Synthesis of heterocycles via 2-thioxo-1,2-dihydropyridine-3-carbonitrile derivative

Article abstract of DOI:10.1080/10426500801963905

The present study aimed to investigate the synthetic potentiality and chemical reactivity of 2-thioxo-1,2-dihydropyridine-3-carbonitrile derivative 1. This goal performed via its reaction with each of 1-chloroacetone and iodomethane to afford the correspo

Full text of DOI:10.1080/10426500801963905

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Phosphorus, Sulfur, and Silicon
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Synthesis of Heterocycles
via 2-Thioxo-1,2-
dihydropyridine-3-carbonitrile
Derivative
Azza M. Abdel-Fattah a , Labeeb M. Shaif a & Fawzy
A. Attaby a
a Cairo University, Faculty of Science, Chemistry
Department, Giza, Egypt
Published online: 27 Sep 2008.
To cite this article: Azza M. Abdel-Fattah , Labeeb M. Shaif & Fawzy A. Attaby (2008)
Synthesis of Heterocycles via 2-Thioxo-1,2-dihydropyridine-3-carbonitrile Derivative,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:10, 2443-2456, DOI:
10.1080/10426500801963905
To link to this article: http://dx.doi.org/10.1080/10426500801963905
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Phosphorus, Sulfur, and Silicon, 183:2443–2456, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801963905
Synthesis of Heterocycles via
2-Thioxo-1,2-dihydropyridine-3-carbonitrile Derivative
Azza M. Abdel-Fattah, Labeeb M. Shaif,
and Fawzy A. Attaby
Cairo University, Faculty of Science, Chemistry Department, Giza,
Egypt
The present study aimed to investigate the synthetic potentiality and chemical re-
activity of 2-thioxo-1,2-dihydropyridine-3-carbonitrile derivative 1. This goal per-
formed via its reaction with each of 1-chloroacetone and iodomethane to afford the
corresponding 2-alkylthio derivatives 3 and 9, respectively. Compound 3 underwent
intramolecular cyclization to afford the corresponding thieno[2,3-b]pyridine deriva-
tive 4 which in turn, reacted with dimethylformamide/dimethylacetal followed by
hydrazine hydrate and nitrous acid to afford the corresponding pyridothienopy-
rimidine and pyridothienopyridazine derivatives 6 and 8, respectively. On the other
hand, Compound 9 reacted with hydrazine hydrate to give 3-aminopyrazolo[3,4-
b]pyridine derivative 10, which diazotized with nitrous acid to give the correspond-
ing diazonium salt 11. Compound 11 coupled with several active –CH2- containing
reagents to synthesize the corresponding pyridopyrazolo-triazines 15, 24, 29, and
31. The formulas of all newly synthesized heterocyclic compounds were elucidated
by considering the data of IR, 1H NMR, Mass spectral data, as well as data from
elemental analyses.
Keywords 2-Thioxohydropyridine-3-carbonitrile; pyridopyrazolotriazine; thieno[2,3-
b]pyridine; thienopyridopyridazine; thienopyridopyrimidine
INTRODUCTION
In continuation of our previous efforts,1−20 we investigate here the
synthetic potentiality of 2-thioxo-1,2-dihydropyridine-3-carbonitrile
derivative 1. Compound 1 was obtained by two different procedures21,22
;
on repeating these procedures, we obtained higher yield and differ-
ent melting points. We are interested in investigating the position and
chemical reactivity of functional groups present in 1. The present study
aims to synthesize several new heterocycles via building up new rings—
Received 20 November 2007; accepted 2 December 2007.
Address correspondence to Prof. Dr. Fawzy A. Attaby, Cairo University, Faculty of
Science, Chemistry Department, Giza 12613, Egypt. E-mail: fattaby@hotmail.com
2443

