A novel synthesis of pyridine-2(1H)-thione, pyrazolo[3,4-b]pyridine, pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine, thieno[2,3-b]pyrdine, and pyrido[3',2':4,5]thieno[3,2-d]pyrimidine derivatives containing a naphthyl moiety

Article abstract of DOI:10.1080/10426500601160991

6-Amino-4-naphthyl-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitriles 3a, b were synthesized from the reaction of naphthaldehydes 1a, b and cyanothioacetamide (2). Compounds 3a, b were taken as starting materials for the synthesis of pyrazolo[3,4-b]pyridine 7a, b, and 8a, Pyrido-[2',3':3,4] pyrazolo[1,5-a]pyrimidine 9a, b; thieno[2,3-b]pyridine 16a-d, 18a, b, 21a-d, 24a, b, and 25a; and pyrido[3,2:4,5]thieno[3,2-d]pyrimidine 17a, b derivatives through their reactions with the corresponding reagents. All structures of the newly synthesized heterocyclic compounds were established on the basis of IR, 1H NMR, 13C NMR, mass spectra, and elemental analyses.

Full text of DOI:10.1080/10426500601160991

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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A Novel Synthesis of
Pyridine-2(1H)-thione,
Pyrazolo[3,4-b]pyridine,
Pyrido[2′,3′:3,4]pyrazolo[1,5-
a]pyrimidine, Thieno[2,3-
b]pyrdine, and
Pyrido[3′,2′:4,5]thieno[3,2-
d]pyrimidine Derivatives
Containing a Naphthyl Moiety
Azza M. Abdel Fattah a , Mohamed A. A. Elneairy a &
Mohamed A. M. Gad-Elkareem b
a Chemistry Department, Cairo University, Giza, A.
R., Egypt
b Department of Chemistry, Al-Azhar University
(Assiut branch), Assiut, Egypt
Published online: 29 Aug 2007.
To cite this article: Azza M. Abdel Fattah , Mohamed A. A. Elneairy & Mohamed A.
M. Gad-Elkareem (2007) A Novel Synthesis of Pyridine-2(1H)-thione, Pyrazolo[3,4-
b]pyridine, Pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine, Thieno[2,3-b]pyrdine, and
Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine Derivatives Containing a Naphthyl Moiety,
Phosphorus, Sulfur, and Silicon and the Related Elements, 182:6, 1351-1364, DOI:
10.1080/10426500601160991
To link to this article: http://dx.doi.org/10.1080/10426500601160991

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Phosphorus, Sulfur, and Silicon, 182:1351–1364, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500601160991
A Novel Synthesis of Pyridine-2(1H)-thione,
Pyrazolo[3,4-b]pyridine,
Pyrido[2ꢀ,3ꢀ:3,4]pyrazolo[1,5-a]pyrimidine,
Thieno[2,3-b]pyrdine, and
Pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine Derivatives
Containing a Naphthyl Moiety
Azza M. Abdel Fattah
Mohamed A. A. Elneairy
Chemistry Department, Cairo University, Giza, A. R. of Egypt
Mohamed A. M. Gad-Elkareem
Department of Chemistry, Al-Azhar University (Assiut branch),
Assiut, Egypt
6-Amino-4-naphthyl-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitriles 3a,b were
synthesized from the reaction of naphthaldehydes 1a,b and cyanothioacetamide
(2). Compounds 3a,b were taken as starting materials for the synthesis of
pyrazolo[3,4-b]pyridine 7a,b, and 8a, Pyrido-[2ꢀ,3ꢀ:3,4]pyrazolo[1,5-a]pyrimidine
9a,b; thieno[2,3-b]pyridine 16a–d, 18a,b, 21a–d, 24a,b, and 25a; and
pyrido[3´,2´:4,5]thieno[3,2-d]pyrimidine 17a,b derivatives through their reactions
with the corresponding reagents. All structures of the newly synthesized hetero-
cyclic compounds were established on the basis of IR, 1H NMR, 13C NMR, mass
spectra, and elemental analyses.
Keywords
Pyridine-2(1H)-thiones;
pyrido[2ꢀ,3ꢀ:3,4]pyrazolo-[1,5-a]pyrimidine;
pyrido[3,2:4,5]thieno[3,2-d]pyrimidine; thieno[2,3-b]pyridine
INTRODUCTION
Recently, many chemical structures containing a naphthyl moi-
ety were reported to exhibit diverse biological and pharmaceutical
activities such as anticonvulsant,1 antimicrobial,1,2 anticancer,3,4
anti-allergic,5 antiobesity,6 and antidiabetic6 agents. Moreover, 3,5-
dicyanopyridines were reported to have antiproliferative activity
on human cancer cell lines,7 pyridine-3-carbonitriles were used as
Received October 5, 2006; accepted November 18, 2006.
Address correspondence to Mohamed A. A. Elneairy, Chemistry Department, Faculty
of Science, Cairo University, Giza 12613, Egypt. E-mail: elneairy65@yahoo.com
1351

