Acylation of heteroaromatic amines: Facile and efficient synthesis of a new class of 1,2,3-triazolo[4,5-b]pyridine and pyrazolo[4,3-b]pyridine derivatives

Article abstract of DOI:10.3390/molecules16053723

1,2,3-Triazolo[4,5-b]pyridines and pyrazolo[4 3-b]pyridines can be readily prepared via cyanoacetylation reactions of 5-amino-1,2,3-triazoles 1a,b and 4-aminopyrazole 2 followed by subsequent cyclization of the formed cyanoacetamides. Reactions of amines

Full text of DOI:10.3390/molecules16053723

Molecules 2011, 16, 3723-3739; doi:10.3390/molecules16053723
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Acylation of Heteroaromatic Amines: Facile and Efficient
Synthesis of a New Class of 1,2,3-Triazolo[4,5-b]pyridine and
Pyrazolo[4,3-b]pyridine Derivatives
Hamada Mohamed Ibrahim 1,2, Haider Behbehani 1,*, Saad Makhseed 1 and
Mohamed H. Elnagdi 1
1
Chemistry Department, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060,
Kuwait
2
Chemistry Department, Faculty of Science, Fayoum University, Fayoum, A. R., Egypt
* Author to whom correspondence should be addressed; E-Mail: hbehbehani@live.com;
Tel.: +965-990-630-32; Fax: +965-248-164-82.
Received: 14 March 2011; in revised form: 21 April 2011 / Accepted: 26 April 2011 /
Published: 4 May 2011
Abstract: 1,2,3-Triazolo[4,5-b]pyridines and pyrazolo[4,3-b]pyridines can be readily
prepared via cyanoacetylation reactions of 5-amino-1,2,3-triazoles 1a,b and 4-amino-
pyrazole 2 followed by subsequent cyclization of the formed cyanoacetamides. Reactions of
amines 1a,b with a mixture of p-nitrophenylacetic acid and acetic anhydride under microwave
irradiation conditions afforded the corresponding amides 15a,b that underwent cyclization to
form 1,2,3-triazolo[4,5-b]pyridines 16a,b upon heating in DMF solutions containing sodium
acetate. Reactions of 1a,b with active methylene compounds, including 17a-c, in the presence
of zeolites as catalyst also afforded 1,2,3-triazolo[4,5-b]pyridine derivatives 20a-f via the
intermediacy of triazole derivatives 19 and not 18.
Keywords: cyanoacetic acid; cyanoacetamides; triazolo[4,5-b]pyridine; pyrazolo[4,3-b]-
pyridine; p-nitrophenylacetic acid; zeolite
1. Introduction
Pyrazolo[4,3-b]pyridine and triazolo[4,5-b]pyridine derivatives are of interest for their various
applications as vasodilators, hypotensive, hypoglycemic, anti-inflammatory, analgesic, antiasthmatic,

Molecules 2011, 16
3724
antipyretic agents and as substrates of NAD glycohydrolase [1-3]. Owing to these interesting biological
activities and medicinal properties these azolopyridine derivatives have been the targets of
investigations by several research groups [4-8]. The present study describes the results of an
investigation aimed at the preparation of a new class of 1,2,3-triazolo[4,5-b]pyridine and pyrazolo[4,3-
b]pyridine derivatives. Cyanoacetylation of electron rich aromatic compounds and heteroarmatic
amines, initially described by Slatt et al., [9] has found extensive utility in efficient routes for the
preparation of 3-oxoalkanonitriles [10-15] and cyanoacetamides [16-18]. Cyanoacetylation of o-acyl
heteroarmatic amines is expected to give cyanoacetamides in which an active methylene moiety is
located in close proximity to a ketone carbonyl function. This enables ready cyclization of the products
to form fused pyridines. However, to our knowledge this synthetic approach has not been explored to
date. Below, we describe the results of an investigation of the preparation of cyanoacetamides and
arylacetamides of 5-amino-1,2,3-triazoles and 4-aminopyrazoles and their utility in the preparation of
condensed pyridines.
2. Results and Discussion
Readily obtainable (5-amino-2-phenyl-2H-1,2,3-triazol-4-yl)phenylmethanone (1a) [19], 1-(5-
amino-2-phenyl-2H-1,2,3-triazol-4-yl)ethanone (1b) [20] and 4-amino-3-benzoyl-1-phenyl-1H-
pyrazole-5-carbonitrile (2) [21] were found to react with a preheated mixture of acetic anhydride and
cyanoacetic acid under microwave irradiation conditions to yield the corresponding cyanoacetamides 3
and 4 in excellent yields. These substances undergo cyclization to generate the respective fused
pyridones 5 and 6 upon stirring at reflux for 30 min in DMF containing anhydrous sodium acetate (cf.
Scheme 1). The structure of 5a was assigned by using X-ray crystallographic analysis (cf. Table 1 and
Figure 1).
Scheme 1. Reaction of 5-amino-1,2,3-triazoles and 4-aminopyrazole with cyanoacetic acid.
O
O
NH2
CN
NH2
Ph
R
N
N
N
N
N
NCCH2CO2H
AC O,
Ph
2
Ph
1
MW
2
O
O
H
H
CN
CN
N
N
Ph
R
O
O
N
N
N
N
CN
N
Ph
Ph
DMF, anhyd. AcONa
4
3
O
O
NC
Ph
NC
NH
NH
R
N
N
N
CN
N
N
1, 3, 5 a, R = Ph
b, R = Me
Ph
6
Ph
5

Molecules 2011, 16
Figure 1. ORTEP plot of the x-ray crystallographic data determined for 5a. Crystallo-
3725
graphic data have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 804721 [22].
Table 1. Selected bond lengths and bond angles for 5a.
Bond
Bond length
1.327
Bond
Bond angle
102.5
N1-N2
N1-N3
N3-C1
N2-C2
C1-C2
C1-N4
N1-N2-C2
N1-N3-C1
N2-N1-N3
N3-C1-C2
N2-C2-C1
C1-C2-C3
1.356
1.333
1.350
1.384
100.4
117.5
111.6
108.0
1.375
121.4
The acylpyrazole 7 underwent ready cyanoacylation to afford the cyanoacetamide 8 in 93% yield.
Heating a solution of 8 in DMF containing anhydrous sodium acetate leads to production of a
substance whose structure should be either 9 or its isomer 10.
13
The actual structure of the product was assigned as 10 based on its C-NMR spectroscopic data
which showed the absence of an acetyl carbonyl carbon resonance and its replacement by a peak at
186.19 ppm. Moreover, the methyl protons’ resonance at δ = 2.12 ppm displays a HMBC cross peak
with the carbon peak at δ = 105.72 ppm that is assigned as C-6. In addition the X-ray crystallographic
analysis of this product demonstrated that it has the structure represented by 10 (cf. Scheme 2 and
Figure 2).
In a similar manner, bis-acetylpyrazole 11 is readily cyanoacylated to afford the corresponding
cyanoacetamide 12 in excellent yield. Heating a DMF solution of 12 containing anhydrous sodium
acetate afforded a product that may also have the isomeric structures represented by 13 and 14. As
before, the actual structure of the product was shown to be 14 based on its 13C-NMR spectrum, which
contained a carbonyl resonance at 202.41 ppm. This chemical shift is expected for an acyl carbonyl at
the C-3 position of the pyrazole ring and not at C-5 since in the latter case shielding provided by the
N-lone pair should make the resonance appear at a higher field (cf. Scheme 3).