2444
A. M. Abdel-Fattah et al.
e.g., thiophenes, pyrazoles, pyridazines, pyrimidines, or triazines—on
the parent pyridine ring. In the course of our investigations on the ti-
tled compound 1, we were interested in the utilization of the reactivity
of C=S, NH, and CN groups to carry out different types of heterocy-
clizations. Based on the nucleophilicity of S-atom of the SH group we
have developed new procedures for the synthesis of heterocyclic sys-
tems with the aim to find biologically active compounds.23−28
Compound 1 was used as a starting point for the present study; thus,
it has been found that compound 1 reacted with 1-chloroacetone (2) in
stirred methanolic sodium methoxide at room temperature, which af-
forded a reaction product 3 via the dehydrochlorination. The IR (cm−1
)
of compound 3 showed the bands (2212.2, CN) and (1716, CH3CO)
groups. Further confirmation of 3 arose from its cyclization in ethanolic
sodium ethoxide under reflux 5–10 min, which through intramolecular
cyclization gave 4. The IR (cm−1) of compound 4 showed no bands of the
CN group, while that of the newly formed NH2 was detected at 3307.3
and 3471.9;this proved that both -CH2- and CN groups involved in the
cyclization step (cf. Chart 1). The formula of compound 4 elucidated
further through its preparation authentically via the reaction of 1 with
2 in ethanolic sodium ethoxide under reflux for 2–3 h. It is important to
report here that compound 4 was obtained by two pathways—identical
in all physical and chemical properties. The position of NH2 and its ad-
jacent COCH3 in compound 4 was confirmed via its reaction with both
nitrous acid to give the corresponding pyridothienopyridazine deriva-
tive 8 and dimethylformamide/dimethyacetal followed by hydrazine to
give the corresponding pyridothienopyrimidine derivative 6.
By considering the data of both elemental analyses, IR, and 1H NMR,
the formulas of compounds 3–8 were elucidated, in addition to the
data of mass spectra of compounds 4–6 that gave m/z = 380, 435,
and 422, which corresponded to the molecular weights of the formu-
las C20H16O2N2S2, C23H21O2N3S2, and C21H18O2N4S2 of the assigned
formulas, in addition to several peaks that corresponded to fragments,
which confirmed the assigned formulas further (Chart 1 and Experi-
mental section). Work was extended to shed more light on the reactivity
of SH group in 1 towards the electrophilic C-atom of iodomethane; thus,
1 reacted with iodomethane in methanolic sodium methoxide solution
to give the corresponding 2-methylthio derivative 9 in which the nucle-
ophilic substitution reaction of SCH3 group performed by the reaction
with hydrazine hydrate giving a reaction product 10. The IR (cm−1
)
of compound 10 showed no bands of CN function and instead that of
NH2 detected at 3194.0, 3290.4, 3433.3, and this proved that the CN
function consumed in building a new pyrazole ring.

Synthesis via a Carbonitrile Derivative
2445
CH3
O
H
H
S
CN
S
N
N
ClCH2COCH3
(2)
HN
C6H4-p-OCH3
C6H4-p-OCH3
NaOMe/MeOH/stirring at room Temp./15 min.
S
S
1
3
NaOEt/EtOH
Reflux / 5 min.
O
O
S
CH3
S
N
NaNO2/HCl/AcOH
S
N
S
NH2
N
N
C6H4-p-OCH3
C6H4-p-OCH3
7
4
OH
S
N
S
DMF/DMA/Dry Xylene
N
N
C6H4-p-OCH3
8
O
H3C
OH
N
S
CH3
S
N
S
NH2
N2H4
N
S
NMe2
N
N
Reflux/5 hrs
C6H4-p-OCH3
C6H4-p-OCH3
6
5
CHART 1

2446
A. M. Abdel-Fattah et al.
S
N
CN
H3C
CH3I/NaOMe/MeOH
C6H4-p-OCH3
S
N2H4
1
9
N2H4
N
N
N2Cl
NH2
HN
N
HN
N
NaNO2/HCl
S
C6H4-p-OCH3
C6H4-p-OCH3
S
11
10
N
NC
NH
CN
N
S
Ethyl alcohol/Sod. acetate
N
N
CH2(CN)2
(12)
C6H4-p-OCH3
13
NH2
NH
N
H
CN
N
N
N
N
S
CN
N
S
N
N
N
N
C6H4-p-OCH3
15
C6H4-p-OCH3
14
CHART 2
Moreover, the mass spectrum of 9 gave m/z = 338 (36.3%) and
this corresponded to the molecular weight of the molecular formula
C18H14ON2S2 of the assigned formula (Chart 2), 337 (100%, M-1), 323
(26.8%, M-CH3), 291 (2.5%, M-SCH3). On the other hand, the mass
spectrum of 10 gave m/z = 322, which corresponded to a molecular
weight of a molecular formula C17H14ON4S of the assigned formula

