Synthesis of some novel pyrazolo[1,5-a]pyrimidine, 1,2,4-triazolo[1,5-a] pyrimidine, pyrido[2,3-d]pyrimidine, pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives incorporating a thiazolo[3,2-a]benzimidazole moiety

Article abstract of DOI:10.1002/jhet.5570450413

(Chemical Equation Presented) E-3-(N,N-Dimethylamino)-1-(3- methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-one (2) was synthesized by the reaction of 1-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)ethanone (1) with dimethylformamide-dimethylacetal. The reaction of 2 with 5-amino-3-phenyl-1H- pyrazole (4a) or 3-amino-1,2,4-(1H)-triazole (4b) furnished pyrazolo[1,5-a] pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine derivatives 6a and 6b, while the reaction of enaminone 2 with 6-aminopyrimidine derivatives 7a,b afforded pyrido[2,3-d]pyrimidine derivatives 9a,b, respectively. The diazonium salts 11a or 11b coupled with compound 2 to yield the pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives 13a and 13b. Some of the newly synthesized compounds exhibited a moderate effect against some bacterial and fungal species.

Full text of DOI:10.1002/jhet.5570450413

Jul-Aug 2008
1033
Synthesis of Some Novel Pyrazolo[1,5-a]pyrimidine, 1,2,4-
Triazolo[1,5-a]pyrimidine, Pyrido[2,3-d]pyrimidine,
Pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-Triazolo[5,1-c]-1,2,4-
triazine Derivatives Incorporating a Thiazolo[3,2-a]benzimidazole
Moiety
Hatem A. Abdel-Aziz* [a], Nehal A. Hamdy [a], Ahmad M. Farag [b]
and Issa M. I. Fakhr [a]
[a] Applied Organic Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt
[b] Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
Received May 15, 2007
O
Me
Me
N
N
N
Me
S
N
2
Me
N
NH
Me
X
N
X
N
N
N
H
S
N
N
N
O
S
R
9a,b
6a,b
E-3-(N,N-Dimethylamino)-1-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-one (2) was
synthesized by the reaction of 1-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)ethanone (1) with
dimethylformamide-dimethylacetal. The reaction of 2 with 5-amino-3-phenyl-1H-pyrazole (4a) or
3-amino-1,2,4-(1H)-triazole (4b) furnished pyrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine
derivatives 6a and 6b, while the reaction of enaminone 2 with 6-aminopyrimidine derivatives 7a,b
afforded pyrido[2,3-d]pyrimidine derivatives 9a,b, respectively. The diazonium salts 11a or 11b coupled
with compound 2 to yield the pyrazolo[5,1-c]-l,2,4-triazine and l,2,4-triazolo[5,1-c]-l,2,4-triazine
derivatives 13a and 13b. Some of the newly synthesized compounds exhibited a moderate effect against
some bacterial and fungal species.
J. Heterocyclic Chem., 45, 1033 (2008).
INTRODUCTION
C6H4-P-Cl
CH2COOH
N
S
N
N
Tilomisole (WY-18,251) is one of the most important
derivatives [1,2] among thiazolo[3,2-a]benzimidazole
derivatives which shows antinflammatory [3], and
immunomodulatory [4] activities, since the thiazolo-
[3,2-a]benzimidazole system is similar in part to
S
N
Levamisole
Tilomisole (WY-18,251)
O
Me
Me
N
S
N
levamisole
a
well-known immunomodulator [5].
N
N
O
Me
Recently, the gastric antisecretory activity of thiazolo-
[3,2-a]benzimidazol-1-oxide (WY-26,769) was reported
[6]. On the other hand, thiazolo[3,2-a]benzimidazole
derivatives were found to have strong biological activities
including antibacterial [7-9], anti-inflammatory [10],
antiulcer [11,12] and antiviral [13,14] activities.
