Synthesis of tetrahetrocyclic systems including pyrido[2′,3′:3, 4]pyrazolo[1,5-a]pyrimidine fused with pyrazole derivatives and isolated with 1,3,4-oxa-, thiadiazole, and 1,2,4-tetrazole derivatives

Article abstract of DOI:10.1002/jhet.339

(Chemical Equation Presented) A series of isolated and fused tetracyclic compounds, containing pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine linked with 1,3,4-oxa-, thiadiazole, 1,2,4-tetrazole, and pyrazole derivatives were prepared by the reaction of 1,8,10-trimethyl-4-oxo-1,4- dihydropyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine-3-carboxylate and some common reagents to provide the product in satisfactory yields.

Full text of DOI:10.1002/jhet.339

318
Synthesis of Tetrahetrocyclic Systems Including
Pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine Fused with Pyrazole
Derivatives and Isolated with 1,3,4-Oxa-, Thiadiazole, and 1,2,4-
Tetrazole Derivatives
Vol 47
Farag A. El-Essawy*
Faculty of Science, Department of Chemistry, Menoufia University, Shebin El-Koam, Egypt
*E-mail: el_essawy2000@yahoo.com
Received August 19, 2009
DOI 10.1002/jhet.339
Published online 2 March 2010 in Wiley InterScience (www.interscience.wiley.com).
A series of isolated and fused tetracyclic compounds, containing pyrido[20,30:3,4]pyrazolo[1,5-a]py-
rimidine linked with 1,3,4-oxa-, thiadiazole, 1,2,4-tetrazole, and pyrazole derivatives were prepared by
the reaction of 1,8,10-trimethyl-4-oxo-1,4-dihydropyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine-3-carboxy-
late and some common reagents to provide the product in satisfactory yields.
J. Heterocyclic Chem., 47, 318 (2010).
INTRODUCTION
RESULTS AND DISCUSSION
1H-Pyrazolo[3,4-b]pyridines comprise a very interest-
ing class of compounds because of their significant and
versatile biological and pharmacological activities, such
as antimalarial [1], antiproliferative [2], antimicrobial
[3–5] inhibition of cyclin-dependent kinases [6] and car-
diovascular [7–9] antiviral [10–12] and antileishmanial
[13] activities. In general, the pyrazolopyridines are
found to be active antitubercular agents [14,15] active
against gram positive and negative bacteria [16]. As
well as pyrazolopyrimidines [17,18] are selective inhibi-
tors of cyclic 30,50-adenosine mono-phosphat (cAMP)
phosphodiesterases in vitro, and some of them possess
anxiolytic properties comparable to those of benzodiaze-
pines.[19]. Moreover, pyridopyrazolopyrimidines revaled
antiproliferative activity [20] and are used as potent ki-
nase inhibitors [21]. To enhance the activity of pyrazo-
lopyridines and pyrazolopyrimidines, several approaches
were followed to construct another ring over those ring
systems described in the literature [22–26] are available
on preparation of pyridopyrazolopyrimidines which left
much scope for further study. Furthermore, it has been
reported that certain compounds bearing 1,3,4-oxa-,
thiadiazole, and 1,2,4-triazole nucleus possess signifi-
cant anti-inflammatory activity [27–37]. In view of
these reports, we reported herein the synthesis of some
newer heterocyclic systems containing pyridopyrazolo-
pyrimidine system isolated with 1,2,4-triazoles, 1,3,4-
oxa-, and thiadiazoles, and fused with pyrazoles
derivative.
4,6-Dimethyl-1H-pyrazolo[3,4-b]pyridine-3-amine was
prepared according to the reported method [38,39]
which undergo the cyclocondensation reaction with
diethyl ethoxymethylenemalonate yielded directly the
8,10-dimethyl-4-oxo-1,4-dihydropyrido[20,30:3,4]pyrazolo
[1,5-a]pyrimidine-3-carboxylate (2) without the isolation
of the enamine intermediate [40], the structure of 2 was
confirmed by the correctly positioned and coupled 1H
NMR spectrum, which presents signals as triplet at d
1.29, quartet at 4.32 ppm because of the ester group and
as singlet at d 8.68, 12.24 ppm due to the H-2 and NH
protons, respectively. The 13C NMR spectrum of 2
showed a characteristic signals, for the ester group, at d
24.2, 62.0 (CH2CH3), 166.0 (COOEt), and 154.5 (C-4)
ppm. The latter compound 2 was alkylated, by its
reaction with methyl iodide in presence of KOH to
afford
1,8,10-trimethyl-4-oxo-1,4-dihydropyrido[20,30:
3,4]pyrazolo[1,5-a]pyrimidine-3-carboxylate (3), to in-
crease its solubility during its reactions, which was elu-
1
cidated by the appearance of the new signals in the H
NMR spectrum as singlet at d 3.96 ppm due to NACH3.