1352
A. M. Abdel Fattah et al.
cardiotonic agents,8,9 and pyridine-2(1H)-thiones were reported to
have antiviral10 activity. Furthermore, pyrazolo[3,4-b]-pyridines were
used as antimalarial,11 antiproliferative,12 antimicrobial,13 antiviral,14
and inhibitors of cyclin-dependent kinases,15 A1-adenosine receptor
ligands.16 On the other hand, thieno[2,3-b]pyridines were reported
to have antimicrobial,17 antiviral,10,18 and anti-inflammatory19 ac-
tivities. Also pyrido[2ꢀ,3ꢀ:3,4]pyrazolo[1,5-a]pyrimidines revealed
anti-proliferative20 activity. In addition, pyrido[3ꢀ,2ꢀ:4,5]thieno
[3,2-d]-pyrimidines are used as anti-allergic,21 antiprotozoals,22
anti-anaphylactic,23 and antimicrobial17 agents. In view of these
reports and as a continuation of our research program in the chemistry
of pyridines,24−33 we report the synthesis of additional new numbers of
these derivatives that are required in medicinal chemistry programs.
RESULTS AND DISCUSSION
The present work reports a possible route to the synthesis of 6-amino-
3,5-dicyano-4-naphthylpyridine-2(1H)-thiones 3a,b as starting mate-
rials. It has been found that 1-naphthaldehyde (1a) reacted with 2-
cyanoethanethioamide (2a) in a 1:2 molar ratio in ethanolic piperidine
solution under reflux to give the corresponding 6-amino-4-(1-naphthyl)-
2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile (3a). The structure of
3a was established via its elemental analysis, IR, and 1H NMR spectra.
The IR spectrum of 3a revealed NH2 and NH groups at 3450, 3356, and
3302 cm−1 and the CN group at 2214 cm−1, while its 1H NMR spectrum
indicated signals at δ = 7.47–8.08 (m, 7H, Ar-H), 8.12 (s, 2H, NH2), and
13.13 (br, 1H, NH) (cf. Experimental Section and Scheme 1).
SCHEME 1
Similarly, 2-naphthaldehyde (1b) reacted with 2-cyanoethanethio-
amide (2a) in
a 1:2 molar ratio under the same reaction

Pyridine, and Pyrimidine Derivatives
1353
conditions to give the corresponding 6-amino-4-(2-naphthyl)-2-thioxo-1,
2-dihydropyridine-3,5-dicarbonitrile (3b). The structure of 3b was es-
tablished via its elemental analysis, IR spectra (cf. Experimental Sec-
tion and Scheme 1).
The structure 3a,b was elucidated via the synthesis by other routes.
The reaction of 2a with 1a,b gave thiocarboxamidocinnamonitrile
derivatives 4a,b,30 which further reacted with another molecule of 2a
to give 3a,b. Condensation of malononitrile (2b) with 1a,b, followed
by the reaction with 2a, afforded 3a,b. Compounds 3a,b that were pre-
pared by these two routes were found completely identical in all aspects
with 3a,b , which were previously prepared (cf. Scheme 1).
It was found that compound 3a,b reacted with methyl iodide to afford
the corresponding 2-amino-6-(methylthio)-4-(naphthyl)pyridine-3,5-
dicarbonitrile derivatives 5a,b. Compound 5a reacted with hydrazine
hydrate to give a sulfur-free compound corresponding to 3,6-diamino-
4-(1-naphthyl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (7a). The lat-
ter reaction product could be formed via the addition of a hydrazino
group of 6a to the nitrile function. The IR spectrum of 7a showed
the new amino group. Moreover, its mass spectrum gave m/e = 300,
which corresponds to the molecular weight of compound 7a. In the
same manner compound 5b reacted with hydrazine hydrate to give the
corresponding 3,6-diamino-4-(2-naphthyl)-1H-pyrazolo[3,4-b]pyridine-
5-carbonitrile (7b). Compound 7b could be confirmed based on the ele-
mental analysis and spectral data as 7a (cf. Experimental Section and
Scheme 2).
Condensation of 7a with one mole of Dimethylformamide-
dimethylacetal (DMF-DMA) in dry dioxan afforded 6-amino-3-{[(N,N-
dimethylamino)methylene]amino)}-1H-pyrazolo[3,4-b]pyridine deriv-
ative 8a (cf. Scheme 2). The IR spectrum of 8a showed the band at 3424,
3333, and 3216 cm−1, which corresponds to the NH group at the pyra-
zole ring and NH2 on the pyridine ring. Its 1H NMR spectrum revealed
signals at δ 3.09 (s, 3H, CH3, N(CH3)2), 3.19 (s, 3H, CH3, N(CH3)2), 7.32–
7.63 (m, 7H, Ar H), 8.04 (s, 2H, NH2), 8.65 (s, 1H, N CH), and 12.56
(s, 1H, NH). Further elucidation of the structure of 8a was achieved
via its reaction with active methylene compounds such as malononi-
trile (2b) and ethyl cyanoacetate (2c). Compound 8a reacted with mal-
ononitrile (2b) to give the corresponding 4,8-diamino-10-(1-naphthyl)-
pyrido[2ꢀ,3ꢀ:3,4]pyrazolo[1,5-a]pyrimidine-3,9-dicarbonitrile (9a). The
IR spectrum of 9a showed the new amino group on the pyrimidine ring
in addition to the amino group on the pyridine ring.
The 1H NMR spectrum of 9a showed the signals corresponding
to the amino groups. Compound 8a reacted with ethyl cyanoacetate
(2c) to give the corresponding ethyl 4,8-diamino-9-cyano-10-(1-

