and 13C NMR
spectroscopy. The position of the trifluoromethyl group
at the C4 atom was unambiguously established from the
observed long-range coupling constants between the
fluorine atoms of the trifluoromethyl group and the
protons and carbon atoms of the substituent R2 (CH3,
C°H) in the position 3 of pyrazolopyridines IIIa–IIId.
The unambiguous establishment of the regiostructure
of polycyclic nitrogen heterocycles is a complex problem
and as we already have stated before [1] the interpretation
of experimental findings may lead to an erroneous
conclusion [14, 15].
In the 1H NMR spectra of reaction products obtained
from 3-methylaminopyrazoles Ia–Ie and trifluoro-
methyl-containing 1,3-diketones IIa–IIf appeared
a quartet signal of the protons of methyl group with
6
* For communication, II see [1].
a coupling constant J(CF3–CH3) 1.6 Hz, and in the
251

EMELINA et al.
252
R3
N
F3C
R2
R3
R2
CF3
NH2
R2
N N
N
N
R1
N
N
Ia, Ib
N
R1
IIIa_IIId, IVa_IVh, VIa, VIb
R1
CF3COCH2COR3
IIa_IIf
I, R1 = Ph, R2 = Me (a), 4-XC6H4 , X = MeO (b), Me (c), H (d), Cl (e); R1 = Bn, R2 = 4-MeOC6H4 (f), Ph (g); II, R3 = Me
(a), t-Bu (b), C4H3S (c), 4-YC6H4, Y = i-PrO (d), H (e), Br (f); III, R1 = Ph, R3 = Me, R2 = Me (a), 4-XC6H4 , X = Me (b),
H (c), Cl (d); IV, R1 = R3 = Ph, R2 = Me (a), 4-XC6H4 , X = MeO (b), Me (c), H (d), Cl (e); R1 = R2 = Ph, R3 = 4-i-PrOC6H4
(f); R1 = Bn, R2 = R3 = Ph (g); R2 = 4-MeOC6H4, R3 = 4-BrC6H4 (h); V, R1 = Bn, R2 = 4-MeOC6H4, R3 = t-Bu; VI, R1 =
Ph, R3 = C4H3S, R2 = Me (a), Ph (b).
registered without decoupling from protons, and it
F3C
F3C
permitted the assignment of signals from all carbon atoms
and unambiguous establishment of the location of two
methyl (C3CH3, C6CH3) and a trifluoromethyl (C4CF3)
groups. The signal of atom C3CH3 at 14.77 ppm appeared
as a quartet of quartets with a coupling constant
4
6
6
4
N
N
H3C
N
N N
N
Ph
Ph
1
5JC–F 3.6, JC–H 128.6 Hz, and the signal of the carbon
_
1Í NMR: 6J(CF3 CH3)
1Í NMR: δ(Ho) 7.64 ppm
13Ñ NMR: 6J(CF3 Co)
C6CH3 at 25.47 ppm was observed as a quartet of
1.6 Hz
_
doublets (1JC–H 127.9, 3JC–H 4.4 Hz). The observed long-
_
13Ñ NMR: 5J(CF3 CH3)
1.7 Hz
3
range coupling constants J(CF3–C) for atoms
3.5 Hz
3
C3a (109.64 ppm, JC–F ~3 Hz) and C5 (114.15 ppm,
13C NMR spectra the carbon atom of the methyl gave
rise to a quartet with a coupling constant J(CF3–CH3)
3JC-F 4.4 Hz) confirm the position of the trifluoromethyl
5
froup at the atom C4 of the pyridine ring.
3.5 Hz due to the through-space interaction of closely
located CF3 and CH3 groups. In the 13C NMR spectra of
3-phenylpyrazolopyridines a quartet signal was observed
from the ortho-carbon atom of the phenyl group [6J(CF3–
Co) 1.7 Hz] also indicating that the trifluoromethyl group
was attached to C4 atom of the pyridine ring.