S
N
(WY-26,769)
2
some novel heterocycles incorporating a thiazolo[3,2-a]-
benzimidazole moiety starting from E-3-(N,N-
Furthermore,
some
thiazolo[3,2-a]benzimidazole
dimethylamino)-1-(3-methylthiazolo[3,2-a]benzimidazol-
2-yl)prop-2-en-1-one (2) to evaluate their antimicrobial
properties.
derivatives used for treatment of cancer [15], cerebral
infarction [16], neurogenic pain [17], bone diseases [18]
and mGluR1 related diseases (epilepsy, inhibition of
nerve cell death, Parkinson's disease, migraine headache
and anxiety disorder) [19].
RESULTS AND DISCUSSION
1-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)ethanone
(1) was treated with dimethylformamide-dimethylacetal
(DMF-DMA), in dry xylene, at reflux temperature, it
afforded a yellow crystalline product that was identified
In an attempt to achieve new compounds with possible
antimicrobial properties [20,21] and in our continuous
study on the synthesis of new biologically active
heterocycles [20-25], we reported herein the synthesis of

1034
H. A. Abdel-Aziz, N. A. Hamdy, A. M. Farag and I. M. I. Fakhr
Vol 45
as E-3-(N,N-dimethylamino)-1-(3-methylthiazolo[3,2-a]-
benzimidazol-2-yl)prop-2-en-1-one (2) (Scheme I). The
structure of the latter product was established on the basis
revealed a peak corresponding to its molecular ion at m/z
381 (M+).
1
of its elemental analysis and spectral data (ir, H nmr, 13C
Scheme II
nmr and ms). For example, compound 2 assigned the E
conformation on the basis of its H nmr spectrum which
O
R
Me
1
Me
X
N
N
+
NH2
N
N
showed the olefinic protons as two duplets at ꢀ 5.37, 5.41
(=CH-CO) and ꢀ 7.73, 7.77 (=CH-N) with J=12.0 Hz, as
reported for such E-coupled protons, these finding are in
complete agreement with that of recent reports [26,27].
Me
N
pyridine
S
H
2
4a,b
N
R
Me
1
Also, H nmr revealed three singlet signals corresponding
X
N
X
O
N
to three methyl groups at ꢀ 2.92, 3.07 and 3.17 in addition
to the aromatic protons. Its mass spectrum revealed a peak
corresponding to its molecular ion at m/z 285 (M+).
Me
N
N
- NH(Me)2
N
N
H
S
N
H
R
N
N
S
6a,b
5a,b
a: R=Ph, X=CH; b:R=H, X=N
Scheme I
O
Furthermore, the reaction of enaminone 2 with 6-
amino-1H-pyrimidin-2,4-dione (7a) or 6-amino-2-thioxo-
2,3-dihydro-1H-pyrimidin-4-one (7b) in refluxing acetic
acid resulted in the formation of pyrido[2,3-d]pyrimidines
O
Me
Me
Me
N
Me
N
N
N
N
Me
DNF-DMA
xylene
S
S
1
2
1
9a and 9b (Scheme III). Their H nmr spectra revealed
two signals (D2O exchangeable) assigned to 2NH protons,
whereas their mass spectra showed, in each case, a peak
corresponding to their molecular ion values. The latter
reaction was assumed to proceed through an initial
Michael type addition of the amino group in pyrimidines
7a,b to the double bond in enaminone 2 followed by the
elimination of dimethylamine to afford the non-isolable
intermediates 8a,b. which may be cyclized into the
pyrido[2,3-d]pyrimidine derivatives 9a,b or pyrimido[1,6-
a]pyrimidine derivatives 10a,b (Scheme III). However,
O
Me
N
HN
X
X
N
N
S
3a-c
a: X=CH2; b: X=O; C: X= -NMe
Next, the enaminone 2 reacted with some secondary
amines namely piperidine, morpholine or 1-methyl-
piperazine in refluxing ethanol to afford the
corresponding tertiary amines 3a-c, respectively (Scheme
I). The ir spectra of the latter products showed carbonyl
absorption bands in the region 1643-1639 cm-1. Their
mass spectra showed, in each case, a peak corresponding
Scheme III
X
O
Me
Me
N
HN
H2N
NH
1
+
to their molecular ions. Their H nmr spectra are free of
N
N
Me
S
AcOH
O
signals characteristic for the dimethylamine protons in
addition to the appearance of two doublet signals (J=12.3
Hz) corresponding to the E-coupled olefinic protos [27]
(cf. Experimental part).
