Design, synthesis and transformation of some heteroannulated 3-aminopyridines - Purine isosteres with exocyclic nitrogen atom

Article abstract of DOI:10.1016/j.tet.2012.11.026

The synthesis of 1-deazapurines and isosteres bearing the exocyclic nitrogen atom at position-1 was developed basing on the formal [3+3]-cyclization reaction of nitro-malonaldehyde with the set of electron-excessive aminoheterocycles. Through the function

Full text of DOI:10.1016/j.tet.2012.11.026

Tetrahedron 69 (2013) 1217e1228
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Design, synthesis and transformation of some heteroannulated
3-aminopyridinesdpurine isosteres with exocyclic nitrogen atom
,
b
,
a
a
a
Viktor O. Iaroshenko a , Marcelo Vilches-Herrera , Ashot Gevorgyan , Satenik Mkrtchyan ,
*
Knar Arakelyan a c, Dmytro Ostrovskyi a, Muhammad S.A. Abbasi a, Linda Supe a, Ani Hakobyan a
,
,
,c
Alexander Villinger a, Dmitriy M. Volochnyuk d, Andrei Tolmachev b
,
d
a
€
€
Institut fur Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b National Taras Shevchenko University, 62 Volodymyrska str., Kyiv-33, 01033, Ukraine
c Faculty of Chemistry, Yerevan State University, Alex Manoogian 1, 0025 Yerevan, Armenia
d Enamine Ltd, Alexandra Matrosova Str. 23, Kyiv 01103, Ukraine
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of 1-deazapurines and isosteres bearing the exocyclic nitrogen atom at position-1 was
developed basing on the formal [3þ3]-cyclization reaction of nitro-malonaldehyde with the set of
electron-excessive aminoheterocycles. Through the functionalization of the purine-like scaffolds syn-
thesized the diversity of compounds furnished in the possition-1 with aryl, alkinyl, and vinyl rests, were
obtained.
Received 7 September 2012
Received in revised form 30 October 2012
Accepted 6 November 2012
Available online 21 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Heterocyclisation
Purine isosteres
Fused pyridines
Electron-excessive aminoheterocycles
Nitro-malonaldehyde
1. Introduction
laboratories of Hocek,4 Beal5 and Iaroshenko6 have communicated
the synthesis of the purine nucleosides furnished with per-
Purines and purine-like scaffolds are compounds with extensive
application portfolio in the life science and medicine sector.1,2 The
substances from the purine/pseudopurine family have been having
a significant impact on drug design and drug-development. Those
are the structural part of big number of commercially available
drugs and drug candidates, which were developed during the last
several decades. For instance three (Valaciclovir, Tenofovir, Abaca-
vir) drugs are belonging to 200 top selling drugs world-wide are
compounds with purine framework, four (Sildenafil, Pemetrexed,
Temozolomide, Vardenafil) contain heterocyclic scaffolds isosteri-
cally close to purine. In the same time modification of the purine
scaffold very often results in the gaining new bioactivities and
pharmaceutical action.1
fluoroalkyl group in the 2- and 6-position. Some of the represen-
tatives from this family have showed a strong anti-proliferative
action on the endothelium and smooth muscle cells.7
We believe that the heterocyclic scaffolds 4 (Figs. 1 and 2) fur-
nished with nitro-group in the position-3 of the fused pyridine ring
NH2
N
N
N
N
N
Isostere change
N
N
2
1
R
R
purine
1-amino-1-deazapurine
NH2
NO2
NO2
B
B
N
B
A
A
A
During the last decade we have concentrated on the de-
velopment of the new synthetic strategies towards the function-
alized and modified purines and isosteres.3 Recently the
N
N
N
N
NH2
3
6
4
R
R
R
5
A= C, N
B= C, N, S
R= H, Alk, Ar, Het, Sugar, Carbocyclic or
acyclic sugar-mimicking Rests
NO2
NO2
O
O
* Corresponding author. Tel.: þ49 381 4986410; fax: þ49 381 49864112; e-mail
6
Na
7
addresses:
viktor.iaroshenko@uni-rostock.de,
iva108@googlemail.com
(V.O. Iaroshenko).
Fig. 1. Retrosynthetic analysis.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.026

1218
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
NC
O
Me
HO
NO2
NO2
B
N
B
N
N
X
A
A
R
NH2
NH2
N
N
H
H2O
N
N
N
NH2
N
10
OH
R
9
R
R
R
a: R = Ph,
H
H
a: X = S, R = Me;
b: X = S, R = Ph;
II
I
NO2
8
a: R = 4-MeO-Benzyl,
b: R = Cyclohexyl,
c: R = t-Bu
B
N
A
c: X = S, R = cyclohexyl;
d: X = S, R = Et;
Cys
N
HS
Me
R
Cys
S
4
S
Alk2N
NO2
N
NH2
NO2
B
N
N
O
B
NH2
N
A
12
R1
A
11
a: Alk2N = morpholino
b: Alk2N = piperidino
Ph
N
N
N
N
S
R
R
Cys
X
N
NH2
H
OMe
H
R2
IV
13
III
R
a: X = O, R1 = R2 = Me;
b: X = O, R1 = H, R2 = Me;
Fig. 2. Heteroannulated 3-nitropyridines as potentional inhibitors of adenosine
deaminese (ADA) and inosine monophosphate dehydrohynase (IMPHD).
MeO
NH2
Me2N
NH2
14 a: R = H,
b: R = MeO
15
Fig. 3. Structures of the used 1,3-C,N-dinucleophiles.
can find an application as a platform for the design and synthesis of
so-called enzyme pitfalls or enzyme killers,1,8 compounds with the
almost irreversible inhibition of the particular enzymes. Addition-
ally, heteroannulated pyridines can be considered as 1-deasopurine
isosteres and thus are of great interest as privileged drug-like
scaffolds8 in medicinal chemistry and drug design.9e12
Recently the building block concept towards 3-nitroquinolines
was developed by the application of nitro-malonaldehyde 7 onto
anilines.15 Reactions of this type were usually conducted in
a hydrochloric acid. We have started the investigation of hetero-
annulated 3-nitropyridines synthesis by using the previously re-
ported reaction conditions.15
To our great disappointment the reaction in the case of unstable
heteroamines like 10, 12, 27 experienced a failure; in the same time
the rest of the heterocycles has demonstrated relatively low yields,
never exceeded 45%. With these disappointing results in hand we
have turned our attention towards the new, developed during the
last decade, water scavenging system, namely DMF/TMSCl-sys-
tem.17 As a starting point we have chosen the anilines furnished
with electron-excessive groups and studied the reaction with so-
dium salt of nitro-malonaldehyde 7, using the DMF/TMSCl as a re-
action media. Due to the low stability of the nitro-malonaldehyde
we have chosen the correspondent sodium salt 7. The reaction
delivered in good yields hitherto known 3-nitroquinolines 16
(Scheme 1), previously obtained using the same strategy, however
instead of DMF/TMSCl mineral acid were applied.16
The subject of this paper is design and synthesis of the
1-deazapurines and isosteres 3 and 4, containing the exocyclic ni-
trogen function in the position-1 of the pseudopurine framework. We
have a great interest on the nitro-derivatives 4, since our6 recent ex-
perience on the mechanism-based design and synthesis of adenosine
deaminese (ADA)1a,5,13 and inosine monophosphate dehydrohynase
(IMPHD)12a,14 inhibitors gave us an understanding of the possible
application of 4 as a suitable platform for the development of in-
hibitors of these enzyme families. The presence of the electron-
withdrawing nitro-group can facilitate the addition of the water
molecule leading to the formation of hydrated pyridines I, II (Fig. 2).
Thelatestcanbeconsideredfromoneside, asmimeticsoftheputative
transition state of the ADA,1a,5,13 and from the other side as com-
pounds mimicking the transition state of IMPHD.12a,14 Nevertheless,
the formation of the Meisenheimer type adducts III and IV is also
possible, this might lead to the irreversible binding on the active site
of the current enzyme by the nucleophilic attack of the cysteine rest
involved in the transformation of inosine to xanthine, resulting in the
enzyme inhibition (Fig. 2). These both aspects have been recently
demonstrated, in number of works,1,12a,14 to be a valuable tool for the
mechanism-based design of ADA and IMPHD inhibitors.
With these new reaction conditions in hand we have turned
towards the synthesis of heteroannulated 3-nitropyridines by the
method proposed, starting with corresponding electron-excessive
aminoheterocycles 8e13. The reaction proceeded smoothly de-
livering the desired products 17e22 in excellent yields (Scheme 2,
We were interested in the elaboration of the principally new
synthetic strategy giving possibility to prepare diverse libraries of 3
and 4. Basing on the retrosynthetic analysis (Fig. 1) and some
previously known chemical properties of electron-excessive ami-
noheterocycles and taking into account recent experience gained in
the Iaroshenko’s laboratory, we have assumed that the scaffolds 4
can be achieved in two step-synthesis starting from amines 8e13,
by the pyridine ring annulation, using commercially available nitro-
malonaldehyde 7, which can be handled and stored in a form of
a stable sodium salt. The subsequent catalytic reduction of the
nitro-group will give rise to correspondent amines 3.
NO2
O
NaO
NO2
7
R
R
i
N
NH2
16
14, 15
a: R = 3,4,5-tri-OMe-C6H5, 80%
b: R = 3,4-di-OMe-C6H5, 83%
c: R = 3,5-di-OMe-C6H5, 81%
d: R = 3-N,N-di-Me, 82%
Scheme 1. Reagents and conditions: (i): DMF/TMSCl, 100 ꢀC.
NO2
2. Results and discussion
O
NaO
NO2
7
NH2
In the beginning of this research program we have concentrated
on the chemical objects for the investigation. As much promising
we have identified the electron-excessive heterocyclic amines and
anilines, depicted in Fig. 3, and 5-aminoimidazoles 27 (Scheme 3).
The latest can be generated in situ by previously communicated
method.4c
i
ii
N
NH2
N
8-15
17-22
23-26
Scheme 2. Reagents and conditions: (i): DMF/TMSCl, 100 ꢀC; (ii): MeOH, H2, Pd/C
(10 mol %), 20 ꢀC, 24 h.

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
1219
NO2
NO2
O
i
N
NH2
8-15
NO2
7
NaO
N
N
NH2
N
N
N
N
17-22
NO2
i
NO2
ii
O
N
NH2
O
N
R
28
R
27
generated
in situ
R
29
NaO
7
O
30
SiMe3
NO2
NO2
Scheme 3. Reagents and conditions: (i): DCM, AcOH, reflux 5e6 h; (ii): MeOH, H2,
Pd/C (10 mol %), 20 ꢀC, 24 h.
H
Me3Si Cl
O
N
O
O
SiMe3
SiMe3
H
Table 1). In the same time the reaction of 5-aminoimidazoles 27
experienced a failure under our standard reaction condition. After
some reaction optimization study, the optimal reaction condition
for 27 was established, namely, after the generation of the corre-
spondent amine in situ in DCM was completed, the 2 equiv of 7
were added, and then 5 equiv acetic acid were added dropwise at
C
NH2
O2N
SiMe3
NO2
Cl
O
0
ꢀC. Afterwards the reaction mixture was kept under reflux for
O
Me3Si Cl
O
5e6 h. This delivered 1-deazapurines 28 in 32e46 % yields (Scheme
3, Table 2). Increase the yields over this value was not possible.
SiMe3
N
H
H
H
N
A
B
H
Table 1
Synthesis of heteroannulated pyridines 17e26
Scheme 4. Putativereaction mechanism;reagentsandconditions: (i): DMF/TMSCl,100ꢀC.
O
Me
O
the carbonyl, mediated by TMSCl, affords intermediate C, which un-
dergoes aromatization to give fused pyridines 17e22 (Scheme 4).
The second step, according to our synthetic plan, to reach the
scaffolds 3 was the reduction of the fused 3-nitropyridines 17e22,
28. The transformation of the nitro-compounds to amines has been
conducted in the methanol under normal pressure using the 10%
palladium on the charcoal. In many cases the hydrogenation pro-
ceeded quantitatively, thus the subsequent purification was not
demanded. Under this reaction condition the allyl rest in com-
pound 28d has been reduced to n-propyl (Table 2).
R
R1
R
R
N
N
Ph
N
N
N
H
N
X
N
N
N
Ph
R1
19 R = NO2, 81%
25 R = NH2, 91%
17 R = NO2, 88%
23 R = NH2, 85%
a: R = NO
18
2,
R1 = R2 = Me, 91%
b: R = NO2,
NC
Me
R
R
R1 = H, R2 = Me, 95%
N
S
a: R = NH
2,
24
R1 = R2 = Me, 97%
b: R = NH2,
N
N
N
N
R1
a: R = NO2,
R1
20
R1 = H, R2 = Me, 94%
a: R = NO2,
22
It has become evident that purines and purine-like scaffolds
featuring one or two aryl groups in the six-membered ring have
a remarkable record in medicinal chemistry and play a continuing
role in providing lead compounds for the therapeutic application.
Several pronounced examples have to be illustrated here. Hocek
et al.,18 have communicated the synthesis and biological evaluation
of the number of purine derivatives, bearing aryl or heteroaryl
functionality in the 6-postion of the purine core, using the transition
metal catalysed reactions. In the same time 1-deazapurines fur-
nished with aryl or heteroaryl substituents in the position-1 are of
current scientific interest as scaffolds with pronounced bio-
activities.19,20 From the other hand, many representatives among
these structures have found an application in the material science.21
During the last two decades there are number of methods were
developed for the assembling of the 1-deazopurines and isosteres
bearing aryl-,22 vynil-23 and alkynil-24 substituent in the position-1.
Next, we concentrated on the functionalization of the hetero-
amines prepared here. As model scaffolds we took heterocycles 23
and 26, following the deaminativeebrominating pathway we have
reached bromides 31 and 32 in very good yields. Subsequently, we
concentrated on the Pd-mediated CeC coupling protocols, such as
SuzukieMiyaura, Sonogashira and Heck reactions (Scheme 5).
Firstly, the SuzukieMiyaura reaction was considered as a possi-
R1 = tBu, 93%
R
R1 = Me, 83%
b: R = NO2,
S
b: R = NO2,
Alk2N
R1 = Cyclohexyl, 86%
c: R = NO2,
R1 = Et, 84%
c: R = NO2,
N
N
21
R1 = 4-OMe-Bn, 84%
R1 = Cyclohexyl, 79%
d: R = NO2,
a: R = NO2,
Alk2N = Pyperidinyl, 87%
b: R = NO2,
R = NH2,
26
R1 = Ph, 83%
R1 = tBu, 95%
Alk2N = Morpholyl, 84%
Table 2
Synthesis of imidazo[4,5-b]pyridines 28, 29
28, 29
R
(28)a
(29)a
db
a
b
c
d
e
f
g
h
i
n-Heptyl
t-Butyl
Cyclohexyl
Allyl
40
35
36
46
32
48
45
42
45
92
db
96c
95
3,4,5-Trimethoxyphenyl
4-Methoxybenzyl
4-(Methyl)pyridine
3-Phenethyl
98
db
97
3,4-Dimethoxyphenylethyl
db
a
Yields of isolated products.
The hydrogenation was not conducted.
Allyl was reduced to n-propyl.
b
c
ble way for the efficient introducing of Ar-substituent in the
g-
position of the heteroannulated pyridines 31 and 32. These two
compounds readily reacted with the set of diverse boronic acids in
dioxane giving rise to compounds 34 and 35 in yields of 60e95%
(Scheme 5, Table 3). In the same time, to save one step we have
tried to use directly the intermediary formed diazonium salts,
which are known to undergo Pd-catalysed couplings, however, the
yields here were always below 30%. Concerning the Sonogashira
coupling, the reaction with commercially available acetylenes 36
took place under standard reaction condition, namely copper
Mechanistically the pyridine ring formation can be explained by
the putative mechanism depicted inScheme 4. The proposed reaction
cascade most probably starts from the formation of the moiety 30 as
a
product of the initial silylation of correspondent nitro-
malonaldehyde sodium salt. The formation of products 17e22 can
be explained by conjugate addition of enamine carbon atom of the
aminoheterocycle to the CeC-double bond of 30 to give intermediate
A. The subsequent deprotonation and tautomerisation give rise to
intermediate B. The intermolecular attack of the amino group onto