The alkylated derivative 3 was subjected to react with
hydrazine hydrate to give the corresponding carbohydra-
zide derivative 4 which was confirmed by its IR spec-
trum showed a characteristic C¼¼O absorptions at 1640
1
and 1677 cmꢀ1, and its H NMR spectrum agree with
the structure which showed a characteristic a broad sin-
glet band for CONHNH2 at d 4.78 ppm. Hydrazide de-
rivative (4) is versatile synthetic intermediate for the
C
V
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Synthesis of Tetrahetrocyclic Systems Including
Pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine
319
Scheme 1
peaks corresponding to peaks at m/z 327 and 328 corre-
sponding to Mþ and Mþþ1, respectively (Scheme 1).
On treatment of the hydrazide 4 with phenylisothio-
cyanate, in the way like its reaction with ammonium thi-
ocyanate, afforded the corresponding the thiosemicarba-
zide 8 which was considered the key intermediate to
prepare the 1,8,10-trimethyl-3-[5-(phenylamino)-1,3,4-
thiadiazol-2-yl]pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidin-
4(1H)-one (9), 1,8,10-trimethyl-3-(4-phenyl-5-sulfanyl-
4H-1,2,4-triazol-3-yl)pyrido[20,30:3,4]pyrazolo[1,5-a]pyr-
imidin-4(1H)-one (10), and 1,8,10-trimethyl-3-[5-(phe-
nylamino)-1,3,4-oxadiazol-2-yl]pyrido[20,30:3,4]pyrazolo
[1,5-a]pyrimidin-4(1H)-one (11), in about 66–74%
yields, after its treatment with sulfuric acid, 2N sodium
hydroxide, and mercuric oxide, respectively. The pre-
ferred formation of the 1,3,4-thiadiazole derivative 9
under such acidic conditions can be due to the loss of
nucleophilicity of N-4 as a result of its protonation lead-
ing to an increase in the nucleophilicity of the sulfur
atom toward the attack of the carbonyl carbon. On the
other hand, the cyclization of 4 was carried out under
alkaline conditions, the nucleophilicity of N-4 is
enhanced and leads to cyclization with carbonyl carbon
atom to afford the 1,2,4-triazole derivative 10. 1,3,4-
Oxadiazole derivative 11 was performed by mercuric
oxide, the mode of cyclization includes desulfurization,
which introduces the oxygen atom in the cyclization
process. The structure assignment of these derivatives
1
were based on the H NMR spectra showed signals due
to the NHPh present in 9 and 11 at d 9.86, 9.46 ppm, as
a broad singlet, but in derivative 10 showed the broad
singlet at d 13.06 ppm due to the SH group. All the
other aromatic and aliphatic protons were observed at
the expected regions. Mass spectra of these derivatives
showed a [Mþþ1] peak, in agreement with their molec-
ular formula, also the elemental analysis are consistent
with the structure of these derivatives 9, 10, and 11
(Scheme 2).
