Studies of thiazolopyridines, part 6: Synthesis and antimicrobial evaluation of some novel thiazolo[3,2-a] pyridine and thiazolo[2′, 3′:6,1]-pyrido[2,3-d]pyrimidine derivatives

Article abstract of DOI:10.1080/104265090889620

Condensation of thiazolinone 1 with aromatic aldehydes yielded the corresponding methylidene derivatives 2a-f. Cyclization of compounds 2a-f with arylidene-malononitrile 3 (1:1 molar ratio) in ethanol in the presence of piperidine furnished the novel thia

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Studies of Thiazolopyridines,
Part 6: Synthesis
and Antimicrobial
Evaluation of Some Novel
Thiazolo[3,2-a] Pyridine and
Thiazolo[2′,3′:6,1]-pyrido[2,3-
d]pyrimidine Derivatives
G. A. M. El-Hag Ali a , A. K. Khalil b , R. Q. Lamphon
c & A. A. El-Maghraby a
a Department of Chemistry, Al-Azhar University, Nasr
City, Cairo, Egypt
b Department of Chemistry, Ain Shams University
Cairo, Egypt
c Department of Chemistry, King Abdel-Aziz
University, Madine Munawarah, Saudia
Published online: 18 Aug 2006.
To cite this article: G. A. M. El-Hag Ali , A. K. Khalil , R. Q. Lamphon & A. A. El-
Maghraby (2005): Studies of Thiazolopyridines, Part 6: Synthesis and Antimicrobial
Evaluation of Some Novel Thiazolo[3,2-a] Pyridine and Thiazolo[2′,3′:6,1]-pyrido[2,3-
d]pyrimidine Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements,
180:8, 1909-1919
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Phosphorus, Sulfur, and Silicon, 180:1909–1919, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090889620
Studies of Thiazolopyridines, Part 6: Synthesis and
Antimicrobial Evaluation of Some Novel Thiazolo[3,2-a]
Pyridine and Thiazolo[2ꢀ,3ꢀ:6,1]-pyrido[2,3-d]pyrimidine
Derivatives
G. A. M. El-Hag Ali
Department of Chemistry, Al-Azhar University, Nasr City, Cairo, Egypt
A. K. Khalil
Department of Chemistry, Ain Shams University Cairo, Egypt
R. Q. Lamphon
Department of Chemistry, King Abdel-Aziz University, Madine
Munawarah, Saudia
A. A. El-Maghraby
Department of Chemistry, Al-Azhar University, Nasr City, Cairo, Egypt
Condensation of thiazolinone 1 with aromatic aldehydes yielded the correspond-
ing methylidene derivatives 2a–f. Cyclization of compounds 2a–f with arylidene-
malononitrile 3 (1:1 molar ratio) in ethanol in the presence of piperidine furnished
the novel thiazolo[3,2-a]pyridines 5a–v, via Michael adduct 4. Compounds 5p,r
were cyclized with malononitrile in the presence of piperidine to yield thiazolo[3,2-
a][1,8]naphthryidines 7a,b. Thiazolo-[2ꢀ,3ꢀ:1,6]pyrido[2,3-d]pyrimidine 9a–c were
obtained by cyclization of compounds 5c,p,r with formic acid. The structure of the
synthesized compounds was established by analytical and spectral data. Also, some
of the synthesized compounds were screened for antimicrobial activity in vitro.
Keywords Naphthryidine; thiazoline; thiazolo[3,2-a]pyridine;
Thiazolo[3,2-a]pyridines were reported to furnish various biological and
pharmacological activities such as antimicrobial,1 bactericide,2 coro-
nary dilator, antihypertensive, and muscle relaxant3 activities. In con-
tinuation with our work on the synthesis of thiazolo[3,2-a]pyridines,
from readily available starting materials,4−7 we report here on the syn-
thesis of thiazolo[3,2-a] pyridine, thiazolo[3,2-a][1,8]naphthyridine and
Received June 6, 2004; accepted September 7, 2004.
Address correspondence to A. A. El-Maghraby, Department of Chemistry, Al-Azhar
University, Nasr City, Cairo, Egypt. E-mail: m elgaby@hotmail.com
1909