Molecules 2011, 16
Scheme 2. Synthesis of pyrazolo[4,3-b]pyridine-6-carbonitrile 10.
3726
O
NC
Ph
NH
NC
O
O
O
N
O
NH2
N
NH
Ph
DMF
NCCH2CO2H
CH3
Ph
Ph
9
anhyd. AcONa
N
O
AC O,
MW
2
N
N
O
O
N
O
H
Ph
CH3
N
Ph
Ph
CH3
7
8
CN
N
N
CH3
10
Ph
Figure 2. ORTEP plot of the x-ray crystallographic data determined for 10 containing
one DMSO molecule. Crystallographic data have been deposited in the Cambridge
Crystallographic Data Centre as supplementary publication number CCDC 816562 [23].
Scheme 3. Synthesis of pyrazolo[4,3-b]pyridine-6-carbonitrile 14.
O
NC
NH
H3C
NC
O
O
O
N
NH2
O
N
DMF
H3C
NH
CH3
NCCH2CO2H
Ph
13
H3C
anhyd. AcONa
N
O
AC O,
MW
2
N
N
O
O
N
O
H
Ph
CH3
N
H3C
Ph
12
CH3
11
CN
N
N
CH3
14
Ph

Molecules 2011, 16
3727
We have previously [10] suggested that in the mechanistic pathway for the process described by
Slatt [9], the mixed anhydride is formed initially and then it reacts by nucleophilic addition of an
amine or electron rich aromatic system at the more electron deficient cyanoacetyl carbonyl. As a
consequence of this proposal, we believed that other mixed anhydrides could be used as arylacetamide
precursors provided that the reactions occur at the more electron deficient aroyl carbonyl. In fact,
heating p-nitrophenylacetic acid with acetic anhydride, followed by addition of either 1a or 1b and
heating the mixture in a microwave oven for 60 s, afforded the corresponding amides 15a and 15b that
are readily cyclized to form the respective triazolo[4,5-b]pyridines derivatives 16a and 16b upon
heating in DMF containing anhydrous sodium acetate (cf. Scheme 4).
Scheme 4. Reaction of 5-amino-1,2,3-triazoles with p-nitrophenylacetic acid.
O
O
NH2
N
O2N
CH2COOH
R
NO2
R
O
N
N
AC O,
MW
N
N
2
N
N
15
Ph
1
Ph
O2N
DMF, anhyd. AcONa
O
1, 15, 16a, R = Ph
b, R = Me
NH
R
N
N
N
16
Ph
We have explored a possible extension of this methodology, which relies on conversion of
the acetamide derivatives of 1,2,3-triazoles to their corresponding 1,2,3-triazolo[4,5-b]pyridines, by
probing the reactivity 1a,b with other active methylene compounds like 17a-c. The results of this study
showed that 1a,b underwent condensation with 17a-c in presence of zeolite catalysts, followed by heating
to produce the corresponding 1,2,3-triazolo[4,5-b]pyridine derivatives 20a-f. The structure of 20f was
assigned by X-ray crystallographic analysis. Although these products could potentially formed via the
intermediacy of either triazole 18 or 19, it is almost certain that 19 is the intermediate as attempts to
condense N-acetyl-1,2,3-triazole derivatives 21 with active methylene compounds failed. Moreover the
reaction of 20a with another molecule of 1a afforded 22, which is generated via elimination of ethanol
(cf. Figure 3 and Scheme 5).
In contrast, 1b was found to react with ethyl acetoacetate (17b) in absence of zeolite to yield a
condensation product that arises by elimination of one molecule of water. X-ray crystallographic
analysis of this substance demonstrated that it has the structure represented by 23, a product that is
formed via initial addition of the amine to the carbonyl carbon of 17b (Figure 4, Table 2). The fact that
1b reacts with ethyl acetoacetate (17b) to yield either the intermediate 23 or 19f demonstrates the
effect of the zeolite, a microporous catalyst that favors formation of slim molecules like 19 rather than
bulky ones like 23, so the latter is formed in absence of such a catalyst, Also, 23 separated from the
reaction mixture underwent cyclization in refluxing DMF containing anhydrous sodium acetate to
form 24 via loss of another molecule of water. (cf. Scheme 6).

Molecules 2011, 16
Figure 3. ORTEP plot of the x-ray crystallographic data determined for 20f. Crystallo-
3728
graphic data have been deposited in the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 815380 [24].
Scheme 5. Reaction of 5-amino-1,2,3-triazoles with active methylene compounds.
O
H
CH3
N
R
O
N
N
N
Ph
NO Reaction
COOEt
21
X
O
X
COOEt
H
X
N
17
NH2
R
1a, b
R
fusion
/ Zeolite
O
N
N
or
17a, X = COOEt
b, X =
N
N
N
N
CH3CO
c, X = PhCO
Ph
Ph
18
19
H
X
COOEt
R
20
a
b
c
d
e
f
N
O
O
N
O
X
O
N
Ph
Ph
Ph
Ph
H
N
PhCO
N
NH
R
Ph
CH3CO
for 20a
1a
Ph
N
COOEt CH3
N
N
N
N
PhCO
CH3
CH3
N
CH3CO
Ph
Ph
22
20
Scheme 6. Reaction of 1b with ethyl acetoacetate to afford 24.
O
EtOOC
H3C
CH3
N
H
COOEt
N
CH3CO
COOEt
DMF
H3C
1b
H2O
+
CH3
fusion,140 oC
anhyd. AcONa
N
N
N
N
N
23
Ph
N
24
O
Ph
H3COC
O
H
COCH3
N
NH
H3C
H3C
O
N
N
N
N
N
N
Ph
19f
Ph
20f