Synthesis via a Carbonitrile Derivative
2447
N
NC
NH
CSNH2
N
S
Ethyl alcohol/Sod. acetate
CN
N
11
N
C6H4-p-OCH3
(16)
H2NSC
17
NH2
NH
HS
NH
N
H
N
CN
N
N
S
CSNH2
N
S
N
N
N
N
C6H4-p-OCH3
C6H4-p-OCH3
20
18
-H2S
NH2
NH2
N
N
N
CN
CSNH2
N
N
N
S
S
N
N
N
N
C6H4-p-OCH3
C6H4-p-OCH3
19
15
CHART 3
(cf. Chart 2 and Experimental section). The position and chemical re-
activity of NH2 of 10 elucidated through its diazotization with nitrous
acid to give the corresponding diazonium salt 11 whose formula was
established via its coupling with each of malononitrile (12) and/or 1-
cyanoethanethioamide (16) to give 15.
The formation of compound 15 proceeded through dehydrochlori-
nation with intramolecular cyclization via NH2 addition on the CN
function in case of 12 and removal of H2S in case of 16. Formula 15
1
was established by considering the data of IR, H NMR, and elemen-
tal analyses, where IR (cm−1) showed the bands 3417.1, 3273.9 (NH2),
2208.1 (CN), and 1H NMR (δppm), which revealed the signals 3.884 (s,

2448
A. M. Abdel-Fattah et al.
N
NC
NH
COOEt
N
S
Ethyl alcohol/Sod. acetate
CN
N
11
N
(21)
C6H4-p-OCH3
EtOOC
22
Ethanol/piperidine/reflux 2hrs
NH
EtOOC
N
H
N
NH
CN
N
N
S
COOEt
N
S
N
N
N
N
C6H4-p-OCH3
C6H4-p-OCH3
25
23
-EtOH
O
NH2
N
N
N
COOEt
CN
N
N
S
N
S
N
N
N
N
C6H4-p-OCH3
C6H4-p-OCH3
26
24
CHART 4
1
br., 2H, NH2). Considering the previously mentioned IR and H NMR
data, we rejected compound 19.
Moreover, the mass spectrum of 15 gave m/z = 399 (100%) which
corresponded to the molecular weight of the molecular formula C20
H13ON7S of the assigned formula (Charts 2, 3, and Experimental
section). It important to report here that all attempts to isolate
compounds 13, 14, 17, and 20 failed. On contrast to the behavior of
11 towards each of 12 and 16, we found that 11 reacted with ethyl
cyanoacetate (21) to give ethyl cyano{[4-(4-methoxyphenyl)-6-(2-
thienyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-diazenyl}acetate (22), whose
formula was elucidated by considering the data of IR and elemental
analyses (Experimental section).
Compound 22—established via its intramolecular cyclization in
ethanol/piperidine under reflux 2 h—afforded a reaction product, where

Synthesis via a Carbonitrile Derivative
2449
O
Ph
N
N
COPh
N
COOEt
N
N
N
S
S
O
N
N
N
N
COOEt
Ph
27
OCH3
OCH3
28
29
the IR showed no CN function and showed the newly formed NH2; this
confirmed compound 24 and rejected 26. The mass spectrum of this
reaction product gave m/z = 446 (100%), which corresponded to the
molecular weight of the molecular formula C22H18N6O3S of the as-
signed formula 24 and did not give m/z = 400 for the formula 26 with
C20H12N6O2S (cf. Chart 4 and Experimental section).
Similarly,
compound
11
reacted
with
ethyl
3-oxo-3-
phenylpropanoate (27), which gave the reaction product 29, rather
than 28. The rejection of 28 depends on the appearance of the band
at 1727 for CO ester in IR and detection of the signals 1.027 (t, 3H,
CH3CH2COO, J = 7.0), 4.201 (q, 2H, CH3CH2COO-, J = 7.1). Fur-
thermore, the mass spectrum of this reaction product gave m/z = 507,
which corresponded to the molecular weight of the molecular formula
C28H21N5O3S of the assigned formula 29 and did not give m/z = 479
for the formula C26H17N5O3S 28 (cf. Experimental section).
The work extended to investigate further the reactivity of both chlo-
rine atom and NH-pyrazole in compound 11. Thus, it was found that
11 reacted with 3-(4-chlorophenyl)-3-oxopropanenitrile 30 to give the
reaction product 31, which formed via the dehydrochlorination followed
by intramolecular cyclization that involved both CN and NH-pyrazole
groups. Formula of 31 established by considering the data of IR, ele-
mental analyses and mass spectrum (cf. Experimental section) on such
data we reject formula 32.
NH2
O
C6H4-4-Cl
N
N
N
CN
C6H4-4-Cl
N
C6H4-4-Cl
2-Thienyl
N
NC
N
N
2-Thienyl
N
N
O
N
30
C6H4-4-OCH3
C6H4-4-OCH3
31
32

