Synthesis, reactions, and characterization of 6-amino-4-(benzo[b]thiophen- 2-YL)-2-thioxo-1, 2-dihydropyridine-3, 5-dicarbonitrile

Article abstract of DOI:10.1080/10426507.2011.590562

Benzothiophene-2-carbaldehyde 1 reacted with 2-cyanoethanethioamide 2 in 1:2 molar ratios to give the corresponding 6-amino-4-(benzo[b]thiophen-2-yl)-2- thioxo-1, 2-dihydropyridine-3,5-dicarbonitrile 6. The synthetic potentiality of compound 6 was investigated via its reaction with active halogen-containing reagents to afford the corresponding thieno[2,3-b]pyridine derivatives 11a,b, 14, 16, and 19. Also, compound 6 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 21. Compound 21 condensed with 4-(2-thienyl)benzaldehyde to afford pyrazolo[3,4-b]pyridine derivative 23. Structural elucidation of all the newly synthesized heterocyclic compounds was based on elemental analyses, IR, ¹H NMR, and mass spectra. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Full text of DOI:10.1080/10426507.2011.590562

This article was downloaded by: [University of York]
On: 12 April 2013, At: 04:30
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Synthesis, Reactions, and
Characterization of 6-Amino-4-
(Benzo[b]Thiophen-2-YL)-2-Thioxo-1, 2-
Dihydropyridine-3, 5-Dicarbonitrile
Azza M. Abdel-Fattah a & Fawzy A. Attaby a
a Chemistry Department, Faculty of Science, Cairo University, Giza,
Egypt
Version of record first published: 27 Mar 2012.
To cite this article: Azza M. Abdel-Fattah & Fawzy A. Attaby (2012): Synthesis, Reactions, and
Characterization of 6-Amino-4-(Benzo[b]Thiophen-2-YL)-2-Thioxo-1, 2-Dihydropyridine-3, 5-
Dicarbonitrile, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:5, 555-563
To link to this article: http://dx.doi.org/10.1080/10426507.2011.590562
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 187:555–563, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.590562
SYNTHESIS, REACTIONS, AND CHARACTERIZATION
OF 6-AMINO-4-(BENZO[b]THIOPHEN-2-YL)-2-THIOXO-1,
2-DIHYDROPYRIDINE-3, 5-DICARBONITRILE
Azza M. Abdel-Fattah and Fawzy A. Attaby
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt
GRAPHICAL ABSTRACT
Abstract Benzothiophene -2- carbaldehyde 1 reacted with 2-cyanoethanethioamide 2 in
1:2 molar ratios to give the corresponding 6-amino-4-(benzo[b]thiophen-2-yl)-2-thioxo-1,
2-dihydropyridine-3,5-dicarbonitrile 6. The synthetic potentiality of compound 6 was inves-
tigated via its reaction with active halogen-containing reagents to afford the corresponding
thieno[2,3-b]pyridine derivatives 11a,b, 14, 16, and 19. Also, compound 6 reacted with hy-
drazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 21. Compound 21 condensed
with 4-(2-thienyl)benzaldehyde to afford pyrazolo[3,4-b]pyridine derivative 23. Structural elu-
cidation of all the newly synthesized heterocyclic compounds was based on elemental analyses,
IR, 1H NMR, and mass spectra.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords
3-(Benzo[b]thiophen-2-yl)-2-cyanoprop-2-enethioamide;
2-cyano-
ethanethioamide; thieno[2,3-b]pyridine and pyrazolo[3,4-b]pyridine
Received 7 April 2011; accepted 19 May 2010.
Address correspondence to Dr. Azza M. Abdel Fattah, Chemistry Department, Faculty of Science, Cairo
University, Giza 12613, Egypt. E-mail: azza682000@yahoo.com
555

556
A. M. ABDEL-FATTAH AND F. A. ATTABY
INTRODUCTION
Pyridine-2(1H)-thiones containing two CN groups, NH, and C S moieties are
promising synthons in organic synthesis, in particular, for obtaining biologically active
compounds. In conjunction with our previous work,1–12 and the reported biological activ-
ity of each of 2-thioxopyridines,13–15 thienopyridines,16,17and benzothiophene,18 we were
interested to synthesize several derivatives of these ring systems required for chemical
transformations and a medicinal chemistry program.