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V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
Ar
(ATR). Mass spectra were obtained on a HewlettePackard HPGC/MS
5890/5972 instrument (EI, 70 eV) by GC inlet or on a MX-1321 in-
strument (EI, 70 eV) by direct inlet. Column chromatography was
performed on silica gel (63e200 mesh, Merck), silica gel Merck 60F254
plates were used for TLC. All solvents were purified and dried by
standard methods.
Ar-B(OH)2
N
33
34, 35
Me
N
ii
R
Br
R
NH2
N
N
36
Ph
31 (85%)
iii
N
i
N
4.1.1. General procedure for 17e22. 7 (2.0 mmol, 0.38 g) and the
corresponding amine (2.0 mmol) were placed in pressure tube
under the flow of dry argon and dissolved in dry DMF (10 mL)
containing 1 mL of TMSCl. The mixture was heated at 100 ꢀC during
2e12 h (controlled by TLC). Then this solution was evaporated
under reduced pressure, treated with water, filtrated and dried on
the air and recrystallized from an appropriate solvent, or was
subjected to a column chromatography over silica gel.
NC
Ar
39
37, 38
Br
23, 26
iv
N
N
Ar
32 (80%)
N
40, 41
Scheme 5. Reagents and conditions: (i): under Ar, 1.5 equiv tert-butyl-NO, CuBr2
1.3 equiv, CH3CN, rt, 12 h; (ii): under Ar, 1.5 equiv AreB(OH)2 and PdCl2(PPh3)2
(2 mol %), K2CO3, 2 equiv; 1,4-dioxan, 90 ꢀC, 8 h; (iii): under Ar, acetylene 2 equiv,
PdCl2(PPh3)2 (2 mol %), CuI (5 mol %), NEt3 1.3 equiv, DMF, 120 ꢀC, 6e8 h; (iv) under Ar,
Alkene 3 equiv, PdCl2(PPh3)2 4 (mol %), NEt3 4 equiv, DMF, 140 ꢀC, 10e14 h.
4.1.2. General procedure for 23e26, 29. In a 50 mL Schlenk flask
under a flow of dry argon the corresponding nitro-compound
(1.0 mmol) and 0.05 g of Pd/C (10%) were placed. Afterwards,
25 mL of degassed methanol was added. The system was washed
three times with hydrogen. The hydrogenation was conducted with
the help of a glass burette under atmospheric pressure. After 3 equiv
of hydrogenwas consumed, the mixturewas stirredfor a dayat 20 ꢀC
(controlled by TLC). The reaction mixture was filtered through
a Celite pad (2e3 cm). The Celite was washed three times with
methanol. The solvent of the filtrate was removed under reduced
pressure. In many cases the compounds isolated did not demand
further purification, however, some of examples were purified by
preparative chromatography (silica gel, heptane/EtOAc) or recrys-
tallized from appropriate solvent.
Table 3
Synthesis of heteroannulated pyridines 34, 35, 37, 38, 40, 41
Me
R
Me
N
Me
N
Ar
Ar
N
N
N
N
N
N
N
34
Ph
Ph
40
37
Ph
a: Ar = 4-Me-C6H5, 87%
b: Ar = 3,5-di-Me-C6H5, 95%
c: Ar = 4-Cl-C6H5, 90%
d: Ar = 4-F-C6H5, 88%
e: Ar = 4-CF3-C6H5, 91%
f: Ar = 3-Cl-C6H5, 87%
a: Ar = 4-F-C6H5, 65%
R = 4-OMe-C6H5, 85%
b: Ar = 4-OMe-C6H5, 70%
c: Ar = 2-Pyridinyl,71%
R
NC
NC
NC
Ar
Ar
4.1.3. General procedure for 28. To a Schlenk flask, set with reflux,
CH2Cl2 (2.5 mL), correspondent amine (0. 663 mmol), and methyl
N-(cyanomethyl)-formimidate (0.00663 mol) were added under
an argon atmosphere at rt. The reaction mixture was refluxed
during 1 h 20 min and after that, the mixture was cooled down to
room temperature. Afterwards, the reaction mixture was chilled to
0 ꢀC and compound 7 (0. 73 mmol) was added, subsequently AcOH
(5 equiv) was added dropwise and the mixture continued to stir at
the same temperature for 45 min and then refluxed for 5e6 h. The
solvent was evaporated to dryness and the residue was purified by
column chromatography to give desirable product. In a case of
anilines (see comments in the main text) one drop of TMS-triflate
was added of the first stage, when the correspondent amino-
imidazole was generated in situ.
N
N
N
N
N
N
38
35
41
a: R = Ph, 70%
a: Ar = Ph, 60%
a: Ar = Ph, 72%
b: R = 4-Me-C6H5, 65%
c: R = 4-OMe-C6H5, 65%
d: R = 4-tBu-C6H5, 75%
e: R = Buthyl, 60%
b: Ar = 4-Et-C6H5, 70%
c: Ar = 4-OMe-C6H5, 70%
d: Ar = 4-Cl-C6H5, 68%
e: Ar = 4-CF3-C6H5, 67%
b: Ar = 4-Me-C6H5, 68%
c: Ar = 4-tBu-O-C6H5, 69%
iodide (5 mol %), triethylamine (1.5 equiv) and PdCl2(PPh3)2
(2 mol %), in DMF at 120 ꢀC to deliver the set of derivatives 37, 38
(Scheme 5, Table 3). Following the purpose the synthesis of the
alkene-substituted derivatives of 31 and 32, the Heck coupling re-
action of these bromides with alkenes 39 was performed, resulting
the library of purine isosteres 40, 41 was assembled.
The structures of several scaffolds synthesized, namely com-
pounds 32, 35d, 35e, 38a and 41b were corroborated by the means
of 1D and 2D NMR methods and X-ray analysis (Figs. 1e5 in SD).25
4.1.4. General procedure for 31, 32. Anhydrous copper halide
(1.2 mmol), compound 23 or 26 (1.5 mmol), and anhydrous aceto-
nitrile (40 mL) were placed in a threenecked roundbottom flask that
was equipped with a reflux condenser, addition funnel or solid inlet
tube, and a gas outlet tube. The amine (1 mmol) in 5 mL of aceto-
nitrile was slowly added over a period of 5 min to the reaction so-
lution. During this addition, the reaction solution turned completely
black from the initial green colour as nitrogen was evolved. After
complete gas evolution, the reactionwas then poured into 200 mL of
20% aqueous hydrochloric acid and extracted with 200 mL of ether
and organic layer was washed once with 200 mL of 20% aqueous
hydrochloric acid. The resulting ether solution was dried over an-
hydrous magnesium sulfate and the ether was removed under re-
duce pressure.
3. Conclusion
Finally, we have proposed the facile synthesis of 1-nitro-, 1-
amino-1-deazopurines and isosteres. These scaffolds could be
transformed into corresponding 1-bromo derivatives. Subsequent
functionalization of the scaffolds obtained by several CeC coupling
strategies opened an access to 3-functionalized fused pyridines. The
synthesised here libraries can be readily used for the combinatorial
synthesis of new complex biologically active molecules using de-
rivatization by synthetic methods and combinatorial equipments.
4. Experimental section
4.1. General
4.1.5. General procedure for 34, 35. Under argon atmosphere, ap-
propriate boronic acid (1.2 equiv), compounds 31 or 32 (1 equiv),
potassium carbonate (2 equiv) and PdCl2(PPh3)2 (2 mol %) were
placed into a pressure tube and 4 mL of dry 1,4 dioxane were added.
Once the tube was sealed the mixture was heated at 90 ꢀC for
NMR spectra were recorded on a Brucker AV 300 instruments. IR
spectra were recorded on a Perkin Elmer FT IR 1600 spectrometer