7a,b
2
N
Me
NH
X
N
N
N
H
The behavior of enaminone
2
towards some
S
O
heterocyclic amines as convenient access for synthesis a
variety of fused heterocyclic systems [28,29] was
investigated. Thus, when compound 2 was treated with 5-
amino-3-phenyl-1H-pyrazole (4a) or 3-amino-1,2,4-(1H)-
triazole (4b) in refluxing pyridine, it furnished the
pyrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]-
pyrimidine derivatives, 6a and 6b, (Scheme II).
The structures of the latter products were confirmed on
the basis of their elemental analyses and spectral data (ir,
1H nmr, 13C nmr and ms). For example, the ir spectrum of
6a revealed the lack of a band corresponding to carbonyl
function, while its 1H nmr spectrum showed singlet signal
duo to pyrazole proton at ꢀ 5.23. Its mass spectrum
X
9a,b
a: X=O; b:X=S
HN
NH
O
-H2O
Me
O
N
H
N
N
N
N
Me
S
O
N
N
NH
8a,b
S
X
10a,b
structures 10a,b were easily excluded on the basis of the
spectral data of the isolated products.
Finally, The enaminone 2 reacted with the diazonium
salt of 3-phenyl-5-amino-1H-pyrazole 11a or 5-amino-

Jul-Aug 2008
Synthesis of Some Novel Pyrazolo[1,5-a]pyrimidine, 1,2,4-Triazolo[1,5-a]pyrimidine,
1035
l,2,4-(1H)-triazole [30,31] to afford the non-isolable azo-
coupling intermediates 12a,b which cyclized via
dimethylamine elimination to yield the pyrazolo[5,1-c]-
l,2,4-triazine and l,2,4-triazolo[5,1-c]-l,2,4-triazine
derivatives 13a and 13b in good yields (Scheme IV).
action of the compound under investigation. The
fungicide Terbinafin and the bactericide Chloramphenicol
were used as references to evaluate the potency of the
tested compounds under the same conditions.
Measurements were considered after 72 h for fungi and 24
h for bacteria. The results are contained in Table 1.
Scheme IV
Table 1
O
R
Me
Me
X
Antimicrobial activities of the tested compounds.
N
+ -
N2
O-5OC
+
N
Y
N
N
Me
N
S
pyridine
H
No. [a]
Inhibitions [b]
Ca
2
Af
Pi
Sr
Sa
Pa
Bs
Ec
11a,b
3b
6a
6b
9b
13a
St. [c]
+
+
-
+
+
-
+
-
+
-
+
++
+
++
+
-
-
+
-
-
+
+
++
-
++
-
-
-
+
+
+
-
-
-
-
++
+
+
++
-
++
Me
O
Me
O
Me
N
N
N
R
Me
N
N
- NH(Me)2
-
N
N
N
S
N
X
N
S
N
+++ +++ +++ ++
+++ +++
. .
NH
N
[a] Compound 13b revealed no activities against all species. [b] IZD
beyond control / (sign): 0.1-0.5 cm / (+), 0.6-1.0 cm / (++), 1.1-1.5
cm / (+++) and 0 cm / (-). [c] The fungicide Terbinafin and the
bactericide Chloramphenicol were used as standards.
X
13a,b
a: R=Ph, X=CH, Y=Cl; b:R=H, X=N, Y=NO3
R
12a,b
The ir spectra of latter compounds revealed, in each
case, the lack of bands corresponding to endo-cyclic NH
and showed carbonyl absorption bands in the region
1648-1639 cm-1. Their mass spectra showed, in each case,
The results of antimicrobial activity showed that
compound 9b exhibited
a moderate effect against
Syncephalastrum racemosum (Sr), Staphylococcus aureus
(Sa) and Escherichia coli (Ec). Also, both compound 3b
and 6a showed a moderate effect against Escherichia coli
(Ec) and Syncephalastrum racemosum (Sr), respectively.
However, the activity of the tested compounds is less than
those of the standard agents used (Table 1).
a
peak corresponding to the molecular ions (cf.