Molecules 2011, 16
Figure 4. ORTEP plot of the x-ray crystallographic data determined for 23. Crystallo-
3729
graphic data have been deposited in the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 805282 [25].
Table 2. Selected bond lengths and bond angles for 23.
Bond
N1-N2
N1-N3
N3-C7
N2-C8
C8-C9
N4-C7
Bond length
1.317
Bond
Bond angle
103.8
N1-N2-C8
N1-N3-C7
N2-N1-N3
N3-C7-C8
N2-C8-C7
O1-C9-C8
1.359
1.330
1.336
1.462
102.7
116.1
109.0
108.5
1.379
119.5
Inspection of the crystallographically determined bond angles and lengths of the 1,2,3-triazole rings
in both 5a, 20f and 23 indicate that the N3-N1-N2 bond angles deviate significantly from typical sp3
nitrogen values and are close to those that are associated with sp2 nitrogens. However, the N2-C8-C7
or N3-C7-C8 bond angles are close to those expected for sp3 carbons. Similar observations, made
earlier in studies of very similar systems by Elnagdi et al., [19] have been taken as evidence for the
significant contribution of charge separated resonance forms delocalizing N-1 lone pairs to the ring
carbons. Importantly, both 5a, 20f and 23 are planar substances, a fact that adds further support to the
conclusion that resonance delocalization of N-1 lone pair occurs in these systems.
3. Experimental
3.1. General
Melting points were recorded on a Griffin melting point apparatus and are reported uncorrected. IR
spectra were recorded using KBr disks using a Perkin-Elmer System 2000 FT-IR spectrophoto- meter.
1H-NMR (400 MHz) and 13C-NMR (100 MHz) spectra were recorded at 25 °C in CDCl3 or DMSO-d6
as solvent with TMS as internal standard on a Bruker DPX 400 super-conducting NMR spectrometer.

Molecules 2011, 16
3730
Chemical shifts are reported in ppm. Mass spectra were measured using a high resolution GC-MS
(DFS) thermo spectrometers with EI (70 EV). Microanalyses were performed on a LECO CHNS-932
Elemental Analyzer. Reactions were conducted under microwave irradiation in heavy-walled Pyrex
tubes (capacity 10 mL) fitted with PCS caps. Microwave heating was carried out with a single mode
cavity Explorer Microwave synthesizer (CEM Corporation, 3100 Smith Farm Road, Matthews, NC,
USA). The zeolite (≤ 45 µm) was purchased from Fluka Company with product No. 96096. The
crystal structures were determined by a Rigaku R-AXIS RAPID diffractometer using filtered
Mo-Kα radiation at Kuwait University. Compounds 1a,b, 2 and 21 were prepared using literature
procedures [19-21].
3.2. General Procedure for the Preparation of Cyanoacetamides 3, 4, 8 and 12
A solution of cyanoacetic acid (0.45 g, 5 mmol) in Ac2O (5 mL) was heated in the microwave oven
at 85 °C for 10 s then compounds 1, 2, 7 or 11 (5 mmol) were added and the reaction mixture was
heated for further 30 s at 100 °C. The reaction mixture was allowed to cool to room temperature and
the formed crystalline solid was separated by filtration and washed with cold ethanol and then hot
ethanol to afford 3, 4, 8 and 12, respectively, as pure substances.
N-(5-Benzoyl-2-phenyl-2H-1,2,3-triazol-4-yl)-2-cyanoacetamide (3a). Creamy white crystals, yield:
1
98%, m.p. 210 °C; IR (KBr): ꢀ/cm−1 3291 (NH), 2257 (CN), 1692, 1634 (2CO); H-NMR (DMSO-
d6): δ = 4.04 (s, 2H, CH2), 7.50 (t, J = 7.6 Hz, 1H, Ar-H), 7.56–7.64 (m, 4H, Ar-H), 7.73 (t, J = 7.6 Hz,
1H, Ar-H), 8.01 (d, J = 7.6 Hz, 2H, Ar-H), 8.10 (d, J =7.6 Hz, 2H, Ar-H) and 11.23 ppm (s, 1H, NH);
13C-NMR (DMSO-d6): δ 26.03 (CH2), 115.35 (CN), 118.76, 128.64, 128.68, 129.91, 129.97, 133.77,
136.04, 137.22, 138.48, 144.19, 161.40 and 185.82 ppm (Ar-C and CO); MS (EI): m/z (%) 331 (M+,
74.35), 332 (M++1, 16.90). Anal. calcd. for C18H13N5O2 (331.34): C, 65.25; H, 3.95; N, 21.14. Found:
C, 65.28; H, 4.02; N, 21.20.
N-(5-Acetyl-2-phenyl-2H-1,2,3-triazol-4-yl)-2-cyanoacetamide (3b). Buff crystals, yield: 95%,
1
m.p. 205 °C; IR (KBr): ꢀ/cm−1 3302 (NH), 2262 (CN), 1685, 1638 (2CO); H-NMR (DMSO-d6): δ
2.62 (s, 3H, CH3), 4.11 (s, 2H, CH2), 7.51 (t, J = 8.0 Hz, 1H, Ar-H), 7.62 (t, J = 8.0 Hz, 2H, Ar-H),
13
8.03 (d, J = 8.0 Hz, 2H, Ar-H) and 10.67 ppm (s, 1H, NH); C-NMR (DMSO-d6): δ 26.28 (CH2),
27.71 (CH3), 115.51 (CN), 118.79, 128.85, 129.90, 137.79, 138.46, 143.32, 161.66 and 191.69 ppm
(Ar-C and CO); MS (EI): m/z (%) 269 (M+, 100), 270 (M++1, 25.6). Anal. calcd. for C13H11N5O2
(269.26): C, 57.99; H, 4.12; N, 26.01. Found: C, 58.04; H, 4.06; N, 25.93.
N-(3-Benzoyl-5-cyano-1-phenyl-1H-pyrazol-4-yl)-2-cyanoacetamide (4). Creamy white crystals, yield:
1
93%, m.p. 234 °C; IR (KBr): ꢀ/cm−1 3259 (NH), 2227, 2263 (2CN), 1712, 1631 (2CO); H-NMR
(DMSO-d6, 25 °C ): δ = 4.13 (s, 2H, CH2), 7.57–7.72 (m, 6H, Ar-H), 7.83 (d, J = 7.6 Hz, 2H, Ar-H),
13
8.14 (d, J = 7.6 Hz, 2H, Ar-H) and 10.83 ppm (s, 1H, NH); C-NMR (DMSO-d6): δ 25.84 (CH2),
109.64, 110.24, 115.41, 124.20, 128.60, 128.75, 129.76, 130.08, 130.20, 133.74, 135.94, 137.70,
141.38, 161.56 and 186.71 ppm (2CN, Ar-C and CO); MS (EI): m/z (%) 355 (M+, 73.20), 356 (M++1,
20.35). Anal. calcd. for C20H13N5O2 (355.36): C, 67.60; H, 3.69; N, 19.71. Found: C, 67.57; H, 3.75;
N, 19.74.