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
1221
4e6 h. The product was then purified by column chromatography
(eluent: n-heptane/ethylacetate).
5.4. 1,2-Dihydro-5-nitro-2-phenylpyrazolo[3,4-b]pyridin-3-
one (19)
4.1.6. General procedure for 37, 38. Under argon atmosphere, cop-
per iodide (5 mol %), appropriate acetylene (1.2 equiv), compound
31 or 32 (1 equiv), triethylamine (1.5 equiv) and PdCl2(PPh3)2
(2 mol %), were placed into a pressure tube and 4 mL of dry DMF
were added. Once the tube was sealed the mixture was heated at
120 ꢀC for 4e6 h. The product was then purified by column chro-
matography (eluent: n-heptane/ethylacetate).
The product was isolated as a dark brown solid. Yield 81%, mp
341e345 ꢀC. 1H NMR (300 MHz, DMSO-d6):
¼7.07e7.13 (m, 1H,
d
CHAr), 7.36e7.41 (m, 2H, CHAr), 8.20e8.23 (m, 2H, CHAr), 8.31 (s, 1H,
NH), 8.37 (d, 1H, 4J¼2.7 Hz, CHAr), 8.89 (d, 1H, 4J¼2.8 Hz, CHAr). 13
C
NMR (75.5 MHz, DMSO-d6):
d
¼105.6 (C), 118.7, 123.4, 128.4, 128.8
(CH), 130.3, 140.6 (C), 148.1 (CH), 155.7, 160.5 (C). MS (GC, 70 eV): m/
z (%)¼256 (Mþ, 100), 210 (35), 133 (40). HRMS (ESI): calcd for
C
12H8N4O3 (MþH) 257.0669, found 257.0666. IR (ATR, cmꢁ1):
~
4.1.7. General procedure for 40, 41. Under argon atmosphere, ap-
propriate styrene (3 equiv), 31 or 32 (1 equiv), triethylamine
(4 equiv) and PdCl2(PPh3)2 (4 mol %), were placed into a pressure
tube and 4 mL of dry dimethylformamide were added. Once the
tube was sealed the mixture was heated at 140 ꢀC for 8 h. The
product was then purified by column chromatography (eluent: n-
heptane/ethylacetate).
n
¼3065 (w), 1610 (m), 1532 (w), 1435 (m), 1325 (s), 1174 (m), 1057
(m), 1031 (m), 963 (m), 829 (m), 783 (s), 745 (s), 674 (s), 586 (m).
5.5. 1,3-Dimethyl-6-nitro-1H-imidazo[4,5-b]pyridine-2(3H)-
thione (20a)
The product was isolated as an orange solid. Yield 83%, mp
203e205 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼3.77 (s, 3H, NMe), 3.79
5. Analytical data
(s, 3H, NMe), 8.08 (d, 1H, 4J¼2.2 Hz, CHAr), 9.09 (d, 1H, 4J¼2.2 Hz,
CHAr). 13C NMR (75.5 MHz, CDCl3):
d
¼30.3, 31.3 (NMe), 109.7 (CH),
5.1. 3-Methyl-5-nitro-1-phenyl-1H-pyrazolo[3,4-b]pyridine
(17)
125.7 (C), 140.1 (CH), 140.6, 148.8, 174.7 (C). MS (GC, 70 eV): m/z
(%)¼224 (Mþ, 100), 178 (35). HRMS (EI): calcd for C8H8N4S (Mþ)
224.03625, found 224.035823. IR (ATR, cmꢁ1):
n
¼3034 (w), 2924
~
The product was isolated as a yellow solid. Yield 88%, mp
(w), 1615 (w), 1598 (w), 1521 (m), 1487 (m), 1438 (m), 1408 (m),
1330 (s), 1288 (w), 1114 (s), 1070 (m), 1010 (m), 929 (m), 899 (s), 889
(s), 806 (s), 766 (s), 742 (s), 645 (m), 616 (s), 560 (s).
130e132 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d¼2.71 (s, 3H, Me),
7.32e7.38 (m, 1H, Ph), 7.51e7.56 (m, 2H, Ph), 8.18e8.21 (m, 1H, Ph),
8.90 (d, 1H, 4J¼2.5 Hz, CHAr), 9.43 (d, 1H, 4J¼2.5 Hz, CHAr). 13C NMR
(75.5 MHz, CDCl3):
d
¼12.5 (Me), 116.0 (C), 121.3, 126.3, 126.9, 129.2
5.6. 3-Ethyl-1-methyl-6-nitro-1H-imidazo[4,5-b]pyridine-
2(3H)-thione (20b)
(CH), 138.4, 139.2 (C), 145.0 (CH), 145.2, 151.2 (C). MS (GC, 70 eV): m/
z (%)¼254 (Mþ, 100), 208 (14), 167 (12), 140 (12), 77 (15). HRMS
(ESI): calcd for C13H10N4O2 (MþH) 255.08765, found 255.08749. IR
~
The product was isolated as a red solid. Yield 84%, mp
(ATR, cmꢁ1):
n
¼3078 (w), 1593 (m), 1522 (m), 1504 (m), 1476 (m),
200e202 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.42 (t, 3H, 3J¼7.0 Hz
1437 (m), 1383 (w), 1350 (m), 1328 (s), 1265 (m), 1160 (w), 1123 (m),
1030 (w), 1011 (w), 962 (w), 933 (w), 914 (w), 790 (m), 772 (s), 752
(s), 689 (s), 671 (m), 656 (m), 595 (s).
CH2CH3), 3.81 (s, 3H, NMe), 4.48 (q, 2H, 3J¼7.0 Hz, CH2CH3), 8.12 (d,
1H, 4J¼2.5 Hz, CHAr), 9.14 (d, 1H, 4J¼2.5 Hz, CHAr). 13C NMR
(75.5 MHz, CDCl3):
d
¼12.9 (Me), 31.2 (CH2), 39.2 (Me), 109.6 (CH),
125.8 (C), 140.1 (CH), 140.6, 148.4, 173.9 (C). MS (GC, 70 eV): m/z
(%)¼238 (Mþ, 100), 210 (57), 192 (12), 164 (60), 64 (22). HRMS (EI):
calcd for C9H10N4O2S (Mþ) 238.05190, found 238.051930. IR (ATR,
~
5.2. 1,3-Dimethyl-6-nitropyrido[2,3-d]pyrimidine-2,4(1H,3H)-
dione (18a)
cmꢁ1):
n
¼3054 (w), 2981 (w), 2942 (w), 1771 (w), 1619 (w), 1525
The product was isolated as a white solid. Yield 91%, mp
(m), 1483 (m), 1458 (m), 1430 (s), 1392 (m), 1361 (m), 1333 (s), 1298
(s), 1262 (s), 1215 (m), 1116 (s), 1087 (s), 1021 (m), 959 (m), 939 (m),
902 (m), 808 (s), 770 (s), 744 (s), 671 (w), 617 (s).
202e204 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼3.51 (s, 3H, NMe), 3.78
(s, 3H, NMe), 9.20 (d, 1H, 4J¼2.7 Hz, CHAr), 9.46 (d, 1H, 4J¼2.7 Hz,
CHAr). 13C NMR (62.9 MHz, CDCl3):
d
¼28.9, 30.4 (Me), 110.0 (C),
133.5 (CH), 140.0 (C), 149.7 (CH), 150.7, 153.7, 159.7 (C). MS (GC,
70 eV): m/z (%)¼236 (Mþ, 100), 208 (11), 124 (53), 78 (11). HRMS
(ESI): calcd for C9H8N4O4 (MþH) 237.0618, found 237.0622. IR (ATR,
~
5.7. 3-Cyclohexyl-1-methyl-6-nitro-1H-imidazo[4,5-b]pyri-
dine-2(3H)-thione (20c)
cmꢁ1):
n
¼3059 (w), 2923 (w), 2853 (w), 1722 (w), 1666 (m), 1591
The product was isolated as a yellow solid. Yield 79%, mp
(s), 1536 (m), 1471 (m), 1412 (m), 1376 (m), 1334 (s), 1280 (s), 1163
(m), 1097 (s), 1005 (m), 981 (m), 949 (m), 910 (w), 829 (m), 796 (s),
751 (s), 733 (s), 711 (m), 675 (m), 580 (m).
198e200 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d¼1.24e1.50 (m, 6H,
CH2cyclhex), 1.63e1.66 (m, 2H, CH2cyclhex), 1.77e1.80 (m, 2H,
CH2cyclhex), 2.89e2.96 (m, 1H, NCHcyclhex), 3.45 (s, 3H, Me), 7.62 (d,
1H, 4J¼2.11 Hz, CHAr), 8.86 (d, 1H, 3J¼8.5 Hz, CHAr). 13C NMR
5.3. 1-Methyl-6-nitropyrido[2,3-d]pyrimidine-2,4(1H,3H)-di-
one (18b)
(62.9 MHz, DMSO-d6):
d
¼24.7, 25.5 (CH2), 31.4 (Me), 33.4 (CH2),
64.7 (CH),106.7 (CH),125.8 (C),136.7 (CH),137.3,143.1,155.1 (C). MS
(GC, 70 eV): m/z (%)¼292 (Mþ, 43), 263 (16), 249 (100), 237 (13),
203 (20). HRMS (EI): calcd for C13H16O2N4S (Mþ) 292.09885, found
~
The product was isolated as a white solid. Yield 95, mp
202e204 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼3.54 (s, 3H, NMe),
292.099655. IR (ATR, cmꢁ1):
n
¼3097 (w), 2922 (s), 2852 (s), 1732
3.78 (s, 3H, NMe), 8.80 (d, 1H, 4J¼2.8 Hz, CHAr), 9.48 (d, 1H,
(w),1647 (s),1583 (m),1519 (s),1448 (s),1430 (s),1395 (m),1336 (s),
1285 (s), 1261 (s), 1218 (m), 1147 (s), 1106 (s), 1076 (s), 1013 (m), 970
(s), 916 (s), 892 (m), 871 (m), 822 (s), 795 (m), 743 (s), 600 (s).
4J¼2.8 Hz, CHAr), 12.13 (s, 1H, NH). 13C NMR (62.9 MHz, DMSO):
d
¼29.0 (Me), 111.0 (C), 131.6 (CH), 139.5 (C), 149.4 (CH), 150.3, 155.0,
160.1 (C). MS (GC, 70 eV): m/z (%)¼222 (Mþ, 100), 124 (46). HRMS
(ESI): calcd for C8H6N4O4 (MþH) 221.0316, found 221.0317. IR (ATR,
5.8. 1-Methyl-6-nitro-3-phenyl-1H-imidazo[4,5-b]pyridine-
2(3H)-thione (20d)
cmꢁ1):
n
¼3183 (w), 3043 (m), 2922 (w), 2848 (w), 1674 (s), 1588 (s),
~
1525 (m), 1463 (s), 1356 (m), 1327 (s), 1266 (s), 1179 (m), 1147 (m),
1072 (m), 989 (w), 954 (m), 938 (m), 813 (m), 794 (m), 744 (m), 704
(m), 666 (m), 585 (m).
The product was isolated as a red solid. Yield 83%, mp
260e262 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d¼3.86 (s, 3H, NMe),