1910
G. A. M. El-Hag Ali et al.
thiazolo[2ꢀ,3ꢀ:1,6]pyrido-[2,3-d]pyrimidine derivatives in order to inves-
tigate the antimicrobial activity of them.
RESULTS AND DISCUSSION
The starting material 1 was synthesized by cyclocondensation of
cyanoacetamide with thioglycolic acid.8 Thiazoline 1 was condensed
with various aromatic aldehydes in ethanol in the presence of piperidine
under reflux to furnish 2-acetamido-5-arylmethylidene-4,5-dihydro-4-
thiazolinones 2a–f (Scheme 1). Cyclocondensation of compounds 2a–f
with benzylidenemalononitriles 3 (1:1 molar ratio) in ethanol at reflux
temperature in the presence of piperidine yielded the novel thiazolo[3,2-
a]-pyridines 5a–v in high yields (Scheme 1). The structures of all
the compounds 5a–c were established using microanalysis and spec-
troscopy. The infrared spectra of thiazolopyridines 5a–v exhibited the
presence of amino, cyano, and carbonyl (thiazolinone and carbamoyl)
1
function groups. Also, the H-NMR spectra revealed a signal charac-
teristic for the 4H-pyridine. The formation of thiazolopyridine 5 is as-
sumed to proceed via Michael addition of methylene function group
in compound 2 to the benzylidene moiety 3 to yield Michael adduct 4
followed by intramolecular cyclization7 at the cyano group to form thi-
azolopyridine 5 (Scheme 1). Also, the structure of thiazolopyridine 5
was established by another synthetic route by ternary condensation of
compound 2, aromatic aldehyde, and malononitrile (1:1:1 molar ratio)
in ethanol in the presence of piperidine under reflux.
The reactivity of thiazolopyridine 5 towards malononitrile was stud-
ied. Thus, when compound 5p,r were allowed to react with malononi-
trile in ethanol containing piperidine under reflux, the condensed pyri-
dine derivatives 7a,b were obtained. On the basis of analytical and
spectral data, the other possible structure 6 was ruled out. The infrared
spectrum of compound 7a showed νC at 1698 cm−1 characteristic for
O
thiazolinone and νC
at 1674 cm−1 (CONH2). Formation of 7 is as-
O
sumed to proceed through the addition of an amino group in 3 to the
cyano group of malononitrile followed by intramolecular cyclization to
furnish 7 (Scheme 2).
Cyclization of compounds 5c,p,r with formic acid furnished the
novel thiazolo[2ꢀ,3ꢀ:6,1]pyrido[2,3-d]pyrimidines 9a–c, via intermediate
amide formation9 8 followed by intramolecular cyclization with formic
acid. Also, cyclocondensation of compound 5c with acetic anhydride un-
der reflux yielded the corresponding thiazolopyridopyrimidine deriva-
tive 10 (Scheme 3). Compound 10 was characterized through the ab-
sence of cyano functional group in its infrared spectrum.

Novel Pyrimidine Derivatives
1911
SCHEME 1
ANTIMICROBAL ACTIVITY
Some of the synthesized compounds were screened in vitro for their
antimicrobal activities against three strains: Staphylococcus aureus