1354
A. M. Abdel Fattah et al.
SCHEME 2
naphthyl)Pyrido-[2ꢀ,3ꢀ:3,4]pyrazolo[1,5-a]pyrimidine-3-carboxylate
(9b). Compound 9b was confirmed based on elemental analysis and
spectral data.
It has been found that 5a reacted with DMF-DMA to give the for-
mamidine derivative 10. Its IR spectrum showed the absence of the
amino groups. The 1H NMR spectrum of 10 revealed signals for N(CH3)2
and N CH protons and the absence of any signal attributed to the NH2
protons. The reaction of 10 with hydrazine hydrate did not give the ex-
pected product 13, but gave compound 7a. The formation of 7a in this

Pyridine, and Pyrimidine Derivatives
1355
SCHEME 3
reaction is assumed to proceed via the first formation of the non-isolable
hydrazino derivative 11, which would then cyclize via an addition to the
nitrile function at position-3 with the N,N-dimethylaminomethylene
exchange of the hydrazino at position-6 under the applied reaction
conditions leading to regeneration of the amino group27,34 at that po-
sition, and hence the formation of 7a (cf. Experimental Section and
Scheme 2). The structure of 3a,b was confirmed via the reaction of
3a,b with halogenated compounds such as ethyl chloroacetate (14a)
and chloroacetamide (14b) (cf. Scheme 3). Thus, it was found that
compound 3a reacted with ethyl chloroacetate (14a) in methanolic
sodium methoxide solution to yield the corresponding ethyl [6-amino-
3,5-dicyano-4-(1-naphthyl)pyridin-2-yl]thioacetate (15a) via dehydro-
chloronation. The structure of 15a was confirmed by elemental anal-
ysis and spectral data. The IR spectrum of 15a showed the presence
of absorption bands due to CN, NH2and ester CO functional groups
(cf. Scheme 3 and Experimental Section). In a similar manner, com-
pound 3a reacted with 14b to afford the corresponding 2-[6-amino-3,5-
dicyano-4-(1-naphthyl)pyridin-2-yl]thioacetamide (15c). Compound 3b
reacted with each of 14a,b to give the corresponding [6-amino-3,5-
dicyano-4-(2-naphthyl)pyridin-2-yl]thio derivatives 15b,d. The struc-
tures of 15a–d were further elucidated via their cyclization to the
corresponding thieno[2,3-b]pyridine derivatives 16a–d upon boiling in

