Synthesis of some new heterocycles derived from ethyl 7-amino-3-(3-methyl- 5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-5h-thiazolo[3,2-a]pyrimidine-6- carboxylate of biological importance

Article abstract of DOI:10.1002/jhet.735

Ethyl 7-amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-5H- thiazolo[3,2-a]pyrimidine-6-carboxylate was synthesized by the reaction of 4-(2-aminothiazol-4-yl)-3-methyl-5-oxo-1-phenyl-2-pyrazoline with arylidene ethyl cyanoacetate and it transformed to related fused heterocyclic systems via reaction with various reagents. The biological activities of these compounds were evaluated.

Full text of DOI:10.1002/jhet.735

March 2013
Synthesis of Some New Heterocycles Derived from Ethyl
7-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-5H-
thiazolo[3,2-a]pyrimidine-6-carboxylate of Biological
Importance
179
*
Mohamed Salah K. Youssef, Mohamed S. Abbady, Ragaa A. Ahmed, and
Ahmed A. Omar
Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt
*
E-mail: salah_kamel2000@yahoo.com
Received August 7, 2010
DOI 10.1002/jhet.735
Published online 20 March 2013 in Wiley Online Library (wileyonlinelibrary.com).
Ethyl 7-amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-5H-thiazolo[3,2-a]pyrimidine-6-
carboxylate was synthesized by the reaction of 4-(2-aminothiazol-4-yl)-3-methyl-5-oxo-1-phenyl-2-pyrazoline
with arylidene ethyl cyanoacetate and it transformed to related fused heterocyclic systems via reaction with
various reagents. The biological activities of these compounds were evaluated.
J. Heterocyclic Chem., 50, 179 (2013).
INTRODUCTION
3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-arylthiazolo
[3,2-a]pyrimidine 3a,b. With hydrazine hydrate, 1a,b gave
the corresponding carbohydrazide derivatives 7-amino-3-(3-
methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-5H-thiazolo
[3,2-a]pyrimidine-6-carbohydrazide 4a,b. Interaction of 1a,b
with phenyl isothiocyanate gave the fused tricyclic com-
pounds 3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-
5-aryl-7-phenyl-7,9-dihydro-5H-thiazolo[3,2-a]pyrimido
[4,5-d]pyrimidine-8-thione 5a,b, which were alkylated
with ethyl iodide to give 8-ethylthio-3-(3-methyl-5-oxo-
1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-aryl-7-phenyl-5,7-
dihydrothiazolo[3,2-a]pyrimido[4,5-d]pyrimidine 6a,b.
Reaction of compound 6a,b with hydrazine hydrate afforded
3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-aryl-
7-phenyl-5,7-dihydro-8-hydrazinothiazolo-[3,2-a]pyrimido
[4,5-d]pyrimidine 7a,b (Scheme 1).
The formation of a new fused heterocyclic ring is an
important task for heterocyclic chemistry from various
points of view. The reactions of thiazolo[3,2-a]pyrimidines
have attracted the attention of many chemists and used
them in the synthesis of different heterocycles [1–15]
possessing biological [10–14] and medicinal activities
[15]. These observations in continuation with our general
interest in these compounds led us to examine the chemistry
of pyrazolinyl thiazolopyrimidine carboxylate to be used as
starting material for the synthesis of novel thiazolopyrimidines
and thiazolopyrimidopyrimidines bearing pyrazolone moiety,
which have biological activities.
RESULTS AND DISCUSSION
This investigation was directed toward the synthesis
of novel pyrazolinyl thiazolopyrimidine and pyrazolinyl
thiazolopyrimidopyrimidine derivatives. We report herein
reactions of ethyl 7-amino-3-(3-methyl-5-oxo-1-phenyl-2-
pyrazolin-4-yl)-5-aryl-5H-thiazolo[3,2-a]pyrimidine-6-carbox-
ylate 1a,b to synthesize new compounds containing both
pyrazolone, thiazole and pyrimidine moieties, and evaluate
their biological activities. Thus reaction of compound 1a,b
with acetyl and/or benzoyl chloride gave the corresponding
acetyl- or benzoyl derivatives 7-acetylamino-6-carboethoxy-
3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-arylthiazolo
[3,2-a]pyrimidine 2a,b and/or 7-benzoylamino-6-carboethoxy-
The o-amino carbohydrazide function of compound 4a,
b was exploited to synthesize further fused pyrimidine
derivatives. Thus, reaction of 4a,b with formic acid, acetic
anhydride, and/or urea afforded 3-(3-methyl-5-oxo-1-
phenyl-2-pyrazolin-4-yl)-6-oxo-5-aryl-7-N-formylamino-
5,7-dihydro -5H-thiazolo[3,2-a]pyrimido[4,5-d]pyrimidine
8a,b, 3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-
5-aryl-8-methyl-7-N,N-diacetylamino-5,7-dihydrothiazolo
[3,2-a]pyrimido[4,5-d]pyrimidine 9a,b, and 3-(3-methyl-
5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-7-amino-7,9-dihydro-
5H-thiazolo[3,2-a]pyrimido[4,5-d]pyrimidine-6,8-dione 10a,b
respectively.
© 2013 HeteroCorporation

180
M. S. K. Youssef, M. S. Abbady, R. A. Ahmed, and A. A. Omar
Vol 50
Scheme 1
Reaction of carbohydrazide compound 4a,b with
The biocidal activity of the synthesized compounds
was tested against Gram-positive and Gram-negative bac-
teria as well as against yeast-like and filamentous fungi
(Table 1). All microbes are potentially pathogenic espe-
cially for debilitated, malnourished, or immunosuppressed
individuals. Different compounds showed varying antimi-
crobial action depending on the microorganism species
and the compound itself. Compounds 2b, 4b, 5a, and
8a proved to be excellent candidates as antibacterial
agents being able to inhibit all bacterial species tested.
Staphylococcus aureus was the most sensitive organism
being inhibited with ≤2.5 mg/mL of these compounds.
Compounds 3a, 6b, 7a, 9a, and 10b were also effective
but often at higher concentrations ranging from 10–20
mg/mL. The rest of the tested compounds showed
narrower spectrum of antibacterial activity.
Regarding the antifungal action, compounds 3a, 4b, 8a,
8b, and 9a were inhibitory to most or all tested fungi with
MICs ≤ 20 mg/mL. Geotrichum candidum (frequently
reported to cause geotrichosis in human and animals) was
sensitive to 12 out of the 20 compounds tested. Aspergillus
flavus (a famous allergenic, pathogenic, and toxigenic
mold) showed sensitivity to 7 compounds and was mark-
edly inhibited by compound 8b with MIC 10 mg/mL and
high sensitive to 9a with MIC 2.5 mg/mL. Candida
acetylacetone or triethyl orthoformate gave 4-(7-amino-6-
(3,5-dimethyl-1H-pyrazole-1-carbonyl)-5-aryl-5H-thiazolo
[3,2-a]pyrimidin-3-yl)-3-methyl-1-phenyl-2-pyrazolin-5-one
11a,b or 3-(3-methyl-5-oxo-1-phenyl-2-pyraz-olin-4-yl)-6-
oxo-5-aryl-7-ethoxymethyleneamino-5,7-dihydro-5H-thiazolo
[3,2-a]pyrimido[4,5-d]pyrimidine 12a,b (Scheme 2).