RESULTS AND DISCUSSION
The present work reports a possible routes to the synthesis of 6-amino-4-
(benzo[b]thiophen-2-yl)-2-thioxo-1, 2-dihydropyridine-3, 5-dicarbonitrile 6 as a starting
material. It has been found that benzothiophene 2 carbaldehyde 1 reacted with 2-
cyanoethanethioamide 2 to afford 3-(benzo[b]thiophen-2-yl)-2-cyanoprop-2-enethioamide
3 which in turn reacted with a second mole of 2 to give the reaction product 6 via the
nonisolable structures 4 and 5. The IR (cm−1) of this reaction product showed the bands of
1
NH2, NH, and CN functions, and its H NMR (δ ppm) revealed the signals of NH2, NH,
and aromatic protons. Moreover, its mass spectrum gave m/z = 308, which corresponded
to the molecular formula C15H8N4S2 of the assigned structure (cf. Experimental section
and Scheme 1). By considering the previously mentioned data in addition to the data
of elemental analyses, compound 7 was rejected and we concluded that this reaction
product underwent auto-oxidation under the experimental conditions to afford 6, which
was formulated as 6-amino-4-(benzo[b]thiophen-2-yl)-2-thioxo-1,2-dihydropyridine-3,5-
dicarbonitrile. (cf. Scheme 1 and Experimental section).To authenticate, compound 6 was
also obtained by the reaction of both 1 and 2 in 1:2 molar ratio in a one pot reaction. It is
remarkable to report here that compound 6 obtained through both pathways was identical
in all physical and chemical properties.
The synthetic potential compound of 6 was investigated through its reaction with sev-
eral active halogen containing compounds, e.g., 2-chloro-N-(4-bromophenyl) acetamide,
chloroacetonitrile (8a,b). Thus, it has been found that compound 6 reacted with 2-chloro-
N-(4-bromophenyl)acetamide (8a) in 1:1 ratio in methanolic sodium methoxide through
dehydrochlorination to afford the corresponding 2-{[6-amino-4-(benzo[b]thiophen-2-yl)-
3,5-dicyanopyridin-2-yl]sulfanyl}N-(4-bromophenyl)acetamide 9a. The IR spectrum of 9a
showed the presence of absorption bands at 2224 and 1672 cm−1 due to CN and CO func-
tions, respectively. The structure of compound 9a was further elucidated via its cyclization
in ethanolic potassium hydroxide solution to afford the corresponding thieno[2,3-b]pyridine
derivative 11a via the nonisolable intermediate 10a.
The 1H NMR spectrum of compound 11a revealed the signals at 6.10 and 9.40 ppm
corresponded to 2NH2 and NH protons, respectively. Moreover, its mass spectrum gave the
parent peak at m/z = 520, which corresponded to the molecular formula C23H14BrN5OS2 of
the assigned structure, in addition to several peaks corresponding to fragments that confirm
its structure (cf. Experimental section and Scheme 2). In a similar manner, compound 6
reacted with chloroacetonitrile (8b) under the same reaction conditions to afford directly
the corresponding thieno[2,3-b]pyridine derivatives 11b. The IR (cm−1) of the reaction
product showed bands corresponding to NH2 and CN functions. On the other hand, its 1H
NMR spectrum revealed signals of NH2 protons. Moreover, its mass spectrum gave the
parent peak at m/z = 346, which corresponded to the molecular formula C17H9N5S2 of

SYNTHESIS, REACTIONS, AND CHARACTERIZATION
557
(2)
CNCH2CSNH2
NH2
S
CHO
S
EtOH /piperidine
S
1
NC
3
2
Two moles of 2
NC
NC
S
S
NC
NC
S
NH2
NH2
NH2
SH
S
S
NH2
5
4
NH3
H2S
NC
NC
NC
S
S
NH
SH
NH
NH2
S
S
NC
6
7
Scheme 1
the assigned structure 11b. The formation of compound 11b proceeded via the nonisolable
products 9b and 10b, respectively (cf. Scheme 2 and Experimental part).