The chemical shifts of proton and
19.4
25.3 carbon signals of groups C4CH3
142.9
4
159.2
6
[fragment –C=C–CH3] and C6CH3
[fragment –C(CH3)=N] were un-
ambiguously established by an
example of 3,4,6-trimethylpyrazolo-
[3,4-b]pyridine (VIII) by using
N
N N
Ph
The chemical shift of the carbon atom C4CF3
(fragment –C=C–CF3 ) is characteristic for the whole
series of the trifluoromethyl-containing pyrazolo-
pyridines and equals 132–133 ppm. At the same time
the chemical shift of the carbon atom C6CF3 [fragment
–C(CF3)=N] revealed in the analysis of the 13C NMR
spectrum of methyl-4,6-bis(trifluoromethyl)-1-phenyl-
1H-pyrazolo[3,4-b]pyridine (VII) appears significantly
downfield (~147 ppm). It turned out that the chemical
shifts of carbons in the fragments –C(CF3)=N– and
–C=C–CF3 are virtually identical for pyrazolo[3,4-b]-
pyridines, pyrazolo[1,5-a]-pyrimidines [15], and triazolo-
[1,5-a]pyrimidines [16] and consequently they are suf-
ficiently characteristic and can be used for elucidating
the position of the CF3 group in the heterocyclic
compounds containing the mentioned fragments.
COLOC pulse sequence. The analysis of spectra obtained
demonstrated that the CH3 group whose signals appeared
in the H and 13C NMR spectra at δH 2.65 and
1
δC 25.3 ppm was located at the atom C6 (δC 159.2 ppm),
and the CH3 group having chemical shifts of signals δH
2.75 and δC 19.4 ppm, at the atom C4 (δC 142.9 ppm). It
was revealed from the 13C NMR spectra of pyrazolo-
pyridines IIIa–IIId that the chemical shifts of carbon
signals of methyl groups and pyridine ring (C6CH3) were
virtually constant for all compounds III and coincided
with the corresponding values of the C6CH3 group of
3,4,6-trimethylpyrazolo[3,4-b]pyridine (VIII).
Thus the above reasoning permitted unambiguous
establishing of the position of the trifluoromethyl group
in compounds III–VI at the atom C4, and therefore the
phenyl group of compounds IVa–IVh and the thienyl
The 13C NMR spectrum of 3,6-dimethyl-4-trifluoro-
methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine (IIIa) was
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α-AMINOAZOLES IN SYNTHESIS OF HETEROCYCLES: III.
Characteristic chemical shifts of carbon atoms in 13C NMR
253
Ph
F3C
spectra of pyrazolo[3,4-b]pyridines, δ, ppm
Fragment CH3 Fragment
C6
C6(Me)=N ~159.5 25–26 C4(Me)=C ~143.5 19–20
Ph
Ph
147.0
132
156.9
156.8
C4
CH3
N
N
N N
N N
C6(Ph)=N ~157.0
C6(CF3)=N ~147.5
C4(Ph)=C
C4(CF3)=C ~132–
133
~147.5
Ph
Ph
N
N
Ph
Ph
156.2
155.7
N
N
N
N
146.0
133.7
3(5)-Aminopyrazoles Ia–Ih were prepared as
described in [17, 18], fluorocontaining 1,3-diketones IIa–
IIc were synthesized by procedure [19].
CF3
Ph
group of compounds VIa and VIb were attached to
Pyrazolo[3,4-b]pyridines. a. Equimolar amounts of
compounds I and II dissolved in acetic acid were mixed
at 18–20°C, then the mixture was boiled for 2–4 h, the
acetic acid was distilled off at a reduced pressure, and
the residue was recrystallized from ethanol.
atom C6.
In the spectra of compounds IVa–IVh the chemical
shift of the atom C6 [fragment –C6(C6H5)=N] is virtually
identical and coincides with the chemical shift of the C6
in the spectrun of 3-methyl-1,4,6-triphenyl-1H-pyrazolo-
[3,4-b]pyridine (IX) and also with the characteristic
chemical shifts of the fragment C–C(Ph)=N of a series
of pyrazolo[1,5-a]pyrimidines [15].
b. Equimolar amounts of compounds I and II were
mixed and heated at 120–140°C for 10–30 min.