Also, reaction of 4a,b with nitrous acid gave 7-amino-3-
(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-5H-
thiazolo[3,2-a]pyrimidine-6-carboazide 13a,b, which refluxed
with toluene underwent Curtius rearrangement to give 7-(3-
methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-9-aryl-2-oxo-
1,3-dihydro-9H-imidazo[4,5-d]thiazolo[3,2-a]pyrimidine
14a,b.
Condensation of 4a,b with benzaldehyde in the presence
of a catalytic amount of piperidine gave benzaldehyde,7-
amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-
5H-thiazolo[3,2-a]- pyrimidine-6-carbohydrazone 15a,b,
which reacted with triethyl orthoformate to give 7-
benzylideneamino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-6-oxo-5-aryl-5H-thiazolo[3,2-a]pyrimido-[4,5-d]
pyrimidine 16a,b (Scheme 3).
The structure of new compounds was confirmed on the
basis of elemental analyses and spectral data (1H NMR,
13C NMR, IR, and MS).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2013 Synthesis of Some New Heterocycles Derived from Ethyl 7-Amino-3-(3-methyl-5-oxo-1-phenyl-2- 181
pyrazolin-4-yl)-5-aryl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate of Biological Importance
Scheme 2
spectrometer, and a varian 1H-Gemini 400 spectrometer with
albicans (cause of candidosis in humans and animals) and
Scopulariopsis brevicaulis (often reported as a cause of
nail infections) were also inhibited by some compounds
as shown in Table 1. Trichophyton rubrum (usually involved
chemical shifts expressed in δ ppm using TMS as the internal
reference.13C NMR spectra were obtained on a varian 1H-Gemini
400 spectrometer. The mass spectra were run on JOEL JMS 600
spectrometer.
in skin and nail infections) was successfully inhibited by
7-Amino-6-carboethoxy-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
compounds 3a, 8b, and 9a at MIC of 20 mg/mL. Fusarium
oxysporum (one of famous plant pathogens) was also
sensitive to compounds 3a, 4b, 5a, and 8b (MICs between
10–20 mg/mL).
4-yl)-5-phenyl-5H-thiazolo[3,2-a] pyrimidine [16] (1a). A
mixture of 4-(2-aminothiazol-4-yl)-3-methyl-5-oxo-1-phenyl-
2-pyrazoline (10 mmol) and benzylidene ethyl cyanoacetate
(10 mmol) in ethanol (30 mL) and piperidine (five drops) was
refluxed for 10 h. The reaction mixture was poured into cold
water, and the solid precipitate was collected, dried, and
crystallized from toluene to give 1a.
CONCLUSIONS
7-Amino-6-carboethoxy-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-5-pchlorophenyl-5H-thiazolo[3,2-a]pyrimidine (1b). A mixture
of 4-(2-aminothiazol-4-yl)-3-methyl-5-oxo-1-phenyl-2-pyrazoline
(10 mmol) and p-chlorobenzylidene ethyl cyanoacetate (10
mmol) in ethanol (30 mL) and piperidine (five drops) was
refluxed for 10 h. The reaction mixture was poured into cold
water and the solid precipitate was collected, dried, and
crystallized from toluene to give pale yellow crystals, yield
3.65 g (72%), mp 286–288°C; IR (KBr): 3100–3250 (NH2),
2915 (CH aliphatic), 1710 (CO ester), 1640 (CO pyrazolone)
cm-1. 1H NMR (CDCl3, 400 MHz): δ = 7.64–7.24 (m, 5H,
phenyl protons), 7.15–7.00 (m, 4H, phenyl protons), 6.90
(s, thiazole-H), 6.70 (s, pyrimidine-H), 6.60 (s, pyrazolone-H),
5.40 (s, NH2 exchangable with D2O), 4.19 (q, J = 7.00 Hz,
CH2), 2.25 (s, pyrazolone CH3), 1.20 (t, J = 7.00Hz, CH3) ppm.
13C NMR (CDCl3, 400 MHz): δ = 170 (CO pyrazolone),
167 (CO ester), 162 (C═N pyrimidine), 159 and 105 (C═C
This investigation was directed toward the synthesis of
novel pyrazolinyl thiazolopyrimidine and pyrazolinyl
thiazolopyrimidopyrimidine derivatives by the reaction of
amino ester derivatives with various reagents. The synthe-
sized compounds were tested against some strains of bacteria
and fungi and some of them exhibit antimicrobial activity.
EXPERIMENTAL
Melting points were determined on APP. Digital ST 15 melting
point apparatus and are uncorrected. Elemental analyses (C, H, N,
S) were conducted using a Vario EL C, H, N, S Analyzer;
their results were found to be in good agreement ( 0.3%) with
the calculated values. The IR spectra were obtained on a Pye-
Unicam SP 3-100 spectrophotometer using the KBr disc technique
1
(νmax in cm1). H NMR spectra were recorded on EM 90 NMR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

182
M. S. K. Youssef, M. S. Abbady, R. A. Ahmed, and A. A. Omar
Vol 50
Scheme 3
pyrimidine), 157 (C═N pyrazolone), 154 (C thiazole), 141–127
(C and CH phenyl rings), 89 (CH thiazole), 60 (CH2 ethyl),
50 (CH pyrazolone), 45 (CH pyrimidine), 18 (CH3 pyrazolone),
14 (CH3 ethyl) ppm. EI ms: m/z = 509.38 [M++2] (15), 506.89
[M+] (49), 473.01(35), 456.51 (24), 444.14 (41), 387.01(40),
316.12 (51), 271.92 (19), 174.00 (71), 37.05 (11), 35.27 (17).
7-Acetylamino-6-carboethoxy-3-(3-methyl-5-oxo-1-phenyl-
2-pyrazolin-4-yl)-5-aryl-5H-thiazolo [3,2-a]pyrimidine 2a,b. A
mixture of 1a or 1b (10 mmol) and acetyl chloride (5 mL) in
pyridine (15 mL) was refluxed for 3 h. The reaction mixture
was cooled, poured into cold water, and the solid separated
pyridine (15 mL) was refluxed for 3 h. The reaction mixture was
cooled and the solid product thus separated was filtered off,
treated with pet. ether (60–80°C) and crystallized from the proper
solvent to give 3a and 3b, respectively.
7-Benzoylamino-6-carboethoxy-3-(3-methyl-5-oxo-1-phenyl-2-
pyrazolin-4-yl)-5-phenyl-5H-thiazolo[3,2-a]pyrimidine (3a). Crystallized
from ethanol to give pale brown powder, yield 4.04 g (70%), mp
215–217°C. IR (KBr): 3250 (NH exchangable with D2O), 2915
(CH aliphatic), 1710 (CO ester), 1690 (CO benzoyl), 1640 (CO
pyrazolone) cm−1. 1H NMR (DMSO-d6, 90MHz): δ = 7.90 (s, NH
exchangable with D2O), 7.70–7.10 (m, 15H, phenyl protons), 7.00
(s, thiazole-H), 6.90 (s, pyrimidine-H), 6.80 (s, pyrazolone-H),
4.00 (q, J = 6.70 Hz, CH2 ester), 2.30 (s, pyrazolone-CH3), 1.20
(t, J = 6.70 Hz, CH3 ester) ppm.