1222
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
7.51e7.65 (m, 5H, Ph), 8.78 (d, 1H, 4J¼2.3 Hz, CHAr), 9.05 (d, 1H,
5.13. 1-(4-Methoxybenzyl)-5-nitro-1H-pyrrolo[2,3-b]pyri-
dine-3-carbonitrile (22c)
4J¼2.3 Hz, CHAr). 13C NMR (75.5 MHz, CDCl3):
d¼31.6 (Me), 111.9
(CH), 126.2 (C), 128.5, 129.2, 129.3 (CH), 134.0 (C), 137.0 (CH), 141.0,
148.7, 173.8 (C). MS (GC, 70 eV): m/z (%)¼286 (Mþ, 100), 239 (45),
224 (12), 77 (12). HRMS (EI): calcd for C13H10N2O2S (Mþ) 286.05190,
~
The product was isolated as a yellow solid. Yield 84%, mp
130e132 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼3.71 (s, 3H, OCH3),
found 286.051426. IR (ATR, cmꢁ1):
n
¼3021 (w), 1597 (w), 1567 (w),
5.54 (s, 2H, CH2), 6.89 (d, 2H, 3J¼8.7 Hz, CHAr), 7.33 (d, 2H, 3J¼8.7 Hz,
1536 (m), 1486 (w), 1444 (w), 1414 (w), 1393 (w), 1322 (m),1283 (s),
1248 (m), 1127 (m), 1061 (m), 950 (m), 938 (m), 900 (m), 771 (s),
744 (m), 719 (m), 657 (m), 631 (m), 564 (m).
CHAr), 8.90 (s, 1H, CHAr), 8.95 (d, 1H, 4J¼2.5 Hz, CHAr), 9.30 (d, 1H,
4J¼2.5 Hz, CHAr). 13C NMR (62.9 MHz, DMSO-d6):
¼48.2 (CH2), 55.0
d
(OCH3), 85.5, 113.8 (C), 114.1 (CH), 118.2 (C), 124.5 (CH), 128.0 (C),
129.3 (CH), 140.3 (C), 141.0, 141.4 (CH), 147.6, 159.0 (C). MS (GC,
70 eV): m/z (%)¼121 (Mþ, 100), 77 (6). HRMS (EI): calcd for
5.9. 6-Nitro-2-(piperidin-1-yl)thiazolo[4,5-b]pyridine (21a)
C
18H12N4O3 (Mþ) 308.09039, found 308.09124. IR (ATR, cmꢁ1):
~
n
¼3104 (w), 2221 (s), 1734 (s), 1603 (m), 1579 (m), 1513 (s), 1342 (s),
The product was isolated as a yellow solid. Yield 87%, mp
214e216 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.74 (s, 6H, CH2), 3.75 (s,
1240 (s), 1171 (s), 1027 (m), 948 (w), 795 (m).
4H, CH2), 8.60 (s, 1H, 4J¼2.12 Hz, CHAr), 9.28 (s, 1H, CHAr). 13C NMR
5.14. 3-Methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-amine
(23)
(62.9 MHz, CDCl3):
d
¼23.9, 25.4, 50.3 (CH2), 124.1 (CH), 124.9, 137.8
(C), 143.8 (CH), 168.2, 172.6 (C). MS (EI, 70 eV): m/z (%)¼264 (Mþ,
100), 249 (20), 235 (53), 209 (31), 181 (23), 163 (15), 108 (13). HRMS
(EI): calcd for C11H12O2N4S (Mþ) 264.06755, found 264.067764. IR
~
The product was isolated as a grey solid. Yield 85%, mp
102e104 ꢀC. 1H NMR (300 MHz, DMSO-d6):
(s, 2H, NH2), 7.32e7.38 (m, 1H, Ph), 7.19e7.24 (m, 1H, Ph), 7.26 (d,
1H, 4J¼2.5 Hz, CHAr), 7.46e7.52 (m, 2H, Ph), 8.17 (d, 1H, 4J¼2.5 Hz,
CHAr), 8.25e8.27 (m, 2H, Ph). 13C NMR (75.5 MHz, DMSO-d6):
d¼2.49 (s, 3H, Me), 5.27
(ATR, cmꢁ1):
n
¼3048 (w), 2967 (w), 1582 (w), 1563 (m), 1530 (m),
1484 (m), 1438 (m), 1384 (m), 1290 (m), 1260 (m), 1239 (s), 1107 (s),
1067 (m), 1054 (m), 1028 (m), 937 (m), 890 (m), 801 (w), 769 (s),
744 (m), 707 (w), 659 (m).
d
¼12.1 (Me), 109.8 (CH), 117.2 (C), 118.7, 124.2, 129.0, 139.6 (CH),
139.7,140.4,140.8,144.8 (C). MS (GC, 70 eV): m/z (%)¼224 (Mþ,100).
5.10. 2-Morpholino-6-nitrothiazolo[4,5-b]pyridine (21b)
HRMS (ESI): calcd for C13H12N4 (MþH) 225.11232, found 225.11233.
IR (ATR, cmꢁ1):
n
¼3346 (w), 1632 (w), 1591 (m), 1503 (s), 1441 (w),
~
The product was isolated as an orange solid. Yield 84%, mp
1410 (m),1385 (m),1268 (m),1201 (w),1128 (m),1066 (m), 966 (m),
906 (m), 862 (m), 754 (s), 717 (m), 691 (s), 671 (s).
248e250 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼3.80e3.85 (m, 8H, CH2),
8.66 (d, 1H, CHAr), 9.24 (s, 1H, CHAr). 13C NMR (62.9 MHz, CDCl3):
due to bed solubility it was not possible to measure. MS (EI, 70 eV):
m/z (%)¼266 (Mþ, 67), 222 (11), 209 (100), 181 (35), 163 (21), 108
(14). HRMS (EI): calcd for C10H10O3N4S (Mþ) 266.04681, found
~
5.15. 6-Amino-1,3-dimethylpyrido[2,3-d]pyrimidine-
2,4(1H,3H)-dione (24a)
266.046719. IR (ATR, cmꢁ1):
n
¼3048 (w), 2967 (w), 1582 (w), 1563
The product was isolated as a green solid. Yield 97%, mp
(m), 1531 (m), 1484 (m), 1438 (m), 1384 (m), 1309 (m), 1290 (m),
1260 (m), 1239 (s), 1107 (s), 1066 (m), 1054 (m), 1028 (m), 937 (m),
890 (m), 801 (w), 769 (s), 744 (m), 707 (w), 636 (m), 562 (m).
208e210 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼3.45 (s, 3H, NMe), 3.65
(s, 3H, NMe), 3.80 (br s, 2H, NH2), 7.23 (d, 1H, 4J¼3.0 Hz, CHAr), 8.16
(d, 1H, 4J¼3.0 Hz, CHAr). 13C NMR (75.5 MHz, CDCl3):
¼28.5, 29.3
d
(Me), 110.7 (C), 121.2 (CH), 139.1 (C), 141.9 (CH), 143.9, 151.1, 161.6
(C). MS (GC, 70 eV): m/z (%)¼206 (Mþ, 100), 177 (14), 121 (30), 94
(32). HRMS (ESI): calcd for C9H10N4O2 (MþH) 207.0877, found
~
5.11. 1-tert-Butyl-5-nitro-1H-pyrrolo[2,3-b]pyridine-3-
carbonitrile (22a)
207.0875. IR (ATR, cmꢁ1):
n
¼3415 (w), 3345 (w), 3239 (w), 2929
The product was isolated as an orange solid. Yield 93%, mp
(w), 1696 (m), 1640 (s), 1504 (s), 1472 (s), 1421 (s), 1379 (m), 1353
(m), 1323 (m), 1292 (s), 1163 (w), 1070 (m), 1010 (w), 975 (m), 893
(m), 780 (s), 745 (s), 682 (m), 616 (m).
218e220 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.79 (s, 9H, (CH3)3), 8.00
(s, 1H, CHAr), 8.82 (d, 1H, 4J¼2.6 Hz, CHAr), 9.24 (d, 1H, 4J¼2.5 Hz,
CHAr). 13C NMR (62.9 MHz, CDCl3):
d
¼29.1 (CH3)3, 59.9, 86.0, 113.7,
120.3 (C), 124.1, 136.6 (CH), 140.0 (C), 140.1 (CH), 148.7 (C). MS (GC,
70 eV): m/z (%)¼244 (Mþ, 24), 188 (100),142 (28). HRMS (ESI): calcd
for C12H13N4O2 (MþH) 245.1033, found 245.1032. IR (ATR, cmꢁ1):
~
5.16. 6-Amino-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-
dione (24b)
n
¼3167 (w), 2974 (w), 2222 (s), 1604 (m), 1575 (m), 1515 (s), 1414
The product was isolated as a green solid. Yield 94%, mp
202e204 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼3.42 (s, 3H, NMe),
(m), 1333 (s), 1292 (s), 1196 (s), 1119 (m), 912 (m), 776 (m), 744 (m),
660 (m), 619 (m).
5.46 (s, 2H, NH2), 7.50 (d, 1H, 4J¼2.8 Hz, CHAr), 8.12 (d, 1H, 4J¼2.8 Hz,
CHAr), 11.45 (s, 1H, NH). 13C NMR (75.5 MHz, DMSO-d6):
d¼27.9
5.12. 1-Cyclohexyl-5-nitro-1H-pyrrolo[2,3-b]pyridine-3-
carbonitrile (22b)
(Me), 111.0 (C), 118.5 (CH), 140.7 (C), 141.5 (CH), 143.0, 150.1, 161.6
(C). MS (GC, 70 eV): m/z (%)¼192 (Mþ, 100), 121 (22), 94 (33). HRMS
(ESI): calcd for C8H8N4O2 (MþH) 193.072, found 193.0723. IR (ATR,
~
The product was isolated as a brown solid. Yield 86%, mp
cmꢁ1):
n
¼3446 (w), 3366 (w), 3181 (w), 3045 (w), 2922 (w), 2850
211e213 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼1.18e1.33 (m, 1H, CH2),
(w), 1681 (s), 1634 (s), 1582 (m), 1504 (s), 1423 (m), 1383 (m), 1326
(m),1286 (s), 1231 (m), 955 (m), 688 (m), 807 (m), 780 (m), 745 (m),
727 (m), 669 (m).
1.45e1.81 (m, 5H, CH2), 1.88e2.15 (m, 4H, CH), 7.94 (s, 1H, CHAr),
8.86 (d, 1H, 4J¼2.3 Hz, CHAr), 9.24 (d, 1H, 4J¼2.3 Hz, CHAr). 13C NMR
(62.9 MHz, CDCl3):
d
¼25.1, 25.5, 33.3 (CH2), 55.4 (CH), 87.0, 113.6,
119.0 (C), 124.5, 135.9 (CH), 140.5 (C), 141.1 (CH), 147.9 (C). MS (GC,
70 eV): m/z (%)¼270 (Mþ, 46), 189 (61), 188 (100). HRMS (EI): calcd
for C14H14N4O2 (Mþ) 270.11113, found 270.11097. IR (ATR, cmꢁ1):
~
5.17. 5-Amino-1,2-dihydro-2-phenylpyrazolo[3,4-b]pyridin-3-
one (25)
n
¼3151 (w), 2938 (m), 2226 (s), 1604 (m), 1578 (m), 1521 (m), 1509
The product was isolated as a green solid. Yield 91%, mp
(s),1428 (m),1327 (s),1197 (m),1077 (m), 915 (m), 785 (m), 746 (m),
615 (s).
295e297 ꢀC. 1H NMR (300 MHz, DMSO-d6):
7.19e7.27 (m, 2H, CHAr), 7.45e7.50 (m, 2H, CHAr), 8.37 (d, 1H,
d
¼5.29 (s, 2H, NH2),

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
1223
4J¼2.7 Hz, CHAr), 7.90 (d, 1H, 3J¼8.7 Hz, CHAr), 8.13 (d, 1H, 4J¼2.6 Hz,
(m), 1178 (m), 1139 (w), 1070 (m), 995 (w), 912 (m), 885 (w), 840
(w), 811 (m), 796 (s), 756 (s), 748 (s), 681 (m), 635 (m).
CHAr), 10.42 (s, 1H, NH). 13C NMR (62.9 MHz, DMSO-d6):
d¼111.3 (C),
113.9,119.0,124.7,128.9 (CH),137.7,141.6 (C),142.5 (CH),151.2,156.6
(C). MS (GC, 70 eV): m/z (%)¼226 (Mþ, 100), 197 (49). HRMS (ESI):
calcd for C12H10N4O (MþH) 225.0782, found 225.0776. IR (ATR,
~
5.22. 3-Allyl-6-nitro-3H-imidazo[4,5-b]pyridine (28d)
cmꢁ1):
n
¼3207 (w), 3064 (w), 1651 (s), 1593 (m), 1496 (s), 1422 (m),
The product was isolated as a yellow solid. Yield 46%, mp
122e123 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼4.97 (dt, 2H, 3J¼5.8 Hz,
1359 (m), 1273 (m), 1232 (m), 1198 (m), 1076 (s), 1031 (w), 971 (w),
891 (m), 827 (m), 783 (m), 743 (s), 646 (s), 586 (s).
4J¼1.5 Hz, NCH2), 5.23e5.40 (m, 2H, CHCH2), 6.00e6.15 (m, 2H,
CHCH2), 8.28 (s, 1H, CHAr), 8.90 (d, 1H, 4J¼2.2 Hz, CHAr), 9.34 (d, 1H,
4J¼2.2 Hz, CHAr). 13C NMR (62.9 MHz, CDCl3):
¼46.2 (CH2), 119.9
d
5.18. 1-tert-Butyl-5-amino-1H-pyrrolo[2,3-b]pyridine-3-
carbonitrile (26a)
(CH2), 123.8 (CH), 127.4 (C), 131.0 (CH), 134.0 (C), 141.1 (CH), 147.5,
149.8 (C). MS (GC, 70 eV): m/z (%)¼204 (Mþ, 100), 176 (12), 157 (31),
131 (23). HRMS (ESI): calcd for C9H8N4O2 (MþH) 205.072, found
The product was isolated as a brown solid. Yield 95%, mp
129e131 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.71 (s, 9H, (CH3)3), 3.60
205.07185. IR (ATR, cmꢁ1): ¼3035 (w), 1593 (s), 1521 (s), 1496 (m),
~
n
(br s, 2H, NH2), 7.22 (d, 1H, 4J¼2.6 Hz, CHAr), 7.65 (s, 1H, CHAr), 7.89
1466 (m), 1422 (w), 1401 (m), 1335 (s), 1309 (s), 1256 (m), 1202 (s),
1093 (w), 1069 (m), 991 (m), 917 (s), 839 (w), 796 (m), 769 (s), 748
(s), 691 (m), 634 (s).
(d, 1H, 4J¼2.6 Hz, AreH). 13C NMR (62.9 MHz, DMSO-d6):
¼28.6
d
(CH3)3, 57.6 (C), 79.4 (C), 108.7 (CH), 116.2 (C), 121.7 (C), 133.6 (CH),
134.0 (CH), 140.0 (C), 140.8 (C). MS (GC, 70 eV): m/z (%)¼214 (Mþ,
20), 158 (100), 130 (10). HRMS (EI): calcd for C12H14N4 (Mþ)
~
5.23. 3-(3,4,5-Trimethoxyphenyl)-6-nitro-3H-imidazo[4,5-b]
pyridine (28e)
214.12130, found 214.12134. IR (ATR, cmꢁ1):
n
¼3349 (w), 2202 (s),
1613 (w), 1519 (m), 1417 (s), 1305 (m), 1087 (m), 862 (w), 725 (m),
692 (m), 620 (s).
The product was isolated as a yellow solid. Yield 32%, mp
173e175 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼3.91 (s, 3H, OMe), 3.93 (s,
5.19. 3-Heptyl-6-nitro-3H-imidazo[4,5-b]pyridine (28a)
6H, 2ꢂ OMe), 4.57 (t, 2H, 3J¼6.8 Hz, CH2), 6.89 (s, 2H, CHAr), 8.48 (s,
1H, CHAr), 8.96 (d, 1H, 4J¼2.4 Hz, CHAr), 9.37 (d, 1H, 4J¼2.4 Hz, CHAr).
The product was isolated as a yellow solid. Yield 40%, mp
13C NMR (62.9 MHz, CDCl3):
d
¼56.4, 60.9 (OMe), 101.9, 124.2 (CH),
56e58 ꢀC. 1H NMR (300 MHz, CDCl3):
CH3(CH2)4CH2CH2), 1.24e1.33 (m, 8H, CH3(CH2)4CH2CH2), 1.91e1.96
(m, 2H, CH3(CH2)4CH2CH2) 4.34 (t, 2H, 3J¼7.3 Hz,
CH3(CH2)4CH2CH2), 8.24 (s, 1H, CHAr), 8.86 (s, 1H, CHAr), 9.31 (s, 1H,
d¼0.82e0.86 (m, 3H,
129.5, 134.8, 138.5, 141.2 (C), 141.5, 147.1 (CH), 149.8, 154.1 (C). MS
(GC, 70 eV): m/z (%)¼330 (Mþ, 100), 115 (74), 287 (21), 269 (12), 241
(15). HRMS (EI): calcd for C15H14N4O5 (Mþ) 330.09587, found
~
330.095802. IR (ATR, cmꢁ1):
n
¼3085 (w), 2930 (w), 2838 (w), 1813
CHAr). 13C NMR (62.9 MHz, CDCl3):
d
¼11.9 (Me), 22.4, 26.6, 28.6,
(w), 1588 (s), 1509 (s), 1460 (m), 1417 (m), 1343 (s), 1318 (s), 1297
(m),1231 (s), 1218 (s), 1177 (m), 1124 (s), 1074 (m),1023 (m), 990 (s),
913 (m), 857 (m), 827 (s), 794 (m), 773 (m), 746 (s), 691 (m), 660 (s).
29.8, 31.5, 44.4 (CH2), 123.8 (CH), 134.3 (C), 140.9 (CH), 147.8, 153.6
(C). MS (GC, 70 eV): m/z (%)¼262 (Mþ, 86), 233 (24), 219 (64), 205
(42), 191 (40), 178 (100), 164 (45), 131 (28), 119 (15). HRMS (ESI):
calcd for C13H18N4O2 (MþH) 263.14112, found 263.14113. IR (ATR,
~
cmꢁ1):
n
¼3072 (w), 2916 (w), 1589 (s), 1523 (s), 1499 (m), 1456 (m),
5.24. 3-(4-Methoxybenzyl)-6-nitro-3H-imidazo[4,5-b]pyri-
dine (28f)
1381 (w), 1343 (s), 1325 (s), 1261 (m), 1218 (m), 1076 (m), 929 (m),
847 (w), 793 (s), 748 (s), 722 (m), 665 (m), 633 (s).
The product was isolated as a yellow solid. Yield 48%, mp
161e163 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼3.72 (s, 3H, OMe), 5.38 (s,
5.20. 3-tert-Butyl-6-nitro-3H-imidazo[4,5-b]pyridine (28b)
2H, CH2), 6.80e6.83 (m, 2H, CHAr), 7.21e7.24 (m, 2H, CHAr), 8.13 (s,
1H, CHAr), 8.80 (d, 1H, 4J¼2.4 Hz, CHAr), 9.28 (d, 1H, 4J¼2.4 Hz, CHAr).
The product was isolated as a white solid. Yield 35%, mp
13C NMR (62.9 MHz, CDCl3):
d
¼47.3 (CH2), 55.3 (OMe), 114.5, 123.9
112e114 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.86 (s, 9H, NMe3), 8.35
(s, 1H, CHAr), 8.85 (d, 1H, 4J¼2.4 Hz, CHAr), 9.31 (d, 1H, 4J¼2.4 Hz,
(CH), 126.6 (C), 129.6 (CH), 134.2 (C), 141.1, 147.5 (CH), 150.1, 154.9,
159.9 (C). MS (GC, 70 eV): m/z (%)¼284 (Mþ, 64), 121 (100). HRMS
(EI): calcd for C14H12N4O3 (MþH) 285.09336, found 285.09337. IR
~
CHAr). 13C NMR (75.5 MHz, CDCl3):
d
¼29.0 (Me), 58.3 (C), 123.4
(CH), 135.6 (C), 139.8 (CH), 140.5 (C), 145.6 (CH), 150.6 (C). MS (GC,
70 eV): m/z (%)¼220 (Mþ, 62), 165 (100), 118 (22), 57 (20). HRMS
(EI): calcd for C10H12N4O2 (Mþ) 220.09548, found 220.095401. IR
~
(ATR, cmꢁ1):
n
¼3042 (w), 1767 (w), 1613 (w), 1589 (s), 1528 (m),
1516 (s), 1496 (m), 1469 (s), 1411 (w), 1386 (w), 1352 (s), 1303 (s),
1254 (s),1234 (s),1194 (s),1174 (m),1117 (m),1074 (w),1022 (s), 944
(m), 886 (w), 857 (m), 841 (s), 817 (m), 799 (m), 766 (s), 750 (s), 714
(m), 656 (s).
(ATR, cmꢁ1):
n
¼3093 (w), 2986 (w), 1640 (w), 1585 (m), 1529 (m),
1515 (m), 1481 (m), 1459 (m), 1395 (w), 1368 (w), 1326 (s), 1306 (s),
1264 (m), 1250 (m), 1225 (s), 1193 (s), 1072 (m), 957 (w), 933 (m),
910 (m), 848 (w), 819 (w), 785 (s), 749 (s), 708 (m), 642 (m), 577 (s).
5.25. 6-Nitro-3-((pyridin-4-yl)methyl)-3H-imidazo[4,5-b]pyr-
5.21. 3-Cyclohexyl-6-nitro-3H-imidazo[4,5-b]pyridine (28c)
idine (28g)
The product was isolated as a yellow solid. Yield 36%, mp
The product was isolated as a brown solid. Yield 45%, mp
118e120 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.23e1.58 (m, 3H,
154e156 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼5.67 (s, 2H, CH2),
CH2cyclhex), 1.79e2.01 (m, 5H, CH2cyclhex), 2.19e2.24 (m, 2H,
CH2cyclhex), 4.58e4.69 (m, 1H, NCHcyclhex), 8.35 (s, 1H, CHAr), 8.86 (d,
1H, 4J¼2.3 Hz, CHAr), 9.30 (d, 1H, 4J¼2.3 Hz, CHAr). 13C NMR
7.24e7.26 (m, 2H, CHAr), 8.51e8.53 (m, 2H, CHAr), 8.96e8.98 (m, 2H,
CHAr), 9.25 (d, 1H, 4J¼2.3 Hz, CHAr). 13C NMR (62.9 MHz, DMSO-d6):
d
¼45.8 (CH2), 122.1, 123.6 (CH), 130.4, 133.8 (C), 140.6 (CH), 140.9,
(75.5 MHz, DMSO):
d
¼24.7, 25.0, 32.0 (CH2), 54.3 (CH), 123.2 (CH),
145.0 (C), 149.9, 150.0 (CH). MS (GC, 70 eV): m/z (%)¼255 (Mþ, 81),
133.9 (C), 139.9 (CH), 140.5 (C), 147.9 (CH), 149.6 (C). MS (GC, 70 eV):
m/z (%)¼246 (Mþ, 27),165 (100),119 (16), 67 (12). HRMS (ESI): calcd
for C12H14N4O2 (Mþ1) 247.11895, found 247.11901. IR (ATR, cmꢁ1):
~
254 (100), 208 (32), 92 (20). HRMS (EI): calcd for C12H9N5O2 (MþH)
256.0829, found 256.08237. IR (ATR, cmꢁ1):
¼3069 (w), 1601 (m),
~
n
1590 (m), 1520 (s), 1504 (m), 1466 (m), 1409 (m), 1390 (w), 1346 (s),
1270 (m), 1200 (m), 1158 (w), 1080 (w), 994 (w), 941 (w), 918 (m),
857 (w), 792 (m), 780 (m), 762 (s), 750 (s), 731 (m), 664 (s), 630 (m).
n
¼2933 (w), 2851 (w), 1643 (w), 1601 (m), 1586 (m), 1515 (m), 1491
(m),1448 (m),1401 (w),1342 (m),1319 (s), 1275 (m),1256 (m),1206