Molecules 2011, 16
3731
N-(5-Acetyl-3-benzoyl-1-phenyl-1H-pyrazol-4-yl)-2-cyanoacetamide (8). Orange crystals, yield: 93%,
1
m.p. above 300 °C; IR (KBr): ꢀ/cm−1 3297 (NH), 22114 (CN), 1687 (br), 1636 (3CO); H-NMR
(DMSO-d6): δ = 2.40 (s, 3H, CH3), 4.02 (s, 2H, CH2), 7.53–7.60 (m, 7H, Ar-H), 7.69 (t, J = 7.2 Hz,
1H, Ar-H), 8.10 (d, J = 7.6 Hz, 2H, Ar-H) and 10.45 ppm (s, 1H, NH); 13C-NMR (DMSO-d6): δ 25.72
(CH2), 29.87 (CH3), 115.54 (CN), 122.13, 125.61, 128.48, 129.13, 129.17, 130.14, 133.42, 135.78,
136.26, 139.65, 142.76, 162.14, 187.20 and 189.62 ppm (Ar-C and CO); MS (EI): m/z (%) 372 (M+,
30.20), 373 (M++1, 8.57). Anal. calcd. for C21H16N4O3 (372.39): C, 67.73; H, 4.33; N, 15.05. Found:
C, 67.69; H, 4.31; N, 15.10.
2-Cyano-N-(3,5-diacetyl-1-phenyl-1H-pyrazol-4-yl)acetamide (12). Creamy white crystals, yield:
1
89%, m.p. 230 °C; IR (KBr): ꢀ/cm−1 3284 (NH), 2260 (CN), 1685 (br), 1637 (3CO); H-NMR
(DMSO-d6): δ = 2.33 (s, 3H, CH3), 2.57 (s, 3H, CH3), 4.03 (s, 2H, CH2), 7.49–7.57 (m, 5H, Ar-H) and
10.34 ppm (s, 1H, NH); 13C-NMR (DMSO-d6): δ 26.16 (CH2), 27.72 (CH3), 30.22 (CH3), 116.01
(CN), 125.95, 127.94, 129.63, 129.68, 137.18, 140.05, 143.17, 162.64, 190.18 and 193.80 ppm (Ar-C
and CO); MS (EI): m/z (%) 310 (M+, 55.1), 311 (M++1, 10.75). Anal. calcd. for C16H14N4O3 (310.31):
C, 61.93; H, 4.55; N, 18.05. Found: C, 61.88; H, 4.57; N, 17.98.
3.3. General Procedure for the Cyclization of Cyanoacetamides to Azolo Pyridines 5, 6, 10 and 14
Independent solutions of cyanoacetamides 3, 4, 8 and 12 (5 mmol), in DMF (10 mL) containing
anhydrous sodium acetate (1 g) were stirred at reflux for 1 h. Then, the reaction mixture was cooled to
room temperature and poured into ice cold water. The formed crude products were collected by
filtration, washed with water and recrystallized from the appropriate solvent to afford the
corresponding azolo pyridine derivatives 5, 6, 10 and 14, respectively.
5-Oxo-2,7-diphenyl-4,5-dihydro-2H-[1,2,3]triazolo[4,5-b]pyridine-6-carbonitrile (5a). Recrystallized
from a EtOH/dioxane (1:1) mixture as yellow crystals, yield: 87%, m.p. above 300 °C; IR (KBr):
1
ꢀ/cm−1 3437 (NH), 2230 (CN), 1651 (CO); H-NMR (DMSO-d6): δ 7.47 (t, J = 7.6 Hz, 1H, Ar-H),
7.56 (t, J = 8.0 Hz, 2H, Ar-H), 7.65–7.67 (m, 3H, Ar-H), 7.89 (d, J = 7.6 Hz, 2H, Ar-H), 7.97 (d,
13
J = 8.0 Hz, 2H, Ar-H) and 13.30 ppm (s, 1H, NH); C-NMR (DMSO-d6): δ 105.22, 115.73 (CN),
119.10, 128.81, 129.21, 129.53, 129.95, 130.53, 131.14, 131.51, 138.62, 148.07, 151.23 and 160.14
ppm (Ar-C and CO); MS (EI): m/z (%) 313 (M+, 100), 314 (M++1, 21.40). Anal. calcd. for C18H11N5O
(313.32): C, 69.00; H, 3.54; N, 22.35. Found: C, C, 69.03; H, 3.48; N, 22.39.
3.3.1. Crystallographic Analysis for 5a
The crystals were mounted on a glass fiber. All measurements were performed on a Rigaku
R-AXIS RAPID diffractometer using filtered Mo-Kα radiation. The data were collected at a
temperature of 20 ± 1 °C to a maximum 2θ value of 55.0° using the ω scanning technique. The
structure was solved by charge flipping method and expanded using Fourier techniques. The
non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model.