1356
A. M. Abdel Fattah et al.
ethanolic potassium hydroxide solution. The structures of 16a–d were
inferred from analyses, spectral data, and chemical transformations.
The IR spectra of compounds 16a–d showed the presence of the ab-
sorption bands of the new NH2 group (cf. Scheme 3 and Experimental
Section).
Compounds 16c,d reacted with formic acid to give the corresponding
pyrido[2ꢀ, 3ꢀ:5,4]thieno[3,2-d]pyrimidine derivatives 17a,b. The struc-
ture of compounds 17a,b was confirmed from elemental analyses and
spectral data. Reaction of compounds 15a,b with hydrazine hydrate
gave compounds 7a,b and not the expected acid hydrazide products
18a,b. Compounds 18a,b were prepared via the reaction of 16a,b with
1
hydrazine hydrate. The elemental analyses, IR, H NMR, 13C NMR
and mass spectra of 18a,b were found in good agreement with the as-
signed structures. The mass spectrum of 18a indicated the M+ at m/z
374 (22.3%) and the base peak at m/z 343 (100%), which correspond to
M+ (374)–NHNH2 (31) (cf. Scheme 3 and Experimental Section).
Furthermore, 3a reacted with each of ω–bromoacetophenone deriva-
tives 19a,b in ethanol/piperidine solution under reflux to afford the
corresponding thieno[2,3-b]pyridine derivatives 21a,b, respectively (cf.
Scheme 4). Compounds 21a,b were formed via the non-isolable interme-
diates 20a,b. The other analogue 3b reacted with 19a,b under the same
reaction conditions to give the corresponding thieno[2,3-b]pyridine
SCHEME 4

Pyridine, and Pyrimidine Derivatives
1357
derivatives 21c,d through the non-isolable intermediates 20c,d. Struc-
tures of 21a–d were elucidated on the basis of IR, 1H NMR and elemen-
tal analyses data (cf. Scheme 4 and Experimental Section).
Compounds 3a,b reacted with chloroacetone (22a) in methanolic
sodium methoxide solution at room temperature to afford the cor-
responding thieno[2,3-b]pyridine derivatives 24a,b through the non-
isolable intermediates 23a,b. The reaction seemed to proceed through
dehydrochlorination to give the non-isolable intermediates 23a,b,
which underwent cyclization via addition of the methine or a methylene
group to the nitrile function. Elemental analyses and spectral data were
the basis of which the structures of 24a,b were established. Moreover,
compounds 24a,b were authenticated via the reaction of each of 3a,b
with α-chloroacetylacetone (22b) via the intermediacy of each of the
non-isolable 23c,d. The non-isolable intermediates 23c,d are assumed
to be cyclized to give the corresponding non-isolable 3-imino deriva-
tives that hydrolyzed readily with liberation of one molecule of acetic
acid under the applied reaction conditions to afford the final isolable
24a,b. On the other hand, compound 3a reacted with chloroacetonitrile
to give the corresponding thieno[2,3-b]pyridine derivative 25. Its struc-
ture was confirmed on the basis of elemental analysis and spectral data
(cf. Scheme 4 and Experimental data).
EXPERIMENTAL
Melting points were measured with a Gallenkamp apparatus and are
uncorrected. IR spectra from KBr discs were recorded on a Bruker Vec-
1
tor 22 FT-IR spectrophotometer. H and 13C NMR spectra were deter-
mined 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.
Compounds 4a,b30 were prepared according to the literature proce-
dure.
Synthesis of 6-Amino-4-(naphthyl)-2-thioxo-1,2-
dihydropyridine-3,5-dicarbonitriles 3a,b:
General Procedures
Method A
An equimolecular amount of arylidine 4a,b (0.238 g, 1.0 mmole),
cyanoethanethioamide (2a) (0.1 g, 1.0 mmole) and piperidine (0.5 mL)

