Microwave-assisted synthesis and antibacterial evaluation of new derivatives of 1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one

Article abstract of DOI:10.1515/hc-2015-0145

Synthesis of new 1,2-dihydro-3H-pyrazolo[3,4-d] pyrimidin-3-ones 4-6 starting with ethyl 4-hydroxy-2-methylthio-pyrimidine-5-carboxylate (1) under classical heating and microwave-induced conditions is reported. The antibacterial activities of the synthesized compounds were evaluated using chloramphenicol and streptomycin as reference drugs.

Full text of DOI:10.1515/hc-2015-0145

Heterocycl. Commun. 2016; aop
Zahra Ebrahimpour, Ali Shiri, Mehdi Bakavoli*, Seyed Mohammad Seyedi,
Masoumeh Bahreini and Fatemeh Oroojalian
Microwave-assisted synthesis and antibacterial
evaluation of new derivatives of 1,2-dihydro-3H-
pyrazolo[3,4-d]pyrimidin-3-one
DOI 10.1515/hc-2015-0145
different types of enzymes such as cyclin-dependent
kinase [10, 11, 12] adenosine deaminase [12] glycogen syn-
thase kinase-3 [13] and epidermal growth factor receptor
protein tyrosine kinase [14].
Most synthetic approaches to pyrazolopyrimidines
start from substituted pyrimidines or pyrazoles [15].
The cyclization of pyrimidines with hydrazines pro-
vides pyrazolopyrimidines via the construction of the
fused pyrazole ring [16]. Alternatively, pyrazolopyrimi-
dines can also be synthesized through the construction
Received July 27, 2015; accepted October 14, 2015
Abstract: Synthesis of new 1,2-dihydro-3H-pyrazolo[3,4-d]
pyrimidin-3-ones 4–6 starting with ethyl 4-hydroxy-
2-methylthio-pyrimidine-5-carboxylate (1) under classical
heating and microwave-induced conditions is reported.
The antibacterial activities of the synthesized compounds
were evaluated using chloramphenicol and streptomycin
as reference drugs.
Keywords: antibacterial; microwave; pyrazolo[3,4-d] of the pyrimidine ring using substituted pyrazoles [10].
pyrimidin-3-one; synthesis.
Recently, some new methods have been reported based
on using microwave irradiation [16], ionic liquids [17],
supported solid catalysts [17, 18] and under solvent-free
conditions [19].
Dedication: In the memory of Professor Mohammad Rahimizadeh
As part of our ongoing program aimed at develop-
ing new protocols for preparation of biologically active
heterocyclic compounds [20], we wish to report the
result of our investigations on the synthesis and anti-
Introduction
Pyrazolo[3,4-d]pyrimidines and related fused derivatives microbial activities of new derivatives of pyrazolo[3,4-d]
are a pharmaceutically important class of compounds pyrimidin-3(2H)-ones.
[1]. They exhibit diverse pharmaceutical activities such
as antifungal [2], antibacterial [2, 3], neuroleptic [4], anti-
hypertensive [5] and antileishmanial [6] properties. Also,
Results and discussion
pyrazolopyrimidines have been exploited as ATP com-
petitive inhibitors of kinases [7], cAMP phosphodiesterase
The starting material, ethyl 4-hydroxy-2-methylthio-pyrim-
[8] and DNA polymerase [9]. Some of these compounds
idine-5-carboxylate (1 in Scheme 1), was prepared accord-
have demonstrated antitumor activities [10] by inhibiting
ing to the previously published method [21]. The treatment
of 1 with morpholine, pyrolidine and piperidine, led to the
selective SNAr displacement of the thiomethyl moiety and
*Corresponding author: Mehdi Bakavoli, Faculty of Science,
gave the respective pyrimidines 2a–c. Then, the chloro-
Department of Chemistry, Ferdowsi University of Mashhad,
pyrimidines 3a–c were obtained by heating compounds
91775-1436 Mashhad, Iran, e-mail: mbakavoli@um.ac.ir;
2a–c in a mixture of PCl5 and POCl3 (1:14) [22–24]. Com-
pounds 3a–c served as direct precursors to the desired
products 4a–c, 5a–c and 6a–c by the reaction with hydra-
zine, methylhydrazine and phenylhydrazine, respectively.