Experimental part).
Antimicrobial Evaluation. The antibacterial and
antifungal activities were carried out at the Regional
Centre for Mycology and Biotechnology at Al-Azhar
University, Cairo, Egypt. Some of the newly synthesized
compounds were screened for their antimicrobial activity
using the diffusion agar technique [32], where six
compounds were tested against four fungal species
namely Aspergillus fumigatus (Af), Penicillium italicum
(Pi), Syncephalastrum racemosum (Sr) and Candida
albicans (Ca) as well as against four bacterial species
namely Staphylococcus aureus (Sa), Pseudomonas
aeruginosa (Pa), Bacillus subtilis (Bs) and Escherichia
coli (Ec) for their antimicrobial activity using 5 mg/mL of
each compound in dimethylformamide. Inhibition zone
diameter (IZD) in cm was taken as the criterion for
antimicrobial activity. The antimicrobial activity was
assayed biologically using a spore suspension of the
fungal species (1 mL of sterile water containing
approximately 108 conidia) or spreading bacterial
suspension over a solidified malt agar medium. The layer
was allowed to set for 30 min. A solution of each of the
tested compounds (5 mg/mL) was placed onto sterile 5
mm filter paper discs and allowed to dry, then the discs
were placed onto the center of the malt agar plate and
incubated at the optimum incubation temperature,
28±2°C. A clear zone around the disc was taken as an
indication of the inhibition of the test organism growth.
The size of the clear zone is proportional to the inhibitory
EXPERIMENTAL
Melting points were measured with a Gallenkamp apparatus
and are uncorrected. IR spectra were recorded on Shimadzu
FT-IR 8101 PC infrared spectrophotometer. The NMR spectra
were recorded on
a Varian Mercury VX-300 NMR
spectrometer. 1H spectra were run at 300 MHz and 13C spectra
were run at 75.46 MHz in deuterated dimethylsulphoxide
(DMSO-d6). Chemical shifts are quoted in ꢀ and were related
to that of the solvents. Mass spectra were measured on a
GCMS-QP1000 EX spectrometer at 70 eV. Elemental
analyses were carried out at the Microanalytical Center of
Cairo University. 1-(3-Methyl-thiazolo[3,2-a]benzimidazol-2-
yl)ethanone (1) [33] and 5-amino-3-phenyl-1H-pyrazole (4a)
[34] were prepared by the reported methods. 3-Amino-1,2,4-
(1H)-triazole (4b), 6-amino-1H-pyrimidin-2,4-dione (7a) or 6-
amino-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (7b) were
used as obtained commercially.
E-3-(N,N-Dimethylamino)-1-(3-methylthiazolo[3,2-a]benz-
A
imidazol-2-yl)prop-2-en-1-one (2).
mixture of 1-(3-
methylthiazolo[3,2-a]benzimidazol-2-yl)ethanone (1) (2.3 g, 10
mmol) and dimethylformamide-dimethylacetal (DMF-DMA)
(1.34 g, 10 mmol) in dry xylene (50 mL) was refluxed for 5 h.
The solvent was evaporated and the resulting yellow crystals
were taken by ether, collected by filtration, washed thoroughly
with ether, dried and finally recrystallized from ethanol/
dimethylformamide to afford the enaminone 2 in 62% yield; mp:

1036
H. A. Abdel-Aziz, N. A. Hamdy, A. M. Farag and I. M. I. Fakhr
Vol 45
240-241˚C; ir: 1624 (C=O), 1535 (C=N) cm-1; 13C nmr (DMSO-
d6): ꢀ 14.9 (-CH3), 44.6, 44.7 (-N=(CH3)2), 108.6 (-S-C=C-CH3),
110.1 (-CO-CH=), 121.8, 122.5, 124.9, 125.2, 130.2, 137.6
(C6H4), 148.4 (C of imidazole), 149.1 (=CH-N), 154.7 (-S-C=C-
3-Methyl-2-(2-phenyl-pyrazolo[1,5-a]pyrimidin-7-yl)thiaz-
olo[3,2-a]benzimidazole (6a). This compound was obtained as
yellow crystals, mp >300˚C; ir: 1612 (C=N) cm-1; 13C nmr
(DMSO-d6): ꢀ 15.1 (-CH3), 94.2 (C of pyrazole), 109.7, 113.9,
114.0, 116.0, 123.6, 123.7, 125.4, 126.3, 126.4, 129.0, 129.4,
130.1, 131.9, 136.0, 139.2, 146.0, 149.7, 150.0, 154.2, 154.6; 1H
nmr (DMSO-d6): ꢀ 3.11 (s, 3H, CH3), 5.23 (s, 1H, pyrazole),
7.04-8.27 (m, 10H; 9 ArH and 1H, J=4.2 Hz, pyrimidine), 8.66,
8.67 (d, 1H, J=4.2 Hz, pyrimidine); ms: m/z 382 (M++1), 381
(M+), 274, 240, 89, 77. Anal. Calcd. for C22H15N5S: C, 69.27; H,
3.96; N, 18.36; S, 8.41. Found: C, 69.50; H, 4.12; N, 18.59; S,
8.26.