1358
A. M. Abdel Fattah et al.
TABLE I Elemental Analyses of the Newly Synthesized Compounds
Solvent
of Cry.
Yield %
% Analysis Calcd./ Found
Compound
No.
Color
Mol. Formula
Mol. wt
M.P., ◦
C
C
H
N
S
Cl
3a
Ethanol
65
Ethanol
60
Ethanol
55
Ethanol
68
Ethanol
65
Ethanol
75
Dioxane
67
Ethanol
70
Yellow
294–296
Yellow
276–278
Yellow
264–268
White
254–256
Yellow
296–298
Yellow
278–280
Yellow
308
C17H10N4S
302
67.54 3.31 18.54 10.59
67.30 3.30 18.40 10.50
67.54 3.31 18.54 10.59
67.40 3.20 18.30 10.40
68.35 3.79 17.72 10.12
68.30 3.60 17.60 10.20
68.35 3.79 17.72 10.12
68.20 3.70 17.60 10.10
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
3b
C
17H10N4S
302
5a
C18H12N4S
316
5b
C
18H12N4S
316
7a
C
17H12N6
300
67.54 4.67 27.80
67.40 4.50 27.70
67.54 4.67 27.80
67.30 4.50 27.60
67.61 4.79 27.61
67.50 4.70 27.60
67.02 3.19 29.70
67.10 3.10 29.70
65.25 4.02 23.17
65.20 3.90 23.10
—
—
—
—
—
—
—
—
—
—
7b
C
17H12N6
300
8a
C
20H17N7
355
9a
Red
354–356
C21H12N8
376
C21H12N8
423
C21H17N5S
371
9b
Acetic acid Yellow
64
Dioxane
70
Ethanol
60
Ethanol
65
Ethanol
64
Ethanol
55
Ethanol
68
Ethanol
55
Ethanol
64
Ethanol
54
Ethanol
70
Ethanol
50
Ethanol
65
320
Yellow
284–286
10
67.92 4.58 18.87 8.63
67.80 4.50 18.70 8.50
15a
15b
15c
15d
16a
16b
16c
16d
17a
17b
18a
18b
Yellow C21H16N4O2S 64.94 4.12 14.43 8.24
202–204
Yellow
210
Yellow
264
388
21H16N4O2S 64.94 4.12 14.43 8.24
388 64.70 4.10 14.20 8.10
C19H13N5OS 63.51 3.62 19.49 8.91
359 63.40 3.50 19.30 8.80
19H13N5OS 63.51 3.62 19.49 8.91
359 63.30 3.50 19.30 8.80
21H16N4O2S 64.94 4.12 14.43 8.24
388 64.70 4.00 14.20 8.20
21H16N4O2S 64.94 4.12 14.43 8.24
388 64.70 4.10 14.20 8.10
19H13N5OS 63.51 3.62 19.49 8.91
359 63.40 3.50 19.30 8.80
C19H13N5OS 63.51 3.62 19.49 8.91
359 63.40 3.40 19.40 8.80
20H11N5OS 65.04 2.98 18.97 8.67
369 65.10 2.80 18.80 8.60
20H11N5OS 65.04 2.98 18.97 8.67
369 64.90 2.90 18.80 8.60
19H14N6OS 60.96 3.74 22.46 8.56
374 60.80 3.60 22.40 8.40
19H14N6OS 60.96 3.74 22.46 8.56
374 60.80 3.60 22.30 8.40
(Continued on next page)
64.80 4.10 14.30 8.20
C
Yellow
220
C
White
310–312
Yellow
>300
Yellow
310
Yellow
272–274
Yellow
200
Yellow
>300
Yellow
278
Yellow
200
C
C
C
C
C
C
C
Ethanol
60

Pyridine, and Pyrimidine Derivatives
1359
TABLE I Elemental Analyses of the Newly Synthesized Compounds
(Continued)
Solvent
% Analysis Calcd./ Found
Compound
No.
of Cry.
Color
Mol. Formula
Mol. wt
Yield % M.P., ◦
C
C
H
N
S
Cl
21a
21b
21c
21d
24a
24b
25
Ethanol
65
Ethanol
55
Ethanol Orange
60 318–320
Ethanol Orange
68
Ethanol
55
Yellow
322–324
Yellow
C25H16N4OS
420
71.42 3.80 13.33 7.61
71.20 3.70 13.20 7.50
—
—
C25H15N4OSC 66.00 3.30 12.32 7.04 7.8
344–346
454.5 65.90 3.20 12.30 6.80 7.8
C25H16N4OS
420
71.42 3.80 13.33 7.61
71.20 3.70 13.20 7.50
—
—
C25H15N4OSC 66.00 3.30 12.32 7.04 7.8
330–332
Yellow
320–322
Yellow
318
454.5
20H14N4OS
358
66.10 3.20 12.30 6.80 7.8
C
67.03 3.91 15.64 8.94
67.10 4.10 15.50 8.80
67.03 3.91 15.64 8.94
67.10 4.10 15.50 8.80
66.86 3.23 20.53 9.38
66.70 3.20 20.40 9.30
—
—
—
—
—
—
Ethanol
65
DMF
68
C20H14N4OS
358
Green
286
C19H11N5S
341
in ethanol (30 mL) was heated under reflux for 5 h. The excess of the
ethanol was evaporated by vacuum. The solid obtained was collected
by filtration and crystallized from ethanol to give 3a,b, respectively (cf.
Tables I and II).
Method B
A mixture of 1- or 2-naphthalaldehyde (1a,b) (0.156 g, 1.0 mmole),
cyanoethanethioamide (2a) (0.2 g, 2.0 mmole), and piperdine (0.5 mL)
in ethanol (30 mL) was heated under reflux for 5 h. The excess of the
ethanol was evaporated by vacuum. The solid obtained was collected
by filtration and crystallized from ethanol to give 3a,b, respectively (cf.
Tables I and II).
Method C
A mixture of 1- or 2-naphthalaldehyde (1a,b) (0.156 g, 1.0 mmole),
cyanoethanethioamide (2a) (0.1 g, 1 mmole), malononitrile (2b) (0.066
g, 1.0 mmole), and piperdine (0.5 mL) in ethanol (30 mL) was heated
under reflux for 5 h. The excess of ethanol was evaporated by vacuum.
The solids obtained were collected by filtration and crystallized from
ethanol to give 3a,b, respectively (cf. Tables I and II).