Classical synthesis of pyrazolo[1,5-a]pyrimidines 4–6
was performed by heating the reactants in ethanol in the
presence of sodium ethoxide (Method A in Scheme 1).
The observed different regioselectivities for the reaction
mbakavoli@yahoo.com
Zahra Ebrahimpour, Ali Shiri and Seyed Mohammad Seyedi:
Faculty of Science, Department of Chemistry, Ferdowsi University of
Mashhad, 91775-1436 Mashhad, Iran
Masoumeh Bahreini: Faculty of Science, Department of Biology,
Ferdowsi University of Mashhad, Mashhad, Iran
Fatemeh Oroojalian: Faculty of New Sciences and Technologies,
Department of Life Science Engineering, University of Tehran,
14395-1561 Tehran, Iran
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ꢀZ. Ebrahimpour et al.: Pyrazolopyrimidines: synthesis and antibacterial evaluation
O
O
O
O
N
OEt
N
OEt
R2NH
MeS
N
H
R2N
N
H
EtOH/∆
O
NH2NH2
N
1
2a–c
NH
N
R2N
N
H
POCl /PCl ,
∆
4a–c
3
5
O
O
a:
R2NH =
O
NH
Method A or
Method B
MeNHNH2
N
OEt
N
N
NH
R2N
N
Cl
N
R2N
N
b:
c:
R2NH =
R2NH =
NH
NH
Me
3a–c
5a–c
O
Method A: NaOEt/EtOH, 60°C, 2–8 h
Method B: MW, rt, 400 W, 2–6 min
PhNHNH2
N
Ph
N
R2N
N
H
6a–c
Scheme 1ꢀ
with methylhydrazine to give product 5 and for the reac- (Escherichia coli ATCC 25922, and Pseudomonas aerugi-
tion with phenylhydrazine leading to product 6 are in nosa ATCC 9027) bacteria. The results of antibacterial
full agreement with the literature data [25–27]. A similar, properties of active compounds are shown in Table 1. The
microwave-assisted organic synthesis (MAOS) [28, 29] is results indicate that compound 6c shows the strongest
designated in Scheme 1 as Method B. Comparison of the antibacterial properties against all tested bacteria. The
results of the two methodologies reveals that the use of minimum inhibitory concentration (MIC) and minimum
microwave irradiation greatly reduces the reaction time bactericidal concentration (MBC) of compound 6c against
(from 2–8 h to 2–6 min) and significantly increases the E. coli are significantly better than those of chlorampheni-
yield. The structures of products 4–6 are fully supported col, the reference drug. Inhibition activity of 6c against P.
1
13
by the results of IR, H NMR, C NMR, MS and elemental aeruginosa is the same as that of streptomycin. Finally, the
analysis. A literature survey [30, 31] reveals that synthetic antibacterial activity of 6c against S. aureus is higher than
approaches to pyrazolopyrimidines mostly involve a het- that of chloramphenicol and is equal to streptomycin.
erocyclization reaction of pyrimidine moiety onto the
pyrazole core [15]. Our synthetic protocol is different and
based on the construction of the pyrazole moiety at the
pyrimidine core.
Conclusion
Compounds 4–6 were tested for antibacterial activ-
ity against Gram-positive (Staphylococcus aureus ATCC In summary, we applied classical conditions and MAOS
25923, Bacillus cereus ATCC 11778) and Gram-negative to the preparation of pyrazolo[3,4-d]pyrimidin-3(2H)-ones
Table 1ꢀAntibacterial activities (MIC and MBC μg/mL) of active compounds.