Molecules 2011, 16
3732
3.3.2. Crystal Data
C18H11N5O, M = 313.32, triclinic, a = 6.861(4)Å, b = 11.229(6)Å, c = 12.987(7)Å,
V = 869.3(8)Å3, α = 110.560(9)°, β = 103.584(9)°, γ = 100.858(9)°, space group: P-1, Z = 2,
Dcalc = 1.365 g cm−3 , No. of reflection measured 3956, 2θmax = 55.0°, R1 = 0.12. Figure 1 illustrates
the structure as determined. Full data can be obtained on request from the CCDC [22].
7-Methyl-5-oxo-2-phenyl-4,5-dihydro-2H-[1,2,3]triazolo[4,5-b]pyridine-6-carbonitrile (5b). Recrystallized
from an EtOH/dioxane (2:1) mixture as yellow crystals, yield: 83%, m.p. above 300 °C; IR (KBr):
1
ꢀ/cm−1 3410 (NH), 2228 (CN), 1658 (CO); H-NMR (DMSO-d6,): δ = 2.64 (s, 3H, CH3), 7.48 (t,
J = 8.0 Hz, 1H, Ar-H), 7.58 (t, J = 8.0 Hz, 2H, Ar-H), 8.00 (d, J = 8.0 Hz, 2H, Ar-H), and 13.04 ppm
13
(s, 1H, NH); C-NMR (DMSO-d6): δ = 16.94 (CH3), 107.37, 115.30 (CN), 119.39, 129.57, 130.41,
131.96, 139.07, 147.66, 152.55 and 160.07 ppm (Ar-C and CO); MS (EI): m/z (%) 251 (M+, 100), 252
(M++1, 30.58). Anal. calcd. for C13H9N5O (251.25): C, 62.15; H, 3.61; N, 27.87. Found: C, 62.19; H,
3.55; N, 27.91.
5-Oxo-2,7-diphenyl-4,5-dihydro-2H-pyrazolo[4,3-b]pyridine-3,6-dicarbonitrile (6). Recrystallized
from a EtOH/dioxane (1:1) mixture as beige crystals, yield: 80%, m.p. above 300 °C; IR (KBr):
1
ꢀ/cm−1 3375 (NH), 2227 (br, 2CN), 1656 (CO); H-NMR (DMSO-d6): δ 7.64–7.66 (m, 6H, Ar-H),
7.79 (d, J = 7.6 Hz, 2H, Ar-H), 7.85 (d, J = 7.2 Hz, 2H, Ar-H) and 13.30 ppm (s, 1H, NH); 13C-NMR
(DMSO-d6): δ = 100.37, 105.99, 109.67, 115.83, 124.37, 129.02, 129.91, 130.18, 130.77, 131.22,
131.71, 133.12, 135.46, 138.11, 152.78 and 159.81 ppm (2CN, Ar-C and CO); MS (EI): m/z (%) 337
(M+, 100), 338 (M++1, 25.0). Anal. calcd. for C20H11N5O (337.34): C, 71.21; H, 3.29; N, 20.76. Found:
71.19; H, 3.36; N, 20.83.
3-Benzoyl-7-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile (10). Rec-
rystallized from DMSO as brown crystals, yield: 77%, m.p. 238–240 °C; IR (KBr): ꢀ/cm−1 3381
1
(NH), 2223 (CN), 1681, 1658 (2CO); H-NMR (DMSO-d6 ): δ 2.12 (s, 3H, CH3), 7.56–7.81 (m, 8H,
13
Ar-H), 8.22 (d, J = 7.2 Hz, 2H, Ar-H) and 12.02 ppm (s, 1H, NH); C-NMR (DMSO-d6): δ 18.23
(CH3), 105.72, 115.34 (CN), 126.28, 127.04, 127.57, 128.59, 129.15, 129.45, 129.60, 130.07, 130.63,
133.52, 136.00, 138.95, 159.17 and 186.19 ppm (Ar-C and CO); MS (EI): m/z (%) 354 (M+, 100), 355
(M++1, 27.1). Anal. calcd. for C21H14N4O2 (354.37): C, 71.18; H, 3.95; N, 15.81. Found: 71.24; H,
4.02; N, 15.77.
3.3.3. Crystallographic Analysis for 10
The crystals were mounted on a glass fiber. All measurements were performed on a Rigaku
R-AXIS RAPID diffractometer using filtered Mo-Kα radiation. The data were collected at a
temperature of 20 ± 1 °C to a maximum 2θ value of 55.0° using the ω scanning technique. The
structure was solved by charge flipping method and expanded using Fourier techniques. The
non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model.

Molecules 2011, 16
3733
3.3.4. Crystal Data
C21H14N4O2+ one DMSO molecule, M = 354.37, monoclinic, a = 11.518(2) Å, b = 9.386(2)Å,
c = 19.655(3)Å, V = 2123.5(5) Å3, α = γ = 90.00° , β = 92.069(7)°, space group: P21/n, Z = 4,
Dcalc = 1.353g cm−3, No. of reflection measured 4731, 2θmax = 55.0 °, R1 = 0.1088. Figure 2 illustrates
the structure as determined. Full data can be obtained on request from the CCDC [23].
3-Acetyl-7-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile(14). Recrystallized
from DMF as buff crystals, yield: 80%, m.p. above 300 °C; IR (KBr): ꢀ/cm−1 3183 (NH), 2221 (CN),
1
1673, 1639 (2CO); H-NMR (DMSO-d6): δ 2.15 (s, 3H, CH3), 2.60 (s, 3H, CH3), 7.49–7.71 (m, 5H,
13
Ar-H) and 11.91 ppm (s, 1H, NH); C-NMR (TFA-d): δ 19.82 (CH3), 27.25 (CH3), 107.63, 116.18
(CN), 125.08, 129.39, 131.18, 131.62, 132.45, 134.48, 138.03, 140.46, 154.60 and 202.41 ppm (Ar-C
and CO); MS (EI): m/z (%) 292 (M+, 100), 293 (M++1, 20.45). Anal. calcd. for C16H12N4O2 (292.30):
C, 65.75; H, 4.14; N, 19.17. Found: C, 65.81; H, 4.17; N, 19.19.
3.4. General Procedure for the Preparation of 15
Independent solutions of p-nitrophenylacetic acid (0.9 g, 5 mmol) in Ac2O (5 mL) were heated in a
microwave oven at 100 °C for 20 s. To these mixtures, 1a,b (5 mmol) were added and the mixtures
were heated for further 60 s at the same temperature. The reaction mixtures were cooled to room
temperature the crystalline solid formed were separated by filtration and washed by cold ethanol and
then hot ethanol to afford 15a,b, respectively, as pure substances.
N-(5-Benzoyl-2-phenyl-2H-1,2,3-triazol-4-yl)-2-(4-nitrophenyl)acetamide (15a). White crystals, yield:
90%, m.p. 196 °C; IR (KBr): ꢀ/cm−1 3294 (NH), 1690, 1632 (2CO); 1H-NMR (CDCl3): δ 4.02 (s, 2H,
CH2), 7.43 (t, J = 7.6 Hz, 1H, Ar-H), 7.50–7.62 (m, 6H, Ar-H), 7.68 (t, J = 7.6 Hz, 1H, Ar-H), 8.15 (d,
J = 8.0 Hz, 2H, Ar-H), 8.27 (d, J = 7.6 Hz, 2H, Ar-H), 8.43 (d, J = 8.0 Hz, 2H, Ar-H) and 10.02 ppm
(s, 1H, NH); 13C-NMR (CDCl3): δ 43.90 (CH2), 119.47, 124.05, 128.59, 128.76, 129.41, 130.41,
130.54, 132.99, 133.95, 135.98, 138.99, 141.04, 147.40, 148.35, 166.42 and 187.60 ppm (Ar-C and
CO); MS (EI): m/z (%) 427 (M+, 56.75), 428 (M++1, 15.55). Anal. calcd. for C23H17N5O4 (427.42): C,
64.63; H, 4.01; N, 16.39. Found: 64.59; H, 3.94; N, 16.43.
N-(5-Acetyl-2-phenyl-2H-1,2,3-triazol-4-yl)-2-(4-nitrophenyl)acetamide (15b). Beige crystals, yield:
1
87%, m.p. 207 °C; IR (KBr): ꢀ/cm−1 3358 (NH), 1686, 1641(2CO); H-NMR (CDCl3): δ 2.69 (s, 3H,
CH3), 3.99 (s, 2H, CH2), 7.43 (t, J = 7.6 Hz, 1H, Ar-H), 7.51 (t, J = 7.6 Hz, 2H, Ar-H), 7.60 (d,
J = 8.0 Hz, 2H, Ar-H), 8.12 (d, J = 7.6 Hz, 2H, Ar-H), 8.26 (d, J = 8.0 Hz, 2H, Ar-H) and 9.51 ppm (s,
1H, NH); 13C-NMR (CDCl3): δ 27.02 (CH3), 43.81 (CH2), 119.38, 124.06, 128.74, 129.42, 130.56,
133.67, 138.99, 140.97, 146.14, 147.43, 166.43 and 195.23 ppm (Ar-C and CO); MS (EI): m/z (%)
365 (M+, 27.35), 366 (M++1, 6.91). Anal. calcd. for C18H15N5O4 (365.35): C, 59.18; H, 4.14; N, 19.17.
Found: C, 59.24; H, 4.07; N, 19.14.