The chemical reactivity and synthetic potentiality of compound 6 were further in-
vestigated through its reaction with chloromethylbenzimidazole 12 to afford the reaction
product 13 formed by dehydrochlorination. The IR of the reaction product 13 showed the
bands of NH2, NH, and CN functions and its 1H NMR spectrum exhibited a singlet signal
at δ = 4.15 ppm assignable for SCH2. Moreover, the mass spectrum of this reaction product
gave the parent peak at m/z = 438, which corresponding to the molecular weight of the
assigned structure, (cf. Scheme 3 and Experimental part). The structure of compound 13
was further elucidated via its cyclization to the corresponding thieno[2,3-b]pyridine 14
upon boiling in ethanol containing potassium hydroxide. Similarly, compound 6 reacted
with p-chlorophenacyl bromide (15) under the same experimental conditions to afford di-
1
rectly the corresponding thieno[2,3-b] pyridine derivative 16. The H NMR spectrum of

558
A. M. ABDEL-FATTAH AND F. A. ATTABY
X
H
H
N
S
S
-HCl
6
ClCH2X
N
+
8a,b
NH2
NC
9a, [b]
Cyclization
X
H
X
HN
H2N
S
N
S
N
S
S
NC
NH2
NC
11a,b
NH2
10a,b
a, X= CONHPh-Br-p
b, X= CN
Scheme 2
compound 16 exhibited the broad signal at δ = 7.03 ppm assignable to 2NH2 and additional
aromatic protons.
In further investigation, compound 6 reacted with ethylchloroacetate 17 in sodium
methoxide solution to afford the reaction product 18 which was formed via dehydrochlo-
rination. The IR of compound 18 showed the absorption bands corresponding to NH2,
1
CN, and ester CO; its H NMR spectrum revealed the signals of the COOCH2CH3 pro-
tons. Also, 13C NMR Of compound 18 was found in good agreement with the assigned
structure. Considering the previously mentioned data and the data of elemental analy-
ses, such reaction product could be formulated as {[6-amino-4-(benzo[b]thiophen-2-yl)-
3,5-dicyanopyridin-2-yl]sulfanyl}acetate 18. The structure of compound 18 was further
elucidated via its cyclization to the corresponding ethyl 3, 6-diamino-4-(benzo[b]thiophen-
2-yl)-5-cyanothieno[2,3-b]pyridine-2-carboxylate 19 upon boiling in ethanolic potassium
hydroxide solution. Finally, it was found that compound 6 reacted with methyl io-
dide to afford the corresponding 2-amino-4-(benzo[b]thiophen-2-yl)-6-(methylsulfanyl)
pyridine-3, 5-dicarbonitrile (20). Compound 20 reacted with hydrazine hydrate to give

SYNTHESIS, REACTIONS, AND CHARACTERIZATION
559
N
NH
NC
NC
S
Cl
N
HCl
N
+
6
N
H
NaOMe
S
NH2
12
13
EtOH/ NaOEt
Cyclization
NaOMe ClC6H4COCH2Br
15
Cl
O
N
NH
H2N
H2N
S
S
N
N
S
S
NC
NH2
NC
NH2
16
14
Scheme 3
the corresponding 3, 6-diamino-4-(benzo[b]thiophen-2-yl)-1H- pyrazolo[3,4-b]pyridine-
1
5-carbonitrile (21). The H NMR Spectrum of compound 21 showed the newly formed
NH2 and NH groups at δ = 4.59 and 11.79 ppm. Moreover, its mass spectrum gave the
parent peak at m/z = 306, which corresponds to the molecular weight of the assigned
structure 21.
An authentic sample of compound 21 was obtained via the reaction of compound 18
with hydrazine hydrate and the reaction product was found to be identical in all physical
and chemical properties with that given from the reaction of compound 20 with hydrazine
hydrate. A chemical identification of compound 21 arose from its condensation with 4(2-
thienyl) benzaldehyde (22) in pyridine to afford 6-amino-4-(benzo[b]thiophen-2-yl)-3-({-
[4-(thiophen-2-yl)phenyl]methylidene}amino) 1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
1
(23).The H NMR spectrum of this reaction product revealed signals at (δ ppm) 4.59
(br, 2H, NH2), 7.18–7.94 (m, 12H, Ar-H’s), 8.74 (s, 1H, N=CH) and 11.90 (br, 1H, NH). Its
mass spectrum gave m/z = 476, which corresponds to the molecular weight of compound
23.