1912
G. A. M. El-Hag Ali et al.
SCHEME 2
SCHEME 3

Novel Pyrimidine Derivatives
1913
TABLE I Antimicrobial Activity of the Synthesized Compounds and
Inhibition Zones (mm). Standard: for Gram Positive and Gram
Negative Bacteria, Ampicillin 25 µg mL−1; for fungi: Mycostatine
30 µg mL−1
Compound
no.
Staphylococcus aureus
Saracia maxima
(ATCC-33910)
Aspergillus
funigatus
(NCTC-7447)
5b
5d
5f
5h
5k
5p
5q
5r
5s
5t
16
12
12
14
17
19
15
18
20
12
13
20
21
19
12
19
17
12
18
18
14
20
13
18
21
20
14
18
18
14
16
15
17
12
25
13
12
20
22
5v
7a
9b
(NCTC-7447), Saracia maxima (ATCC-33910), and Aspergillus funi-
gatus by the agar diffusion techniques.10 The tested compounds were
dissolved in N,N-dimethylformamide (DMF) to get a solution of 1000 µg
mL−1 concentration. The bacteria and fungi cultures were maintained
on nutrient agar and Czapek’s-Dox agar media, respectively. DMF
showed no inhibition zones. The agar media were incubated with differ-
ent microorganisms culture tested. After 24 h of incubation at 30◦C for
bacteria and 48 h of incubation at 28◦C for fungi, the diameter of inhi-
bition zone (mm) was measured (Table I). Ampicillin in a concentration
25 µg mL−1 and mycostatine in a concentration 30 µg mL−1 were used
as references for antibacterial and antifungal activities, respectively.
The results are illustrated in Table I. None of the tested compounds
showed a superior activity than the reference.
EXPERIMENTAL
Melting points are uncorrected. IR spectra were recorded (KBr) on a
Perkin Elmer 1650 spectrophotometer. 1H NMR spectra were recorded
on a Varian Gemini spectrometer 200 (200 MHz), using DMSO-d6
as a solvent and TMS as an internal standard. Chemical shifts are
expressed as δ ppm units. Microanalytical data were obtained from the
Microanalytical Data Unit at Cairo University. Physical data for the
synthesized compounds are given in Table II. Also, the spectral data
are collected in Table III.

1914
G. A. M. El-Hag Ali et al.
TABLE II Characteristics Data for the Prepared Compounds
Elemental analysis
Calcd./Found %
Compound Yield
Solvent
cryst.
M.p.
(◦C)
Molecular
formula (Mol. Wt.)
no.
(%)
C
H
N
2a
2b
2c
2d
2e
2f
62
Benzene/ 240–2
ethanol
Ethanol 197–8
C12H9ClN2O2S
(280)
51.42
51.40
60.10
60.05
51.42
51.30
54.96
54.80
56.52
56.50
55.42
55.40
57.44
57.40
56.28
56.30
58.60
58.60
64.18
64.20
61.53
61.50
61.53
61.50
58.60
58.60
57.44
57.40
56.28
56.30
64.18
64.20
58.60
58.60
58.60
58.60
61.88
3.21
3.00
4.61
4.60
3.21
3.20
3.81
3.90
4.34
4.30
4.43
4.40
3.52
3.50
2.98
3.00
3.32
3.30
4.18
4.20
3.79
3.80
3.79
3.80
3.32
3.30
3.52
3.50
2.98
2.90
4.18
4.20
3.32
3.30
3.32
3.30
4.03
10.00
10.10
10.76
10.70
10.00
10.10
10.68
10.70
10.14
10.10
9.55
10.00
11.65
11.60
11.94
11.90
12.43
12.40
13.02
13.10
12.48
12.50
12.48
12.40
12.43
12.40
11.65
11.60
11.94
11.90
13.02
13.10
12.43
12.40
12.43
12.40
12.55
57
71
83
62
56
63
77
81
69
88
79
74
64
66
75
80
90
72
82
59
77
C
13H12N2O2S
(260)
Benzene 241–3
C
12H9ClN2O2S
(280)
Benzene/ 190–2
ethanol
Benzene 230–2
C
12H10N2O3S
(262)
C13H12N2O3S
(276)
Benzene 220–2
Dioxane 256–8
Benzene 258–9
Benzene 286–8
C
13H13N2O4S
(293)
5a
5b
5c
5d
5e
5f
C23H17ClN4O4S
(480.5)
C
22H14Cl2N4O2S
(469)
C22H15ClN4O3S
(450.5)
C23H18N4O3S
(430)
Benzene
>300
Benzene 220–2
Benzene 226–8
Benzene 271–3
Dioxane 262–4
Benzene 253–5
C23H17ClN4O2S
(448.5)
C23H17ClN4O2S
(448.5)
5g
5h
5i
C
C
22H15ClN4O3S
(450.5)
23H17ClN4O4S
(480.5)
C22H14Cl2N4O2S
(469)
5j
Benzene
>300
C
23H18N4O3S
(430)
5k
5l
Benzene/ 270–2
ethanol
Dioxane 260–2
C
C
22H15ClN4O3S
(450.5)
22H15ClN4O3S
(450.5)
5m
5n
5o
5p
Benzene 282–4
Benzene 254–6
Benzene 262–4
Dioxane 190–2
C
23H18N4O4S
(446)
61.70 4.000 12.50
C23H18N4O5S
(462)
59.74
59.70
60.50
60.40
59.41
59.40
3.89
3.90
4.20
4.20
3.65
3.50
12.12
12.10
11.76
11.80
12.05
12.10
C
24H20N4O5S
(476)
C23H17ClN4O3S
(464.5)
(Continued on next page)