Compounds obtained were recrystallized from ethanol.
3,6-Dimethyl-4-trifluoromethyl-1-phenyl-1H-
pyrazolo[3,4-b]pyridine (IIIa). Yield 90%, mp 61.5°C.
1H NMR spectrum (CDCl3), δ, ppm: 2.71 d (3H, C6CH3,
4J H–H 1.0 Hz), 2.78 s (3H, C3CH3), 7.32 c (1H, C5H),
7.30–8.26 m (5H, C6H5). 13C NMR spectrum (CDCl3),
δ, ppm (reported coupling constants were obtained from
the 13C NMR spectrum registered without decoupling
from protons): 14.77 q.q (C3CH3, 1JC–H 128.6, 5JC–F 3.6
Hz), 25.47 q.d (C6CH3, 1JC–H 127.9, 3JC–H 4.4 Hz), 109.64
q (C3a, 3JC-F ~3 Hz), 114.15 d.q.q (C5, 1JC–H 164.9, 3JC–H
At the same time the value of the chemical shift of
the carbon atom C4Ph [147.0 ppm, fragment C–C(Ph)=C]
obtained from the 13C NMR spectrum of compound VIII
differed by 10 ppm from the chemical shift of the carbon
atom C6C6H5 [156.9 ppm, fragment C–C(Ph)=N].
The characteristic chemical shifts of the carbon atoms
of the regioisomeric pyrazolopyridines make it possible
to establish unambiguously the structure of regioisomers
(see the table).
3
1
3
4.3, JC–F 4.4 Hz), 122.70 q.d (CF3, JC–F 273.2, JC–H
5.1 Hz), 131.84 q (C4CF3, 2JC–F 34.9 Hz), 141.36 q (C3,
2JC–H 7.5 Hz), 152.21 s (C7a), 159.48 q.d (C6, 2JC–H 5.8,
2JC–H 2.2 Hz), 121.07, 126.47, 129.40, 139.49 (Ph).
Found, %: C 55.30; H 3.30. C15H12F3N3. Calculated, %:
C 61.85; H 4.15.
Thus by cyclocondensation of N-substituted 5-amino-
pyrazoles with fluorinated 1,3-diketones we synthesized
4-trifluoromethyl-substituted pyrazolo[3,4-b]pyridines as
the only reaction products. The characteristic chemical
shifts of carbon signals in the 13C NMR spectra of sub-
stituted pyrazolo[3,4-b]pyridines were estimated permit-
ting establishing the regioisomeric structure of the
compounds.
6-Methyl-3-(p-tolyl)-4-trifluoromethyl-1-phenyl-
1H-pyrazolo[3,4-b]pyridine (IIIb). Yield 93%, mp
1
145°C. H NMR spectrum (CDCl3), δ, ppm: 2.48 s (3H,
CH3), 2.83 s (3H, C6CH3), 7.39 s (1H, C5H), 7.30–7.60,
8.30–8.33 m (9H, Ph, Ar). 13C NMR spectrum, δ, ppm:
21.80 (CH3), 25.46 (C6CH3), 109.25 (C3a), 115.40 q (C5,
3JC–F 5.0 Hz), 122.89 q (CF3, 1JC–F 273.7 Hz), 132.47 q
(C4CF3, 2JC–F 34.8 Hz), 145.43 (C3), 151.96 (C7a), 159.68
(C6), 122.38, 126.85, 129.03, 129.40, 130.08, 138.97,
139.45 (Ph,Ar). Found, %: C 68.43; H 4.59. C21H16F3N3.
Calculated, %: C 68.66; H 4.39.
EXPERIMENTAL
1H and 13C NMR spectra were registered on a
spectrometer Bruker DPX-300 (300.13 and 75.47 MHz
respectively) at 22°C. Chemical shifts were measured
from the signals of deuterated solvent [CDCl3 (7.28 and
76.90 ppm), DMCO-d6 (2.50 and 39.50 ppm)]. ABruker
program package for pulse sequence COLOC was used
with optimization on 8 Hz.