560
A. M. ABDEL-FATTAH AND F. A. ATTABY
ClCH2COOEt (17)
6
NaOMe
CH3I
COOEt
H3C
NC
NC
S
N
NC
S
N
S
S
NH2
NC
NH2
20
18
Cyclization
NH2NH2
COOEt
N
H2N
H2N
S
NH
N
N
S
S
NC
NH2
NH2
NC
21
19
S
N
NC
N
S
OHC
N
H
H2N
N
S
22
23
Scheme 4
EXPERIMENTAL
Melting points were measured with a Gallenkamp apparatus and are uncorrected. IR
spectra from KBr discs were recorded on a Bruker Vector 22 FT-IR spectrophotometer.
1H and 13C NMR spectra were determined in DMSO-d6 and CDCl3 at 300 MHz on a
Varian Mercury VX spectrometer using TMS as an internal standared. Chemical shifts are
expressed as δ or ppm. Mass spectra were recorded on a GCMS-QP 1000 EX spectrometer
at 70 eV. Elemental analyses were carried out at the Microanalytical Center of Cairo
University, Giza, Egypt.

SYNTHESIS, REACTIONS, AND CHARACTERIZATION
561
Synthesis of Compound 6 (General Procedures)
Method A. An equimolar amount of arylidine 3 (0.24 g, 1.0 mmol), cya-
noethanethioamide (2) (0.10 g, 1.0 mmol) and piperidine (0.5 mL) in ethanol (30 mL) was
heated under reflux for 5 h. The excess of ethanol was evaporated under vacuum. The solid
obtained was collected by filtration and crystallized from ethanol to give compound 6.
Method B. A mixture of benzothiophene-2-carbaldehyde (0.16g, 1.0 mmol),
cyanoethane-thioamide (2) (0.20 g, 2.0 mmol), and piperdine (0.5 mL) in ethanol
(30 mL) was heated under reflux for 5 h. The excess of ethanol was evaporated under
vacuum. The solid obtained was collected by filtration and crystallized from ethanol to
give compound 6.
6-Amino-4-(benzo[b]thiophen-2-yl)-2-thioxo-1,2-dihydropyridine-3,5-di-
◦
carbonitrile 6: Yellow crystals, mp 270 C; IR (ν cm−1): 3447, 3347, 3227, 3141 (NH2
and NH), 2202 (CN at C-3), 2178 (CN at C-5), and 1538 (C S); MS (m/z): 308 (M+,
100% corresponding to the molecular formula C15H8N4S2 of the assigned structure), 307
1
(M+- H, 73.6%), 290 (M+ -NH2, 2H, 8.8%), 264(M+ -CN, NH2, 2H, 16.5%); H NMR
(δ ppm): 6.80 (br, 2H, NH2), 7.41–8.08 (m, 5H, aromatic H’s), and 8.60 (br, 1H, NH). Anal.
for C15H8N4S2 (308), Calcd./Found (%): C (58.42/58.32) H (2.61/2.50) N (18.17/17.92) S
(20.80/20.60).
Synthesis of compounds 9a, 11b, 13, 16, 18, and 20: A solution of 6 (0.5 mmol,
0.15 g) and the appropriate reagent 8a (0.5 mmol, 0.124 g), 8b (0.5mmol, 0.04g), 12 (0.5
mmol, 0.83 g), 15 (0.5 mmol, 0.12 g), 17 (1 mmol, 0.124g), and methyl iodide (2 mmol,
0.284 g) in methanol containing sodium methoxide (prepared by 0.6 g of sodium in 40 mL
methanol) was stirred for 5 h. The product that formed was collected by filtration, washed
with cold ethanol, and then recrystallized from ethanol to give 9a, 11b, 13, 16, 18, and 20,
respectively.
2-{[6-Amino-4-(benzo[b]thiophen-2-yl)-3, 5-dicyanopyridin-2-yl]sulfanyl}-N-
◦
(4-bromophenyl)acetamide 9a: Yellow crystals, mp 270 C; IR (ν cm−1): 3447, 3347,
1
3227, 3141 (NH2 and NH), 2202 (CN) and 1670 (amidic CO); H NMR (δ ppm): 4.73
(s, 2H, SCH2); 6.10 (br, 2H, NH2); 7.34–8.13 (m, 9H, aromatic H’s) and 9.20 (br, 1H,
NH); Anal. for C23H14BrN5OS2 (520), Calcd./Found (%): C (53.08/53.20) H (2.71/2.50)
Br (15.35/15.25) N (13.46/13.30) S (12.32/12.20).