7-Benzoylamino-6-carboethoxy-3-(3-methyl-5-oxo-1-phenyl-
2-pyrazolin-4-yl)-5-p-chlorophenyl-5H-thiazolo[3,2-a]pyrimidine
(3b). Crystallized from ethanol to give red powder, yield 4.28 g
(70%), mp 200–202°C. IR (KBr): 3250 (NH), 2915 (CH aliphatic),
1710 (CO ester), 1690 (benzoyl), 1640 (pyrazolone) cm−1. 1H
NMR (DMSO-d6, 90MHz): δ = 7.90 (s, NH exchangable with
D2O), 7.70–7.20 (m, 14H, phenyl protons), 7.00 (s, thiazole-H),
6.90 (s, pyrimidine-H), 6.80 (s, pyrazolone-H), 4.00 (q, J = 6.60
Hz, CH2 ester), 2.30 (s, CH3-pyrazolone), 1.20 (t, J = 6.60 Hz,
CH3 ester) ppm.
product was filtered off to give 2a and 2b, respectively.
7-Acetylamino-6-carboethoxy-3-(3-methyl-5-oxo-1-phenyl-2-
pyrazolin-4-yl)-5-phenyl-5H-thiazolo [3,2-a]pyrimidine (2a). Crystallized
from benzene to give white crystals, yield 3.86 g (72%), mp
210–212°C. IR (KBr): 3100–3250 (NH2), 2915 (CH aliphatic),
1710 (CO ester), 1685 (CO acetyl), 1640 (CO pyrazolone) cm−1
.
1H NMR (CDCl3, 90 MHz): δ = 8.30 (s, NH exchangable with
D2O), 7.70–7.20 (m, 10H, phenyl protons), 7.00 (s, thiazole-H),
6.90 (s, pyrimidine-H), 6.80 (s, pyrazolone-H), 4.10 (q, J = 6.70
Hz, CH2), 3.20 (s, CH3 acetyl), 2.30 (s, pyrazolone-CH3), 1.3
(t, J = 6.70 Hz, CH3) ppm.
7-Acetylamino-6-carboethoxy-3-(3-methyl-5-oxo-1-phenyl-2-
pyrazolin-4-yl)-5-p-chlorophenyl-5H-thiazolo[3,2-a]pyrimidine (2b).
Crystallized from benzene to give white powder, yield 3.74g (68%),
mp 219–221°C. IR (KBr): 3100–3250 (NH2), 2915 (CH aliphatic),
1710 (CO ester), 1685 (CO acetyl), 1640 (CO pyrazolone) cm−1. 1H
NMR (DMSO-d6, 90 MHz): δ = 8.20 (s, NH exchangable with
D2O), 7.70–7.40 (m, 9H, phenyl protons), 7.00 (s, thiazole-H),
6.90 (s, pyrimidine-H), 6.80 (s, pyrazolone-H), 4.10 (q, J = 10
Hz, CH2), 3.20 (s, CH3 acetyl), 2.30 (s, CH3 pyrazolone), 1.3
(t, J = 10 Hz, CH3) ppm.
7-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-
5H-thiazolo[3,2-a]pyrimidine-6-carbohydrazide 4a,b. A mixture of
1a or 1b (10 mmol) and hydrazine hydrate 98% (1.5 mL,
10 mmol) was refluxed for 2 h. The reaction mixture was cooled,
and the solid thus formed was collected and crystallized from the
proper solvent to give 4a and 4b, respectively.
7-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-phenyl-
5H-thiazolo[3,2-a] pyrimidine-6-carbohydrazide (4a). Crystallized
from ethanol to give white crystals, yield 3.08 g (67%), mp
270–272°C. ir (KBr): 3250–3450 (NHNH2, NH2), 1680 (CO
7-Benzoylamino-6-carboethoxy-3-(3-methyl-5-oxo-1-phenyl-
2-pyrazolin-4-yl)-5-aryl-5H-thiazolo [3,2-a]pyrimidine 3a,b. A
mixture of 1a or 1b (10 mmol) and benzoyl chloride (5 mL) in
1
carbohydrazide), 1635 (CO pyrazolone) cm−1. H NMR (CDCl3,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2013 Synthesis of Some New Heterocycles Derived from Ethyl 7-Amino-3-(3-methyl-5-oxo-1-phenyl-2- 183
pyrazolin-4-yl)-5-aryl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate of Biological Importance
Table 1
The minimum inhibitory concentrations of the compounds tested (mg/mL).
2a 2b 3a 3b 4a 4b
5a 5b 6a 6b 7a 7b 8a
8b
9a 9b 10a 10b 11a 11b
Ref*
Bacteria
Bacillas cereus
(Gram positive)
Staphylococcus aureus
(Gram positive)
Pseudomonas aeruginosa
(Gram negative)
Serratia marcescens
(Gram negative)
Escherichia coli
–
10 20
20 10
–
–
–
–
1.25 20
–
–
–
–
–
–
20
2.5
–
–
10 20
–
20
–
–
–
–
–
20 20
–
–
–
–
–
–
0.25
–
–
0.25 10
20
–
2.5
2.5
–
–
0.25 2.5 0.25
–
–
20
20
0.125
–
–
–
–
2.5 20
20
–
20
20
–
20
–
20
5
20 2.5 20
10
20
10 20 10 10
–
–
20 20 20
1.25
1.25
–
10
20
20 2.5 20 20 20
–
20
–
20
20
20
–
–
–
(Gram negative)
Fungi
Geotrichum candidum
Candida albicans
Fusarium oxysporum
Aspergillus flavus
Scopulariopsis brevicaulis 20
Trichophyton rubrum
–
20
–
–
20
20 20
20
–
–
–
–
–
–
–
–
–
10
10
10
20
10
–
–
20
20
–
–
20
–
–
–
–
–
–
–
–
–
20
–
–
20
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
20
–
20
20
20 10
20 20 20 20 20
2.5
2.5
2.5
2.5
2.5
2.5
–
–
–
–
–
20
–
10
–
20
2.5
–
–
–
–
–
–
–
–
–
–
–
–
20
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
10 20
20 20
–
20
–
–
–
–
–
*Ref. = Reference drugs = (chloramphenicol as antibacterial and clotrimazole as antifungal).
(–) = No antimicrobial action.
400 MHz): δ = 9.50 (s, NH exchangable with D2O), 7.64–7.24 (m,
5H, phenyl protons), 7.19 (s, NH2 exchangable with D2O), 7.14–
7.06 (m, 5H, phenyl protons), 6.90 (s, thiazole-H), 6.70
(s, pyrimidine-H), 6.60 (s, pyrazolone-H), 5.39 (s, NH2 pyrimidine
exchangable with D2O), 2.21 (s, CH3 pyrazolone) ppm. 13C NMR
(CDCl3, 400 MHz): δ 170 (CO pyrazolone), 164 (CONH), 162
(C═N pyrimidine), 157 and 103 (C═C pyrimidine), 155 (C═N
pyrazolone), 154 (C thiazole), 142–124 (C and CH phenyl rings),
89 (CH thiazole), 50 (CH pyrazolone), 45 (CH pyrimidine), 18
(CH3 pyrazolone) ppm. EI ms: m/z: 458.79 [M+] (67), 452.12
(24), 431.40 (23), 382.32 (42), 285.90 (59), 173 (71).
7-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-p-
chlorophenyl-5H-thiazolo[3,2-a]-pyrimidine-6-carbohydrazide
(4b). Crystallized from benzene to give pale yellow crystals,
yield 3.19 g (65%), mp: 262–263°C. IR (KBr): 3250–
3450 (NHNH2, NH2), 1680 (CO carbohydrazide), 1635 (CO
pyrazolone) cm-1. 1H NMR (DMSO-d6, 90 MHz): δ = 9.30 (s, NH
exchangable with D2O), 7.73–7.29 (m, 9H, phenyl protons),
7.19 (s, NH2 exchangable with D2O), 7.05 (s, thiazole-H), 6.90
(s, pyrimidine-H), 6.80 (s, pyrazolone-H), 5.39 (s, NH2 pyrimidine
exchangable with D2O), 2.3 (s, CH3 pyrazolone) ppm.