Molecules 2011, 16
3734
3.5. General Procedure for the Preparation of 16
Independent solutions of amides 15a,b (5 mmol) in DMF (10 mL) containing anhydrous sodium
acetate (1 g) were stirred at reflux for 1 h. Then, the reaction mixtures were cooled to rt and poured
onto ice cold water. The crude products were collected by filtration, washed with water and
recrystallized from the appropriate solvent to afford the corresponding azolo pyridine derivatives
16a,b respectively.
6-(4-Nitrophenyl)-2,7-diphenyl-2,4-dihydro[1,2,3]triazolo[4,5-b]pyridin-5-one (16a). Recrystallized
from an EtOH/dioxane (1:1) mixture as yellow crystals, yield: 82%, m.p. 302 °C; IR (KBr): ꢀ/cm−1
1
3435 (NH), 1645 (CO); H-NMR (DMSO-d6): δ 7.32–7.35 (m, 5H, Ar-H), 7.44 (d, J = 8.0 Hz, 3H,
Ar-H), 7.56 (t, J = 7.6 Hz, 2H, Ar-H), 8.00 (d, J = 8.0 Hz, 2H, Ar-H), 8.10 (d, J = 8.0 Hz, 2H, Ar-H) and
12.90 ppm (s, 1H, NH); 13C-NMR (DMSO-d6): δ 118.62, 122.51, 128.18, 128.25, 128.89, 129.82,
129.86, 130.66, 132.29, 132.64, 133.14, 139.02, 140.68, 142.80, 146.36, 146.65 and 161.83 ppm
(Ar-C and CO); MS (EI): m/z (%) 409 (M+, 100), 410 (M++1, 30.72). Anal. calcd. for C23H15N5O3
(409.41): C, 67.48; H, 3.69; N, 17.11. Found: C, 67.51; H, 3.70; N, 17.08.
7-Methyl-6-(4-Nitrophenyl)-2-phenyl-2,4-dihydro[1,2,3]triazolo[4,5-b]-pyridin-5-one (16b). Recrysta-
llized from an EtOH/dioxane (2:1) mixture as buff crystals, yield: 85%, m.p. 298 °C; IR (KBr): ꢀ/cm−1
1
3285 (NH), 1643 (CO); H-NMR (DMSO-d6): δ = 2.30 (s, 3H, CH3), 7.46 (t, J = 7.6 Hz, 1H, Ar-H),
7.58–7.63 (m, 4H, Ar-H), 8.05 (d, J = 8.0 Hz, 2H, Ar-H), 8.30 (d, J = 8.0 Hz, 2H, Ar-H), and
12.67 ppm (s, 1H, NH); 13C-NMR (DMSO-d6): δ 15.16 (CH3), 118.48, 122.99, 128.13, 129.84, 131.14,
131.86, 133.08, 138.08, 139.10, 142.38, 145.94, 146.81 and 161.63 ppm (Ar-C and CO); MS (EI): m/z
(%) 347 (M+, 100), 348 (M++1, 21.87). Anal. calcd. for C18H13N5O3 (347.34): C, 62.25; H, 3.77; N,
20.16. Found: C, 62.19; H, 3.81; N, 20.12.
3.6. General Procedure for the Preparation of 20a-f
Independent mixtures of 5-amino-1,2,3-triazoles 1a,b (10 mmol), active methylene compounds
17a-c (15 mmol) and zeolite (10% by weight) were heated at 150 °C for 1 h. Dioxane was added to the
reaction mixtures followed by filtration to remove the zeolite. The crystals formed upon cooling the
filtrates were collected by filtration and washed with methanol.
Ethyl-5-oxo-2,7-diphenyl-4,5-dihydro-2H-[1,2,3]triazolo[4,5-b]pyridine-6-carboxylate (20a). Pale
1
orange crystals, yield: 76%, m.p. 205 °C; IR (KBr): ꢀ/cm−1 3391(NH), 1733, 1650 (2CO); H-NMR
(DMSO-d6): δ 1.30 (t, J = 7.2 Hz, 3H, CH3CH2), 4.13 (q, J = 7.2 Hz, 2H, CH3CH2), 7.46 (t, J = 7.6 Hz,
1H, Ar-H), 7.56–7.60 (m, 5H, Ar-H), 7.65–7.67 (m, 2H, Ar-H), 8.00 (d, J = 7.6 Hz, 2H, Ar-H) and
13
13.00 ppm (s, 1H, NH); C-NMR (DMSO-d6): δ 13.65 (CH3CH2), 61.17 (CH3CH2), 118.81, 128.54,
128.57, 128.67, 129.86, 129.87, 130.10, 130.85, 132.11, 138.97, 140.27, 146.93, 160.14 and 165.01
ppm (Ar-C and CO); MS (EI): m/z (%) 360 (M+, 100), 361 (M++1, 24.55). Anal. Calcd. for
C20H16N4O3 (360.38): C, 66.66; H, 4.48; N, 15.55. Found: C, 66.72; H, 4.40; N, 15.49.
6-Benzoyl-2,7-diphenyl-2,4-dihydro[1,2,3]triazolo[4,5-b]pyridin-5-one (20b). Canary yellow crystals,
yield: 80%, m.p. above 300 °C; IR (KBr): ꢀ/cm−1 3423 (NH), 1672, 1644 (2CO); 1H-NMR (DMSO-