3,6-Diamino-4-(benzo[b]thiophen-2-yl)thieno[2,3-b]pyridine-2,5-dicarbo-
◦
nitriles 11b: Yellow crystals, mp 170 C; IR (ν cm−1): 3450, 3336, 3221 (NH2), and
2216, 2191 (2CN); MS (m/z): 346 (M+-1, 0.2% corresponding to the molecular formula
1
C17H9N5S2); H NMR (δ ppm): 6.10 (br, 4H, 2NH2) and 7.51–8.23 (m, 5H, aromatic
H’s). Anal. for C17H9N5S2 (347), Calcd./Found (%): C (58.78/58.60) H (2.59/2.50)
N (20.17/19.80) S (18.44/18.30).
2-Amino-6-[(1H-benzimidazol-2-ylmethyl)sulfanyl]-4-(benzo[b]thiophen-2-
yl)pyridine-3,5-dicarbonitrile 13: White crystals, mp 300 ◦C; IR (ν cm−1): 3327,
3164 (NH2 and NH), and 2208 (CN); MS (m/z): 438 (M+, 100% corresponding to the
molecular formula C23H14N6S2 of the assigned structure), 437 (M+- H, 81.1%), and 319
1
(M+- benzimidazolyl ring, 2H, 73.6%). H NMR (δ ppm): 4.15 (s, 2H, SCH2), 4.73
(s, 2H, NH2), and 7.15–8.13 (m, 10H, aromatic H’s, and NH). Anal. for C23H14N6S2(438),
Calcd./Found (%): C (62.99/62.90) H (3.22/3.12) N (19.16/18.90) S (14.62/14.50).
3,6-Diamino-4-(benzo[b]thiophen-2-yl)-2-[(4-chlorobenzoyl)]thieno[2,3-
b]pyridine-5-carbonitrile 16: Red crystals, mp >300 ◦C; IR (ν cm−1): 3454, 3343
1
(NH2) and 2215 (CN); H NMR (δ ppm): 7.03 (br, 4H, 2NH2) and 7.51–8.18 (m, 9H,

562
A. M. ABDEL-FATTAH AND F. A. ATTABY
aromatic H’s). Anal. For C23H13ClN6OS2 (460), Calcd./Found (%): C (59.93/59.90)
H (2.84/2.7) Cl (7.69/7.5) N (12.15/12.0) S (13.91/13.60).
{[6-Amino-4-(benzo[b]thiophen-2-yl)-3,5-dicyanopyridin-2-yl]sulfanyl} acetate
◦
18: Yellow crystals, mp 220 C; IR (ν cm−1): 3422, 3326, 3225 (NH2), 2209 (CN), and
1
1724 (ester CO); H NMR (δ ppm): 1.23 (t, 3H, –CH2CH3, J = 7.2Hz); 4.13 (q, 2H,
–CH2CH3, J = 7.2 Hz); 4.22 (s, 2H, SCH2); and 7.48–8.12 (m, 7 H, aromatic H’s, and
NH2); 13C NMR (DMSO-d6) (δ ppm): 13.8, 31.9, 44.9, 61.2, 86.6, 93.5, 114.5, 120.7,
124.6, 125.9, 127.4, 132.9, 138.5, 140.1, 150.8, 159.3, 165.7, 167.7, and 184.3. Anal. for
C19H14N4O2S2(394), Calcd./Found (%): C (57.85/57.62) H (3.58/3.40) N (14.20/14.10)
S (16.26/16.30).
2-Amino-4-(benzo[b]thiophen-2-yl)-6-(methylsulfanyl)-pyridine-3,5-di-
carbonitrile 20: Pale yellow crystals mp 250 ◦C; IR (ν cm−1): 3415, 3326, 3226
1
(NH2), 2210 (CN); H NMR (δ ppm):2.43 (s, 3H, CH3); 6.80 (br, 2H, NH2); 7.41–8.07
(m, 5H, aromatic H’s). Anal. for C16H10N4S2 (322), Calcd./Found (%): C (63.35/63.30) H
(3.11/3.10) N (17.39/17.20) S (19.87/19.60).