Entry
ꢁꢁ
B. subtilis ATCCꢁꢁ
12711
S. aureus ATCCꢁꢁ
25923
E. coli ATCCꢁꢁ
25922
P. Aeruginosa
ATCC 9027
MICꢁ
MBC
MICꢁ
MBC
MICꢁ
MBC
MICꢁ
MBC
5a
5b
6a
6b
6c
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
416.6ꢂ
500ꢂ
844ꢂ
500ꢂ
500ꢂ
250ꢂ
125ꢂ
250ꢂ
62.5ꢂ
78ꢂ
250ꢂ
62.5ꢂ
62.5ꢂ
31ꢂ
125ꢂ
31ꢂ
104ꢂ
500ꢂ
125ꢂ
125ꢂ
62.5ꢂ
250ꢂ
31ꢂ
104ꢂ
250ꢂ
250ꢂ
125ꢂ
31ꢂ
125ꢂ
250ꢂ
208ꢂ
250ꢂ
500ꢂ
125ꢂ
31ꢂ
250ꢂ
250ꢂ
416ꢂ
500ꢂ
500ꢂ
250ꢂ
125ꢂ
250ꢂ
125ꢂ
416
500
500
250
125
250
125
500ꢂ
125ꢂ
62.5ꢂ
250ꢂ
Chloramphenicolꢂ
Streptomycin
ꢂ
62.5ꢂ
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Z. Ebrahimpour et al.: Pyrazolopyrimidines: synthesis and antibacterial evaluationꢃ
ꢃ51
4a–c, 5a–c and 6a–c. In all cases, reaction times and yields General procedures for the synthesis of 4a-c, 5a-c
of products were dramatically improved under the MAOS and 6a–c
protocol. Compound 6c has a very good antimicrobial activ-
ity compared to chloramphenicol and streptomycin.
Method AꢀA solution of sodium ethoxide obtained from sodium
metal (1 mmol, 0.023 g)] and absolute ethanol (5 mL) was treated with
3a–c (1 mmol) and hydrazine, methylhydrazine or phenylhydrazine
(1.2 mmol). The mixture was heated on a water bath at 60°C and, afer
completion of the reaction as was monitored by TLC using CHCl3/
MeOH (20:1), the solvent was removed under reduced pressure. The
solid residue was dissolved in water and the solution acidified with
acetic acid. The resulting precipitate was filtered, washed with water
(2 ꢁ×ꢁ 30 mL), dried and crystallized from methanol to give the product
4a–c, 5a–c or 6a–c.
Experimental
Melting points were recorded on an Electrothermal type 9100 melt-
ing point apparatus. The IR spectra were obtained in KBr discs on an
Avatar 370 FT-IR Thermo Nicolet instrument. The 1H NMR (400 MHz)
and the 13C NMR (100 MHz) spectra were recorded in DMSO-d6 on
a Bruker Avance DRX-400 spectrometer. The electron impact mass
spectra were scanned on a Varian Mat CH-7 instrument at 70 eV.
Elemental analyses were performed on a Thermo Finnigan Flash EA
microanalyzer. The in vitro antibacterial activities of the compounds
were determined using the broth microdilution method according to
the Clinical and Laboratory Standards Institute (CLSI) recommended
MIC protocol with minor modifications [32]. The minimum bacteri-
cidal concentrations (MBC) we also determined [33]. Volumes of 5 μL
of every well without growth were transferred to agar plates and
incubated at 37°C for 24 h. The lowest concentration of the synthetic
compounds where no viable bacteria were identified was taken as
MBC [33].
Method BꢀA mixture of compound 3a–c (1 mmol) and an excess
amount of the appropriate hydrazine (0.1 mL) was subjected to micro-
wave irradiation in the absence of solvent (maximum power 400W
during 2–6 min at room temperature) using a focused microwave
reactor (Milestone). Afer the completion of the reaction, water (5 mL)
was added. The solid product was collected by filtration and crys-
tallized from methanol to give the corresponding compounds 4a–c,
5a–c or 6a–c.