1224
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
5.26. 6-Nitro-3-phenethyl-3H-imidazo[4,5-b]pyridine (28h)
(d, 1H, 4J¼2.4 Hz, CHAr), 8.65 (s, 1H, CHAr). 13C NMR (62.9 MHz,
DMSO-d6):
d¼56.2, 60.2 (OMe), 110.4, 110.6 (CH), 131.5 (C), 133.4
The product was isolated as a brown solid. Yield 42%, mp
(CH), 136.1, 136.4, 139.1, 142.0 (C), 143.3 (CH), 153.2 (C). MS (GC,
70 eV): m/z (%)¼300 (Mþ, 100), 285 (76), 227 (10). HRMS (EI): calcd
for C15H16N4O3 (Mþ1) 300.12169, found 300.121338. IR (ATR,
~
99e101 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼3.22 (t, 2H, 3J¼7.1 Hz,
CH2), 4.60 (t, 2H, 3J¼7.1 Hz, CH2), 7.01e7.04 (m, 2H, CHAr), 7.22e7.29
(m, 3H, CHAr), 7.87 (s, 1H, CHAr), 8.86 (d, 1H, 4J¼2.2 Hz, CHAr), 9.34
cmꢁ1):
n
¼3376 (w), 2961 (w), 1599 (s), 1512 (s), 1466 (m), 1427 (m),
(d, 1H, 4J¼2.2 Hz, CHAr). 13C NMR (62.9 MHz, CDCl3):
d¼35.9, 46.0
1382 (m), 1291 (w), 1237 (s), 1167 (m), 1124 (s), 1002 (s), 876 (m),
835 (m), 811 (m), 764 (s), 727 (s), 643 (s), 626 (s).
(CH2), 123.7, 127.3, 128.6, 128.9 (CH), 134.1, 136.8 (C), 141.0 (CH),
147.8 (C). MS (GC, 70 eV): m/z (%)¼268 (Mþ, 31), 104 (100), 91 (26).
HRMS (EI): calcd for C14H12N4O2 (MþH) 269.1033, found 269.10343.
~
5.31. 3-(4-Methoxybenzyl)-3H-imidazo[4,5-b]pyridin-6-
amine (29f)
IR (ATR, cmꢁ1):
n
¼3051 (w), 2923 (w), 1591 (m), 1519 (s), 1495 (m),
1464 (m),1406 (m),1386 (w),1369 (w), 1346 (s), 1256 (m),1197 (m),
1152 (w), 1101 (w), 1067 (w), 1006 (w), 956 (m), 914 (m), 871 (w),
839 (w), 796 (m), 783 (m), 758 (m), 745 (s), 702 (s), 634 (m).
The product was isolated as a yellow solid. Yield 98%, mp
76e78 ꢀC. 1H NMR (250 MHz, DMSO-d6):
d
¼3.70 (s, 3H, OMe), 4.97
(s, 2H, NH2), 5.28 (s, 2H, CH2), 6.85e6.89 (m, 2H, CHAr), 7.16 (d, 1H,
4J¼2.4 Hz, CHAr), 7.26e7.29 (m, 2H, CHAr), 7.82 (d, 1H, 4J¼2.4 Hz,
5.27. 3-(3,4-Dimethoxyphenethyl)-6-nitro-3H-imidazo[4,5-b]
pyridine (28i)
CHAr), 8.26 (s, 1H, CHAr). 13C NMR (62.9 MHz, DMSO):
d
¼45.5 (CH2),
55.0 (OMe), 110.3, 113.9, 129.0 (CH), 129.5 (C), 133.2 (CH), 135.6,
139.6, 141.4 (C), 144.1 (CH), 158.7 (C). MS (GC, 70 eV): m/z (%)¼254
(Mþ, 69), 121 (100). HRMS (EI): calcd for C14H14N4O (Mþ) 254.11621,
~
The product was isolated as a yellow solid. Yield 45%, mp
112e114 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼3.15 (t, 2H, 3J¼6.8 Hz,
CH2), 3.77 (s, 3H, OMe), 3.83 (s, 3H, OMe), 4.57 (t, 2H, 3J¼6.8 Hz,
CH2), 6.50e6.55 (m, 2H, CHAr), 6.74 (d, 1H, 3J¼8.0 Hz, CHAr), 7.86 (s,
1H, CHAr), 8.86 (d, 1H, 4J¼2.4 Hz, CHAr), 9.34 (d, 1H, 4J¼2.4 Hz, CHAr).
found 254.116180. IR (ATR, cmꢁ1):
n
¼3 (s), 1363 (m), 1292 (m), 1269
(w), 1244 (s), 1225 (s), 1176 (m), 1151 (s), 1118, 1035 (s), 971 (s), 916
(w), 867 (m), 836 (m), 808 (s), 772 (m), 653 (s).
13C NMR (62.9 MHz, CDCl3):
d
¼35.5, 45.9 (CH2), 55.8 (OMe), 114.4,
111.6, 120.7, 123.7 (CH), 129.3, 134.1 (C), 140.8 (CH), 140.9 (C), 147.9
(CH), 148.1, 149.1, 149.9 (C). MS (GC, 70 eV): m/z (%)¼328 (Mþ, 8),
164 (100), 151 (19). HRMS (EI): calcd for C16H16N4O4 (MþH)
~
5.32. 3-Phenethyl-3H-imidazo[4,5-b]pyridin-6-amine (29h)
The product was isolated as a white solid. Yield 97%, mp
329.12556, found 329.12557. IR (ATR, cmꢁ1):
n
¼3034 (w), 1588 (m),
113e115 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼3.14 (t, 2H, 3J¼7.1 Hz,
1511 (s), 1456 (m), 1406 (w), 1381 (w), 1337 (s), 1321 (s), 1296 (m),
1257 (s), 1235 (s), 1199 (m), 1154 (s), 1076 (w), 1023 (s), 941 (w), 852
(w), 816 (m), 796 (m), 778 (s), 747 (m), 727 (m), 660 (w), 634 (s).
CH2), 4.40 (t, 2H, 3J¼7.1 Hz, CH2), 4.96 (s, 2H, NH2), 7.12e7.28 (m, 6H,
CHAr), 7.84 (d, 1H, 4J¼2.4 Hz, CHAr), 7.96 (s, 1H, CHAr). 13C NMR
(62.9 MHz, CDCl3):
d
¼35.1, 44.1 (CH2), 110.4, 126.4, 128.3, 128.6,
133.0 (CH), 135.6, 138.2, 139.7, 141.3 (C), 144.1 (CH). MS (GC, 70 eV):
5.28. 3-tert-Butyl-3H-imidazo[4,5-b]pyridin-6-amine (29b)
m/z (%)¼238 (Mþ, 46), 147 (33), 134 (100). HRMS (EI): calcd for
C
14H14N4 (Mþ1) 239.12336, found 239.12340. IR (ATR, cmꢁ1):
The product was isolated as a green solid. Yield 92%, mp
~
n
¼3371 (m), 3204 (m), 2925 (w), 1641 (w), 1604 (w), 1581 (w), 1504
155e157 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼1.71 (s, 9H, NMe3),
(s), 1455 (m), 1410 (s), 1379 (m), 1362 (s), 1302 (m), 1248 (m), 1230
(s), 1171 (s), 1153 (s), 1103 (m), 1030 (m), 862 (s), 840 (m), 767 (s),
721 (s), 693 (s).
4.94 (s, 2H, NH2), 7.15 (d, 1H, 4J¼2.5 Hz, CHAr), 7.82 (d, 1H, 4J¼2.5 Hz,
CHAr), 8.13 (s, 1H, CHAr). 13C NMR (62.9 MHz, DMSO-d6):
d¼28.6
(Me), 55.8 (C), 110.2, 132.4 (CH), 136.9, 140.1, 140.8 (C), 141.7 (CH).
MS (GC, 70 eV): m/z (%)¼190 (Mþ, 35), 134 (100). HRMS (ESI): calcd
for C10H14N4 (Mþ) 190.1213, found 190.121307. IR (ATR, cmꢁ1):
~
5.33. 5-Bromo-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyri-
dine (31)
n
¼3326 (w), 3218 (w), 2938 (w), 1650 (w), 1605 (w), 1495 (s), 1474
(s), 1400 (s), 1369 (m), 1331 (m), 1291 (m), 1232 (s), 1157 (s), 1026
(w), 860 (s), 839 (m), 762 (m), 652 (s).
The product was isolated as a white solid. Yield 85%, mp
110e112 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼2.56 (s, 3H, Me),
7.28e7.34 (m, 1H, CHAr), 7.50e7.56 (m, 2H, CHAr), 8.15e8.19 (m, 2H,
CHAr), 8.66 (dd, 2H, 3J¼9.1 Hz, 4J¼2.2 Hz, CHAr). 13C NMR (62.9 MHz,
5.29. 3-Propyl-3H-imidazo[4,5-b]pyridin-6-amine (29d)
DMSO-d6):
d
¼12.0 (Me), 112.2, 118.3 (C), 119.9, 125.6, 129.1, 132.6
The product was isolated as a green solid. Yield 96%, mp
3
80e81 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼0.82 (t, 3H, J¼7.5 Hz,
(CH),138.7,142.4,148.4 (C),149.5 (CH). MS (GC, 70 eV): m/z (%)¼287
(Mþ, 100), 272 (13), 207 (18), 167 (12), 140 (130), 77 (40). HRMS
(ESI): calcd for C13H10N3Br (Mþ) 287.00526, found 287.004794. IR
4
CH3CH2), 1.78e1.85 (m, 2H, CH3CH2), 4.10 (t, 2H, J¼6.7 Hz, NCH2),
4.96 (s, 2H, NH2), 7.18 (d, 1H, 4J¼2.3 Hz, CHAr), 7.83 (d, 1H, 4J¼2.3 Hz,
CHAr), 8.17 (s, 1H, CHAr). 13C NMR (62.9 MHz, DMSO-d6):
d
¼11.0
(ATR):
n
¼1592 (m), 1564 (w), 1504 (s), 1438 (m), 1414 (s), 1380 (m),
1321 (m), 1266 (s), 1209 (w), 117 (w), 1114 (m), 1070 (m), 1010 (w),
949 (m), 904 (w), 883 (m), 820 (m), 766 (s), 744 (s), 688 (s), 668 (s),
651 (m).
(Me), 22.6, 44.4 (CH2), 110.4, 133.0 (CH), 135.6, 139.9, 141.2 (C), 144.2
(CH). MS (GC, 70 eV): m/z (%)¼176 (Mþ, 77), 147 (57), 134 (100).
HRMS (ESI): calcd for C9H12N4 (MþH) 177.11256, found 177.11257.
~
IR (ATR, cmꢁ1):
n
¼3364 (w), 3207 (w), 3103 (w), 2960 (w),1640 (w),
1604 (w), 1505 (s), 1488 (m), 1447 (m), 1409 (s), 1364 (m), 1301 (m),
1262 (w), 1226 (s), 1162 (s), 1120 (m), 975 (w), 866 (s), 831 (w), 795
(w), 765 (m), 652 (s).
5.34. 1-tert-Butyl-5-bromo-1H-pyrrolo[2,3-b]pyridine-3-
carbonitrile (32)
The product was isolated as a white solid. Yield 80%, mp 183 ꢀC.
5.30. 3-(3,4,5-Trimethoxyphenyl)-3H-imidazo[4,5-b]pyridin-
6-amine (29e)
1H NMR (300 MHz, CDCl3):
d
¼1.73 (s, 9H, (CH3)3), 7.78 (s, 1H, CHAr),
8.08 (d, 1H, 4J¼2.3 Hz, CHAr), 8.36 (d, 1H, 4J¼2.3 Hz, CHAr). 13C NMR
(62.9 MHz, CDCl3):
d
¼29.0 (CH3)3, 58.9, 82.9, 114.1, 114.8 (C), 122.8
The product was isolated as a yellow solid. Yield 95%, mp
(C), 129.9, 134.1, 144.9 (CH), 145.4 (C). MS (GC, 70 eV): m/z (%)¼279
168e171 ꢀC. 1H NMR (300 MHz, DMSO-d6):
3.85 (s, 6H, 2ꢂ OMe), 5.16 (s, 2H, NH2), 7.26e7.27 (m, 3H, CHAr), 7.89
d
¼3.71 (s, 3H, OMe),
(Mþ, 16), 223 (100), 142 (28); HRMS (ESI): calcd for C12H13BrN3
(MþH) 278.02866, found 278.02874; IR (ATR, cmꢁ1):
¼2972 (w),
n