Novel Pyrimidine Derivatives
1915
TABLE II Characteristics Data for the Prepared Compounds
(Continued)
Elemental analysis
Calcd./Found %
Compound Yield
Solvent
cryst.
M.p.
(◦C)
Molecular
formula (Mol. Wt.)
no.
(%)
C
H
N
5q
5r
5s
5t
67
Ethanol
Dioxane
160–2
258–9
C23H17ClN4O3S
(464.5)
59.41
59.40
64.86
64.80
61.88
61.70
59.74
59.70
62.60
62.60
57.44
57.40
58.81
58.80
63.52
63.50
57.68
57.70
58.47
58.50
3.65
3.40
4.50
4.40
4.03
4.10
3.89
3.90
4.34
4.30
3.53
3.50
3.58
3.60
4.31
4.20
2.92
2.90
3.45
3.40
12.05
12.00
12.61
12.60
12.55
12.50
12.12
12.10
12.17
12.20
11.65
11.60
15.83
15.80
16.74
16.70
11.70
11.70
11.37
11.40
87
67
72
68
85
69
59
70
81
63
71
C
C
C
24H20N4O3S
(444)
23H18N4O4S
(446)
23H18N4O5S
(462)
Benzene 240–2
Dioxane >300
5u
5v
7a
7b
9a
9b
9c
10
Benzene/ 238–9
ethanol
Dioxane
C24H20N4O4S
(460)
270–2
C23H17ClN4O4S
(480.5)
Benzene/ 288–9
ethanol
Benzene/ 218–9
ethanol
C26H19ClN6O3S
(530.5)
C
27H22N6O3S
(510)
Dioxane
290
C23H15ClN4O4S
(478.5)
Benzene 210–2
C24H17ClN4O3S
(492.5)
Dioxane
Dioxane
>300
>300
C
25H20N4O4S
(472)
63.55 4.233 11.86
63.50
58.48
58.50
4.20
3.45
3.60
11.50
11.37
11.30
C24H17ClN4O4S
(492.5)
2-(Acetamido-2-yl)-5-arylmethylidene-4,5-dihydro-4-
thiazolinones (2a–f)
A mixture of compound 1 (0.01 mole), aromatic aldehyde (0.01 mole),
and piperidine (0.5 mL) in ethanol (40 mL) was heated under reflux for
3 h. The product obtained was recrystallized from suitable solvent to
give 2a–f.
5-Amino–7-aryl-8-carbamoyl-3-oxo-2-arylmethylidene-2,3-
dihydro-H-thiazolo[3,2-a]pyridine-6-carbonitriles (5a–v)
Method (A):
A mixture of compound 2 (0.01 mole), benzylidene-malononitrile 3
(0.01 mole), and piperidine (0.5 mL) in ethanol (30 mL) was heated