Molecules 2011, 16
3735
d6): δ 7.39–7.41 (m, 3H, Ar-H), 7.46 (t, J = 8.0 Hz, 3H, Ar-H), 7.52–7.62 (m, 5H, Ar-H), 7.89 (d,
J = 8.0 Hz, 2H, Ar-H), 8.02 (d, J = 8.0 Hz, 2H, Ar-H) and 12.99 ppm (s, 1H, NH); 13C-NMR (DMSO-
d6): δ = 118.79, 128.14, 128.45, 128.88, 129.01, 129.73, 129.89, 131.40, 131.67, 132.08, 133.17,
133.90, 136.41, 139.06, 140.49, 147.13, 161.25 and 193.91 ppm (Ar-C and CO); MS (EI): m/z (%)
392 (M+, 100), 393 (M++1, 27.84). Anal. calcd. for C24H16N4O2 (392.42): C, 73.46; H, 4.11; N, 14.28.
Found: C, 73.52; H, 4.08; N, 14.36.
6-Acetyl-2,7-diphenyl-2,4-dihydro[1,2,3]triazolo[4,5-b]pyridin-5-one (20c). Pale yellow crystals,
1
yield: 79%, m.p. 249 °C; IR (KBr): ꢀ/cm−1 3299 (NH), 1709, 1646 (2CO); H-NMR (DMSO-d6): δ
2.33 (s, 3H, CH3), 7.47 (t, J = 7.6 Hz, 1H, Ar-H), 7.53–7.60 (m, 7H, Ar-H), 7.99 (d, J = 7.6 Hz, 2H,
Ar-H) and 12.96 ppm (s, 1H, NH); 13C-NMR (DMSO-d6): δ 31.57 (CH3), 118.72, 128.43, 128.60,
128.96, 129.76, 129.80, 131.38, 132.13, 133.69, 138.95, 139.20, 146.64, 160.80 and 201.47 ppm
(Ar-C and CO); MS (EI): m/z (%) 330 (M+, 100), 331(M++1, 19.84). Anal. calcd. for C19H14N4O2
(330.35): C, 69.08; H, 4.27; N, 16.96. Found: C, 68.98; H, 4.35; N, 16.88.
Ethyl-7-methyl-5-oxo-2-phenyl-4,5-dihydro-2H-[1,2,3]triazolo[4,5-b]pyridine-6-carboxylate
(20d).
Yellow crystals, yield: 82%, m.p. 219 °C; IR (KBr): ꢀ/cm−1 3263 (NH), 1735, 1659 (2CO); 1H-NMR
(DMSO-d6): δ 1.31 (t, J = 7.2 Hz, 3H, CH3CH2), 2.44 (s, 3H, CH3), 4.33 (q, J = 7.2 Hz, 2H, CH3CH2),
7.47 (t, J = 8.0 Hz, 1H, Ar-H), 7.60 (t, J = 8.0 Hz, 2H, Ar-H), 8.04 (d, J = 8.0 Hz, 2H, Ar-H) and 12.74
ppm (s, 1H, NH); 13C-NMR (DMSO-d6): δ 14.04 (CH3CH2), 14.31(CH3), 61.28 (CH3CH2), 118.52,
127.22, 128.33, 129.61, 129.76, 131.86, 138.90, 146.12, 159.82 and 165.08 ppm (Ar-C and CO); MS
(EI): m/z (%) 298 (M+, 61.90), 299 (M++1, 12.75). Anal. calcd. for C15H14N4O3 (298.30): C, 60.40; H,
4.73; N, 18.78. Found: C, 60.33; H, 4.84; N, 18.76.
6-Benzoyl-7-methyl-2-phenyl-2,4-dihydro[1,2,3]triazolo[4,5-b]pyridin-5-one (20e). Creamy white
crystals, yield: 79%, m.p. 298 °C; IR (KBr): ꢀ/cm−1 3429 (NH), 1668, 1641 (2CO); 1H-NMR (DMSO-
d6): δ 2.30 (s, 3H, CH3), 7.47 (t, J = 7.6 Hz, 1H, Ar-H), 7.55 (t, J = 8.0 Hz, 2H, Ar-H), 7.61 (t,
J = 7.6 Hz, 2H, Ar-H), 7.69 (t, J = 7.6 Hz, 1H, Ar-H), 7.92 (d, J = 7.6 Hz, 2H, Ar-H), 8.06 (d,
J = 8.0 Hz, 2H, Ar-H) and 12.75 ppm (s, 1H, NH); 13C-NMR (DMSO-d6): δ 14.18(CH3), 118.62,
128.34, 129.01, 129.04, 129.89, 131.90, 132.57, 134.12, 136.24, 138.83, 139.08, 146.45, 161.04 and
194.41 ppm (Ar-C and CO); MS (EI): m/z (%) 330 (M+, 100), 331 (M++1, 22.88). Anal. calcd. for
C19H14N4O2 (330.35): C, 69.08; H, 4.27; N, 16.96. Found: C, 69.15; H, 4.21; N, 17.02.
6-Acetyl-7-methyl-2-phenyl-2,4-dihydro[1,2,3]triazolo[4,5-b]pyridin-5-one (20f). Yellow crystals,
1
yield: 86%, m.p. 242 °C; IR (KBr): ꢀ/cm−1 3435 (NH), 1694, 1648 (2CO); H-NMR (DMSO-d6): δ
2.36 (s, 3H, CH3), 2.47 (s, 3H, CH3), 7.44 (t, J = 8.0 Hz, 1H, Ar-H), 7.57 (t, J = 8.0 Hz, 2H, Ar-H),
13
8.00 (d, J = 8.0 Hz, 2H, Ar-H) and 12.71 ppm (s, 1H, NH); C-NMR (DMSO-d6): δ 13.98 (CH3),
30.98 (CH3), 118.57, 128.34, 129.79, 132.46, 133.31, 138.53, 138.95, 146.09, 160.99 and 201.93 ppm
(Ar-C and CO); MS (EI): m/z (%) 268 (M+, 76.45), 269 (M++1, 13.89). Anal. calcd. for C14H12N4O2
(268.28): C, 62.68; H, 4.51; N, 20.88. Found: C, 62.74; H, 4.47; N, 20.94.