6-(Morpholin-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-
3-one (4a)ꢀReaction time 5 h (method A), 4 min (method B); yield
1
68% (A), 84% (B); yellow solid; mp 297–299°C; H NMR: δ 3.64 (t,
4H, J ꢁ=ꢁ 4.8 Hz, 2-CH2N), 3.74 (t, 4H, J ꢁ=ꢁ 4.4 Hz, 2-CH2O), 8.66 (s, 1H,
CH-pyrimidine), 11.19 (br s, 2H, 2-NH, D2O exchangeable); 13C NMR:
δ 44.7, 66.4, 98.7, 153.9, 157.6, 158.8, 161.5; IR: ν 3120, 2965, 2917, 2847,
General procedure for the synthesis of compounds 3a-c
+
1631, 1564 cm-1; MS: m/z 221 (M ). Anal. Calcd for C9H11N5O2: C, 48.86;
Phosphorus pentachloride (2.7 mmol, 0.5 g) was added to a suspen-
sion of ethyl 2-(substituted)amino-6-oxo-1,6-dihydropyrimidine-
5-carboxylate (3.5 mmol, 1.0 g) in phosphorus oxychloride (7 mL).
Afer the mixture had been heated under reflux for 3 h, the residue
was cooled and poured onto ice (~30 g). The resulting solid was
filtrated and crystallized from petroleum ether.
H, 5.01; N, 31.66. Found: C, 48.91; H, 4.98; N, 31.72.
6-(Pyrrolidin-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-
3-one (4b)ꢀReaction time 6 h (A), 5 min (B); yield 58% (A), 80%
(B); yellow powder; mp 325–328°C (decomp.); 1HNMR: δ 1.96 (m, 4H,
2-CH2), 3.53 (t, 4H, J ꢁ=ꢁ 6.8 Hz, 2-CH2N), 8.77 (s, 1H, CH-pyrimidine),
12.64 (br s, 2H, 2-NH); 13C NMR: δ 25.3, 47.2, 112.5, 159.9, 160.0, 160.9,
Ethyl 4-chloro-2-(morpholin-1-yl)dihydropyrimidine-5-carboxy-
late (3a)ꢀYield 68%; white solid; mp 82°C; 1H NMR: δ 1.39 (t, 3H, J ꢁ=ꢁ
7.2 Hz, CH3), δ 3.77 (t, 4H, J ꢁ=ꢁ 5.1 Hz, 2-CH2N), 3.93 (t, 4H, J ꢁ=ꢁ 5.1 Hz,
2-CH2O), 4.36 (q, 2H, J ꢁ=ꢁ 7.1 Hz, CH2), 8.84 (s, 1H, CH-pyrimidine); IR:
+
166.3; IR: ν 3158, 2974, 2884, 1635, 1556 cm-1; MS: m/z 205 (M ). Anal.
Calcd for C9H11N5O: C, 52.67; H, 5.40; N, 34.13. Found: C, 52.71; H, 5.37;
N, 34.09.
+
ν 2974, 2913, 2859, 1724, 1696, 1587 cm-1; MS: m/z 271 (M ). Anal. Calcd
for C11H14ClN3O3: C, 48.63; H, 5.19; N, 15.47. Found: C, 48.55; H, 5.24;
N, 15.62.