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
1225
2217 (s), 1519 (s), 1407 (m), 1372 (m), 1271 (s), 1190 (s), 1073 (w),
881 (m), 832 (m), 617 (s).
1117 (m), 1076 (m), 1012 (w), 957 (w), 901 (m), 855 (m), 834 (s), 804
(m), 762 (s), 969 (s), 665 (s), 588 (m).
5.35. 3-Methyl-1-phenyl-5-p-tolyl-1H-pyrazolo[3,4-b]pyri-
dine (34a)
5.39. 5-(4-(Trifluoromethyl)phenyl)-3-methyl-1-phenyl-1H-
pyrazolo[3,4-b]pyridine (34e)
The product was isolated as a yellow solid. Yield 87%, mp
The product was isolated as a yellow solid. Yield 91%, mp
130e132 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼2.36 (s, 3H, Me), 2.63
144e145 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼2.65 (s, 3H, Me),
(s, 3H, Me), 7.27e7.32 (m, 3H, CHAr), 7.54 (t, 2H, 3J¼8.2 Hz, CHAr),
7.68 (d, 1H, 3J¼7.8 Hz, CHAr), 8.30 (d, 2H, 3J¼8.2 Hz, CHAr), 8.53 (s,
7.29e7.33 (m, 1H, CHAr), 7.55 (t, 2H, 3J¼8.0 Hz, CHAr). 7.86 (d, 2H,
3J¼8.0 Hz, CHAr), 8.04 (d, 2H, 3J¼8.0 Hz, CHAr), 8.29 (d, 2H, 3J¼7.8 Hz,
1H, CHAr), 8.90 (s, 1H, CHAr). 13C NMR (62.9 MHz, DMSO-d6):
d
¼12.1,
CHAr), 8.71 (d, 1H, 4J¼2.1 Hz, CHAr), 9.00 (d, 1H, 4J¼2.1 Hz, CHAr). 19
F
NMR (282 MHz, DMSO-d6):
d
¼ꢁ60.9. 13C NMR (62.9 MHz, DMSO-
20.6 (Me), 116.9 (C), 125.2, 126.8, 127.6, 129.1, 129.6, 129.7 (CH),
134.4, 137.0, 139.2, 143.2 (C), 148.1 (CH), 149.5 (C). MS (GC, 70 eV):
m/z (%)¼299 (Mþ, 100). HRMS (EI): calcd for C20H17N3 (Mþ)
d6): due to bed solubility it was not possible to measure. MS (GC,
70 eV): m/z (%)¼353 (Mþ, 100), 338 (14). HRMS (EI): calcd for
299.14170, found 299.141349. IR (ATR, cmꢁ1):
n
¼3023 (w), 1612 (w),
C
n
20H14N3F3 (Mþ) 353.11343, found 353.113271. IR (ATR, cmꢁ1):
1594 (s), 1504 (s), 1416 (s), 1381 (m), 1344 (m), 1279 (m), 1256 (m),
1212 (w), 1118 (m), 1078 (m), 1011 (w), 957 (w), 903 (m), 852 (w),
816 (s), 760 (s), 695 (s), 665 (s), 589 (m), 569 (m).
¼1612 (m), 1598 (m), 1505 (m), 1408 (w), 1441 (w), 1418 (m), 1384
(w), 1324 (s), 1283 (m), 1258 (m), 1163 (s), 1104 (s), 1067 (s), 1012
(m), 955 (m), 904 (m), 849 (m), 837 (s), 773 (m), 752 (s), 702 (m),
689 (s), 668 (m), 635 (w), 594 (s), 552 (w).
5.36. 3-Methyl-5-(3,5-dimethylphenyl)-1-phenyl-1H-pyrazolo
[3,4-b]pyridine (34b)
5.40. 5-(3-Chlorophenyl)-3-methyl-1-phenyl-1H-pyrazolo
[3,4-b]pyridine (34f)
The product was isolated as an orange solid. Yield 95%, mp
96e98 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼2.36 (s, 6H, 2ꢂ Me),
The product was isolated as an orange solid. Yield 87%, mp
2.65 (s, 3H, Me), 7.05 (s, 1H, CHAr), 7.30 (t, 1H, 3J¼7.2 Hz, CHAr), 7.41
(s, 2H, CHAr), 7.52e7.58 (m, 2H, CHAr), 8.30 (d, 2H, 3J¼7.9 Hz, CHAr),
8.57 (d, 1H, 4J¼2.0 Hz, CHAr), 8.91 (d, 1H, 4J¼2.0 Hz, CHAr). 13C NMR
140e142 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼2.64 (s, 3H, Me), 7.30
(t, 1H, 3J¼7.2 Hz, CHAr), 7.46e7.57 (m, 4H, CHAr), 7.79 (d, 1H,
3J¼7.5 Hz, CHAr), 7.91 (s, 1H, CHAr), 8.29 (d, 1H, 3J¼7.5 Hz, CHAr), 8.68
(d, 1H, 4J¼2.0 Hz, CHAr), 8.97 (d, 1H, 4J¼2.0 Hz, CHAr). 13C NMR
(62.9 MHz, DMSO-d6):
d
¼12.2, 21.0 (Me), 116.9 (C), 119.7, 124.8,
125.2, 128.0, 129.0, 129.1 (CH), 130.0, 137.2, 138.1, 139.2, 143.3 (C),
148.3 (CH), 149.6 (C). MS (GC, 70 eV): m/z (%)¼313 (Mþ, 100). HRMS
(EI): calcd for C21H19N3 (Mþ) 313.15735, found 313.156954. IR (ATR,
(62.9 MHz, DMSO-d6):
d
¼12.7 (Me), 116.9 (C), 119.8, 125.4, 125.7,
126.8, 127.4 (CH), 128.3 (C), 128.6, 129.1, 130.8 (CH), 133.9, 139.1,
139.5, 143.5 (C), 148.3 (CH), 149.8 (C). MS (GC, 70 eV): m/z (%)¼319
(Mþ, 100). HRMS (EI): calcd for C19H14N3Cl (Mþ) 319.08708, found
cmꢁ1):
n
¼2914 (w), 1589 (m), 1504 (m), 1430 (m), 1411 (m), 1365
(w), 1272 (m), 1219 (m), 1181 (w), 1118 (m), 1030 (w), 960 (w), 898
(m), 880 (w), 836 (s), 757 (s), 683 (s), 669 (s), 603 (m), 589 (m).
319.087283. IR (ATR, cmꢁ1):
n
¼3031 (w), 1594 (m), 1569 (m), 1497
(m), 1460 (m), 1436 (m), 1412 (m), 1383 (m), 1273 (m), 1251 (m),
1176 (w), 1097 (m), 1075 (m), 1045 (m), 957 (w), 896 (m), 878 (m),
787 (s), 775 (m), 742 (s), 697 (s), 683 (s), 607 (m), 589 (s).
5.37. 5-(4-Chlorophenyl)-3-methyl-1-phenyl-1H-pyrazolo
[3,4-b]pyridine (34c)
5.41. 1-tert-Butyl-5-phenyl-1H-pyrrolo[2,3-b]pyridine-3-
carbonitrile (35a)
The product was isolated as a yellow solid. Yield 90%, mp
157e159 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼2.64 (s, 3H, Me), 7.30
(t, 1H, 3J¼7.6 Hz, CHAr), 7.52e7.59 (m, 4H, CHAr), 7.84 (d, 1H,
3J¼8.4 Hz, CHAr), 8.29 (d, 1H, 3J¼8.4 Hz, CHAr), 8.63 (d,1H, 4J¼1.8 Hz,
CHAr), 8.95 (d, 1H, 4J¼1.8 Hz, CHAr). 13C NMR (62.9 MHz, DMSO-d6):
The product was isolated as a white solid. Yield 60%, mp 182 ꢀC.
1H NMR (300 MHz, DMSO-d6):
d
¼1.84 (s, 9H, (CH3)3), 7.42e7.58 (m,
3H, CHAr), 7.85 (d, 2H, 3J¼7.4 Hz, CHAr), 8.36 (s,1H, CHAr), 8.60 (s,1H,
d
¼12.2 (Me), 116.8 (C), 119.7, 125.3, 128.2, 128.5, 128.7, 129.0, 129.1
CHAr), 8.80 (s, 1H, CHAr). 13C NMR (62.9 MHz, DMSO-d6):
d
¼28.7
(CH), 132.6, 136.2, 139.1, 143.4 (C), 148.2 (CH), 149.7 (C). MS (GC,
70 eV): m/z (%)¼232 (Mþ, 100), 304 (10). HRMS (EI): calcd for
(CH3)3, 58.6, 82.0, 115.6, 120.9 (C), 125.4, 127.3, 127.7, 129.1 (CH),
130.4 (C), 136.7 (CH), 137.7 (C), 143.0 (CH), 146.1 (C). MS (GC, 70 eV):
m/z (%)¼275 (Mþ,17), 219 (100). HRMS (EI): calcd for C18H17N3 (Mþ)
C
n
19H14N3Cl (Mþ) 319.08708, found 319.086462. IR (ATR, cmꢁ1):
¼3037 (w), 1611 (w), 1593 (m), 1558 (w), 1500 (s), 1440 (m), 1414
275.14170, found 275.14181. IR (ATR, cmꢁ1):
1603 (w), 1523 (m), 1407 (m), 1396 (m), 1208 (s), 891 (m), 760 (s),
702 (s).
n
¼3138 (w), 2212 (m),
(s), 1343 (m), 1277 (m), 1255 (m), 1210 (w), 1118 (m), 1093 (m), 1076
(m), 1010 (m), 956 (w), 902 (m), 849 (m), 827 (s), 762 (s), 695 (s),
647 (m), 586 (m).
5.38. 5-(4-Fluorophenyl)-3-methyl-1-phenyl-1H-pyrazolo
[3,4-b]pyridine (34d)
5.42. 1-tert-Butyl-5-(4-ethylphenyl)-1H-pyrrolo[2,3-b]pyri-
dine-3-carbonitrile (35b)
The product was isolated as a yellow solid. Yield 88%, mp
The product was isolated as a white solid. Yield 70%, mp 160 ꢀC.
168e169 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼2.63 (s, 3H, Me),
1H NMR (300 MHz, DMSO-d6):
d
¼1.24 (t, 3H, 3J¼7.6 Hz, CH3),1.81 (s,
7.27e7.38 (m, 3H, CHAr), 7.50e7.56 (m, 2H, CHAr), 7.81e7.86 (m, 2H,
9H, (CH3)3), 2.68 (q, 2H, 3J¼7.4 Hz, CH2), 7.35 (d, 2H, 3J¼8.1 Hz,
CHAr), 7.72 (d, 2H, 3J¼8.1 Hz, CHAr), 8.29 (d, 1H, 4J¼2.3 Hz, CHAr),
8.57 (s, 1H, CHAr), 8.74 (d, 1H, 4J¼2.1 Hz, CHAr). 13C NMR (62.9 MHz,
CHAr), 8.27e8.30 (m, 2H, CHAr), 8.57 (d, 1H, 4J¼2.2 Hz, CHAr). 19F
NMR (282 MHz, DMSO-d6):
d
¼ꢁ115.1. 13C NMR (62.9 MHz, DMSO-
d6):
d
¼12.1 (Me), 115.7, 116.0 (CH), 116.8 (C), 119.7, 125.2, 128.1,
DMSO-d6):
d
¼15.5 (CH3), 27.8 (CH2), 28.5 (CH3)3, 58.4, 81.8, 115.5,
128.8, 129.0, 129.1, 129.2 (CH), 133.8 (d, J¼3.0 Hz, C), 139.1, 143.3 (C),
148.2 (CH), 149.5, 162.0 (d, J¼245 Hz, C). MS (GC, 70 eV): m/z (%)¼
303 (Mþ, 100). HRMS (EI): calcd for C19H14N3F (Mþ) 303.11663,
120.8 (C), 124.9, 127.1, 128.4 (CH), 130.3, 134.9 (C), 136.4, 142.7 (CH),
143.2, 145.9 (C). MS (GC, 70 eV): m/z (%)¼303 (Mþ, 29), 247 (100),
232 (62). HRMS (EI): calcd for C20H21N3 (M) 303.1730, found
found 303.116054. IR (ATR, cmꢁ1):
n
¼1610 (w), 1594 (s), 1563 (w),
303.1732. IR (ATR, cmꢁ1):
n
¼3150 (w), 2216 (m), 1526 (w), 1366 (w),
1504 (s), 1490 (s), 1416 (s), 1346 (w), 1259 (m), 1224 (s), 1163 (m),
1208 (m), 903 (w), 833 (s), 777 (m).