1
CH3), 180.4 (C=O); H nmr (DMSO-d6): ꢀ 2.92 (s, 3H, CH3),
3.07 (s, 3H, CH3), 3.17 (s, 3H, CH3), 5.37, 5.41 (d, 1H, J=12.0
Hz, -CO-CH=), 7.27-7.70 (m, 3H ArH), 7.73, 7.77 (d, 1H,
J=12.0 Hz, =CH-N-), 8.00-8.02 (m, 1H ArH); ms: m/z 286
(M++1,), 285 (M), 241, 188, 136, 98, 71, 55. Anal. Calcd. for
C15H15N3OS: C, 63.13; H, 5.30; N, 14.72; S, 11.24. Found: C
63.44; H, 5.02; N, 14.95; S, 11.13.
General Procedure for the Reaction Enaminone 2 with
Secondary Amines. A mixture of E-3-(N,N-dimethylamino)-1-
(3-methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-one (2)
(1.93 g, 5 mmol) and the appropriate secondary amine
(piperidine, morpholine or 1-methylpiperazine) (3 mL) in
ethanol (30 mL) was refluxed for 4 h, then left to cool. The
precipitated product was collected by filtration, washed with
ethanol and dried. Recrystallization from ethanol/ dimethyl-
formamide afforded 3a, 3b and 3c in 88, 74 and 83% yield,
respectively.
3-Methyl-2-(1,2,4-triazolo[1,5-a]pyrimidin-7-yl)thiazolo-[3,
2-a]benzimidazole (6b). This compound was obtained as
1
yellow crystals, mp 290-292˚C; ir: 1616 (C=N) cm-1; H nmr
(DMSO-d6): ꢀ 3.02 (s, 3H, CH3), 7.34-8.14 (m, 5H, 4 ArH and
1H, J=3.9 Hz, pyrimidine), 8.78 (s, 1H, triazole), 8.97, 8.98 (d,
1H, J=3.9 Hz, pyrimidine); ms: m/z 306 (M+), 242, 186, 118, 51.
Anal. Calcd. for C15H10N6S: C, 58.81; H, 3.29; N, 27.43; S,
10.47. Found: C, 58.64; H, 3.51; N, 27.42; S, 10.23.
General procedure for the Reaction of Enaminone 2 with
Aminopyrimidine derivatives 7a,b.
E-1-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-(piperid-
in-1-yl)prop-2-en-1-one (7a). This compound was obtained as
yellow needles, mp 233-235˚C; ir: 1639 (C=O), 1576 (C=N)
A mixture of the
enaminone (2.85 g, 10 mmol) and the appropriate
2
aminopyrimidine derivatives 7a or 7b (10 mmol) in acetic acid
(25 mL) was refluxed for 12 h, then left to cool. The solid
product filtered off, washed with ethanol, dried and finally
recrystallized from dimethylformamide/H2O to afford the
corresponding pyrido[2,3-d]pyrimidine derivatives 9a and 9b in
74 and 86% yield, respectively.