6-(Piperidin-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-
3-one (4c)ꢀReaction time 6 h (A), 4 min (B); yield 75% (A), 87% (B);
1
brown powder; mp 298–300°C; H NMR: δ 1.50 (m, 4H, 2-CH2),1.62
Ethyl 4-chloro-2-(pyrrolidin-1-yl)-pyrimidine-5-carboxylate (3b)ꢀ
(m, 2H, CH2) 3.78 (t, 4H, J ꢁ=ꢁ 5.2 Hz, 2-CH2N), 8.61 (s, 1H, CH-pyrim-
idine), 10.94 (br s, 1H, NH, D2O exchangeable), 11.21 (br s, 1H, NH,
D2O exchangeable); 13C NMR: δ 24.7, 25.7, 45.1, 98.1, 130.6, 154.1, 160.0,
161.4; IR: ν 3154, 3131, 3043, 2931, 2853, 1630, 1564 cm-1; MS: m/z 219
1
Yield 67%; white solid; mp 60°C; H NMR: δ 1.39 (t, 3H, J ꢁ=ꢁ 7.2 Hz,
CH3), 2.04 (m, 4H, 2-CH2), 3.67 (t, 4H, J ꢁ=ꢁ 6.3 Hz, 2-CH2N), 4.36 (q, 2H,
J ꢁ=ꢁ 7.2 Hz, CH2), 8.85 (s, 1H, CH-pyrimidine); IR: ν 2978, 2855, 1716,
+
1586 cm-1; MS: m/z 255 (M ). Anal. Calcd for C11H14ClN3O2: C, 51.67;
+
(M ). Anal. Calcd for C10H13N5O: C, 54.78; H, 5.98; N, 31.94. Found: C,
H, 5.52; N, 16.43. Found: C, 51.85; H, 5.37; N, 16.65.
54.73; H, 6.03; N, 32.01.
Ethyl 4-chloro-2-(piperidin-1-yl)-pyrimidine-5-carboxylate (3c)ꢀ
1
Yield 70%; white solid; mp 50°C; H NMR: δ 1.36 (t, 3H, J ꢁ=ꢁ 7.2 Hz, 1-Methyl-6-morpholino-1,2-dihydro-3H-pyrazolo[3,4-d]
CH3), 1.65 (m, 6H, 3-CH2), 3.85 (t, 4H, J ꢁ=ꢁ 5.1 Hz, 2-CH2N), 4.32 (q, 2H, pyrimidin-3-one (5a)ꢀReaction time 2 h (A), 2 min (B); yield 73%
1
J ꢁ=ꢁ 7.2 Hz, CH2), 8.79 (s, 1H, CH-pyrimidine); IR: ν 3113, 3039, 2960, (A), 89% (B); white powder; mp 231–235°C; H NMR: δ 3.53 (s, 3H,
+
2921, 2859, 1746, 1641, 1585 cm-1; MS: m/z 269 (M ). Anal. Calcd for CH3), 3.65 (t, 4H, J ꢁ=ꢁ 4.8, 2-CH2N), 3.77 (t, 4H, J ꢁ=ꢁ 4.8, 2-CH2O), 8.60
C12H16ClN3O2: C, 53.43; H, 5.98; N, 15.58. Found: C, 53.55; H, 5.94; (s, 1H, CH-pyrimidine), 12.23 (br s, 1H, NH, D2O exchangeable);
N, 15.72.
13C NMR: δ 32.4, 44.7, 66.4, 98.4, 153.2, 155.1, 155.6, 160.8; IR: ν 3007,
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ꢀZ. Ebrahimpour et al.: Pyrazolopyrimidines: synthesis and antibacterial evaluation
2970, 2904, 2868, 1672, 1621, 1563 cm-1; MS: m/z 235 (M ); Anal.
Calcd for C10H13N5O2, C, 51.06; H, 5.57; N, 29.77. Found: C, 51.13; H,
5.49; N, 29.80.
+
References
[1] Zhang, X.; Lin, Q.; Zhong, P. A facile one-pot synthesis of
1-arylpyrazolo[3,4-d]pyrimidin-4-ones. Molecules 2010, 15,
3079–3086.
[2] Holla, B. S.; Mahalinga, M.; Karthikeyan, M. S.; Akberali, P. M.;
Shetty, N. S. Synthesis of some novel pyrazolo[3,4-d]pyrimi-
dine derivatives as potential antimicrobial agents. Bioorg.
Med. Chem. 2006, 14, 2040–2047.