preparation of many heterocyclic moieties. In view of
this report, we report herein some reactions of this hy-
drazide 4 to obtain new heterocyclic rings attached and/
or fused to the pyridopyrazolopyridine moiety. Reaction
of hydrazide 4 with CS2 in alc. KOH at reflux tempera-
ture afforded the corresponding 1,8,10-trimethyl-3-(5-
sulfanyl-1,3,4-oxadiazol-2-yl)pyri-
do[20,30:3,4]pyrazolo[1,5-a]pyrimidin-4(1H)-one
(5)
which was elucidated, besides the elemental analysis,
1H NMR spectrum represented the presence of the
characteristic broad singlet due to the SH group at d
13.12 ppm and its mass spectrum revealed the molecu-
lar ion peak at m/z 328 indicated the molecular weight
of 5. The 13C NMR spectrum showed a characteristic
isooxazole signals at d 162.0 and 171.3 ppm. Also the
reaction of 4 with ammonium thiocyanate in absolute
ethanol gave the corresponding thiosemicarbazide 6
which undergo the cyclization reaction through its
treatment with sodium hydroxide giving 1,8,10-trimethyl-3-
(5-sulfanyl-4H-1,2,4-triazol-3-yl)pyrido[20,30:3,4]pyrazolo[1,5-
a]pyrimidin-4(1H)-one (7) which was confirmed by 1H
NMR spectrum which showed the presence of signals as
a broad bands at d 10.92 and 12.55 ppm due to the NH
and SH groups, respectively, its mass spectrum presents
The starting material, pyridopyrazolopyrimidine
carboxylate 2 was transformed into ethyl 4-chloro-8,10-
dimethylpyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine-3-
carboxylate by phosphorous oxychloride at boiling
temperature thus providing intermediate precursor 12
for all four new final compounds. They furnished
fused tetracyclic compounds 13a–d by reaction with
various purchased hydrazines in boiling xylene. The
previously reported method, consisting of a nucleo-
phylic substitution of the chlorine atom with the hy-
drazine derivative followed by cyclization [41], again
showed itself to be useful and profitable for the aims
proposed. 6,8-dimethyl-2,3-dihydro-3H-pyrazolo[3,2-
d]pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine-3-one
derivatives 13a–d were elucidated by the IR spectra
which presented strong peaks at 1640–1620, 3466–3409,
Journal of Heterocyclic Chemistry
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320
F. A. El-Essawy
Vol 47
Scheme 2
and 2210 cmꢀ1 which were attributed to the carbonyl
(C¼¼O) and ANH groups on the pyrazole and pyrimi-
dine, respectively. The mass spectra of these compounds
13a–d indicated that the molecular ion peaks were
refluxed for 10 h cooling to room temperature and poured into
ice/water. The solid product was collected by filtration, washed
with water, dried, and recerystalization from methanol to
afford the yellow crystals of 2, 3.12 g (91%), mp 222–223ꢁC;
1H NMR (DMSO-d6): d 1.29 (t, 3H, J ¼ 7 Hz, CH3CH2), 2.66
(s, 3H, CH3), 2.91 (s, 3H, CH3), 4.32 (q, 2H, J ¼ 7.0 Hz
CH3CH2), 7.03 (s, 1H, ArH), 8.68 (s, 1H, ArH), 12.24 (bs, 1H,
NH); 13C NMR (DMSO-d6): d 14.3, 19.2, 24.2, 62.0, 91.2,
116.8, 122.2, 145.8, 148.2, 151.2, 153.6, 154.5, 158.3, 166.0;
ms (EI): m/z 287 (Mþþ1, 5), 286 (Mþ, 26), 241 (23), 240
(100). Anal. Cacld. for C14H14N4O3 (286.29): C, 58.73; H,
4.93, N, 19.57. Found: C, 58.60; H, 4.75; N, 19.35.
1,8,10-Trimethyl-4-oxo-1,4-dihydropyrido[20,30:3,4]pyrazolo
[1,5-a]pyrimidine-3-carboxylate (3). A solution of 1.77 g (6.2
mmol) of 2 in 20 mL of acetone, cooled by immersion in a
water/ice bath, was added to 1.74 g (31.0 mmol) of powdered
KOH. On vigorous stirring, 1.76 g of methyl iodide (12.4
mmol) was added and the mixture was stirred for 30 min at
room temperature. After the addition of 90 mL of toluene, a
precipitate of inorganic salt had formed, which was filtered
1
observed as Mþ and MþþH. From their H NMR spec-
tra, it is possible to observe the presence of signals cor-
responding to the NH of pyrimidine at the range d
10.99–11.15 ppm, the absence of the ester group and
presence the new signals in aliphatic region such as in
compound 13a at d 4.18 ppm due to the NACH3 and
the increase of signals in the aromatic part because the
presence of phenyl derivatives in compounds 13b–d. In
addition, the elemental analysis is consistent with the
structure of theses compounds 13a–d (Scheme 3).