1
cm-1; H nmr (DMSO-d6): ꢀ 2.34-2.49 (m, 6H, piperidine), 3.01
(s, 3H, CH3), (m, 4H, piperidine), 5.56, 5.60 (d, 1H, J=12.3 Hz,
-CO-CH=), 7.25-7.70 (m, 3H ArH), 7.71, 7.75 (d, 1H, J=12.3
Hz, =CH-N-), 8.02-8.04 (m, 1H ArH); ms: m/z 326 (M++1), 325
(M+), 188, 83. Anal. Calcd. for C18H19N3OS: C, 66.43; H, 5.88;
N, 12.91; S, 9.85. Found: C, 66.12; H, 5.65; N, 12.60; S, 9.97.
E-1-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-(morph-
olin-4-yl)prop-2-en-1-one (7b). This compound was obtained as
pale yellow needles, mp 267-269˚C; ir: 1643 (C=O), 1551
5-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-1H-pyrido-
[2,3-d]pyrimidine-2,4-dione (9a). This compound was obtained
as orange powder, mp >300˚C; ir: 3233, 3098 (2NH), 1709,
1639 (2C=O), 1616 (C=N) cm-1; 13C nmr (DMSO-d6): ꢀ 14.9 (-
CH3), 107.5, 108.5, 115.0, 121.8, 122.6, 124.9, 125.1, 130.2,
137.6, 148.1, 148.4, 149.3, 152.8, 154.2, 159.7 (C=O), 161.1
(C=N) cm-1; 1H nmr (DMSO-d6):
ꢀ 2.55-2.59 (m, 4H,
morpholine), 3.03 (s, 3H, CH3), (m, 4H, morpholine), 5.56, 5.60
(d, 1H, J=12.2 Hz, -CO-CH=), 7.23-7.70 (m, 3H ArH), 7.71,
7.75 (d, 1H, J=12.3 Hz, =CH-N-), 8.01-8.03 (m, 1H ArH); ms:
m/z 328 (M++1), 327 (M+), 140, 118, 85. Anal. Calcd. for
C17H17N3O2S: C, 62.37; H, 5.23; N, 12.83; S, 9.79. Found: C,
62.54; H; 5.37; N, 12.64; S, 9.56.
E-1-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-(4-meth-
ylpiperazin-1-yl)prop-2-en-1-one (7c). This compound was
obtained as pale yellow needles, mp 195-197˚C; ir: 1642 (C=O),
1566 (C=N) cm-1; 1H nmr (DMSO-d6): ꢀ 2.22 (s, 3H, CH3
piperazine), 2.37-2.40 (m, 4H, piperazine) 3.08 (s, 3H, CH3),
3.45-3.50 (m, 4H, piperazine), 5.57, 5.61 (d, 1H, J=12.3 Hz, -
CO-CH=), 7.23-7.70 (m, 3H ArH), 7.70, 7.74 (d, 1H, J=12.3 Hz,
=CH-N-), 8.02-8.04 (m, 1H ArH); ms: m/z 341 (M++1), 340
(M+), 241, 201, 71, 70. Anal. Calcd. for C18H20N4OS: C, 63.50;
H, 5.92; N, 16.46; S, 9.42. Found: C, 63.73; H, 6.01; N, 16.11;
S, 9.60.
1
(C=O); H nmr (DMSO-d6): ꢀ 3.16 (s, 3H, CH3), 7.28-8.33 (m,
6H; 4 ArH and 2H pyridine), 10.56 (br. s, 1H, NH, D2O
exchangeable), 10.69 (br, s, 1H, NH, D2O exchangeable); ms:
m/z 351 (M++2), 350 (M++1), 349 (M+), 240, 231, 118. Anal.
Calcd. for C17H11N5O2S: C, 58.44; H, 3.17; N, 20.05; S, 9.18.
Found: C, 58.53; H, 3.01; N, 19.87; S, 9.34.