Synthesis of compounds 11a, 14, and 19: A solution of the compounds 9a, 13, or
18 (0.5 mmol, 0.26 g for 9a, 0.22 g for 13 and 0.20 g for 18) in ethanol (30 mL) and
potassium hydroxide was heated under reflux for 4 h. The mixture was cooled, poured onto
ice-cold water, and acidified with hydrochloric acid. The solid products were collected by
filtration, washed with water, and crystallized from ethanol to give compounds 11a, 14, and
19, respectively.
3,6-Diamino-4-(benzo[b]thiophen-2-yl)-N-(4-bromophenyl)-5-cyanothieno-
◦
[2,3-b]pyridine-2-carboxamide 11a: Yellow crystals, mp 310 C; IR (ν cm−1): 3464,
3324, 3215 (NH2 and NH) and 2228 (CN); MS (m/z): 522 (M++2, 5.4%), 521 (M++1,
8.9%), 520 (M+, 21.4% corresponding to the molecular formula C23H14BrN5OS2 of
the assigned structure), 519 (M+- H, 12.7%), 349 (M+-NHPh-Br, 100%) and 321
1
(M+-CONHPh-Br, 17.3%); H NMR (δ ppm): 6.10 (br, 4H, 2NH2); 7.43–8.16 (m, 9H,
aromatic H’s) and 9.40 (br, 1H, NH); Anal. for C23H14BrN5OS2 (520), Calcd./Found (%):
C (53.08/53.10) H (2.71/2.60) Br (15.35/15.15) N (13.46/13.20) S (12.32/12.20).
3,6-Diamino-2-(1H-benzimidazol-2-yl)-4-(benzo[b]thiophen-2-yl)thieno[2,3-
◦
b]pyridine-5-carbonitrile 14: Red crystals, mp 160 C; IR (ν cm−1): 3339, 3213 (NH2
and NH), 3056 (aromatic CH) and 2214 (CN). 1H NMR (δ ppm): 6.80 (br, 4H, 2NH2) and
7.15–8.13 (m, 10H, aromatic H’s and NH). Anal. for C23H14N6S2 (438); Calcd./Found
(%): C (62.99/62.80) H (3.22/3.20) N (19.16/18.80) S (14.62/14.40).
Ethyl 3, 6-diamino-4-(benzo[b]thio◦phen-2-yl)-5-cyanothieno[2,3-b]pyridine-2-
carboxylate 19: Yellow crystals, mp 240 C; IR (ν cm−1): 3419, 3324, 3225 (NH2),
2209 (CN) and 1690 (ester CO with H-bonding); 1H NMR (δ ppm): 1.32 (t, 3H, –CH2CH3,
J = 6.9 Hz); 4.32 (q, 2H, –CH2CH3, J = 6.9Hz); 6.11 (br, 4H, 2NH2) and 7.52–8.26 (m,
5 H, aromatic H’s); Anal. for C19H14N4O2S2 (394), Calcd./Found (%): C (57.85/57.70)
H (3.58/3.40) N (14.20/14.10) S (16.26/16.10).
Synthesis of compound 21: A solution of compound 18 (0.39 g, 1 mmol) or 20
(0.322 g, 1 mmol) in hydrazine hydrate (15 mL) and ethanol (20 mL) was heated under
reflux for 5 h; the excess solvents were evaporated and cooled. The solid was collected by
filtration, dried, and crystallized from ethanol to give 21.
3,6-Diamino-4-(benzo[b]thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbo-
◦
nitrile 21: Yellow crystals, mp 300 C; IR (ν cm−1): 3370, 3317, 3194 (NH2 and NH)
and 2214 (CN); MS (m/z): 306 (M+, 80%), 305 (M+ -1, 50%); H NMR (δ ppm): 4.59
1
(s, 2H, NH2)∗; 6.86(s, 2H, NH2)∗, 7.47–8.13 (m, 5H, aromatic H’s), and 11.79 (br, 1H,

SYNTHESIS, REACTIONS, AND CHARACTERIZATION
563
NH)∗. Anal. for C15H10N6S (306), Calcd./Found (%): C (58.81/58.50) H (3.29/3.10)
N (27.43/27.20) S (10.47/10.30).
Synthesis of compound 23: A solution of 21 (0.306 g, 1 mmol) and 22 (0.188 g,
1 mmol) in pyridine (15 mL) and ethanol (20 mL) was heated under reflux for 5h; the
excess solvents were evaporated and cooled. The solid was collected by filtration, dried,
and crystallized from ethanol to give 23.