5H, phenyl protons), 6.90 (s, thiazole-H), 6.80 (s, pyrimidine-
H), 6.75 (s, pyrazolone-H), 2.20 (s, CH3 pyrazolone) ppm. 13
C
NMR (CDCl3, 400 MHz): δ = 178 (C═S pyrimidine), 170 (CO
pyrazolone), 167 (C═O pyrimidine), 162 (C═N pyrimidine),
159 and 103 (C═C pyrimidine), 155 (C═N pyrazolone), 154
(C thiazole), 142–124 (C and CH phenyl rings), 89 (CH thiazole),
50 (CH pyrazolone), 45 (CH pyrimidine), 18 (CH3 pyrazolone)
ppm. EI ms: m/z: 562.21[M+] (67), 527 (21), 485.41 (52), 173.12
(76), 77 (61).
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-p-
chlorophenyl-7-phenyl-7,9-dihydro-5H-thiazolo[3,2-a]pyrimido
[4,5-d]pyrimidine-8-thione (5b). Crystallized from benzene to
give white crystals, yield 4.11g (69%) mp 245–247°C. IR (KBr):
2300 (NH), 1695 (CO pyrimidine), 1635 (CO pyrazolone), 1510
(C═S) cm−1. 1H NMR (CDCl3, 90 MHz): δ = 10.00 (s, NH
exchangable with D2O), 7.74–7.30 (m, 14H, phenyl protons), 7.10
(s, thiazole-H), 7.00 (s, pyrimidine-H), 6.92 (s, pyrazolone-H),
2.20 (s, CH3 pyrazolone) ppm.
8-Ethylthio-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-
oxo-5-aryl-7-phenyl-5,7-dihydro thiazolo[3,2-a]pyrimido[4,5-
d]pyrimidine 6a,b. To a solution of 5a or 5b (10 mmol) in hot
ethanol containing sodium acetate (0.75 g, 10 mmol), ethyl
iodide (1.56 mL, 10 mmol) was added with stirring for 3 h. The
solid precipitate was collected, dried, and crystallized from the
proper solvent to give 6a and 6b, respectively.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-aryl-7-
phenyl-7,9-dihydro-5H-thiazolo-[3,2-a]pyrimido[4,5-d]pyrimidine-
8-thione 5a,b. A mixture of 1 a,b (10 mmol) and phenyl
isothiocyanate (1.4 g, 10 mmol) in pyridine (30 mL) was refluxed
for 8 h. The cooled reaction mixture was poured into ice water
mixture, acidified with acetic acid, and the precipitated solid was
collected and crystallized from the proper solvent to give 5a and
5b, respectively.
8-Ethylthio-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-
oxo-5,7-diphenyl-5,7-dihydro thiazolo [3,2-a]pyrimido[4,5-d]
pyrimidine (6a). Crystallized from ethanol to give white
crystals, yield 3.96 g (67%), mp 230–232°C. IR (KBr):
disappearance of (NH), 2950 (CH aliphatic), 1695 (CO
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5,7-diphenyl-
7,9-dihydro-5H-thiazolo- [3,2-a]pyrimido[4,5-d]pyrimidine-8-thione
(5a). Crystallized from benzene to give pale green powder, yield
3.66 g (65%), mp 237–239°C. IR (KBr): 3250 (NH), 1695 (CO
pyrimidine), 1640 (CO pyrazolone) cm−1 1H NMR (CDCl3,
.
90 MHz): δ = 8.10–7.50 (m, 15H, phenyl protons), 7.00
(s, thiazole-H), 6.90 (s, pyrimidine-H), 6.80 (s, pyrazolone-H),
4.10 (q, J = 6.7Hz, CH2), 2.20 (s, CH3 pyrazolone), 1.00
(t, J = 6.7Hz, CH3) ppm; EI ms: m/z: 590.32 [M+] (49),
559.12 (68), 173.12 (76), 77 (61), 29 (12).
pyrimidine), 1635 (CO pyrazolone), 1510 (C═S) cm−1 1H
.
NMR (CDCl3, 400 MHz): δ = 10.00 (s, NH exchangable with
D2O), 7.64–7.24 (m, 10H, phenyl protons), 7.14–7.06 (m,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

184
M. S. K. Youssef, M. S. Abbady, R. A. Ahmed, and A. A. Omar
Vol 50
Table 2
The elemental analyses of the prepared compounds.
Elemental analyses
Compound
Formula
C
H
N
S
Cl
1b
C
25H22N5O3SCl
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
Calcd.
Found
59.11
58.89
62.90
62.74
58.96
58.82
66.54
66.34
62.79
62.68
60.12
60.01
55.92
55.81
64.04
63.91
60.34
60.25
65.06
64.97
61.48
61.40
64.27
64.16
60.55
60.48
60.35
60.29
56.44
56.36
61.36
61.30
57.85
57.80
59.37
59.24
55.44
55.32
64.23
64.28
60.26
60.18
61.70
61.58
57.91
57.86
58.71
58.62
54.71
54.60
62.43
62.34
57.92
57.83
65.80
65.71
61.90
62.18
66.77
66.66
62.89
62.78
4.37
4.24
4.89
4.75
4.40
4.28
4.71
4.61
4.28
4.16
4.61
4.46
4.08
3.98
3.94
3.72
3.54
3.43
4.44
4.37
4.03
3.91
4.31
4.25
3.90
3.76
3.85
3.78
3.41
3.35
4.44
4.36
4.02
3.92
3.94
3.97
3.49
3.41
4.81
4.64
4.33
4.40
4.41
4.34
3.96
3.87
3.86
3.74
3.39
3.31
4.10
4.01
3.59
3.49
4.60
4.52
4.16
4.03
4.16
4.11
3.75
3.69
13.79
13.67
13.58
13.34
12.73
12.61
12.12
12.06
11.44
11.32
21.34
21.21
19.85
19.71
14.94
14.81
14.07
13.94
14.23
14.20
13.44
13.32
19.99
19.90
18.83
18.71
19.71
19.64
18.43
18.32
17.27
17.18
16.29
16.20
20.19
20.12
18.86
18.75
18.73
18.61
17.57
17.45
18.65
18.54
17.51
17.43
23.82
23.71
22.19
22.10
18.99
18.87
17.62
17.53
17.90
17.79
16.84
16.73
17.58
17.47
16.56
16.50
6.31
6.21
6.22
6.16
5.83
5.71
5.55
5.48
5.24
5.10
6.98
6.87
6.49
6.36
11.40
11.65
10.74
10.61
10.86
10.80
10.26
10.14
5.72
5.63
5.39
5.31
6.45
6.36
6.03
5.93
5.65
5.52
5.33
5.25
6.60
6.51
6.17
6.08
6.12
6.17
5.73
5.66
6.10
6.01
5.73
5.65
6.82
6.70
6.35
6.40
7.25
7.14
6.72
6.64
5.86
5.71
5.51
5.39
5.75
5.63
5.42
5.34
6.98
6.81
–
2a
C27H24N5O4SCI
C27H25N5O4SCl
C32H27N5O4S
C32H26N5O4SCl
C23H21N7O2S
C23H20N7O2SCl
C30H22N6O2S2
C30H21N6O2S2Cl
C32H26N6O2S2
C32H25N6O2S2Cl
C30H24N8O2S
C30H23N8O2SCl
C25H19N7O3S
C25H18N7O3SCl
C29H25N7O4S
C29H24N7O4Cl
C24H19N7O3S
C24H18N7O3S Cl
C28H25N7O2S
C28H24N7O2SCl
C27H23N7O3S
C27H22N7O3SCl
C23H18N8O2S
C23H17N8O2SCl
C23H18N6O2S
C23H17N6O2SCl