6-Methyl-4-trifluoromethyl-1,3-diphenyl-1H-
pyrazolo[3,4-b]pyridine (IIIc). Yield 95%, mp 125°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008

EMELINA et al.
254
1H NMR spectrum (CDCl3), δ, ppm: 2.83 s (3H, C6CH3),
7.39 s (1H, C5H), 7.34–8.33 m (9H, Ph, Ar). 13C NMR
spectrum (CDCl3), δ, ppm: 25.48 (C6CH3), 109.19
Hz), 133.18 q (C4CF3, 2JC–F 34.4 Hz), 145.57 (C3), 152.17
(C7a), 157.47 (C6), 126.84, 128.01, 129.12, 129.47,
130.54, 130.71, 138.24, 139.10, 139.52 (2Ph,Ar). Found,
%: C 72.47; H 4.46. C26H18F3N3. Calculated, %: C 72.72;
H 4.22.
3
(C3a), 115.52 q (C5, JC–F 5.0 Hz), 122.73 q (CF3,
1JC–F 273.7 Hz), 132.44 q (C4CF3, 2JC–F 34.7 Hz), 145.33
(C3), 151.95 (C7a), 159.82 (C6), 122.44, 126.95, 128.32,
129.16, 129.42, 130.25, 133.87, 139.40 (Ph, Ar). Found,
%: C 68.10; H 4.20. C20H14F3N3. Calculated, %: C 67.98;
H 3.99.
4-Trifluoromethyl-1,3,6-triphenyl-1H-pyrazolo-
[3,4-b]pyridine (IVd). Yield 96%, mp 164°C. 1H NMR
spectrum (CDCl3), δ, ppm: 8.00 s (1H, C5H), 7.37–
8.44 m (15H, 3Ar). 13C NMR spectrum (CDCl3), δ, ppm:
109.18 (C3a), 111.74 q (C5, 3JC–F 5.1 Hz), 122.17 q (CF3,
1JC–F 273.0 Hz), 132.44 q (C4CF3, 2JC–F 34.7 Hz), 144.75
(C3), 151.38 (C7a), 156.82 (C6), 126.18, 127.27, 127.63,
127.84, 128.73, 128.50, 129.51, 130.00, 132.68, 138.64,
137.44 (3Ph). Found, %: C 55.30; H 3.30. C20H13BrF3N3.
Calculated, %: C 55.57; H 3.03.
6-Methyl-4-trifluoromethyl-1-phenyl-3-(4-
chlorophenyl)-1H-pyrazolo[3,4-b]pyridine (IIId).
1
Yield 95%, mp 122°C. H NMR spectrum (CDCl3), δ,
ppm: 2.83 s (3H, C6CH3), 7.44 s (1H, C5H), 7.32–
8.30 m (9H, 2Ar). 13C NMR spectrum (CDCl3), δ, ppm:
25.50 (C6CH3), 100.98 (C3a), 115.68 q (C5, 3JC–F 5.0 Hz),
1
122.85 q (CF3, JC–F 273.7 Hz), 132.23 q (C4CF3,
4-Trifluoromethyl-3-(4-chlorophenyl)-1,6-
2JC–F 34.4 Hz), 144.08 (C3), 151.93 (C7a), 160.04 (C6),
122.44, 127.12, 128.63, 129.47, 131.58, 132.05, 135.36,
139.25 (Ph, Ar). Found, %: C 62.10; H 3.60.
C20H13ClF3N3. Calculated, %: C 61.95; H 3.38.
diphenyl-1H-pyrazolo[3,4-b]pyridine (IVe). Yield
1
93%, mp 161–162°C. H NMR spectrum (CDCl3), δ,
ppm: 8.00 s (1H, C5H), 7.36–8.41 m (14H, 2Ph, Ar).