1226
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
5.43. 1-tert-Butyl-5-(4-methoxyphenyl)-1H-pyrrolo[2,3-b]
pyridine-3-carbonitrile (35c)
8.11 (d, 1H, 4J¼1.9 Hz, CHAr), 8.49 (d, 1H, 4J¼2.1 Hz, CHAr). 13C NMR
(62.9 MHz, CDCl3):
d¼29.1 (CH3)3, 58.8, 83.4, 86.7, 91.3, 114.3, 115.0,
120.8,122.9 (C), 128.4,128.5,130.4,131.6, 133.9 (CH),145.9 (C),146.9
(CH). MS (GC, 70 eV): m/z (%)¼299 (Mþ, 23), 243 (100). HRMS (EI):
calcd for C20H17N3 (Mþ) 299.1417, found 299.14203. IR (ATR, cmꢁ1):
The product was isolated as a white solid. Yield 70%, mp 130 ꢀC.
1H NMR (300 MHz, CDCl3):
d
¼1.77 (s, 9H, (CH3)3), 3.79 (s, 3H,
OCH3), 6.95 (d, 2H, 3J¼9 Hz, CHAr), 7.49 (d, 2H, 3J¼9 Hz, CHAr), 7.79
n
¼3144 (w), 2217 (m), 1610 (w), 1491 (m), 1407 (m), 1208 (s), 896
(s, 1H, CHAr), 8.07 (d, 2H, 4J¼2 Hz, CHAr), 8.55 (d, 2H, 4J¼2 Hz, CHAr).
(m), 753 (s), 688 (s), 634 (m), 584 (m). The structure was in-
13C NMR (62.9 MHz, CDCl3):
d
¼29.1 (CH3)3, 55.4 (OCH3), 58.5, 83.1
dependently confirmed by X-ray analysis.
(C), 114.6 (CH), 115.6, 121.5 (C), 125.4, 128.5 (CH), 130.8, 131.1 (C),
133.4,143.2 (CH),146.2,159.4 (C). MS (GC, 70 eV): m/z (%)¼305 (Mþ,
36), 249 (100), 234 (29). HRMS (EI): calcd for C19H19N3O (Mþ)
5.48. 1-tert-Butyl-5-(2-p-tolylethynyl)-1H-pyrrolo[2,3-b]pyri-
dine-3-carbonitrile (38b)
305.15226, found 305.15261. IR (ATR, cmꢁ1):
n
¼3145 (w), 2213 (m),
1606 (m), 1519 (m), 1399 (m), 1295 (m), 1246 (m), 830 (s).
The product was isolated as an orange solid. Yield 65%, mp
185e187 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.74 (s, 9H, (CH3)3), 2.30
5.44. 1-tert-Butyl-5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyri-
dine-3-carbonitrile (35d)
(s, 3H, CH3), 7.10 (d, 2H, 3J¼7.9 Hz, CHAr), 7.38 (d, 2H, 3J¼8.1 Hz,
CHAr), 7.78 (s, 1H, CHAr), 8.09 (d, 1H, 4J¼2.1 Hz, CHAr), 8.47 (d, 1H,
4J¼1.9 Hz, CHAr). 13C NMR (62.9 MHz, CDCl3):
¼21.6, 29.1 (CH3),
d
The product was isolated as a white solid. Yield 68%, mp
58.8, 83.4, 86.0, 91.5, 114.5, 115.1, 119.8, 120.8 (C), 129.2, 130.3, 131.5,
133.9 (CH), 138.7, 145.8 (C), 146.9 (CH). MS (GC, 70 eV): m/z (%)¼313
(Mþ, 31), 257 (100). HRMS (EI): calcd for C21H19N3 (Mþ) 313.15735,
189e190 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.78 (s, 9H, (CH3)3),
7.36e7.41 (m, 2H, CHAr), 7.45e7.50 (m, 2H, CHAr), 7.82 (s, 1H, CHAr),
8.08 (d, 1H, 4J¼2 Hz, CHAr), 8.54 (d, 1H, 4J¼2 Hz, CHAr). 13C NMR
found 313.15732. IR (ATR, cmꢁ1):
1509 (w), 1407 (s), 1361 (m), 1206 (s), 894 (m), 812 (s), 774 (m), 634
(m).
n
¼3149 (w), 2219 (m), 1609 (w),
(62.9 MHz, CDCl3):
d
¼29.1 (CH3)3, 58.7, 83.4, 115.4, 121.5 (C), 125.8,
128.6, 129.3 (CH), 130.2 (C), 133.8 (CH), 133.9, 136.9 (C), 143.1 (CH),
146.6 (C). MS (GC, 70 eV): m/z (%)¼309 (Mþ, 17), 253 (100). HRMS
(EI): calcd for C18H16N3Cl (Mþ) 309.10273, found 309.10261. IR (ATR,
5.49. 1-tert-Butyl-5-(2-(4-methoxyphenyl)ethynyl)-1H-pyr-
rolo[2,3-b]pyridine-3-carbonitrile (38c)
cmꢁ1):
n
¼3145 (w), 2217 (m), 1608 (w), 1524 (m), 1469 (m), 1414
(m), 1368 (m), 1207 (s), 1089 (m), 830 (s).
The product was isolated as a white solid. Yield 65%, mp
5.45. 1-tert-Butyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrrolo
[2,3-b]pyridine-3-carbonitrile (35e)
211e213 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.75 (s, 9H, (CH3)3), 3.76
(s, 3H, OCH3), 6.82 (d, 2H, 3J¼9 Hz, CHAr), 7.42 (d, 2H, 3J¼9 Hz, CHAr),
7.78 (s, 1H, CHAr), 8.08 (d, 1H, 4J¼2 Hz, CHAr), 8.46 (d, 1H, 4J¼2 Hz,
The product was isolated as a white solid. Yield 67%, mp
CHAr). 13C NMR (62.9 MHz, CDCl3):
d
¼29.1 (CH3)3, 55.3 (OCH3), 58.8,
177e179 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.79 (s, 9H, (CH3)3), 7.68
83.3, 85.4, 91.3, 114.1, 114.7 (C), 114.9 (CH), 115.1, 120.8 (C), 130.1
(CH), 133.1, 133.8 (CH), 145.7 (C), 146.8 (CH), 159.8 (C). MS (GC,
70 eV): m/z (%) 329 (Mþ, 49), 273 (100), 258 (35). HRMS (EI): calcd
for C21H19N3O (Mþ) 329.15226, found 329.15221. IR (ATR, cmꢁ1):
(s, 4H, CHAr), 7.85 (s, 1H, CHAr), 8.15 (s, 1H, 4J¼2 Hz, CHAr), 8.60 (d,
1H, 4J¼2 Hz, CHAr). 13C NMR (62.9 MHz, CDCl3):
¼29.1 (CH3)3, 58.8,
d
83.5, 115.3, 121.5 (C), 126.1 (q, CF3, 1J¼3.36, 2J¼7.78 Hz), 126.2 (C),
127.7 (CH), 129.5, 129.9 (C), 134.0 (CH), 142.0 (C), 143.3 (CH), 144.0,
n
¼3119 (w), 2212 (m), 1738 (w), 1511 (s), 1406 (w), 1242 (m), 1211
146.9 (C). 19F NMR (300 MHz, CDCl3):
d
¼ꢁ62.48 Hz. MS (GC, 70 eV):
(m), 1033 (m), 821 (s), 636 (m).
m/z (%)¼343 (Mþ, 11), 287 (100). HRMS (EI): calcd for C19H16N3F3
(Mþ) 343.1290, found 343.1289. IR (ATR, cmꢁ1):
n
¼3143 (w), 2218
5.50. 1-tert-Butyl-5-(2-(4-tert-butylphenyl)ethynyl)-1H-pyr-
rolo[2,3-b]pyridine-3-carbonitrile (38d)
(m), 1608 (m), 1523 (m), 1399 (m), 1322 (s), 1208 (m), 1164 (m), 1111
(s), 1070 (m), 835 (m).
The product was isolated as an orange solid. Yield 75%, mp
5.46. 5-(2-(4-Methoxyphenyl)ethynyl)-3-methyl-1-phenyl-
1H-pyrazolo[3,4-b]pyridine (37)
143e145 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.26 (s, 9H, (CH3)3), 1.75
(s, 9H, (CH3)3), 7.29e7.35 (m, 2H, CHAr), 7.39e7.46 (m, 2H, CHAr),
7.79 (s,1H, CHAr), 8.09 (d,1H, 4J¼1.9 Hz, CHAr), 8.48 (d,1H, 4J¼1.9 Hz,
The product was isolated as a yellow solid. Yield 85%, mp
CHAr). 13C NMR (62.9 MHz, CDCl3):
d
¼29.1, 31.2 (CH3), 34.8, 58.8,
92e94 ꢀC. 1H NMR (250 MHz, DMSO-d6):
d
¼2.62 (s, 3H, Me), 3.81 (s,
83.4, 86.0, 91.5, 114.6, 115.1, 119.9, 120.8 (C), 125.5, 130.3, 131.4, 133.8
(CH), 145.8 (C), 146.9 (CH), 151.9 (C). MS (GC, 70 eV): m/z (%)¼355
(Mþ, 47), 299 (32), 284 (100). HRMS (EI): calcd for C24H25N3 (Mþ)
3H, OMe), 7.01 (d, 2H, 3J¼8.9 Hz, CHAr), 7.29e7.35 (m, 1H, CHAr),
7.53e7.59 (m, 4H, CHAr), 8.523 (d, 2H, 3J¼8.3 Hz, CHAr), 8.56e8.57
(m, 1H, CHAr), 8.76e8.77 (m, 1H, CHAr). 13C NMR (62.9 MHz, DMSO-
355.2043, found 355.2042. IR (ATR, cmꢁ1):
n
¼3143 (w), 2218 (m),
d6):
d
¼12.0 (Me), 55.2 (OMe), 85.3, 90.9, 113.0, 113.9 (C), 114.4 (CH),
1604 (w), 1520 (w), 1405 (s), 1347 (m), 1266 (m), 1205 (s), 894 (m),
831 (s), 775 (m), 635 (m).
116.3 (C), 120.0, 125.6, 129.1, 132.9 (CH), 138.8, 143.3, 148.5 (C), 151.3
(CH), 159.6 (C). MS (GC, 70 eV): m/z (%)¼339 (Mþ, 100), 324 (31).
HRMS (EI): calcd for C22H17N3O (Mþ) 339.13661, found 339.136346.
5.51. 1-tert-Butyl-5-(2-(4-butylphenyl)ethynyl)-1H-pyrrolo
[2,3-b]pyridine-3-carbonitrile (38e)
IR (ATR):
n
¼2916 (w), 1595 (s), 1556 (m), 1504 (s), 1455 (m), 1438
(s), 1413 (s), 1382 (s), 1351 (m), 1299 (s), 1265 (m), 1242 (s), 1206
(m), 1173 (s), 1117 (s), 1066 (m), 1031 (s), 970 (m), 911 (m), 896 (m),
824 (s), 772 (s), 746 (s), 671 (s), 649 (m), 593 (s), 563 (m), 531 (s).
The product was isolated as a white solid. Yield 60%, mp
102e104 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼0.89 (t, 3H, 3J¼7.2 Hz,
CH3), 1.39e1.57 (m, 4H, CH2), 1.73 (s, 9H, (CH3)3), 2.37 (t, 2H,
5.47. 1-tert-Butyl-5-(2-phenylethynyl)-1H-pyrrolo[2,3-b]pyri-
dine-3-carbonitrile (38a)
3J¼6.9 Hz, CH2), 7.76 (s, 1H, CHAr), 7.96 (d, 1H, 4J¼1.9 Hz, CHAr), 8.35
(d, 1H, 4J¼2.1 Hz, CHAr). 13C NMR (62.9 MHz, CDCl3):
¼29.0, 13.6
d
(CH3), 19.1, 22.0, 30.7 (CH2), 58.6, 83.1, 92.4, 115.1, 115.2, 120.7 (C),
130.3, 133.6 (CH), 138.2, 145.5 (C), 146.9 (CH). MS (GC, 70 eV): m/z
(%)¼279 (Mþ, 49), 223 (100), 208 (89), 194 (58); HRMS (EI): calcd
for C18H21N3 (Mþ) 279.17300, found 279.17307; IR (ATR, cmꢁ1):
The product was isolated as a brown solid. Yield 70%, mp
136e138 ꢀC. 1H NMR (300 MHz, CDCl3):
7.27e7.33 (m, 3H, CHAr), 7.47e7.52 (m, 2H, CHAr), 7.80 (s, 1H, CHAr),
d
¼1.76 (s, 9H, (CH3)3),