C30H25N7O2S
C30H24N7O2SCl
C31H23N7O2S
C31H22N7O2SCl
–
2b
6.45
6.30
–
3a
–
3b
5.79
5.66
–
4a
–
4b
7.18
7.05
–
5a
–
5b
5.94
5.84
–
6a
–
6b
5.67
5.56
–
7a
–
7b
5.96
5.85
–
8a
–
8b
6.66
6.57
–
9a
–
9b
5.89
5.82
–
10a
10b
11a
11b
12a
12b
13a
13b
14a
14b
15a
15b
16a
16b
–
6.82
6.71
–
–
6.35
6.26
–
–
6.33
6.21
–
–
7.02
6.90
–
–
7.43
7.34
–
–
6.09
5.88
–
–
5.99
5.84
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2013 Synthesis of Some New Heterocycles Derived from Ethyl 7-Amino-3-(3-methyl-5-oxo-1-phenyl-2- 185
pyrazolin-4-yl)-5-aryl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate of Biological Importance
8-Ethylthio-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-
5-p-chlorophenyl-7-phenyl-5,7-dihydrothiazolo[3,2-a]pyrimido
[4,5-d]pyrimidine (6b). Crystallized from ethanol to give yellow
crystals, yield 4.06 g (65%), mp 240–242°C. IR (KBr): 2915 (CH
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-p-
chlorophenyl-7-N-formylamino-5,7-dihydro-5H-thiazolo[3,2-a]
pyrimido[4,5-d]pyrimidine (8b). Crystallized from ethanol to
give pale yellow crystals, yield 3.49 g (68%), mp 222–224°C. IR
(KBr): 3350 (NH), 1705 (CO formyl), 1690 (CO pyrimidine),
1645 (CO pyrazolone) cm-1. 1H NMR (CDCl3, 90 MHz):
δ = 10.80 (s, NH exchangable with D2O), 8.60 (s, formyl-H),
8.00 (s, pyrimidine-H), 7.60–7.20 (m, 9H, phenyl protons), 7.00
(s, thiazole-H), 6.80 (s, pyrimidine-H), 6.60 (s, pyrazolone-H),
2.30 (s, CH3 pyrazolone) ppm.
aliphatic), 1695 (CO pyrimidine), 1640 (CO pyrazolone) cm−1
.
1H NMR (DMSO-d6, 90MHz): δ = 8.00–7.30 (m, 14H, phenyl
protons), 7.00 (s, thiazole-H), 6.90 (s, pyrimidine-H), 6.80 (s,
pyrazolone-H), 4.10 (q, J = 10 Hz, CH2), 2.20 (s, CH3
pyrazolone), 1.00 (t, J = 10 Hz, CH3) ppm.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-aryl-
7-phenyl-5,7-dihydro-8-hydrazino thiazolo[3,2-a]pyrimido[4,5-d]
pyrimidine 7a,b. To a solution of 6a or 6b (10 mmol) in pyridine
(30 mL), hydrazine hydrate 98% (0.49 mL, 10 mmol) was added
and the reaction mixture was refluxed for 2 h. The product thus
formed was filtered-off, dried, and crystallized from the proper
solvent to give 7a and 7b, respectively.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-aryl-
8-methyl-7-N,N-diacetylamino-5,7-dihydrothiazolo[3,2-a]
pyrimido[4,5-d]pyrimidine 9a,b. A mixture of 4a or 4b (10
mmol) and acetic anhydride (20 mL) was refluxed for 3 h. The
reaction mixture was diluted with water and allowed to stand at
room temperature for 1 h. The precipitate thus obtained was
collected, dried, and crystallized from the proper solvent to give
9a and 9b, respectively.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5,7-
diphenyl-5,7-dihydro-8-hydrazinohiazolo[3,2-a]pyrimido[4,5-d]
pyrimidine (7a). Crystallized from benzene to give pale yellow
crystals, yield 3.92 g (55%), mp 245–247°C. IR (KBr): 3400–3150
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-phenyl-
8-methyl-7-N,N-diacetylamino-5,7-dihydrothiazolo[3,2-a]pyrimido
[4,5-d]pyrimidine (9a). Crystallized from ethanol to give white
crystals, yield 3.92 g (69%), mp 240–242°C. IR (KBr): 3000–2915
(CH aliphatic), 1760–1690 (2CO acetyl), 1645 (CO pyrazolone)
1
(NHNH2), 1690 (CO pyrimidine), 1630 (CO pyrazolone) cm−1; H
NMR (DMSO-d6, 90 MHz): δ = 10.40 (s, NH exchangable with
D2O), 7.90–7.30 (m, 15H, phenyl protons), 7.10 (s, thiazole-H),
7.00 (s, pyrimidine-H), 6.90 (s, pyrazolone-H), 5.50 (s, NH2
exchangable with D2O), 2.20 (s,CH3 pyrazolone) ppm. EI ms:
m/z: 559.72 [M+] (71), 544.13 (21), 483.12 (53), 329.10 (15),
173.12 (76), 77 (61).
1
cm-1. H NMR (CDCl3, 400 MHz): δ = 7.64–7.24 (m, 5H, phenyl
protons), 7.14–7.06 (m, 5H, phenyl protons), 6.92 (s, thiazole-H),
6.80 (s, pyrimidine-H), 6.71 (s, pyrazolone-H), 2.40 (s, 2CH3),
2.20 (s, CH3 pyrazolone), 1.20 (s, CH3 pyrimidine) ppm. 13C
NMR (CDCl3, 400 MHz): δ = 175 (2CO acetyl), 170 (CO
pyrazolone), 167 (C═O pyrimidine), 164 (CH═N pyrimidine), 161
(C═N pyrimidine), 159 and 103 (C═C pyrimidine), 155 (C═N
pyrazolone), 154 (C thiazole), 142–124 (C and CH phenyl rings),
89 (CH thiazole), 50 (CH pyrazolone), 45 (CH pyrimidine),
18 (CH3 pyrazolone), 14 (CH3 pyrimidine), 16 (2CH3 acetyl) ppm.
EI ms: m/z: 566.96 [M+] (69), 524.38 (10), 481.30 (15), 173.12
(76), 77 (61).
3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-p-chlorophenyl-
8-methyl-7-N,N-diacetylamino-5,7-dihydrothiazolo[3,2-a]pyrimido
[4,5-d] pyrimidine (9b). Crystallized from ethanol to give yellow
powder, yield 4.15 g (69%), mp 253–255°C. IR (KBr): 3000–2915
(CH aliphatic), 1760–1690 (2CO acetyl), 1645 (CO pyrazolone)
cm-1. 1H NMR (DMSO-d6, 90 MHz): δ = 7.60–7.20 (m, 9H,
phenyl protons), 7.00 (s, thiazole-H), 6.82 (s, pyrimidine-H), 6.60
(s, pyrazolone-H), 2.40 (s, 2CH3), 2.26 (s, CH3 pyrazolone), 1.20
(s, CH3 pyrimidine) ppm.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-p-
chlorophenyl-7-phenyl-5,7-dihydro-8-hydrazinothiazolo[3,2-a]
pyrimido[4,5-d]pyrimidine (7b). Crystallized from ethanol
to give yellow crystals, yield 4.16 g (70%), mp 251–253°C.