13C NMR spectrum (CDCl3), δ, ppm: 109.72 (C3a),
12.67 q (C5, 3JC–F 5.1 Hz), 122.86 q (CF3, 1JC–F 273.0 Hz),
3-Methyl-4-trifluoromethyl-1,6-diphenyl-1H-
pyrazolo[3,4-b]pyridine (IVa). Yield 91%, mp 151°C.
1H NMR spectrum (CDCl3), δ, ppm: 2.76 s (3H, CH3),
7.91 s (1H, C5H), 7.31–8.36 m (10H, 2Ph). 13C NMR
spectrum (CDCl3), δ, ppm: 14.85 (CH3), 110.44 (C3a),
2
133.02 q (C4CF3, JC–F 34.3 Hz), 144.26 (C3), 152.14
(C7a), 159.82 (C6), 122.33, 127.10, 128.03, 128.70,
129.52, 130.86, 131.60, 131.95, 135.47, 138.07, 139.31
(2Ph, Ar). Found, %: C 66.46; H 3.52. C25H15ClF3N3.
Calculated, %: C 66.75; H 3.36.
3
111.14 q (C5, JC–F 4.4 Hz), 123.22 q (CF3,
1JC–F 273.1 Hz), 132.53 q (C4CF3, 2JC–F 34.3 Hz), 141.55
(C3), 152.37 (C7a), 157.26 (C6), 121.75, 126.45, 127.95,
129.42, 130.59, 138.31, 139.54 (2Ph). Found, %:
C 67.69; H 4.15. C20H14F3N3. Calculated, %: C 67.98;
H 3.99.
6-(4-Isopropoxyphenyl)-4-trifluoromethyl-1,3-
diphenyl-1H-pyrazolo[3,4-b]pyridine (IVf). Yield
1
94%, mp 152°C. H NMR spectrum (CDCl3), δ, ppm:
1.45 d [9H, (CH3)2, JH–H 5.5 Hz], 4.69 septet [1H,
CH(CH3)2, JH–H 5.5 Hz], 7.92 s (1H, C5H), 7.28–8.08 m
(13H, 2Ph, Ar). 13C NMR spectrum (CDCl3), δ, ppm:
21.94 (CH3), 70.00 (OCH), 108.86 (C3a), 111.40 q (C5,
3JC–F 5.6 Hz), 122.54 q (CF3, 1JC–F 273.8 Hz), 132.50 q
(C4CF3, 2JC–F 31.9 Hz), 145.02 (C3), 151.74 (C7a), 158.85
(C6), 116.02, 120.71, 121.79, 126.30, 127.87, 128.71,
128.95, 129.01, 129.80, 133.14, 139.08, 160.00 (2Ph,
Ar). Found, %: C 72.51; H 4.43. C28H22F3N3O.
Calculated, %: C 71.03; H 4.68.
3-(4-Methoxyphenyl)-4-trifluoromethyl-1,6-
diphenyl-1H-pyrazolo[3,4-b]pyridine (IVb). Yield
1
95%, mp 166°C. H NMR spectrum (CDCl3), δ, ppm:
3.92 s (3H, CH3O), 7.99 s (1H, C5H), 7.04–8.44 m (14H,
2Ph, Ar). 13C NMR spectrum (CDCl3), δ, ppm: 55.73
3
(CH3O), 110.08 (C3a), 112.42 q (C5, JF 5.1 Hz),
1
122.86 q (CF3, JF 273.0 Hz), 133.19 q (C4CF3,
2JC–F 34.3 Hz), 145.30 (C3), 152.17 (C7a), 157.47 (C6),
113.88, 128.02, 131.56, 160.54 (Ar), 122.27, 126.84,
129.47, 139.48 (N1 Ph), 125.80, 130.72, 138.24 (C6Ph).
Found, %: C 69.90; H 4.29. C26H18F3N3O. Calculated,
%: C 70.11; H 4.07.
1-Benzyl-4-trifluoromethyl-3,6-diphenyl-1H-
pyrazolo[3,4-b]pyridine (IVg). Yield 95%, mp 160°C.