1360
A. M. Abdel Fattah et al.
TABLE II Spectral Data of the Newly Synthesized Compounds
Compound
No.
Spectral data, IR (cm−1), 1H NHR, 13C NMR and MS
3a
IR: 3450, 3356, 3302 (NH2 and NH) and 2214 (CN); 1H NMR:
(DMSO-d6)δ 7.47–8.08 (m, 7H, Ar-H), 8.12 (s, 2H, NH2, and 13.13 (br.,
1H, NH); 13C NMR (DMSO-d6)δ 82.94, 103.82, 114.15, 116.05, 124.36,
125.31, 125.79, 126.55, 127.24, 128.41, 129.15, 130.0, 132.04, 132.87,
154.43, 158.02 and 179.25.
3b
5a
IR: 3442, 3365, 3308 (NH2 and NH) and 2216 (CN).
IR: 3315, 3193 (NH2) and 2215 (CN); 1H NMR: (DMSO-d6)δ 2.75 (s, 3H,
SCH3), 7.38–7.88 (m, 7H, Ar-H), 8.11 (s, 2H, NH2).
5b
7a
IR: 3320, 3195 (NH2) and 2214 (CN).
IR: 3473, 3354, 3300, 3155 (two NH2and NH) and 2213 (CN); 1H NMR:
(DMSO-d6)δ 6.54 (s, 2H, NH2), 7.42–7.75 (m, 7H, Ar-H), 8.24 (s, 2H,
NH2) and 12.18 (s, 1H, NH); MS: m/z 300 (33%), 301 (100%).
IR: 3460, 3355, 3306, 3150 (two NH2 and NH) and 2215(CN); 1H NMR:
(DMSO-d6)δ 6.79 (s, 2H, NH2), 7.60–8.08 (m, 7H, Ar-H), 8.14 (s, 2H,
NH2) and 11.91 (s, 1H, NH).
7b
8
IR: 3424, 3333 and 3216 (NH2 and NH) and 2214 (CN); 1H NMR:
(DMSO-d6)δ 3.09 (s, 3H, CH3, N(CH3)2), 3.19 (s, 3H, CH3, N(CH3)2),
7.32–7.63 (m, 7H, Ar-H), 8.04 (s, 2H, NH2), 8.65 (s, 1H, N=CH) and
12.56 (s, 1H, NH); 13C NMR (DMSO-d6)δ 32.39, 34.37, 105.13, 117.49,
124.79, 125.22, 125, 64, 126.14, 126.82, 127.79, 128.50, 129.85, 130.92,
132.55, 150.19, 152.40, 153.04, 155.94, 156.01 and 162.47.
IR: 3427, 3391, 3310, 3289 (two NH2), 2214 (CN); 1H NMR: (DMSO-d6)δ
8.04–8.96 (m, 7H, Ar-H), 9.01 (s, 2H, NH2), 9.66 (s, 1H, N=CH) and
9.98 (s, 2H, NH2); 13C NMR (DMSO-d6)δ 78.86, 100.46, 101.93, 114.78,
116.68, 118.49, 118.80, 125.15, 125.92, 128.19, 129.28, 130.18, 131.87,
132.81, 144.08, 148.78, 152.64, 159.40 and 164.42.
9a
9b
IR: 3400, 3336, 3273, 3235, (two NH2); 2218 (CN) and 1694 (ester CO); 1
NMR: (DMSO-d6)δ 1.23–1.27 (t, J = 7.5 Hz, 3H, CH2CH3), 4.26–4.28 (q,
J = 7.5 Hz, 2H, CH2CH3), 7.39–8.13 (m, 9H, Ar-H and NH2), 8.38 (s,
2H, NH2) and 8.83 (s, 1H, CH).
H
10
IR: 2221 (CN); 1H NMR: (DMSO-d6)δ 2.82 (s, 3H, SCH3), 3.06 (s, 3H,
CH3, N(CH3)2), 3.11 (s, 3H, CH3, N(CH3)2), 7.42–7.83 (m, 7H, Ar-H)
and 8.55 (s, 1H, N=CH).
15a
15b
IR: 3479, 3325 (NH2), 2214 (CN) and 1743 (ester CO).
IR: 3475, 3320, (NH2), 2218 (CN), and 1745 (ester CO); 1H NMR:
(DMSO-d6)δ 1.21–1.26 (t, J = 7.2 Hz, 3H, CH2CH3), 4.13–4.20 (q, J =
7.2 Hz, 2H, CH2CH3), 4.22 (s, 2H, SCH2), 7.61–8.09 (m, 7H, Ar-H), and
8.15 (s, 2H, NH2).
15c
15d
16a
IR: 3450, 3417, 3294, 3178 (two NH2), 2217 (CN) and 1651 (amidic CO).
IR: 3452, 3402, 3332, 3224 (two NH2), 2214(CN) and 1643 (amidic CO).
IR: 3478, 3367, 3294, 3198 (two NH2), 2218 (CN) and 1690 (CO-ester with
H-bond).
16b
IR: 3400, 3356, 3273, 3178 (two NH2), 2216 (CN) and 1694 (CO-ester with
H-bond); MS: m/z 388 (53.2%), 316 (100%).
(Continued on next page)