IR (KBr): 3400–3150 (NHNH2), 1690 (CO pyrimidine),
1
1630 (CO pyrazolone) cm−1. H NMR (DMSO-d6, 90 MHz): δ
= 10.40 (s, NH exchangable with D2O), 7.90–7.20 (m, 14H,
phenyl protons), 7.00 (s, thiazole-H), 6.90 (s, pyrimidine-H),
6.81 (s, pyrazolone-H), 5.50 (s, NH2 exchangable with D2O),
2.20 (s, CH3 pyrazolone) ppm.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-aryl-
7-N-formylamino-5,7-dihydro-5H-thiazolo[3,2-a]pyrimido[4,5-
d]pyrimidine 8a,b. A mixture of 4a or 4b (10 mmol) with formic
acid (20 mL) was refluxed for 4 h. The precipitate thus formed
after cooling was collected, dried, and crystallized from the
proper solvent to give 8a and 8b, respectively.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-phenyl-
7-N-formylamino-5,7-dihydro-5H-thiazolo[3,2-a]pyrimido[4,5-d]
pyrimidine (8a). Crystallized from ethanol to give white powder,
yield 3.39 g (68%), mp 215–217°C. IR (KBr): 3350 (NH), 1705
(CO formyl), 1690 (CO pyrimidine), 1645 (CO pyrazolone)
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-7-amino-
7,9–dihydro-5H-thiazolo[3,2-a]-pyrimido[4,5-d]pyrimidine-
6,8-dione 10a,b. A mixture of 4a or 4b (10 mmoles) and urea
(0.6 g, 10 mmol) was refluxed in decalin (30 mL) for 3 h. The
solid product thus obtained on cooling was filtered off, washed
with pet. ether 60–80 and crystallized from the proper solvent to
give 10a and 10b, respectively.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-phenyl-7-amino-
7,9–dihydro-5H-thiazolo [3,2-a]pyrimido[4,5-d]pyrimidine-
6,8-dione (10a). Crystallized from benzene to give white crystals,
yield 2.80 g (68%), mp 271–273°C; IR (KBr): 3400 (NH2),
3150 (NH), 1720–1695 (2 C═O pyrimidine), 1640 (C═O
pyrazolone) cm-1. 1H NMR (DMSO-d6, 400MHz): δ = 10.50
(s, NH exchangable with D2O), 9.70 (s, NH2 exchangable
with D2O), 7.64–7.24 (m, 5H, phenyl protons), 7.14–7.06
(m, 5H, phenyl protons), 6.95 (s, thiazole-H), 6.85 (s,
pyrimidine-H), 6.71 (s, pyrazolone-H), 2.25 (s, CH3
cm−1 1H NMR (400 MHz, DMSO-d6): δ = 10.80 (s, NH
.
exchangable with D2O), 8.51 (s, formyl-H), 7.72 (s, pyrimidine-
H), 7.64–7.24 (m, 5H, phenyl protons), 7.14–7.06 (m, 5H,
phenyl protons), 7.00 (s, thiazole-H), 6.90 (s, pyrimidine-H),
6.76 (s, pyrazolone-H), 2.23 (s, CH3 pyrazolone) ppm. 13C
NMR (DMSO-d6, 400 MHz): δ = 170 (CO pyrazolone), 167
(C═O pyrimidine), 165 (CHO), 163 (CH═N pyrimidine), 161
(C═N pyrimidine), 159 and 103 (C═C pyrimidine), 155 (C═N
pyrazolone), 154 (C thiazole), 142–124 (C and CH phenyl
rings), 89 (CH thiazole), 50 (CH pyrazolone), 45 (CH
pyrimidine), 18 (CH3 pyrazolone) ppm. EI ms: m/z: 497.02
[M+] (72), 479.01 (49), 469.11(39), 173.12 (76), 77 (61), 28 (5),
18 (10).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

186
M. S. K. Youssef, M. S. Abbady, R. A. Ahmed, and A. A. Omar
Vol 50
pyrazolone) ppm; 13C NMR (DMSO-d6, 400 MHz): δ = 170 (CO
pyrazolone), 167 (C═O pyrimidine), 161 (C═N pyrimidine),
159 and 103 (C═C pyrimidine), 155 (C═N pyrazolone), 154
(C thiazole), 150 (C═O pyrimidine), 142–124 (C and CH
phenyl rings), 89 (CH thiazole), 50 (CH pyrazolone), 45
(CH pyrimidine), 18 (CH3 pyrazolone) ppm. EI ms: m/z: 484.80
[M+] (80), 469.45 (71), 467.13 (34), 331.10 (24), 173.12
(76), 77 (61).
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-p-chlorophenyl-
7-amino-7,9-dihydro-5H-thiazolo[3,2-a]pyrimido[4,5-d]pyrimidine-
6,8-dione (10b). Crystallized from ethanol to give brown
powder, yield 3.38 g (65%), mp 265–267°C. IR (KBr): 3400
(NH2), 3150 (NH), 1720–1695 (2 C═O pyrimidine), 1640
(C═O pyrazolone) cm-1. 1H NMR (DMSO-d6, 90 MHz): δ =
10.70 (s, NH exchangable with D2O), 9.70 (s, NH2 exchangable
with D2O), 7.60–7.20 (m, 9H, phenyl protons), 7.00 (s, thiazole-
H), 6.90 (s, pyrimidine-H), 6.70 (s, pyrazolone-H), 2.20 (s, CH3
pyrazolone) ppm.
J = 6.7Hz, CH3) ppm. EI ms: m/z: 525.05 [M+] (69), 479.16 (42),
173.12 (76), 77 (61), 46 (12) 44.12 (5).
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-p-
chlorophenyl-7-ethoxymethyleneamino-5,7-dihydro-thiazolo
[3,2-a]pyrimido[4,5-d] pyrimidine (12b). Crystallized from
ethanol to give white crystals, yield 1.96 g (70%), mp 240–241°
C. IR (KBr): 2960 (CH aliphatic), 1680 (CO pyrimidine), 1635
(CO pyrazolone), 1580 (C═N) cm-1. 1H NMR (DMSO-d6, 90
MHz): δ = 7.90–7.60 (m, 9H, phenyl protons and N═CH), 7.50
(s, pyrimidine-H), 7.20 (s, thiazole-H), 7.00 (s, pyrimidine-H),
6.90 (s, pyrazolone-H), 4.00 (q, J = 6.7 Hz, CH2), 2.40 (s, CH3
pyrazolone), 1.3 (t, J = 6.7 Hz, CH3) ppm. EI ms: m/z: 561.62
[M++2] (23), 559.53 [M+] (76), 173.12 (76), 77 (61), 37.20 (9),
35.10 (19).
7-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-
aryl-5H-thiazolo[3,2-a]pyrimidine-6-carboazide 13a,b. To a
cold solution of 4a or 4b (10 mmol) in glacial acetic acid (30
mL), sodium nitrite solution (0.69 g, 10 mmol) in water (5 mL)
was added dropwise with stirring during 10 min at room
temperature. The formed precipitate was collected, dried, and
crystalized from the proper solvent to give 13a and 13b,
respectively.