1916
G. A. M. El-Hag Ali et al.
TABLE III Spectral Data of the Synthesized Compounds
Compound
no.
IR/.ν
(cm−1
)
1H NMR(δ/ppm)(DMSO-d6)
max
2a
2b
2e
3379, 3147 (NH2), 2977 (CH-aliph), 3.15 (s, 3H, CH2), 5.40 (s, 2H,
1720 (C O; thiazolinone),
1666 (C O, amide).
NH2), 6.40–7.62 (m, 5H, Ar-H and
methine-H).
3334, 3127 (NH2), 2977 (CH-alph),
1710 (C O; thiazolinone),
1658 (C O; amide).
2.20 (s, 3H, CH3), 3.10 (s, 2H, CH2),
5.20 (s, 2H, NH2), 6.30–7.70 (m,
5H, Ar-H and methine-H).
3300, 3180 (NH2), 2980 (CH-aliph), 3.20 (s, 2H, CH2), 3.60 (s, 3H,
1712 (C O; thiazolinone),
1660 (C O; amide).
OCH3), 5.30 (s, 2H, NH2),
6.25–7.82 (m, 5H, Ar-H and
methine-H).
2f
3379, 3147 (NH2), 2930 (CH-aliph), 3.21 (s, 2H, CH2), 3.85 (s, 3H,
1720 (C O; thiazolinone),
1666 (C O; amide).
OCH3), 5.76 (s, 2H, NH2),
6.90–7.46 (m, 4H, Ar-H and
methine-H), 10.80 (s, 1H, OH).
3.81 (s, 3H, OCH3), 3.99 (s, 1H,
pyridine-H), 5.65 (s, 2H, NH2),
6.66–7.25 (m, 8H, Ar-H and
methine-H), 7.39 (s, 3H, NH2),
10.10 (br, 1H, OH).
5a
3471, 3433 (NH2), 2180 (C N),
1710 (C O; thiazolinone),
1651 (C O; amide).
5b
5c
3386, 3170 (NH2); 2183 (C N),
1697 (C O; thiazolinone),
1651 (C O; amide).
3433, 3332 (NH2); 2183 (C N);
1700 (C O; thiazolinone),
1658 (C O; amide).
3.99 (s, 1H, pyridine-H), 5.76 (s, 2H,
NH2), 6.73–7.50 (m, 9H, Ar-H and
methine-H), 7.54 (s, 2H, NH2).
4.08 (s, 1H, pyridine-H), 5.73 (s,
2H, NH2), 6.74–7.43 (m, 9H, Ar-H
and methine-H), 7.47 (s, 1H,
NH2), 10.90 (br, 1H, OH).
5d
3433, 3147 (NH2), 2109 (C N);
1720 (C O; thiazolinone),
1666 (C O; amide).
2.19 (s, 3H, CH3), 4.15 (s, 1H,
pyridine-H), 5.46 (s, 2H, NH2),
5.87–6.40 (m, 9H, Ar-H and
methine-H), 6.42 (s, 2H, NH2),
10.30 (br, 1H, OH).
5e
5g
5h
3359, 3225 (NH2), 2191 (C N),
1681 (C O; thiazolinone),
1651 (C O; amide).
2.20 (s, 3H, CH3), 4.00 (s, 1H,
pyridine-H), 5.10 (s, 2H, NH2),
6.74–7.51 (m, 9H, Ar-H and
methine-H), 7.54 (s, 2H, NH2).
4.09 (s, 1H, pyridine-H), 5.73 (s,
2H, NH2), 6.74–7.42 (m, 9H, Ar-H
and methine-H), 7.54 (s, 2H,
NH2), 10.90 (br, 1H, OH).
3.90 (s, 3H, OCH3), 4.08 (s, 1H,
pyridine-H), 5.70 (s, 2H, NH2),
6.75–7.48 (m, 8H, Ar-H and
methine-H), 8.04 (s, 2H, NH2),
10.90 (br, 1H, OH).
3433, 3320 (NH2), 2214 (C N),
1720 (C O; thiazoline),
1666 (C O; amide).
3440, 3350 (NH2), 2191 (C N),
1681 (C O; thiazolinone),
1651 (C O; amide).
(Continued on next page)