[3] Curran, K. J.; Verheijen, J. C.; Kaplan, J.; Richard, D. J.;
Toral Barza, L.; Hollander, I.; Lucas, J.; Kaloustian, S. A.; Yu, K.;
Zask, A. Pyrazolopyrimidines as highly potent and selective,
ATP-competitive inhibitors of the mammalian target of rapa-
mycin (mTOR): optimization of the 1-substituent. Bioorg. Med.
Chem. Lett. 2010, 20, 1440–1444.
[4] Kim, I.; Song, J. H.; Park, C. M.; Jeong, J. W.; Kim, H. R.;
Ha, J. R.; No, Z.; Hyun, Y. L.; Cho, Y. S.; Kang, N. S.; et al.
Design, synthesis, and evaluation of 2-aryl-7-
(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel
PDE-4 inhibitors. Bioorg. Med. Chem. Lett. 2010, 20, 922–926.
[5] Ali, H. I.; Fujita, T.; Akaho, E.; Nagamatsu, T. A comparative
study of autoDock and PMF scoring performances and SAR of
2-substituted pyrazolotriazolopyrimidines and 4-substituted
pyrazolopyrimidines as potent xanthine oxidase inhibitors
Mol. Design 2010, 24, 57–75.
[6] Schenone, S.; Brullo, C.; Bruno, O.; Bondavalli, F.;
Mosti, L.; Maga, G.; Crespan, E.; Carraro, F.; Manetti, F.;
Tintori, C.; et al. Synthesis, biological evaluation and docking
studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines.
Eur. J. Med. Chem. 2008, 43, 2665–2676.
[7] Gilbert, A. M.; Nowak, P.; Brooijmans, N.; Bursavich, M. G.;
Dehnhardt, C.; Santos, E. D.; Feldberg, L. R.; Hollander, I.;
Kim, S.; Lombardi, S.; et al. Novel purine and pyrazolo[3,4-d]
pyrimidine inhibitors of PI3 kinase-α: hit to lead studies.
Bioorg. Med. Chem. Lett. 2010, 20, 636–639.
1-Methyl-6-(pyrrolidin-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]
pyrimidin-3-one (5b)ꢀReaction time 2 h (A), 2 min (B); yield 69%
1
(A), 86% (B); white powder; mp 230–236°C; H NMR: δ 1.90 (m, 4H,
2-CH2), 3.49 (s, 3H, CH3), 3.52 (t, 4H, J ꢁ=ꢁ 6.7 Hz, 2-CH2N), 8.61 (s, 1H,
CH-pyrimidine), 10.91 (br s, 1H, NH, D2O exchangeable); 13C NMR: δ
25.3, 32.5, 46.4, 97.7, 153.2, 155.6, 156.5, 159.7; IR: ν 3023, 2970, 2929,
+
2761, 2667, 2569, 1658, 1617, 1587 cm-1; MS: m/z 219 (M ). Anal. Calcd for
C10H13N5O: C, 54.78; H, 5.98; N, 31.94. Found: C, 54.83; H, 6.07; N, 31.89.
1-Methyl-6-(piperidin-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]
pyrimidin-3-one (5c)ꢀReaction time 2 h (A), 2 min (B); yield 76%
1
(A), 88% (B); yellow powder; mp 249–251°C; H NMR: δ 1.53 (m, 4H,
2-CH2), 1.63 (m, 2H, CH2), 3.34 (s, 3H, CH3), 3.82 (t, 4H, J ꢁ=ꢁ 5.6 Hz,
2-CH2N), 8.63 (s, 1H, CH-pyrimidine), 11.04 (s, 1H, NH, D2O exchange-
able); 13C NMR: δ 24.6, 25.7, 32.5, 45.1, 97.5, 153.9, 154.1, 156.4, 161.0; IR:
+
ν 3007, 2923, 2851, 2774, 2689, 1682, 1627, 1565 cm-1; MS: m/z 233 (M ).
Anal. Calcd for C9H11N5O2: C, 56.64; H, 6.48; N, 30.02. Found: C, 56.60;
H, 6.42; N, 30.08.