5-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-2-thioxo-2,3-
dihydro-1H-pyrido[2,3-d]pyrimidin-4-one (9b). This compound
was obtained as orange powder, mp >300˚C; ir: 3216, 3105
1
(2NH), 1648 (C=O), 1613 (C=N) cm-1; H nmr (DMSO-d6): ꢀ
3.15 (s, 3H, CH3), 7.29-8.35 (m, 6H; 4 ArH and 2H, pyridine),
11.83 (br. s, 1H, NH, D2O exchangeable), 12.17 (br. s, 1H, NH,
D2O exchangeable); ms: m/z 366 (M++1), 365 (M+), 254, 118.
Anal. Calcd. for C17H11N5OS2: C, 55.88; H, 3.03; N, 19.16; S,
17.55. Found: C, 56.09; H, 3.28; N, 18.87; S, 17.70.
General Procedure for the Reaction of Enaminone 2 with
Diazonium Salts of Heterocyclic Amines 11a,b. To a stirred
cold solution of the enaminone 4 (0.57 g, 2 mmol) in pyridine
(30 mL) was added the appropriate diazonium salt of 5-amino-
3-phenyl-1H-pyrazole 11a or 3-amino-l,2,4-(1H)-triazole 11b (2
mmol) portion-wise over a period of 30 min at 0-5ºC. After
complete addition, the reaction mixture was stirred for further 3
h at 0-5ºC. The solid that precipitated was collected by filtration,
washed with water and dried. Recrystallization from
dimethylformamide/H2O afforded the corresponding fused ring
system 13a and 13b in 82 and 74% yield, respectively.
General Procedure for the Reaction of Enaminone 2 with
Heterocyclic Amines 4a,b. A mixture of enaminone 2 (2.85 g,
10 mmol) and the appropriate heterocyclic amine 5-amino-3-1H-
phenylpyrazole (4a) or 3-amino-l,2,4-(1H)-triazole (4b) (10
mmol) in pyridine (25 mL) was refluxed for 12 h, then left to
cool. The reaction mixture was poured into cold water and the
solid product was collected by filtration, washed with water,
dried and finally recrystallized from dimethylformamide/H2O to
afford the corresponding pyrazolo[1,5-a]pyrimidine
triazolo[1,5-a]pyrimidine, derivatives 6a and 6b in 72 and 66%
and
yield, respectively.

Jul-Aug 2008
Synthesis of Some Novel Pyrazolo[1,5-a]pyrimidine, 1,2,4-Triazolo[1,5-a]pyrimidine,
1037
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141763y.
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3-Methyl-2-(7-phenyl-pyrazolo[5,1-c]-1,2,4-triazin-3-oyl)-
thiazolo[3,2-a]benzimidazole (13a). This compound was
obtained as yellow powder, mp >300˚C; ir: 1648 (C=O), 1602
1
(C=N) cm-1; H nmr (DMSO-d6): ꢀ 2.62 (s, 3H, CH3), 6.53 (s,
1H, pyrazole), 7.27-7.81 (m, 10H; 9 ArH and 1H triazine); ms:
m/z 411 (M++1), 410 (M+), 345, 301, 239, 134, 92, 77. Anal.
Calcd. for C22H14N6OS: C, 64.38; H, 3.44; N, 20.47; S, 7.81.
Found: C, 64.23; H, 3.67; N, 20.31; S, 7.95.
3-Methyl-2-(1,2,4-triazolo[5,1-c]-1,2,4-triazin-3-oyl)thiaz-
olo[3,2-a]benzimidazole (13b). This compound was obtained as
yellow crystals, mp >300˚C; ir: 1639 (C=O), 1562 (C=N) cm-1;
13C nmr (DMSO-d6): ꢀ 15.0 (-CH3), 112.9, 122.0, 123.1, 124.4,
125.3, 130.2, 137.6, 140.4, 151.5, 154.2, 156.2, 158.2, 162.4,
1
189.8 (C=O); H nmr (DMSO-d6): ꢀ 3.23 (s, 3H, CH3), 6.78-
8.58 (m, 6H; 4 ArH, 1H triazole and 1H triazine); ms: m/z 337
(M++2), 336 (M++1), 335 (M+), 188, 144, 74. Anal. Calcd. for
C15H9N7OS: C, 53.73; H, 2.71; N, 29.24; S, 9.56. Found: C,
53.57; H, 2.52; N, 29.22; S, 9.34.
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