Novel Pyrimidine Derivatives
1917
TABLE III Spectral Data of the Synthesized Compounds (Continued)
Compound
no.
IR/.ν
(cm−1
)
1H NMR(δ/ppm)(DMSO-d6)
max
5i
3379, 3309 (NH2), 2190 (C N),
1720 (C O; thiazolinone),
1666 (C O; amide).
3425, 3340 (NH2), 2180 (C N),
1700 (C O; thiazolinone),
1666 (C O; amide).
4.08 (s, 1H, pyridine-H), 5.70 (s, 2H,
NH2), 6.82–7.33 (m, 9H, Ar-H and
methine-H), 7.52 (s, 2H, NH2).
4.09 (s, 1H, pyridine-H), 5.73 (s,
2H, NH2), 6.79–7.52 (m, 9H, Ar-H
and methine-H), 7.62 (s, 2H,
NH2), 10.72 (br, 1H, OH).
5k
5l
3386, 3170 (NH2), 2183 (C N);
1690 (C O; thiazolinone),
1658 (C O; amide).
4.24 (s, 1H, pyridine-H), 5.70 (s,
2H, NH2), 6.74–7.58 (m, 9H, Ar-H
and methine-H), 7.62 (s, 2H,
NH2), 10.00 (br, 1H, OH).
5n
5o
3433, 3355 (NH2), 2191 (C N),
1700 (C O; thiazolinone),
1658 (C O; amide).
3.74 (s, 3H, OCH3), 4.32 (s, 1H,
pyridine-H), 5.71 (s, 2H, NH2),
6.73–7.46 (m, 8H, Ar-H and
methine-H), 10.0 (br, 2H, 2OH).
3.76, 3.89 (2s, 6H, 2OCH3), 4.07 (s,
1H, pyridine-H), 5.50 (s, 2H,
NH2), 6.45–7.59 (m, 8H, Ar-H and
methine-H), 8.03 (s, 2H, NH2),
11.20 (br, 1H, OH).
3433, 3355 (NH2), 2214 (C N),
1700 (C O; thiazolinone),
1651 (C O; amide).
5p
5q
5r
3440, 3209 (NH2), 2214 (C N),
1700 (C O; thiazolinone),
1651 (C O; amide).
3.70 (s, 3H, OCH3), 4.12 (s, 1H,
pyridine-H), 5.71 (s, 2H, NH2),
6.48–7.45 (m, 9H, Ar-H and
methine-H), 7.51 (s, 2H, NH2).
3.74 (s, 3H, OCH3), 3.99 (s, 1H,
pyridine-H), 5.47 (s, 2H, NH2),
6.03–7.42 (m, 9H, Ar-H and
methine-H), 11.70 (s, 2H, NH2).
2.2 (s, 3H, CH3), 3.67 (s, 3H,
OCH3), 3.99 (s, 1H, pyridine-H),
5.67 (s, 2H, NH2), 6.68–7.42 (m,
9H, Ar-H and methine-H), 7.78 (s,
2H, NH2).
3355, 3232 (NH2), 2214 (C N),
1720 (C O; thiazolinone),
1657 (C O; amide).
3463, 3348 (NH2), 2214 (C N),
1689 (C O; thiazolinone),
1651 (C O; amide).
5s
5t
3379, 3147 (NH2), 2191 (C N),
1720 (C O; thiazolinone),
1666 (C O; amide).
3.80 (s, 3H, OCH3), 4.11 (s, 1H,
pyridine-H), 5.70 (s, 2H, NH2),
6.85–7.42 (m, 9H, Ar-H and
methine-H), 7.41 (s, 2H, NH2),
10.56 (s, 1H, OH).
3.78 (s, 3H, OCH3), 4.09 (s, 1H,
pyridine-H), 5.55 (s, 2H, NH2),
6.75–7.90 (m, 8H, Ar-H and
methine-H), 7.90 (s, 2H, NH2),
9.01, 13.00 (2br, 2H, 2OH).
3379, 3147 (NH2), 2221 (C N),
1720 (C O; thiazolinone),
1658 (C O; amide).
(Continued on next page)