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 1217e1228
1227
n
¼2975 (w), 2225 (s), 1545 (s), 1398 (m),1372 (m),1268 (s), 1183 (s),
n
¼3155 (w), 2979 (m), 2214 (m), 1520 (m), 1397 (m), 1371 (m), 1363
880 (m), 825 (m), 612 (s).
(m), 1204 (s), 1083 (w), 949 (s), 746 (s), 687 (s), 631 (s).
5.52. 5-(4-Fluorostyryl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-
b]pyridine (40a)
5.56. 5-(4-Methyl)-1-tert-butyl-1H-pyrrolo[2,3-b]pyridine-3-
carbonitrile (41b)
The product was isolated as a yellow solid. Yield 65%, mp
The product was isolated as a yellow solid. Yield 68%, mp
115e117 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d¼2.60 (s, 3H, Me),
179e181 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.75 (s, 9H, (CH3)3), 2.30
(s, 3H, CH3), 7.08 (s, 2H, CHAr), 7.12 (d, 2H, 3J¼8 Hz, CHAr), 7.37 (d,
7.19e7.30 (m, 3H, CHAr), 7.37e7.39 (m, 2H, CHAr), 7.50e7.55 (m, 2H,
CHAr), 7.62e7.67 (m, 4H, CHAr), 8.26 (d, 2H, 3J¼7.6 Hz, CHAr), 8.50 (d,
1H, 4J¼1.9 Hz, CHAr), 8.81 (d, 1H, 4J¼1.9 Hz, CHAr). 19F NMR
2H, 3J¼8 Hz, CHAr), 7.76 (s, 1H, CHAr), 8.07 (d, 1H, 4J¼2 Hz, CHAr),
8.46 (d, 1H, 4J¼2 Hz, CHAr). 13C NMR (62.9 MHz, CDCl3):
¼21.3, 29.1
d
(62.9 MHz, DMSO-d6):
d
¼ꢁ114.1. 13C NMR (62.9 MHz, DMSO-d6):
(CH3)3, 58.6, 83.1, 115.6, 121.6 (C), 124.0, 124.3, 126.5 (CH), 127.9 (C),
129.5, 129.6, 133.5 (CH), 134.2, 137.9 (C), 143.8 (CH), 146.5 (C). MS
(GC, 70 eV): m/z (%)¼315 (Mþ, 64), 258 (100), 244 (45). HRMS (EI):
calcd for C21H21N3 (Mþ) 315.17300, found 315.1728. IR (ATR, cmꢁ1):
due to bed solubility it was not possible to measure. MS (GC, 70 eV):
m/z (%)¼329 (Mþ, 100). HRMS (EI): calcd for C21H16N3F (Mþ)
329.13228, found 329.131861. IR (ATR, cmꢁ1):
n
¼3035 (w), 1593 (s),
1505 (s), 1440 (m), 1413 (s), 1384 (m), 1280 (m), 1228 (s), 1158 (m),
1118 (m), 1069 (w), 1030 (w), 1012 (w), 950 (m), 900 (m), 853 (m),
771 (m), 750 (s), 687 (m), 668 (m), 588 (m).
n
¼3142 (w), 2976 (m), 2214 (m), 1522 (m), 1414 (m), 1366 (m), 1206
(s), 1089 (w), 972 (m), 854 (m), 806 (m), 744 (m), 633 (s).
5.57. 5-(4-tert-Butoxystyryl)-1-tert-butyl-1H-pyrrolo[2,3-b]
5.53. 5-(4-Methoxystyryl)-3-methyl-1-phenyl-1H-pyrazolo
[3,4-b]pyridine (40b)
pyridine-3-carbonitrile (41c)
The product was isolated as a yellow solid. Yield 69%, mp
143e145 ꢀC; 1H NMR (300 MHz, CDCl3):
d
¼1.31 (s, 9H, (CH3)3), 1.76
The product was isolated as a yellow solid. Yield 70%, mp
131e133 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼2.61 (s, 3H, Me), 3.78
(s, 9H, O(CH3)3), 6.94 (d, 2H, 3J¼8 Hz, CHAr), 7.06 (d, 2H, 3J¼8 Hz,
CHAr), 7.39 (d, 2H, 3J¼8 Hz, CHAr), 7.77 (s, 1H, CHAr), 8.07 (s, 1H,
(s, 3H, OMe), 7.25e7.32 (m, 2H, CHAr), 6.97 (d, 2H, 3J¼8.5 Hz, CHAr),
7.22e7.40 (m, 3H, CHAr), 7.51e7.57 (m, 4H, CHAr), 8.27 (dd, 2H,
3J¼8.6 Hz, 4J¼1.1 Hz, CHAr), 8.49 (d, 1H, 4J¼2.0 Hz, CHAr), 8.81 (d, 1H,
CHAr), 8.46 (s, 1H, CHAr). 13C NMR (62.9 MHz, CDCl3):
d¼27.9
(OCH3)3, 28.1 (CH3)3, 57.5, 77.9, 82.1, 114.6, 120.6 (C), 122.9, 123.0,
123.3, 126.1 (CH), 126.9 (C), 128.1 (CH), 131.1 (C), 132.5, 142.7 (CH),
145.5, 154.4 (C). MS (GC, 70 eV): m/z (%)¼373 (Mþ, 6), 317 (60), 261
(100). HRMS (EI): calcd for C24H27N3O (Mþ) 373.21486, found
4J¼2.0 Hz, CHAr). 13C NMR (62.9 MHz, DMSO-d6):
¼12.2 (Me), 55.1
d
(OMe), 114.2 (CH), 117.0 (C), 119.6, 122.7, 125.2, 125.9 (CH), 127.4 (C),
127.7, 128.6, 129.1 (CH), 129.5, 139.2, 143.1 (C), 148.8 (CH), 149.4,
159.0 (C). MS (GC, 70 eV): m/z (%)¼341 (Mþ, 100). HRMS (EI): calcd
for C22H19N3O (Mþ) 341.15226, found 341.152368. IR (ATR, cmꢁ1):
373.21453. IR (ATR, cmꢁ1):
(m),1406 (m),1364 (m),1257 (s), 893 (m), 859 (m), 796 (s), 633 (m).
n
¼3134 (w), 2963 (m), 2210 (m), 1504
n
¼1593 (m), 1559 (w), 1504 (s), 1436 (m), 1414 (m), 1385 (m), 1281
(m), 1250 (m), 1213 (m), 1176 (m), 1119 (m), 1068 (w), 1019 (m), 964
(m), 951 (s), 902 (m), 581 (s), 810 (m), 773 (s), 747 (s), 688 (s), 671
(m), 588 (s).
Acknowledgements
€
Financial support by the BMBF ‘REMEDIS’-project ‘Hohere Leb-
€
ensqualitat durch neuartige Mikroimplantate’ (Grant No.
5.54. 3-Methyl-1-phenyl-5-((E)-2-(pyridin-2-yl)vinyl)-1H-pyr-
azolo[3,4-b]pyridine (40c)
03IS2081A) is gratefully acknowledged. Financial support by the
DAAD (scholarships for S.M, M.V.-H., L.S., M.S.A.A. and A.G.) is
acknowledged.
The product was isolated as a yellow oil. Yield 71%. 1H NMR
(300 MHz, DMSO-d6):
d
¼2.63 (s, 3H, Me), 7.25e7.32 (m, 2H, CHAr),
Supplementary data
7.47e7.56 (m, 4H, CHAr), 7.78e7.89 (m, 2H, CHAr), 8.27 (d, 2H,
3J¼7.6 Hz, CHAr), 8.59e8.65 (m, 2H, CHAr), 8.92 (d, 1H, 4J¼1.7 Hz,
Experimental procedures, characterization data and 1H and 13C
NMR spectra of all compounds. This material is available free of
charge via the Internet at http://pubs.acs.org. Supplementary data
related to this article can be found online at http://dx.doi.org/
10.1016/j.tet.2012.11.026.
CHAr). 13C NMR (62.9 MHz, DMSO-d6):
d
¼12.2 (Me), 117.0 (C), 119.7,
122.3, 1224, 125.3 (CH), 126.4 (C), 127.3, 128.4, 128.8, 129.1, 136.9
(CH), 139.1, 143.4, 149.5, 149.7, 154.7 (C). MS (GC, 70 eV): m/z (%)¼
312 (Mþ, 29), 311 (100). HRMS (ESI): calcd for C20H17N4 (MþH)
313.14477, found 313.14502. IR (ATR, cmꢁ1):
n
¼2919 (w), 1595 (w),
1582 (s), 1561 (m), 1504 (s), 1467 (s), 1430 (s), 1413 (s), 1384 (m),
1259 (m), 1218 (m), 1148 (m), 1115 (m), 1069 (m), 1011 (w), 964 (s),
604 (m), 849 (w), 752 (s), 739 (s), 689 (s), 670 (s), 588 (s), 568 (m).
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146e148 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼1.72 (s, 9H, (CH3)3), 7.08
(s, 2H, CHAr), 7.15e7.22 (m, 1H, CHAr), 7.24e7.32 (m, 2H, CHAr),
7.42e7.47 (m, 2H, CHAr), 7.73 (s, 1H, CHAr), 8.03 (d, 1H, 4J¼2 Hz,
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calcd for C20H19N3 (Mþ) 301.15735, found 301.1577. IR (ATR, cmꢁ1):

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CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: þ44(1223)336033; E-mail:
deposit@ccdc.cam.ac.uk, or via www.ccdc.cam.ac.uk/data_request/cif.
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