Pyridine, and Pyrimidine Derivatives
1361
TABLE II Spectral Data of the Newly Synthesized Compounds
(Continued)
Compound
No.
Spectral data, IR (cm−1), 1H NHR& 13C NMR and MS
16c
IR: 3479, 3425, 3379, 3325, 3325, 3209 (three NH2), 2214 (CN) and 1635
(amidic-CO with H-bond).
16d
17a
IR: 3490, 3402, 3332, 3224 (three NH2), 2214 (CN) and 1643 (amidic-CO);
1H NMR: (DMSO-d6)δ 5.58 (s, 2H, NH2), 6.97 (s, 2H, NH2), 7.33 (s, 2H,
NH2) and 7.57–8.12 (m, 7H, Ar-H).
IR: 3490, 3332, 3200 (NH2 and NH), 2214 (CN) and 1658 (CO); 1H NMR:
(DMSO-d6)δ 7.55–7.67 (m, 7H, Ar-H), 8.05 (s, 2H, NH2), 8.11 (s, 1H,
CH) and 8.14 (s, 1H, NH).
17b
18a
IR: 3495, 3336, 3204 (NH2 and NH), 2214 (CN) and 1651(CO).
IR: 3463, 3402, 3301, 3186 (three NH2 and NH), 2214 (CN) and 1630(CO);
1H NMR: (DMSO-d6)δ 4.32 (br, 2H, NH2), 5.24 (br, 2H, NH2), 7.36–7.74
(m, 7H, A-rH), 8.19 (s, 2H, NH2) and 8.84 (s, 1H, NH); 13C NMR:
(DMSO-d6)δ 90.66, 115.46, 124.34, 125.42, 126.44, 126.75, 127.48,
128.50, 129.89, 130.86, 132.81, 145.42, 145.70, 150.10, 158.41, 188.71.
IR: 34643, 3400, 3309, 3196 (three NH2 and NH), 2214 (CN) and
1635(CO).
18b
21a
IR: 3467, 3334, 3220, 3178 (two NH2), 2214 (CN) and 1650 (CO); 1H NMR:
(DMSO-d6)δ 5.55 (br, 2H, NH2), 6.68–7.47 (m, 14H, A-rH and NH2); 13
C
NMR: (DMSO-d6)δ 91.58, 99.65, 113.34, 114.99, 124.18, 125.60, 126.40,
126.81, 128.27, 129.52, 130.22, 132.98, 140.78, 150.64, 152.00, 159.24,
166.17, 183.09 and 187.50; MS: m/z 420 (100%), 77 (48.1%).
IR: 3467, 3334, 3220, 3178 (two NH2), 2219 (CN) and 1650 (CO).
IR: 3467, 3334, 3220, 3178 (two NH2), 2217(CN) and 1654 (CO).
IR: 3467, 3334, 3220, 3178 (two NH2), 2214(CN) and 1656 (CO); 1H NMR:
(DMSO-d6)δ 6.75 (br, 2H, NH2), 7.56–8.17 (m, 11H, Ar-H) and 8.21 (s,
2H, NH2).
21b
21c
21d
24a
IR: 3437, 3324, 3210, 3188 (two NH2), 2218(CN) and 1646 (CO with
H-bond); 1H NMR: (DMSO-d6)δ 2.21 (s, 3H, CH3), 5.95 (br, 2H, NH2),
7.38–8.12 (m, 7H, Ar-H) and 8.21 (s, 2H, NH2).
24b
25
IR: 3447, 3354, 3230, 3198 (two NH2), 2216(CN) and 1643 (CO With
H-bond).
IR: 3464, 3229, 3221, 3163 (two NH2), 2193 (CN); 1H NMR: (DMSO-d6)δ
4.96 (s, 2H, NH2), 7.40–8.13 (m, 7H, Ar-H) and 8.23 (s, 2H, NH2).
Synthesis of 2-Amino-6-(methylthio)-4-(naphthyl)pyridine-3,5-
dicarbonitriles 5a, b
A solution of each of 3a,b (0.302 g, 1.0 mmole) and methyl iodide (0.213
mL, 1.5 mmole) in sodium methoxide (prepared from 0.01 mol sodium
metal in 30 mL of methanol) was heated under reflux for 2 h and then
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 5a,b, respectively (cf. Tables I and II).