2450
A. M. Abdel-Fattah et al.
CONCLUSION
Finally, we concluded that the starting material 4-(4-methoxy-phenyl)-
2-[(2-oxopropyl)thio]-6-(2-thienyl)nicotinonitrile (3) contained three
chemically active groups—e.g., NH, SH, and CN—which was used for
several chemical transformations. Furthermore it was used to build a
new ring system, i.e., electrophilic attack on nucleophilic S of SH group
from the electrophilic C-atom of CH3I, and the nucleophilic substitution
of SCH3 group by the nucleophilic hydrazine N.
EXPERIMENTAL
All melting points were uncorrected. I.R. (KBr discs) spectra were
1
recorded on a Shimadzu FTIR-8201PC Spectrophotometer. H NMR
spectra were recorded on a Varian Mercury 300 MHz., and a Varian
Gemini 200 MHz. spectrometers using TMS as an internal standard
and CDCl3, DMSO-d6, and (CD3)2CO as solvents. Chemical shifts were
expressed as δ (ppm) units. Mass spectra were recorded on Shimadzu
GCMS-QP1000EX using an inlet type at 70 eV. The Microanalytical
Center of Cairo University performed the microanalyses.
The Synthesis of 3
A solution of each of 1 (0.324 g, 1 mmol) and chloroacetone (2, 0.092 g,
1 mmol) in sodium methoxide (prepared from 0.023 g of sodium and
methanol 25 mL) was stirred at room temperature for 15 min. The
formed precipitate was collected by filtration, washed with water, dried,
and recrystallized from ethanol to afford 4-(4-methoxyphenyl)-2-[(2-
oxopropyl)thio]-6-(2-thienyl)nicotinonitrile (3) as yellow crystals (84%),
m.p.=194-196 C◦, IR υ(cm−1): 3092.5(C-H, aromatic), 2212.2 (CN), 1716
(CO); anal., for C20H16O2N2S2 (380), calcd./found(%): C(63.13/63.22),
H(4.24/4.31), N(7.36/7.52), S(16.85/16.90).
The Synthesis of 4
Method A
A solution of each of 3 (0.380 g, 1 mmol) in sodium ethoxide so-
lution (prepared from 0.023 g of sodium and 25 mL ethanol) heated
under reflux for 30 min. The solid that formed after cooling, collected
by filtration, washed with water and ethanol, and recrystallized from
chloroform to afford 4.