1H NMR spectrum (CDCl3), δ, ppm: 5.89 s (2H, CH2),
7.94 s (1H, C5H), 7.30–7.42, 7.45–7.61, 8.21–8.23 m
(14H, 3Ph). 13C NMR spectrum (CDCl3), δ, ppm: 51.63
3-(p-Tolyl)-4-trifluoromethyl-1,6-diphenyl-1H-
pyrazolo[3,4-b]pyridine (IVc). Yield 91%, mp 131°C.
1H NMR spectrum (CDCl3), δ, ppm: 2.50 s (3H, CH3),
8.00 s (1H, C5H), 7.34–8.45 m (14H, 2Ph, Ar). 13C NMR
spectrum (CDCl3), δ, ppm: 21.85 (4-CH3), 110.02 (C3a),
112.40 q (C5, 3JC–F 4.6 Hz), 122.96 q (CF3, 1JC–F 273.5
3
(CH2), 112.11 d.q (C5), 108.22 (C3a, JC–H 165.0, JC–F
5.0 Hz), 123.06 q (CF3, 1JC–F 274.2 Hz), 132.99 q (C4CF3,
2JC–F 34.8 Hz), 144.32 (C3), 152.44 (C7a), 157.15 (C6),
127.96, 128.34, 128.83, 129.08, 129.00, 129.44, 130.25,
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α-AMINOAZOLES IN SYNTHESIS OF HETEROCYCLES: III.
255
Found, %: C 65.25; H 3.57. C23H14F3N3S. Calculated,
%: C 65.55; H 3.35.
130.62, 133.80, 137.11, 138.39 (3Ph). Found, %: C 72.51;
H 4.43. C26H18F3N3. Calculated, %: C 72.72; H 4.22.
3-Methyl-4,6-bis(trifluoromethyl)-1-phenyl-1H-
pyrazolo[3,4-b]pyridine (VII). Yield 89%, mp 78–79°C
1-Benzyl-6-(4-bromophenyl)-3-(4-methoxy-
phenyl)-4-trifluoromethyl-1H-pyrazolo[3,4-b]-
pyridine (IVh). Yield 92%, mp 158°C. 1H NMR spec-
trum (CDCl3), δ, ppm: 3.89 s (3H, OCH3), 5.86 s (2H,
CH2,), 7.85 s (1H, C5H), 7.28–8.08 m (13H, 3Ar).
13C NMR spectrum (CDCl3), δ, ppm: 51.15 (CH2), 55.21
1
[10]. H NMR spectrum (CDCl3), δ, ppm: 2.79 s (3H,
CH3), 7.82 s (1H, C5H), 7.40–8.27 m (5H, Ph). 13C NMR
spectrum (CDCl3), δ, ppm: 14.27 (CH3), 109.57 (C5, 3JH–
F 2.8 Hz), 113.09 (C3a), 120.00 q (CF3, 1JH–F 273.7 Hz),
1
120.92 (CF3, JH–F 273.6 Hz), 133.30 q (C4CF3,
3
(OCH3), 108.05 (C3a), 110.98 q (C5, JC–F 5.0 Hz),
2JH–F 36.0 Hz), 141.31 (C3), 146.90 (C6CF3, 2JF 36.0 Hz),
1
122.51 q (CF3, JC–F 272.8 Hz), 132.32 q (C4CF3,
150.33 (C7a), 121.18, 126.71, 129.12, 138.28 (Ph).
2JC–F 34.8 Hz), 143.72 (C3), 151.88 (C7a), 155.30 (C6),
113.82, 124.79, 126.04, 128.33, 128.73, 129.06, 129.39,
131.43, 132.59, 137.03, 137.25, 159.93 (Ph, 2Ar). Found,
%: C 72.51; H 4.43. C27H19BrF3N3O. Calculated, %:
C 60.24; H 3.56.