EXPERIMENTAL
Melting points were determined using Kofter block instru-
ment. The progresses of reactions were monitored by TLC (an-
alytical silica gel plates 60 F254). NMR spectra were recorded
on a Bruker AC 250 FT NMR spectrometer at 300 MHz for
1H NMR and at 75.5 MHz for 13C NMR with TMS as an in-
ternal standard, chemical shifts are reported in ppm (d) and
coupling constants (J) are given in Hz. IR spectra were
recorded on Perkin-Elmer 1430 sectrpphotometer using KBr
disc technique. Mass spectra were measured on a Kratos 50 tc
spectrometers. Elemental analyses were performed at the
Chemistry Institute, Copenhagen University.
Scheme 3
Ethyl
8,10-dimethyl-4-oxo-1,4-dihydropyrido[20,30:3,4]
pyrazolo[1,5-a]pyrimidine-3-carboxylate (2). A mixture of
1.94 g of aminopyrazolopyridine 1 (12 mmol) and 2.59 g of
diethyl ethoxymethylenemalonate (12 mmol) was dissolved in
20-mL glacial acetic acid and the reaction mixture was
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DOI 10.1002/jhet

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Synthesis of Tetrahetrocyclic Systems Including
Pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine
321
off. The organic mixture was treated with 20 mL of saturated
NaCl solution, dried with anhydrous Na2SO4, and evaporated
under reduced pressure. The residue was triturated with etha-
nol and the solid product was collected by filtration, and
recrystalization from ethanol to afford the white powꢀde1r of 3,
Anal. Cacld. for C14H15N7O2S (345.38): C, 48.69; H, 4.38, N,
28.39. Found: C, 48.30; H, 4.22; N, 28.26.
1,8,10-Trimethyl-3-(5-sulfanyl-4H-1,2,4-triazol-3-yl)pyri-
do[20,30:3,4]pyrazolo[1,5-a]pyrimidin-4(1H)-one (7). A mix-
ture of 0.69 g thiosemicarbazid 6 (2 mmol) and 50-mL sodium
hydroxide (2N) was heated under reflux for 2 h. The reaction
mixture was cooled, the precipitate formed was collected by
filtration, dried, and recrystallized from methanol to afford the
yellow crystals of 7, 0.52 g (80%); mp 239–240ꢁC; IR (KBr)
1.52 g (82%); mp 150–152ꢁC; IR (KBr) m cm
1745
1
(CO2Et), 1633 (CO); H NMR (CDCl3): d 1.26 (t, 3H, J ¼ 7
Hz, CH3CH2), 2.56 (s, 3H, CH3), 2.83 (s, 3H, CH3), 3.96 (s,
3H, NACH3), 4.29 (q, 2H, J ¼ 7 Hz, CH3CH2), 7.00 (s, 1H,
ArH), 8.68 (s, 1H, ArH); (EI): m/z 301 (Mþþ1, 20), 300 (Mþ,
100),, 255 (25), 227 (30), 184 (8), 131 (60), 115 (16). Anal.
Cacld. for C15H16N4O3 (300.31): C, 59.99; H, 5.37, N, 18.66.
Found: C, 59.76; H, 5.25; N, 18.45.
1
m cmꢀ1: (NH) 3320,1645 (CO), 2786 (SH); H NMR (DMSO-
d6): d 2.70 (s, 3H, CH3), 2.77 (s, 3H, CH3), 3.93 (s, 3H,
NACH3), 7.15 (s, 1H, ArH), 8.50 (s, 1H, ArH), 10.92 (bs, 1H,
NH), 12.55 (bs, 1H, SH); ms (EI): m/z 328 (Mþþ1, 60), 327
(Mþ, 100), 294 (15), 227 (60), 246 (13), 201 (11), 184 (8).