Synthesis via a Carbonitrile Derivative
2451
Method B
A solution of each of 1 (0.324 g, 1 mmol) and chloroacetone
(2, 0.092 g, 1 mmol) in sodium ethoxide solution (prepared from
0.023 g of sodium and 25 mL ethanol) heated under reflux for
2 h. The solid product that formed after cooling, collected by fil-
tration, washed with water and ethanol, recrystallized from chloro-
form to afford 1-[3-amino-4-(4-methoxyphenyl)-6-(2-thienyl)thieno[2,3-
b]pyridin-2-yl]ethanone (4) as orange crystals (89%), m.p. = 162–164◦C,
IR υ(cm−1), 3471.9, 3307.3 (NH2), 1615.3 (CO); MS: 380 (M+, 100%,
which corresponded to the molecular weight of the molecular for-
mula C20H16O2N2S2 of the assigned formula), 379 (M+-H, 51.5%), 365
(M+-CH3, 43.0%), 364 (379-NH, 4.0%), 337 (M+-COCH3, 14.3%), 297
(M+-CH3COC=C-NH2, 2.9%), and 83 (CH3COC=C-NH2, 1.2 %); anal.,
for C20H16O2N2S2 (380) calcd./found(%): C(63.13/63.31), H(4.24/4.40),
N(7.36/7.40), S(16.85/16.91).
The Synthesis of 5
A solution of each of 4 (0.190 g, 0.5 mmol) and dimethyl formamide-
dimethylacetal (0.106 g, 1 mmol) in dry xylene (30 mL) heated
under reflux for 5 h. The excess solvent evaporated, and the
solid that formed after cooling was collected by filtration, dried,
and recrystallized from dioxane to afford 1-3-[ethylideneamino]-4-
(4-methoxyphenyl)-6-(2-thienyl)thieno[2,3-b]pyridin-2-ylethanone (5):
as yellow crystals (91%), m.p. = 230◦C, IR υ (cm−1): 2995.5, 2920
(aliphatic CH), 1641.3 (CO acetyl); MS: 435 (M+, 100%, which
corresponded to the molecular weight of the molecular formula
C23H21O2N3S2 of the assigned formula), 420 (M+-CH3, 20.1%), 392
(M+-COCH3, 65.5%), 391 (M+-N(CH3)2, 54.1%), 378 (M+-CHN(CH3)2,
8.3%), 364 (M+-N=CHN(CH3)2, 5.6%) 351 (M+-C4H3S, 41%); anal.,
for C23H21O2N3S2 (435) calcd./found: C(65.00/64.62), H(4.46/4.50),
N(6.89/7.10), S(15.78/15.91).
The Synthesis of 6
A solution of each of 5 (0.478 g, 1.1 mmol) and hydrazine
hydrate (10 mL) in ethanol (20 mL) heated under reflux for
5
h. The excess solvent evaporated, and the solid formed
after cooling collected by filtration, dried and recrystallized
from ethanol to afford 3-amino-9-(4-methoxy-phenyl)-4-methyl-7-(2-
thienyl)-3,4-dihydropyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimi- din-4-ol (6) as
red crystals (89%), m.p. = 120◦C, IR υ (cm−1): 3454, (NH2), broad

2452
A. M. Abdel-Fattah et al.
3320–3454 (H-bonded OH) and 1615.1 (C=N); MS: 422 (M+, 39.4%,
which corresponded to the molecular weight of the molecular for-
mula C21H18O2N4S2 of the assigned formula), 421 (M+-H, 54.5%),
406 (M+-NH2, 33.3%), 405 (M+- OH, 77.8%), 335 (M+-CH3(OH)C-
1
N(NH2)CH, 70.7%), 321 (M+ - CH3(OH)C-N(NH2)CH=N, 47.5%); H
NMR(δ ppm): 1.915 (s, 3H, CH3), 3.866 (s, 3H, OCH3), 5.558 (s, br.,
2H, NH2), 8.66 (s, br., 1H, OH), 7.144–8.031 (m, 9H, ArH’s, Thiophene,
Pyridine, Pyrimidine-H’s); anal., for C21H18O2N4S2 (422) calcd./found:
C(59.69/60.11), H(4.29/4.31), N(13.26/13.33), S(15.18/15.20).
The Synthesis of 7
A solution of each of 4 (0.380 g, 1 mmol) in concentrated hydrochloric
acid (5 mL) and glacial acetic acid (5 mL) stirred in an ice bath. Add
sodium nitrite solution (0.138 g, 2 mmol) dropwise with stirring along
30 min. The solid that formed was collected by filtration, washed with
water, dried, and recrystallized from dioxane to afford 9-(4-methoxy-
phenyl)-7-(2-thienyl)pyrido[3’,2’:4,5]thieno[3,2-c]pyridazin-4-ol (7) as
red crystals (91%), m.p. = 115◦C; IR υ(cm−1) 3250–3505 (H-bonded
OH), 3100.9 (=C-H), 2928.6 (aliphatic C-H); 1H NMR (CDCL3, δppm):
3.652 (s, 3H, OCH3), 7.016–7.644 (m, 9H, ArH’s, Thiophene, Pyri-
dine, Pyridazine H’s), and 13.597 (s, 1H, OH); anal., for C20H13O2N3S2
(391): calcd./found (%): C(61.36/61.41), H(3.35/3.37), N(10.73/10.81),
S(16.38/16.41).
Synthesis of 9
A solution of each of 1 (0.324 g, 1 mmol) and methyl iodide
(0.3 g, 2 mmol) in sodium methoxide (prepared from 0.023 g of
sodium and methanol 25 mL) was stirred at room temperature for
15 min. The formed precipitate was collected by filtration, washed
with water, dried, and recrystallized from chloroform to afford 4-
(4-methoxyphenyl)-2-(methylthio)-6-(2-thienyl)-nicotinonitrile (9): as
white crystals (90%), m.p. = 192◦C, IR υ(cm−1): 3058.6 (Aromatic
C-H), 2956.5–2917.7(Aliphatic C-H), and 2212.3 (CN); MS: 337 (M+,
100%), 323 (M+-CH3, 26.8%), 308 (M+-2CH3, 2.4%), 292 (M+-CH3-
OCH3, 5.4%), 291 (M+-SCH3, 2.5%), 260 (M+-OCH3-SCH3, 5.5%); anal.,
for C18H14ON2S2 (338) calcd./found (%):C(63.88/64.00), H(4.17/4.21),
N(8.28/8.31), S(18.95/19.11).