Molecules 2011, 16
3736
3.6.1. Crystallographic Analysis for 20f
The crystals were mounted on a glass fiber. All measurements were performed on a Rigaku
R-AXIS RAPID diffractometer using filtered Mo-Kα radiation. The data were collected at a
temperature of 20 ± 1 °C to a maximum 2θ value of 55.0° using the ω scanning technique. The
structure was solved by charge flipping method and expanded using Fourier techniques. The
non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model.
3.6.2. Crystal Data
C14H12N4O2, M = 268.28, triclinic, a = 4.003(4)Å, b = 13.07(2)Å, c = 13.49(2)Å, V = 643(1)Å3, α =
113.65(1)°, β = 91.13(2)°, γ = 94.89(2)°, space group: P-1, Z= 2, Dcalc = 1.385 g cm−3, No. of reflection
measured 2935, 2θmax= 55.0°, R1= 0.053. Figure 3 illustrates the structure as determined. Full data
can be obtained on request from the CCDC [24].
3.7. N-(5-Benzoyl-2-phenyl--2H-1,2,3-triazol-4-yl)-5-oxo-2,7-diphenyl-4,5-dihydro-2H-[1,2,3]-
triazolo[4,5-b]pyridine-6-carboxamide (22)
A mixture of 5-amino-1,2,3-triazole 1a (0.66 g, 2.5 mmol), pyrazolo[4,3-b]pyridine 20a (0.9 g,
2.5 mmol) and zeolite (10% by weight) in dioxane (10 mL) was stirred at reflux for 2 h, filtered to
remove the zeolite, and cooled to room temperature. The solid which formed was collected by
filtration, washed with ethanol, and recrystallized from dioxane giving beige crystals, yield: 68%, m.p.
1
271 °C; IR (KBr): ꢀ/cm−1 3404, 3314 (2NH), 1711, 1663, 1635 (3CO); H-NMR (DMSO-d6):
δ = 7.49–7.73 (m, 14H, Ar-H), 8.01–8.12 (m, 6H, Ar-H), 11.48 (s, 1H, NH) and 12.93 ppm (s, 1H,
NH); 13C-NMR (DMSO-d6): δ 118.83, 128.52, 128.60, 128.70, 129.04, 129.75, 129.90, 130.87,
131.39, 132.26, 133.67, 136.35, 136.46, 138.61, 139.01, 140.66, 144.50, 147.02, 161.14, 162.51, and
185.99 ppm (Ar-C and CO); MS (EI): m/z (%) 578 (M+, 46.25), 579 (M++1, 17.30). Anal. calcd. for
C33H22N8O3 (578.60): C, 68.51; H, 3.83; N, 19.37. Found: C, 68.44; H, 3.87; N, 19.42.
3.8. (E)-Ethyl-3-(5-acetyl-2-phenyl-2H-1,2,3-triazol-4-ylamino)but-2-enoate (23)
A mixture of 5-amino-1,2,3-triazole 1b (2.02 g, 10 mmol) and ethyl acetoacetate (1.95 g, 15 mmol)
was fused at 140 °C for 20 min. The mixture was poured into water and cooled to room temperature.
The crude solid which formed was collected by filtration, washed with cold ethanol, and recrystallized
from ethanol to give creamy white crystals, yield: 71%, m.p. 158 °C; IR (KBr): ꢀ/cm−1 3435 (NH),
1672, 1620 (2CO); 1H-NMR (CDCl3): δ 1.30 (t, J = 7.2 Hz, 3H, CH3CH2), 2.50 (s, 3H, CH3), 2.68 (s,
3H, CH3CO), 4.27 (q, J = 7.2 Hz, 2H, CH3CH2), 4.93 (s, 1H, olefinic CH), 7.38(t, J = 8.0 Hz, 1H,
Ar-H), 7.49 (t, J = 8.0 Hz, 2H, Ar-H), 8.05 (d, J = 8.0 Hz, 2H, Ar-H) and 11.95 ppm (s, 1H, NH);
13C-NMR (CDCl3): δ 14.55 (CH3CH2), 22.75 (CH3), 26.84 (CH3), 59.40 (CH3CH2), 92.61, 118.76,
128.05, 129.35, 133.81, 139.16, 149.00, 154.87, 168.94 and 193.51 ppm (Ar-C, olefinic C and CO);
MS (EI): m/z (%) 314 (M+, 100), 315 (M++1, 22.85). Anal. Calcd. for C16H18N4O3 (314.35): C, 61.14;
H, 5.77; N, 17.82. Found: C, 61.17; H, 5.75; N, 17.86.

Molecules 2011, 16
3737
3.8.1. Crystallographic Analysis for 23
The crystals were mounted on a glass fiber. All measurements were performed on a Rigaku
R-AXIS RAPID diffractometer using filtered Mo-Kα radiation. The data were collected at a
temperature of 20 ± 1 °C to a maximum 2θ value of 55.0° using the ω scanning technique. The
structure was solved by charge flipping method and expanded using Fourier techniques. The
non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model.
3.8.2. Crystal Data
C16H18N4O3, M = 314.35, monoclinic, a = 4.949(2)Å, b = 14.130(4)Å, c = 23.315(7)Å,
V = 1629.14(9)Å3, α = γ = 90.00°, β = 92.190(2)°, space group: P21/n, Z = 4, Dcalc = 1.282 g cm−3, No.
of reflection measured 3733, 2θmax= 55.0°, R1= 0.0807. Figure 4 illustrates the structure as
determined. Full data can be obtained on request from the CCDC [25].
3.9. Ethyl-5,7-dimethyl-2-phenyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-carboxylate (24)
A solution of 23 (1.57 g, 5 mmol) in DMF (10 mL) containing anhydrous sodium acetate (1 g) was
stirred at reflux for 1 h. The mixture was cooled to room temperature and poured into ice cold water.
The formed solid was collected by filtration, washed with water and recrystallized from EtOH/H2O
1
(2:1) to give pale brown crystals, yield: 71%, m.p. 78 °C; IR (KBr): ꢀ/cm−1 1719 (CO); H-NMR
(DMSO-d6): δ 1.46 (t, J = 7.2 Hz, 3H, CH3CH2), 2.74 (s, 3H, CH3), 2.75 (s, 3H, CH3), 4.50 (q,
J = 7.2 Hz, 2H, CH3CH2), 7.49 (t, J = 8.0 Hz, 1H, Ar-H), 7.57 (t, J = 8.0 Hz, 2H, Ar-H) and 8.40 ppm
(d, J = 8.0 Hz, 2H, Ar-H); 13C-NMR (DMSO-d6): δ 14.27 (CH3), 14.71(CH3), 24.42 (CH3), 61.89
(CH2), 120.59, 128.72, 129.50, 129.55, 136.67, 137.78, 140.14, 154.96, 158.88 and 168.10 pm (Ar-C
and CO); MS (EI): m/z (%) 296 (M+, 100), 297 (M++1, 29.8). Anal. calcd. for C16H16N4O2 (296.33):
C, 64.85; H, 5.44; N, 18.91. Found: C, 64.78; H, 5.51; N, 18.94.
4. Conclusions
A simple and efficient approach to the preparation of condensed pyridines, utilizing o-acyl
heteroarmatic amines as precursors, has been developed. By using the new approach, difficulties with
the classical synthesis of these substances from active methylene compounds and o-aminonitriles are
overcome.
Acknowledgments
Support of this work was provided by the University of Kuwait through a research grant (SC03/07).
The facilities of Analab/SAF supported by research grants GS01/01, GS01/05, GS01/03 and GS03/08
are gratefully acknowledged.

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22. Crystallographic data for 5a (ref. CCDC 804721) can be obtained on request from the director,
Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EW, UK.
23. Crystallographic data for 10 (ref. CCDC 816562) can be obtained on request from the director,
Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EW, UK.
24. Crystallographic data for 20f (ref. CCDC 815380) can be obtained on request from the director,
Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EW, UK.
25. Crystallographic data for 23 (ref. CCDC 805282) can be obtained on request from the director,
Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EW, UK.
Sample Availability: Samples of the compounds 3, 5, 15, 16 and 20 a-f are available from the authors.
© 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).