6-Morpholino-2-phenyl-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimi-
din-3-one (6a)ꢀReaction time 8 h (A), 6 min (B); yield 77% (A), 90%
(B); brown powder; mp 198–201°C; 1H NMR: δ 3.68 (t, 4H, J ꢁ=ꢁ 4.8 Hz,
2-CH2N), 3.82 (t, 4H, J ꢁ=ꢁ 4.4 Hz, 2-CH2O), 7.19 (t, 2H, phenyl), 7.47 (t, 1H,
phenyl), 8.11 (d, 2H, Phenyl), 8.81 (s, 1H, CH-pyrimidine), 11.97 (br
s, 1H, NH, D2O exchangeable); 13C NMR: δ 44.8, 66.4, 100.0, 119.3,
124.6, 129.5, 139.5, 153.5, 154.8, 155.6, 161.0; IR: ν 3035, 2974, 2900,
+
2753, 2680, 2573, 1666, 1613, 1596 cm-1; MS: m/z 297 (M ); Anal. Calcd
for C15H15N5O2: C, 60.60; H, 5.09; N, 23.56. Found: C, 60.63; H, 5.02;
N, 23.54.
2-Phenyl-6-(pyrrolidin-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]
pyrimidin-3-one (6b)ꢀReaction time 8 h (A), 6 min (B); yield 68%
[8] Bergman, M. R.; Holycross, B. J. Pharmacological modulation
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Silver, L.; Young, K. Novel pyrazolo[3,4-d]pyrimidine-based
inhibitors of Staphlococcus aureus DNA polymerase III: design,
synthesis, and biological evaluation. J. Med. Chem. 2003, 46,
1824–1830.
1
(A), 85% (B); white powder; mp 221–224°C; H NMR: δ 1.94 (m, 4H,
2-CH2), 3.56 (t, 4H, J ꢁ=ꢁ 6.8 Hz, 2-CH2N), 7.14 (t, 2H, phenyl), 7.45 (t, 1H,
phenyl), 8.18 (d, 2H, phenyl), 8.75 (s, 1H, CH-pyrimidine), 11.60 (br s,
1H, NH, D2O exchangeable); 13C NMR: δ 25.5, 46.9, 99.2, 118.9, 124.3,
129.4, 139.8, 153.3, 155.2, 155.7, 159.5; IR: ν 3068, 3019, 2970, 2869, 1615,
+
1539; MS: m/z 281 (M ). Anal. Calcd for C15H15N5O: C, 64.04; H, 5.37; N,
24.90. Found: C, 64.12; H, 5.30; N, 24.95.
[10] Abdel-Razik, H. A.; Abdel-Wahab, A. E. Synthesis and biological
evaluation of some novel fused pyrazolopyrimidines as poten-
tial anticancer and antimicrobial agents. Arch. Pharm. Chem.
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1
(A), 87% (B); yellow powder; mp 198–202°C; H NMR: δ 1.55 (m, 4H,
2-CH2), 1.62 (m, 2H, CH2), 3.83 (t, 4H, J ꢁ=ꢁ 5.2 Hz, 2-CH2N), 7.17 (t, 2H,
phenyl), 7.43 (t, 1H, phenyl), 7.95 (d, 2H, phenyl), 8.75 (s, 1H, CH-
pyrimidine), 11.73 (br s, 1H, NH, D2O exchangeable); 13C NMR: δ 24.9,
25.8, 47.2, 102.3, 114.8, 120.7, 125.2, 130.8, 146.6, 152.9, 158.3, 160.4; IR:
+
ν 3051, 2942, 2916, 2851, 1656, 1614 cm-1; MS: m/z 295 (M ). Anal. Calcd
for C16H17N5O: C, 65.07, H, 5.80; N, 23.71. Found: C, 65.14; H, 5.81; N,
23.68.
Acknowledgments: The authors gratefully acknowledge
Ferdowsi University of Mashhad for partial support of this
project (3/25439).
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ꢁꢀꢀꢀ
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