3,4,6-Trimethyl-1-phenyl-1H-pyrazolo[3,4-b]-
pyridine (VIII). Yield 87%, mp 127–128°C [9]. 1H NMR
spectrum (CDCl3), δ, ppm: 2.65 s (3H, C6CH3), 2.68 s
(3H, C3CH3), 2.75 s (3H, C4CH3), 7.23–8.31 m (5H,
C6H5). 13C NMR spectrum (CDCl3), δ, ppm (reported
coupling constants were obtained from the 13C NMR
spectrum registered without decoupling from protons):
1-Benzyl-6-tert-butyl-3-(4-methoxyphenyl)-4-
trifluoromethyl-1H-pyrazolo[3,4-b]pyridine (V).
1
Yield 91%, mp 113°C. H NMR spectrum (CDCl3), δ,
1
15.76 q (C3CH3, JC–H 128.8 Hz), 19.36 q.d (C4CH3,
ppm: 1.54 s [1H, (CH3)3], 3.87 s (3H, OCH3), 5.78 s
(2H, CH2), 7.50 s (1H, C5H), 7.30–8.26 m (9H, Ph, Ar).
13C NMR spectrum (CDCl3), δ, ppm: 30.11 [(CH3)3],
38.32 [C(CH3)3], 51.08 (CH2), 55.18 (OCH3), 106.94 q
(C3a, 3JC–F ~3 Hz), 110.47 (C5, 3JC–F 5.0 Hz), 122.78 q
(CF3, 1JC–F 273.2 Hz), 131.72 q (C4CF3, 2JC–F 34.9 Hz),
143.17 (C3), 169.49 (C6), 113.26, 126.01, 127.75, 128.46,
128.59, 130.94, 136.76, 159.73 (Ph, Ar). Found, %: C
72.51; H 4.43. C25H24F3N3O. Calculated, %: C 68.32;
H 5.50.
3
1
1JC–H 127.1, JC–H 4.1 Hz), 25.28 q.d (C6CH3, JC–H
127.1, JC–H 2.1 Hz), 114.99 s (C3a), 119.02 m (C5 ),
3
142.83 q (C3, 2JC–H 8.7 Hz), 142.93 q (C4, 2JC–H 8.0 Hz),
151.75 C (C7a), 159.20 q (C6, JC–H 8.0 Hz), 122.20,
2
125.57, 129.32, 140.22 (Ph).
3-Methyl-1,4,6-triphenyl-1H-pyrazolo[3,4-b]-
pyridine (IX). Yield 70%, mp 148°C. 13C NMR spectrum
(CDCl3), δ, ppm: 15.80 (CH3), 114.22 (C5), 115.72(C3a),
142.90 (C3), 146.99 (C4), 152.07 (C7a), 156.86 (C6),
121.37, 125.75, 128.01, 128.76, 129.14, 129.20, 129.37,
129.47, 129.85, 138.27, 139.58, 140.24 (3Ph). Found,
%: C 82.91; H 5.47. C25H19N3. Calculated, %: C 83.08;
H 5.30.
3-Methyl-6-(2-thienyl)-4-trifluoromethyl-1-
phenyl-1H-pyrazolo[3,4-b]pyridine (VIa). Yield 92%,
mp 157°C. 1H NMR spectrum (CDCl3), δ, ppm: 2.71 s
(3H, CH3), 7.16 m, 7.37 t (JH–H 7.0 Hz), 7.49 d (3H,
C3H3S, JH–H 4.8 Hz), 7.50–8.03 (5H, Ph), 7.74 c (1H,
C5H). 13C NMR spectrum (CDCl3), δ, ppm: 14.35 q
(CH3, 3JC–F 3.3 Hz), 109.43 q (C5, JC–F 5.5 Hz), 109.80
The study was carried out under a financial support
provided to one of the authors by ProfessorA.de Meijere
Foundation.
1
(C3a), 122.65 q (CF3, JC–F 274.76 Hz), 132.02 q (C4,
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2JC–F 34.3 Hz), 141.23 (C3), 151.38 (C7a), 151.77 (C6),
120.92, 128.94, 129.48, 139.06 (Ph), 125.88, 126.82,
128.30, 143.74 (C4H3S). Found, %: C 59.90; H 3.55.
C18H12F3N3S. Calculated, %: C 60.16; H 3.37.
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