1918
G. A. M. El-Hag Ali et al.
TABLE III Spectral Data of the Synthesized Compounds (Continued)
Compound
no.
IR/.ν
(cm−1
)
1H NMR(δ/ppm)(DMSO-d6)
max
5v
7a
3463, 3348 (NH2), 2214 (C N),
1689 (C O; thiazolinone),
1651 (C O; amide).
3.76 (s, 3H, OCH3), 4.09 (s, 1H,
pyridine-H), 5.55 (s, 2H, NH2),
6.47–7.35 (m, 9H, Ar-H and
methine-H), 7.90 (s, 2H, NH2),
11.30 (br, 1H, OH).
3.60 (s, 3H, OCH3), 4.10 (s, 1H,
pyridine-H), 5.62 (s, 2H, NH2),
6.48–7.45 (m, 9H, Ar-H and
methine-H), 7.53, 8.62 (s, 2H,
NH2).
3376, 3318 (NH2), 2190 (C N),
1698 (C O; thiazolinone),
1674 (C O; amide).
7b
9c
3318, 3200 (NH2), 2188 (C N),
1700 (C O; thiazolinone),
1676 (C O; amide).
3358, 3176 (NH2), 1702 (C O;
thiazolinone), 1656 (C O; amide).
2.30 (s, 3H, CH3), 3.69 (s, 3H,
OCH3), 4.21 (s, 1H, pyridine-H),
5.67 (s, 2H, NH2), 6.75–7.50 (m,
9H, Ar-H and methine-H), 7.78 (s,
1H, NH), 8.90 (s, 1H,
pyrimidine-H).
10
3318, 3200 (NH2), 1700 (C O;
thiazolinone), 1676 (C O; amide).
3.10 (s, 3H, CH3), 4.32 (s, 1H,
pyridine-H), 5.55 (s, 2H, NH2),
6.74–7.43 (m, 9H, Ar-H and
methine-H), 8.54 (s, 1H, NH),
10.72 (br, 1H, OH).
under reflux for 6 h; the solid product which produced on heating was
collected to give 5.
Method (B):
A mixture of compound 2 (0.01 mole), aromatic aldehyde (0.01 mole),
and malononitrile (0.01 mole) in ethanol (40 mL) was heated under
reflux for 6 h; the solid product which produced on heating was collected
to give 5.
5-Aryl-8-arylmethylidene-6-carbamoyl-2,4-diamino-8,9-
dihydro-H-thiazolo[3,2-a][1,8]naphthyridine-3-carbonitriles
(7a,b)
General Procedure
A mixture of compound 5 (0.01 mole), malononitrile (0.01 mole) in
ethanol (30 mL) was heated under reflux for 3 h. The solid product which
precipitated upon heating was collected by filtration and recrystallized
to give 7.

Novel Pyrimidine Derivatives
1919
5-Aryl-8-arylmethylidene-4-oxo-3,4,8,9-tetrahydro-5H-thia-
zolo-[2ꢀ,3ꢀ:1,6]pyrido[2,3-d]pyrimidine-6-carbamoyl (9a–c)
General Procedure
A mixture of compound 5 (0.01 mole) and formic acid (10 mL) was
heated under reflux for 24 h. The reaction mixture was concentrated
in vacuo and the precipitate was collected by filtration, washed with
water, and recrystallized from a proper solvent to give 9.
Formation of thiazolo[2ꢀ,3ꢀ:1,6]pyrido[2,3-d]pyrimidine
derivative (10)
A solution of compound 5c (0.01 mole) in acetic anhydride (5 mL) was
refluxed for 24 h. The solid product, thus formed after cooling, was
collected and recrystallized to give 10.
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