7-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-phenyl-
5H-thiazolo[3,2-a]- pyrimidine-6-carboazide (13a). Crystallized
from benzene to give brown crystals, yield 3.38 g (72%), mp
210–212°C. IR (KBr): 3400–3200 (NH2), 2960 (CH aliphatic),
at 2270 appearance of azide group (N3), 1695 (CO), 1620
(CO pyrazolone) cm-1. 1H NMR (DMSO-d6, 90MHz): δ =
8.00–7.30 (m, 10H, phenyl protons), 7.10 (s, thiazole-H),
7.00 (s, pyrimidine-H), 6.90 (s, pyrazolone-H), 5.50 (s, NH2
exchangable with D2O), 2.30 (s, CH3) ppm.
4-(7-Amino-6-(3,5-dimethyl-1H-pyrazole-1-carbonyl)-5-aryl-
5H-thiazolo[3,2-a]pyrimidin-3-yl)-3-methyl-1-phenyl-2-pyrazolin-
5-one 11a,b. A mixture of 4a or 4b (10 mmol) and acetyl
acetone (1.00 g, 10 mmol) in ethanol (30 mL) was refluxed for
3 h. On cooling, the formed solid product was filtered-off,
dried, and crystallized from the proper solvent to give 11a and
11b, respectively.
4-(7-Amino-6-(3,5-dimethyl-1H-pyrazole-1-carbonyl)-5-phenyl-
5H-thiazolo[3,2-a]pyrimidin- 3-yl)-3-methyl-1-phenyl-2-pyrazolin-
5-one (11a). Crystallized from benzene to give yellow powder,
yield 3.46 g (66%), mp 230–232°C. IR (KBr): 3300–3100
(NH2), 2960 (CH aliphatic), 1660 (CO pyrimidine), 1640
(CO pyrazolone) cm−1 1H NMR (DMSO-d6, 90 MHz): δ =
.
7.95–7.30 (m, 10H, phenyl protons), 7.20 (s, thiazole-H), 7.10
(s, pyrimidine-H), 7.00 (s, pyrazolone-H), 6.85 (s, pyrazole-H),
5.40 (s, NH2 exchangable with D2O), 2.20 (s, CH3), 2.10
(s, 2CH3 pyrazole) ppm.
7-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-p-
chlorophenyl-5H-thiazolo[3,2-a]- pyrimidine-6-carboazide
(13b). Crystallized from benzene to give red crystals, yield
3.58 g (71%), mp 215–217°C; IR (KBr): 3400, 3200 (NH2),
2960 (CH aliphatic), at 2270 appearance of azide group
(N3), 1695 (CO), 1625 (CO pyrazolone) cm-1. 1H NMR
4-(7-Amino-6-(3,5-dimethyl-1H-pyrazole-1-carbonyl)-5-p-
chlorophenyl-5H-thiazolo[3,2-a]- pyrimidin-3-yl)-3-methyl-
1-phenyl-2-pyrazolin-5-one (11b). Crystallized from benzene to
give pale yellow crystals, yield 3.91 g (70%), mp 249–250°C.
IR (KBr): 3300–3100 (NH2), 2960 (CH aliphatic), 1660 (CO
(DMSO-d6, 90 MHz):
δ = 8.10–7.20 (m, 9H, phenyl
protons), 7.10 (s, thiazole-H), 7.00 (s, pyrimidine-H), 6.90
(s, pyrazolone-H), 5.50 (s, NH2 exchangable with D2O), 2.30
(s, CH3 pyrazolone) ppm.
1
pyrimidine), 1640 (CO pyrazolone) cm-1; H NMR (DMSO-d6,
90 MHz): δ = 8.00–7.40 (m, 9H, phenyl protons), 7.20
(s, thiazole-H), 7.11 (s, pyrimidine-H), 7.10 (s, pyrazolone-H),
6.90 (s, pyrazole-H), 5.40 (s, NH2 exchangable with D2O),
2.20 (s, CH3), 2.10 (s, 2CH3 pyrazole) ppm.
7-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-9-aryl-2-
oxo-1,3-dihydro-9H-imidazo[4,5-d]-thiazolo[3,2-a]pyrimidine
14a,b. The carboazide 13 (5 mmol) was heated under reflux for 3
h in dry toluene (30 mL). The reaction mixture was cooled whereby
a precipitated solid was formed. It was collected and crystallized
from the proper solvent to give 14a and 14b, respectively.
7-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-9-phenyl-2-
oxo-1,3-dihydro-9H-imidazo[4,5-d]-thiazolo[3,2-a]pyrimidine
(14a). Crystallized from dioxane to give yellow crystals,
yield 1.61 g (73%), mp 245–246°C. IR (KBr): 3400–3310
(2NH), disappearance of azide and amino groups, 1680 (CO),
1630 (CO pyrazolone) cm-1. 1H NMR (CDCl3, 400 MHz):
δ = 11.10 (s, 2NH exchangable with D2O), 7.64–7.24 (m,
5H, phenyl protons), 7.14–7.06 (m, 5H, phenyl protons), 6.95
(s, thiazole-H), 6.85 (s, pyrimidine-H), 6.71 (s, pyrazolone-H),
2.25 (s, CH3 pyrazolone) ppm. 13C NMR (CDCl3, 400 MHz):
δ = 170 (CO pyrazolone), 161 (C═N pyrimidine), 155 (C═N
pyrazolone), 154 (C thiazole), 142–124 (C and CH phenyl
rings), 111 and 107 (C═C pyrimidine), 89 (CH thiazole), 50 (CH
pyrazolone), 45 (CH pyrimidine), 18 (CH3 pyrazolone) ppm.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-aryl-
7-ethoxymethyleneamino-5,7-dihydro-thiazolo[3,2-a]pyrimido
[4,5-d]pyrimidine 12a,b. A mixture of 4a or 4b (5 mmoles) and
triethyl orthoformate (20 mL) was refluxed for 3 h. The solid
precipitate thus formed on cooling was collected, dried, and
crystallized from the proper solvent to give 12a and 12b,
respectively.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-6-oxo-5-phenyl-
7-ethoxymethyleneamino-5,7-dihydro-thiazolo[3,2-a]pyrimido
[4,5-d]pyrimidine (12a). Crystallized from ethanol to give white
needles, yield 1.81 g (69%), mp 238–239°C. IR (KBr): 2960
(CH aliphatic), 1680 (CO pyrimidine), 1635 (CO pyrazolone),
1
1580 (C═N) cm-1. H NMR (DMSO-d6, 90MHz): δ = 7.90–7.50
(m, 10H, phenyl protons and N═CH), 7.50 (s, pyrimidine-H),
7.20 (s. thiazole-H), 7.00 (s, pyrimidine-H), 6.90 (s, pyrazolone-H),
4.00 (q, J = 6.7 Hz, CH2), 2.40 (s, CH3 pyrazolone), 1.3 (t,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2013 Synthesis of Some New Heterocycles Derived from Ethyl 7-Amino-3-(3-methyl-5-oxo-1-phenyl-2- 187
pyrazolin-4-yl)-5-aryl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate of Biological Importance
7-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-9-p-chlorophenyl-
2-oxo-1,3-dihydro-9H-imidazo[4,5-d]thiazolo[3,2-a]pyrimidine
(14b). Crystallized from dioxane to give pale yellow crystals,
yield 1.72 g (72%), mp 248–250°C. IR (KBr): 3400–3300
(2NH), disappearance of azide and amino groups, 1680 (CO),
1630 (CO pyrazolone) cm-1. 1H NMR (DMSO-d6, 90 MHz):
δ = 11.10 (s, 2NH exchangable with D2O), 7.60–7.20 (m, 9H,
phenyl protons), 7.00 (s, thiazole-H), 6.82 (s, pyrimidine-H),
6.60 (s, pyrazolone-H), 2.30 (s, CH3 pyrazolone) ppm.