1362
A. M. Abdel Fattah et al.
Reactions with Hydrazine Hydrate: General Procedure
A solution of the appropriate 5a, b or 10 (0.316 or 0.371 g, 1.0 mmole)
in hydrazine hydrate (15 mL) and ethanol (20 mL) was heated under
reflux for 5 h. The solid products formed were collected by filtration and
crystallized from the proper solvent to give 7a,b and 7a, respectively
(cf. Tables I and II).
Reactions of 5a and/or 7a with DMF-DMA
A mixture of the appropriate 5a or 7a (0.316 or 0.3 g, 1.0 mmole) and
DMF-DMA (1.692 mg, 1.2 mmole) in dry dioxane (30 mL) was heated
under reflux for 3 h. The solids obtained after cooling were collected by
filtration and crystallized from dioxane to give 10 and 8a, respectively
(cf. Tables I and II).
Synthesis of 4,8-Diamino-10-(1-naphthyl)pyrido[2ꢀ,3ꢀ:3,4]-
pyrazolo[1,5-a]pyrimidine-3,9-dicarbonitrile (9a) and Ethyl
4,8-Diamino-9-cyano-10-(1-naphthyl)pyrido[2ꢀ,3ꢀ:3,4]pyrazolo-
[1,5-a]pyrimidine-3-carboxylate (9b)
A mixture of compound 8a (0.355 g, 1.0 mmole) and either malononi-
trile (2b) or ethyl cyanoacetate (2c) (0.066 g or 0.113 ml, 1.0 mmole)
in ethanol (30 mL) containing 0.5 mL of triethylamine, as a catalyst,
was heated under reflux for 5 h. The solid products formed were col-
lected by filtration and crystallized from the proper solvent to give 9a,b,
respectively (cf. Tables I and II).
Reactions of 3a,b with Halogen-Containing Compounds
General Procedure
A solution of 3a,b (0.302 g, 1.0 mmole) and the appropriate 14a,b,
19a,b, 22a,b and/or chloroacetonitrile (1.0 mmole) in sodium methoxide
(prepared from 0.023 g, 1.0 mmole, of sodium metal in 30 mL methanol)
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
the proper solvent to give 15a–d, 21a–d, 24a,b, and 25, respectively
(cf. Tables I and II).
Cyclization of 15a-d
A solution of the appropriate 15a,b (0.388 g, 1.0 mmole) in ethanol
(30 mL) and potassium hydroxide (0.112 g, 2.0 mmole) was heated under

Pyridine, and Pyrimidine Derivatives
1363
reflux for 4 h. The mixture was cooled, poured on to ice-cold water, and
acidified with hydrochloric acid. The solid products were collected by
filtration, washed with water, and crystallized from the proper solvent
to give 16a–d, respectively (cf. Tables I and II).
Synthesis of 7-Amino-9-(naphthyl)-4-oxo-3,4-dihydropyrido-
[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-8-carbonitriles 17a,b
A solution of 16c,d (0.359 g, 1.0 mmole) in formic acid (20 mL) was
heated under reflux for 5 h. The excess solvent was evaporated by vac-
uum. The solids obtained were collected by filtration and crystallized
from ethanol to give 17a,b (cf. Tables I and II).
Synthesis of 3,6-Diamino-5-cyano-4-(naphthyl)thieno
[2,3-b]pyridine-2-carbohydrazides 18a, b
A solution of 16a,b (0.388 g, 1.0 mmole) in hydrazine hydrate (20 mL)
and ethanol (20 mL) was heated under reflux for 3 h. The solid products
obtained after cooling were collected by filtration and crystallized from
ethanol to give 18a,b (cf. Tables I and II).
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