Synthesis via a Carbonitrile Derivative
2453
Synthesis of 10
Method A
A solution of each of 1 (0.324 g, 1 mmol) in hydrazine hydrate
(10 mL), ethanol (20 mL), and pyridine (10 mL) heated under reflux
for 96 h. The excess solvent evaporated, and the solid formed after cool-
ing was collected by filtration, dried, and recrystallized from ethanol to
afford 10.
Method B
A solution of each of 9 (0.338 g, 1 mmol) in hydrazine hydrate (10
mL) in ethanol (20 mL) heated under reflux for 96 h. The excess
solvent evaporated, and the solid formed after cooling was collected
by filtration, dried, and recrystallized from ethanol to afford 4-(4-
methoxyphenyl)-6-(2-thienyl)-1H-pyrazolo[3,4-b]pyridin-3-amine (10)
as yellow crystals, (81%), m.p. =210◦C, IR υ(cm−1): 3433, 3290 (NH2),
3194 (NH); MS: 322 (M+, 100%), 321 (M+-H, 21.8%), 307 (M+-CH3,
7.2%), 306 (M+-NH2, 3.8%), 305 (306-H, 291 (M+-OCH3, 1.5%); anal.,
for C17H14ON4S (322) calcd./found (%): C(63.33/63.21), H(4.38/4.41),
N(17.38/17.40), S(9.95/10.11).
Synthesis of 11
A solution of each of 10 (0.322 g, 1 mmol) in concentrated hydrochloric
acid (5 mL) and glacial acetic acid (5 mL) was stirred in an ice bath.
Add sodium nitrite solution (0.14 g, 2 mmol) dropwise with stirring
for 30 min. The solid that formed was collected by filtration, washed
with water, and dried to afford 4-(4-methoxyphenyl)-6-(2-thienyl)-1H-
pyrazolo[3,4-b]pyridine-3-diazonium chloride (11) as pale yellow crys-
tals crystallized from ethanol (81%), m.p. =>330◦C, IR υ(cm−1): 3194
(NH), 2156,(N=N); anal., for C17H12ON5SCl (369) calcd./found (%):
C(61.06/60.97), H(3.62/3.71), N(20.94/21.11), S(9.59/9.61).
Reaction of the Diazonium Chloride (11) with Active
Methylene—General Procedure
A solution of each of 12, 16, 21, 27, and 30 (0.066 g, 0.1 g, 0.113 g, 0.192
g, 0.179 g respectively, 1 mmole of each) in ethanol (30 mL) containing
2.0g sodium acetate and 11 (0.369 g, 1 mmole) was stirred at room tem-
perature for 1 h and poured onto ice-cold water. The formed precipitate
collected by filtration, washed with water, and dried to afford 15, 24,
29, and 31 respectively.