Anal. Cacld. for C14H13N7OS (327.36): C, 51.36; H, 4.00, N,
29.95. Found: C, 51.22; H, 3.97; N, 29.86.
1,8,10-Trimethyl-4-oxo-1,4-dihydropyrido[20,30:3,4] pyrazolo
[1,5-a]pyrimidine-3-carbohydrazide (4). A mixture of 3.0 g of
3 (10 mmol) and 1.25 g of hydrazine hydrate (25 mmol) in 30
mL ethanol was heated under reflux for 4 h. The excess of
ethanol was removed under reduced pressure and the resulting
precipitate was filtered off, washed with ethanol, and recrystal-
lized from methanol to give colorless of 4, 2.51 g (88%); mp
266–267ꢁC; IR (KBr) m cmꢀ1: 3310–3212 (NHNH2), 1640,
N0-{[Imino(phenyl)-sulfanylidyne]methyl}-1,8,10-tri-
methyl-4-oxo-1,4-dihydropyrido[20,30:3,4]pyrazolo[1,5-
a]pyrimidine-3-carbohydrazide (8). To a solution of 2.86
g hydrazide 4 (10 mmol) in 10 mL ethanol, 1.35 g phenyliso-
thocyanate (10 mmol) were added. The reaction mixture was
heated under reflux for 2 h. The product that separated on
cooling was filtered off, washed with ethanol, and dried well
1
1677 (2 CO); H NMR (DMSO-d6): d 2.54 (s, 3H, CH3), 2.81
(s, 3H, CH3), 3.86 (s, 3H, NACH3), 4.78 (bs, 2H, NH2), 7.22
(s, 1H, ArH), 8.78 (s, 1H, ArH), 9.45 (bs, 1H, NH); ms (EI):
m/z 287 (Mþþ1, 55), 286 (Mþ, 20), 257 (15), 228 (100), 199
(23), 175 (12), 147 (36). Anal. Cacld. for C13H14N6O2
(286.29): C, 54.54; H, 4.93, N, 29.35. Found: C, 54.33; H,
4.65; N, 29.15.
1
to give white crystals of 8, 3.86 g (92%); mp 173–175ꢁC; H
NMR (DMSO-d6): d 2.65 (s, 3H, CH3), 2.87 (s, 3H, CH3),
3.95 (s, 3H, NACH3), 7.13–7.79 (m, 6H, ArH), 8.81 (s, 1H,
ArH), 9.50 (bs, 1H, ArNH), 9.81 (bs, 1H, CSNH), 10.18 (bs,
1H, CONH); ms (EI): m/z 421 (Mþ, 60), 344 (100), 256 (35),
227 (9), 194 (16), 166 (25), 121 (23), 109 (10). Anal. Cacld.
for C20H19N7O2S (422.48): C, 56.99; H, 4.54, N, 23.26.
Found: C, 56.62; H, 4.33; N, 23.14.
1,8,10-Trimethyl-3-[5-(phenylamino)-1,3,4-thiadiazol-2-yl]
pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidin-4(1H)-one (9). A
solution of 2.11 g thiosemicarbazide 8 (5 mmol) in 10 mL
cold conc. sulfuric acid was stirred until dissolution and the
left at room temperature for 2 h with stirring. The reaction
mixture was poured onto crushed ice and the precipitate prod-
uct was filtered off, washed with water, and recrystallized
from ethanol to give pale yellow crystals of 9, 1.50 g (74%);
mp 207–208ꢁC; 1H NMR (DMSO-d6): d 2.64 (s, 3H, CH3),
2.82 (s, 3H, CH3), 3.96 (s, 3H, NACH3), 7.14–7.65 (m, 6H,
ArH), 8.65 (s, 1H, ArH), 9.86 (bs, 1H, ArNH); 13C NMR
(DMSO-d6): d 15.6, 19.4, 23.5, 93.0, 116.7, 117.3, 117.8,
122.4, 125.1, 129.5, 140.5, 145.9, 148.4, 151.1, 155.0, 152.2,
155.6, 158.9, 159.0, 160.1; ms (EI): m/z 404 (Mþþ1, 30), 403
(Mþ, 100), 326 (21), 271 (15), 240 (24), 174 (12), 145 (22).
Anal. Cacld. for C20H17N7OS (403.46): C, 59.54; H, 4.25, N,
24.30. Found: C, 59.35; H, 4.13; N, 24.17.
1,8,10-Trimethyl-3-(4-phenyl-5-sulfanyl-4H-1,2,4-triazol-
3-yl)pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidin-4(1H)-one
(10). A solution of 2.11 g thiosemicarbazide 8 (5 mmol) in 50
mL sodium hydroxide (2N) was heated under reflux for 4 h.