7.64–7.06 (m, 15H, phenyl protons), 6.95 (s, thiazole-H),
6.85 (s, pyrimidine-H), 6.71 (s, pyrazolone-H), 2.25 (s, CH3
pyrazolone) ppm. 13C NMR (CDCl3, 400 MHz): δ = 170 (CO
pyrazolone), 167 (C═O pyrimidine), 163 (CH═N pyrimidine),
161 (C═N pyrimidine), 159 and 103 (C═C pyrimidine), 157
(N═CH), 155 (C═N pyrazolone), 154 (C thiazole), 142–124
(C and CH phenyl rings), 89 (CH thiazole), 50 (CH pyrazolone),
45 (CH pyrimidine), 18 (CH3 pyrazolone) ppm.
7-Benzylideneamino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-6-oxo-5-p-chlorophenyl-5H-thiazolo[3,2-a]pyrimido[4,5-d]
pyrimidine (16b). Crystallized from dioxane to give yellow
powder, yield 2.07 g (70%), mp 259–261°C. IR (KBr): 1680
Benzaldehyde,7-amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-5-aryl-5H-thiazolo[3,2-a]pyrimidine-6-carbohydrazone
15a,b. A mixture of 4a or 4b (10 mmol) and benzaldehyde
(10 mmol) in ethanol (30 mL) containing few drops of
piperidine was refluxed for 3 h. The solid thus formed was
collected and crystallized from the proper solvent to give 15a
and 15b, respectively.
Benzaldehyde,7-amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-5-phenyl-5H-thiazolo-[3,2-a]pyrimidine-6-carbohydrazone
(15a). Crystallized from dioxane to give yellow powder, yield
3.83 g (70%), mp 250–251°C; IR (KBr): 3350–3250 (NH,
NH2), 1660 (CO pyrimidine), 1640 (CO pyrazolone), 1580 (C═N)
cm-1. 1H NMR (DMSO-d6, 90 MHz): δ =11.10 (s, NH
exchangable with D2O), 9.50 (s, CH), 8.00–7.40 (m, 15H,
phenyl protons) 7.10 (s, thiazole-H), 6.90 (s, H-pyrimidine),
6.80 (s, pyrazolone-H), 5.40 (s, NH2 exchangable with D2O),
2.30 (s, CH3 pyrazolone) ppm.
1
(CO pyrimidine), 1630 (CO pyrazolone), 1580 (C═N) cm-1. H
NMR (CDCl3, 90 MHz): δ = 8.30 (s, CH), 7.78 (s, pyrimidine-
H), 7.67–7.10 (m, 14H, phenyl protons), 7.00 (s, thiazole-H),
6.82 (s, pyrimidine-H), 6.60 (s, pyrazolone-H), 2.30 (s, CH3
pyrazolone) ppm.
Acknowledgments. The authors are grateful to Assiut University
Mycological Center (AUMC) for biological analyses.
REFERENCES AND NOTES
[1] Aly, A. A. J Heterocycl Chem 2009, 45, 993.
[2] Kulakov, I. V. Russ J Org Chem 2009, 45, 1262.
[3] Kulakov, I. V. Chem Heterocycl Comp 2009, 45, 1019.
[4] Kulakov, I. V.; Nurkenov, O. A.; Turdybekov, D. M.;
Issabaeva, G. M.; Mahmutova, A.S.; Turdybekov, K. M. Chem Heterocy-
clic Compds 2009, 45, 1573.
[5] Sayed, H. H.; Shamroukh, A. H.; Rashad, A. E. Acta Pharm
2006, 56, 231.
[6] Mahmoud, M. R.; El-Shahawi, M. M. Phosphorus Sulfur
Silicon 2008, 183, 3097.
[7] Quan, Z. J.; Zhang, Z.; Wang, J. K.; Wang, X. C.; Liu, Y. J.;
Ji, P.Y. Heteroatom Chem 2008, 19, 149.
[8] Kurbanova, M. M. Russ J Org Chem 2006, 42, 1871.
[9] Youssef, M. M.; Mohamed, S. F.; Kotb, E. R.; Salama, M. A.
World J Chem 2009, 4, 149.
Benzaldehyde,7-amino-3-(3-methyl-5-oxo-1-phenyl-2-
pyrazolin-4-yl)-5-p-chlorophenyl-5H-thiazolo[3,2-a]pyrimidine-
6-carbohydrazone (15b). Crystallized from dioxane to give pale
yellow crystals, yield 4.25 (73%), mp 255–257°C; IR (KBr):
3350–3250 (NH, NH2), 1660 (CO pyrimidine), 1640 (CO
1
pyrazolone), 1580 (C═N) cm-1. H NMR (DMSO-d6, 90 MHz):
δ = 11.10 (s, NH exchangable with D2O), 9.50 (s, CH), 8.10–7.40
(m, 14H, phenyl protons), 7.10 (s, thiazole-H), 7.00 (s,
pyrimidine-H), 6.85 (s, pyrazolone-H), 5.40 (s, NH2 exchangable
with D2O), 2.30 (s, CH3 pyrazolone) ppm.
7-Benzylideneamino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-6-oxo-5-aryl-5H-thiazolo- [3,2-a]pyrimido[4,5-d]pyrimidine
16a,b. A mixture of 15a or 15b (5 mmol), triethyl orthoformate
(5 mmol), and acetic anhydride (15 mL) was refluxed for 3 h.
The solid precipitate thus formed on cooling was collected,
dried, and crystallized from the proper solvent to give 16a and
16b, respectively.
[10] Zhi, H.; Chen, L.; Zhang, L.; Liu, S.; Wan, D. C. C.; Lin,
H.; Hu, C. Arkivoc 2008, 13, 266.
[11] Zhi, H.; Chen, L.; Zhang, L.; Liu, S.; Wan, D. C. C.; Lin,
H.; Hu, C. Chem Res Chinese Univ 2009, 25, 332.
[12] Awadallah, F. M. Sci Pharm 2008, 76, 415.
[13] Al Thebeiti, M. S. Boll Chim Farm 2001, 140, 221.
[14] Khobragade, C. N.; Bodade, R. G.; Dawane, B. S.; Konda,
S. G.; Khandare, N. T. J Enzyme Inhib Med Chem 2010, 25, 615.
[15] Alam, O.; Khan, S. A.; Siddiqui, N.; Ahsan, W. Med Chem
Res 2009, 19, 1245.
7-Benzylideneamino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-6-oxo-5-phenyl-5H-thiazolo [3,2-a]pyrimido[4,5-d]pyrimidine
(16a). Crystallized from dioxane to give pale brown powder,
yield 1.92 g (69%), mp 262–264°C. IR (KBr): 1680 (CO
1
pyrimidine), 1630 (CO pyrazolone), 1580 (C═N) cm-1. H NMR
[16] Youssef, M. S. K.; Ahmed, R. A.; Abbady, M. S.; Abd El
Mohsen, A. A.; Omar, A. A.; Monatsh Chem 2008, 139, 55.
(CDCl3, 400 MHz): δ = 8.20 (s, CH), 7.76 (s, pyrimidine-H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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