2454
A. M. Abdel-Fattah et al.
4-Amino-10-(4-methoxyphenyl)-8-(2-thienyl)-
pyrido[2’,3’:3,4]pyrazolo-[5,1-c][1,2,4]triazine-3-carbonitrile (15)
Orange crystals crystallized from ethanol (81%), m.p. =>330◦C,
IR υ(cm−1): 3417.1, 3273.9 (NH2), 2208.1 (CN); MS: 399 (M+, 100%,
which corresponded to the molecular formula C20H13ON7S of the as-
signed formula), 398 (M+-H, 13.8%), 305 (M+-NH2C=CCN, 5.8%), 290
(305-CH3, 10.6%); 1H NMR (δppm): 3.602 (s, 3H, OCH3), 3.884 (s,
br., 2H, NH2), and 7.14–8.08 (m, 8H, ArH’s and PyridineH’s); anal.,
for C20H13ON7S (339) calcd./found(%): C(60.14/60.22), H(3.28/3.32),
N(24.55/24.61), S(8.03%).
Ethyl 2-Cyano{[4-(4-methoxyphenyl)-6-(2-thienyl)-1H-
pyrazolo[3,4-b]-pyridin-3-yl]hydrazono}acetate (22)
Yellow crystals crystallized from ethanol (83%), m.p. = 160◦C, IR
υ(cm−1): 3188.7(NH), 2956.5, 2853 (Aliphatic CH), 2221.9 (CN), 1694.4
(CO); anal., for C22H18O3N6S (446) calcd./found (%): C(59.18/59.22),
H(4.06/4.00), N(18.82/18.91), S(7.18/7.21).
Ethyl 4-Amino-10-(4-methoxyphenyl)-8-(2-thienyl)-
pyrido[2’,3’:3,4]pyr-azolo[5,1-c][1,2,4]triazine-3-carboxylate (24)
Yellow crystals from ethanol (70%), m.p. = 280 C◦, IR υ(cm−1):
3422.6, 3269.3(NH2), 2921.5, 2849.8 (Aliphatic CH), 1696(CO); MS:
446 (M+, 100% , which corresponded to the molecular weight of the
molecular formula C22H18O3N6S of the assigned formula), 373 (M+-
1
COOEt, 11.7%); H NMR (DMSO, δppm): 1.387 (t, 3H, CH3CH2-, J
= 7.2), 4.436 (q, 2H, CH3CH2-, J = 7.2), 3.875 (s, 3H, OCH3), 7.104–
8.125(m, 8H, ArH, thienyl, and pyridine H’s); anal., for C22H18O3N6S
(446) calcd./found(%): C(59.18/59.22), H(4.06/4.11), N(18.82/18.85),
S(7.18/7.21).
Ethyl 10-(4-Methoxyphenyl)-4-phenyl-8-(2-thienyl)pyrido-
[2’,3’:3,4]-pyrazolo[5,1-c][1,2,4]triazine-3-carboxylate (29)
Yellow crystals crystallized from ethanol (83%), m.p. = 300◦C, IR
υ(cm−1): 3067.1 (Aromatic C-H), 2956.2, 2929.1 (Aliphatic C-H), 1727
(CO); MS: 507 (M+, 44.7% , which corresponded to the molecular weight
of the molecular formula of the assigned formula), 434 (M+- COOEt,
100%), 101 (COOEt, N2, 18.4%); 1H NMR (DMSO, δppm): 1.027 (t,
3H, CH3CH2-, J = 7.0), 3.858 (s, 3H, OCH3), 4.201 (q, 2H, CH3CH2-,
J = 7.1), 7.096–8.080 (m, 13H, ArH’s, thienyl and pyridine H’s); anal.,
for C28H21O3N5S (507) calcd./found(%): C(66.26/66.32), H(4.17/4.22),
N(13.80/13.91), S(6.32/6.33).

Synthesis via a Carbonitrile Derivative
2455
{4-Amino-10-(4-methoxyphenyl)-8-(2-thienyl)pyrido[2’,3’:3,4]-
pyrazolo[5,1-c][1,2,4]triazin-3-yl }(4-chlorophenyl)methanone
(31)
Yellow crystals crystallized from ethanol (81%), m.p. = 300◦C, IR
υ(cm−1): 3381.8, 3240.6 (NH2), 2923.4, 2837.4 (Aliphatic C H), 1635.6
(CO); MS: 512 (M+, 24.9%, which corresponded to the molecular weight
of the molecular formula C26H17ClN6O2S of the assigned formula),
511 (M+-H, 11.5%), 496 (M+-NH2, 23.3%), 494 (M+-H2O, 24.7%), 139
(COC6H4-p-Cl, 67.0%); anal., for C26H17ClN6O2S (512) calcd./found (%):
C(60.88/60.91), H(3.34/3.40), Cl(6.91/7.00), N(16.38/16.41), S(6.25/6.3).
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