The reaction mixture was cooled and acidified with hydrochlo-
ric acid (2N). The resulting precipitate was filtered off, washed
with ethanol, and recrystallized from ethanol to afford the yel-
low crystals of 10, 1.40 g (69%), mp 210–211ꢁC; 1H NMR
(DMSO-d6): d 2.66 (s, 3H, CH3), 2.85 (s, 3H, CH3), 3.96 (s,
3H, NACH3), 7.16–7.76 (m, 6H, ArH), 8.33 (s, 1H, ArH),
13.06 (bs, 1H, SH); ms (EI): m/z 404 (Mþþ1, 30), 403 (Mþ,
60), 326 (11), 293 (33), 227 (50), 193 (100), 166 (33), 119
(20), 106 (10). Anal. Cacld. for C20H17N7OS (403.46): C,
59.54; H, 4.25, N, 24.30. Found: C, 59.44; H, 4.17; N, 24.14.
1,8,10-Trimethyl-3-(5-sulfanyl-1,3,4-oxadiazol-2-yl)pyrido
[20,30:3,4]pyrazolo[1,5-a]pyrimidin-4(1H)-one (5). A mixture
of 2.86 g of hydrazide 4 (10 mmol) and 0.6 mL of carbon di-
sulfide (10 mmol) was added to a solution of 0.56 g KOH (10
mmol) in 50 mL water and 50 mL ethanol. The reaction mix-
ture was refluxed for 4 h. After evaporating it to dryness under
reduced pressure, a solid product was obtained. This was dis-
solved in 50 mL water and acidified with conc. HCl. The pre-
cipitate was filtered off, washed with water, and recrystallized
from ethanol to afford the whit crystals of 5, 2.25 g (69%);
mp 210–212ꢁC; 1H NMR (DMSO-d6): d 2.55 (s, 3H, CH3),
2.86 (s, 3H, CH3), 3.88 (s, 3H, NACH3), 7.32 (s, 1H, ArH),
8.95 (s, 1H, ArH), 13.12 (bs, 1H, SH); 13C NMR (DMSO-d6):
d 14.3, 19.2, 24.2, 90.2, 116.7, 121.6, 145.5, 148.4, 151.1,
152.4, 155.3, 157.5, 162.0, 171.3; ms (EI): m/z 329 (Mþþ1,
10), 328 (Mþ, 65), 294 (100), 239 (20), 201 (23), 151 (12), 77
(11). Anal. Cacld. for C14H12N6O2S (328.35): C, 51.21; H,
3.68, N, 25.59. Found: C, 51.12; H, 3.55; N, 25.43.
N0-[(Amino-sulfanylidyne)methyl]-1,8,10-trimethyl-4-oxo-
1,4-dihydropyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine-3-
carbohydrazide (6). To a mixture 0.29 g of hydrazide 4 (1
mmol) and 0.23 g of ammonium thiocyanate (3 mmol), 4 mL
of hydrochloric acid (36%) was added, in 50 mL ethanol. The
reaction mixture was refluxed for 12 h, cooled, and the mix-
ture poured into ice/water with stirring. The solid formed was
collected by filtration, dried, and recrystallized from ethanol to
afford a pale yellow crystals of 6, 0.31 g (89%), mp 225–
226ꢁC; IR (KBr) m cmꢀ1: NH 3300–3200, (NH2, NH), 1655–
1
1640 (CO) cmꢀ1; H NMR (DMSO-d6): d 2.43 (s, 3H, CH3),
2.67 (s, 3H, CH3), 3.89 (s, 3H, NACH3), 5.03 (bs, 2H, NH2),
7.22 (s, 1H, ArH), 8.65 (s, 1H, ArH), 9.71 (bs, 1H, CSNH),
10.17 (bs, 1H, CONH); ms (EI): m/z 346 (Mþþ1, 35), 345
(Mþ, 10), 330 (5), 286 (100), 245 (24), 217 (12), 152 (30).
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F. A. El-Essawy
Vol 47
1,8,10-Trimethyl-3-[5-(phenylamino)-1,3,4-oxadiazol-2-
6,8-Dimethyl-2-(4-methoxy-phenyl)-2,5-dihydro-3H-pyra-
zolo[3,2-d]pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine-3-one
(13c) Yellow powder, mp 270–271ꢁC; 1H NMR (DMSO-d6):
d 2.63 (s, 3H, CH3), 2.78 (s, 3H, CH3), 3.79 (s, 3H, OCH3),
7.16–7.56 (m, 5H, ArH), 8.96 (s, 1H, ArH), 11.12 (bs, 1H,
NH); 13C NMR (DMSO-d6): d 19.6, 24.3, 55.4, 101.3, 109.5,
114.2, 121.6, 122.4, 127.6, 136.7, 132.8, 145.7, 148.6, 150.5,
153.5, 154.9, 155.4, 158.7, 165.1; ms (EI): m/z 361 (Mþþ1,
39), 360 (Mþ, 60), 329 (100), 252 (21), 197 (12), 121 (10),
107 (41). Anal. Cacld. for C19H16N6O2 (360.37): C, 63.32; H,
4.48; N, 23.32. Found: C, 63.19; H, 4.30; N, 23.20.