6-Amino-4-(benzo[b]thiophen-2-yl)-3-({-[4-(thiophen-2-yl)phenyl]methyl-
idene}amino)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile 23: Yellow crystals, mp256
◦C; IR (ν cm−1): 3370, 3317, 3194 (NH2 and NH), and 2214 (CN); MS (m/z): 476(M+,
1
7.4%); H NMR (δ ppm): 4.59 (s, 2H, NH2)∗; 7.18–7.94 (m, 12H, aromatic H’s), 8.74
(s, 1H, N=CH); and 11.90 (br,1H, NH)∗. Anal. for C26H16N6S2 (476), Calcd./Found (%):
C (65.55/65.50) H (3.36/3.20) N (17.65/17.40) S (13.45/13.30).
∗Lost after D2O exchange.
REFERENCES
1. Attaby, F. A.; Abdel-Fattah, A. M.; Shaif, L. M.; Elsayed, M. M. Phosphorus Sulfur Silicon
Relat. Elem. 2010, 185, 668-679.
2. Attaby, F. A.; Abdel-Fattah, A. M.; Shaif, L. M.; Elsayed, M. M. Phosphorus Sulfur Silicon
Relat. Elem. 2010, 185, 129-139.
3. Elneairy, M. A. A. Phosphorus Sulfur Silicon Relat. Elem. 2010, 185, 469-483.
4. Abdel-Fattah, A. M.; Elsayed, M. M. Curr. Org. Chem. 2009, 13, 1751-1757.
5. Attaby, F. A.; Abdel-Fattah, A. M.; Shaif, L. M.; Elsayed, M. M. Afinidad LXVI 2009, 543,
412-419.
6. Attaby, F. A.; Abdel-Fattah, A. M.; Shaif, L. M.; Elsayed, M. M. Curr. Org. Chem. 2009, 13,
1654-1663.
7. Abdel-Fattah, A. M.; Shaif, L. M.; Attaby, F. A. Phosphorus Sulfur Silicon Relat. Elem. 2008,
183, 2443-2456.
8. Abdel-Fattah, A. M.; Elneairy, M. A. A.; Gad-Elkareem, M. A. M. Phosphorus Sulfur Silicon
Relat. Elem. 2007, 182, 1351-1364.
9. Gad-Elkareem, M. A. M.; Abdel-Fattah, A. M.; Elneairy, M. A. A. Can. J. Chem. 2007, 85,
592-599.
10. Elneairy, M. A. A.; Gad-Elkareem, M. A. M.; Abdel-Fattah, A. M. Phosphorus Sulfur Silicon
Relat. Elem. 2006, 181, 1451-1466.
11. Gad-Elkareem, M. A. M.; Abdel-Fattah, A. M.; Elneairy, M. A. A. Phosphorus Sulfur Silicon
Relat. Elem. 2006, 181, 891-911.
12. Attaby, F. A.; Elghandour, A. H. H.; Ali, M. A.; Ibrahem, Y. M. Phosphorus Sulfur Silicon Relat.
Elem. 2007, 182, 695-709.
13. Prachayasittikul, S.; Treeratanapiboon, L.; Ruchirawat, S.; Prachayasittikul, V. EXCLI J. 2009,
8, 121-129.
14. Hamdy, N. A.; Gamal-Eldeen, A. M. Eur. J. Med. Chem. 2009, 44, 4547-4556.
15. Abadi, A. H.; Ibrahim, T. M.; Abouzid, K. M.; Lehmann, J.; Tinsley, H. N.; Gary, B. D.; Piazza,
G. A. Bioorg. Med. Chem. 2009, 17, 5974-5982.
16. Tumey, L. N. Boschelli, D. H.; Lee, J.; Chaudhary, D. Bioorg. Med. Chem. Lett. 2008, 18,
4420-4423.
17. Lockman, J. W.; Reeder, M. D.; Suzuki, K.; Ostanin, K.; Hoff, R.; Bhoite, L.; Austin, H.;
Baichwal, V.; Willardsen, J. A. Bioorg. Med. Chem. Lett. 2010, 20, 2283-2286.
18. Vasoya, S. L.; Patel, M. R.; Dobaria, S. V.; Joshi, H. S. Ind. J. Chem. Sect. B 2005, 44, 405-409.