yl]pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidin-4(1H)-one
(11). Mercuric oxide 2.37 g (11 mmol) was added to a solu-
tion of 4.21 g thiosemicarbazide 8 (10 mmol) in 20 mL meth-
anol and the resulting mixture was refluxed for 4 h. The pre-
cipitated mercuric sulfide was filtered off and washed with
hot methanol. The filtrate on cooling gave a precipitate which
was recrystallized from ethanol to afford the white crystals of
11, 2.55 g (66%), mp 183–184ꢁC; 1H NMR (DMSO-d6): d
2.69 (s, 3H, CH3), 2.83 (s, 3H, CH3), 3.94 (s, 3H, NACH3),
7.12–7.66 (m, 6H, ArH), 8.78 (s, 1H, ArH), 9.46 (bs, 1H,
ArNH); ms (EI): m/z 387 (Mþ, 100), 310 (30), 283 (15), 227
(30), 174 (40), 117 (10). Anal. Cacld. for C20H17N7O2
(387.39): C, 62.01; H, 4.42, N, 25.31. Found: C, 61.94; H,
4.31; N, 25.14.
6,8-Dimethyl-2-(4-chloro-phenyl)-2,5-dihydro-3H-pyra-
zolo[3,2-d]pyrido[20,30:3,4]pyrazolo[1,5-a]pyrimidine-3-one
1
(13d) White powder, mp 240–241ꢁC; H NMR (DMSO-d6): d
2.67 (s, 3H, CH3), 2.79 (s, 3H, CH3), 7.19–7.87 (m, 5H, ArH),
8.98 (s, 1H, ArH), 11.15 (bs, 1H, NH); 13C NMR (DMSO-d6):
d 19.7, 24.5, 99.3, 110.6, 113.4, 119.5, 126.5, 135.7, 131.7,
143.5, 145.7, 149.5, 151.6, 156.8, 157.4, 159.3, 160.5, 164.5;
ms (EI): m/z 365 (Mþþ1, 80), 364 (Mþ, 100), 328 (30), 300
(18), 284 (15), 257 (13), 231 (18), 201 (55), 146 (16), 131
(22), 112 (13). Anal. Cacld. for C18H13ClN6O (364.79): C,
59.27; H, 3.59; N, 23.04. Found: C, 59.18; H, 3.41; N, 22.88.
4-Chloro-8,10-dimethylpyrido[20,30:3,4]pyrazolo[1,5-a]
pyrimidine-3-carboxylate (12). A mixture of 2.86 g of eth-
ylcarboxylate 2 (10 mmol) and 7.75 g of phosphorous oxy-
chloride (50 mmol) was refluxed for 3 h. After cooling, the
suspension was then added to ice/water. Then, with stirring, it
was carefully made alkaline with aqueous sodium hydroxide
(28%) and the resulting precipitate was collected, washed
many times with water, dried, and recrystallized from ethanol
to afford a pale yellow powder of 12, 2.81 g (92%), mp 150–
152ꢁC; 1H NMR (DMSO-d6): d 1.31 (t, 3H, J ¼ 7 Hz,
CH3CH2), 2.68 (s, 3H, CH3), 2.95 (s, 3H, CH3), 4.41 (q,
2H, J ¼ 7.0 Hz CH3CH2), 7.11 (s, 1H, ArH), 8.77 (s, 1H,
ArH); ms (EI): m/z 305 (Mþþ1, 12), 304 (Mþ, 72), 267
(30),240 (100), 223 (15), 195 (15). Anal. Cacld. for
C14H13ClN4O2 (304.73): C, 55.18; H, 4.30; N, 18.39. Found:
C, 55.10; H, 4.22; N, 18.20.
Acknowledgments. The author thanks the Menoufia University
and Chemistry department for funding the analyses and the spec-
tral data in Organic Chemistry Unit.
REFERENCES AND NOTES
´
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