Reactions of 6-aminouracils: The first simple, fast, and highly efficient synthesis of bis(6-aminopyrimidonyl)methanes (BAPMs) using thermal or microwave-assisted solvent-free methods

Article abstract of DOI:10.1080/00397910600943832

A detailed study on the condensation reaction of 6-aminouracils and aldehydes has been investigated, and accordingly we established for the first time two green, fast, and highly efficient methods for the preparation of bis(6-aminopyrimidonyl)methanes (BA

Full text of DOI:10.1080/00397910600943832

This article was downloaded by: [Moskow State Univ Bibliote]
On: 09 December 2013, At: 05:43
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Reactions of 6‐Aminouracils: The First
Simple, Fast, and Highly Efficient Synthesis
of bis(6‐Aminopyrimidonyl)methanes (BAPMs)
Using Thermal or Microwave‐Assisted
Solvent‐Free Methods
a
a
b
Javad Azizian , Mohammad R. Mohammadizadeh , Fatemeh Teimouri
,
a
a
Ali A. Mohammadi & Ali R. Karimi
a
Chemistry Department , Shahid Beheshti University , Tehran, Iran
b
Department of Chemistry , Science and Research Campus, Islamic Azad
University , Tehran, Iran
Published online: 24 Nov 2006.
To cite this article: Javad Azizian , Mohammad R. Mohammadizadeh , Fatemeh Teimouri , Ali A. Mohammadi
Ali R. Karimi (2006) Reactions of 6‐Aminouracils: The First Simple, Fast, and Highly Efficient Synthesis
&
of bis(6‐Aminopyrimidonyl)methanes (BAPMs) Using Thermal or Microwave‐Assisted Solvent‐Free Methods,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
36:23, 3631-3638, DOI: 10.1080/00397910600943832
To link to this article: http://dx.doi.org/10.1080/00397910600943832
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

w
Synthetic Communications , 36: 3631–3638, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600943832
Reactions of 6-Aminouracils: The First
Simple, Fast, and Highly Efficient Synthesis
of bis(6-Aminopyrimidonyl)methanes
(BAPMs) Using Thermal or Microwave-
Assisted Solvent-Free Methods
Javad Azizian and Mohammad R. Mohammadizadeh
Chemistry Department, Shahid Beheshti University, Tehran, Iran
Fatemeh Teimouri
Department of Chemistry, Science and Research Campus, Islamic Azad
University, Tehran, Iran
Ali A. Mohammadi and Ali R. Karimi
Chemistry Department, Shahid Beheshti University, Tehran, Iran
Abstract: A detailed study on the condensation reaction of 6-aminouracils and
aldehydes has been investigated, and accordingly we established for the first time
two green, fast, and highly efficient methods for the preparation of bis(6-aminopyrimi-
donyl)methanes (BAPMs).
Keywords: 6-Aminouracils, bis(6-aminopyrimidonyl)methanes (BAPMs), microwave-
assisted reactions, solvent-free medium
Pyrimidine systems as purine analogues exhibit a wide range of biological
activities. The 6-amino-substituted pyrimidine thioethers have been reported
to constitute a novel class of nonnucleoside HIV-1 reverse transcriptase
inhibitors (NNRTIs) with activity against bis(heteroaryl)piperazine
[
1]
(BHAP)-resistant HIV.
moiety such as dihydropyrimidines (DHPMs), and furo, pyrazolo,
Heterocyclic structures bearing a pyrimidine
[3]
[2]
[4]
Received in the U.K. February 2, 2006
Address correspondence to Javad Azizian, Chemistry Department, Shahid Beheshti
University, 1983963113, Tehran, Iran. E-mail: j-azizian@cc.sbu.ac.ir
3
631

3
632
J. Azizian et al.
[
pyrimido, pyrrolo, pyrido, oxazolino or thiazolino, pyridopyrazolo,
5]
[6]
[7]
[8]
[9]
[
10]
[11]
[12]
pyrazolotriazolo,
long been important to the pharmaceutical industry.
-Amino-uracils, as well as 6-hydroxy-uracils (barbituric acids,
arenopyrano,
and 2-benzamido
pyrimidine have
6
thiobarbituric acids) are key intermediates in the synthesis of purines, which
constitute the basic nucleus of a number of drugs, for example, caffeine,
[13]
penciclovir, theobromine, and theophylline.
6
synthesis of a number of xanthines related to theophyllin.
In medicinal chemistry,
-aminouracils are particularly well known as starting compounds for the
[14]
Additionally,
from these molecules, new condensed heterocycles, which often exhibited
[15]
interesting pharmacological activity, have been synthesized.
Although multistep or one-pot three-component reactions of 6-aminour-
acils and aldehydes with different compounds were previously investi-
[
16]
gated,
with various aldehydes. As part of our continuing program concerning the
surprisingly there is no report on the reaction of 6-aminouracils
[
17]
reaction of uracils,
in pyrimidinones, herein we report the results of our study of the reaction of
and because of the resultant pharmacological interest
6-aminouracils 1 with aldehydes 2 (Scheme 1).
When a mixture of 6-amino-1,3-dimethyluracil 1 and aldehyde 2 in
ethanol was refluxed in a preheated oil bath, a condensation reaction was
initiated and completed after 4–5 h (Scheme 1, method A) to afford
products 3 in good yields. Pure products 3 were achieved by simple filtration
of the reaction mixture and washing the filtrate with ethanol. The results are
summarized in Table 1 (column 5).
All products 3 are new compounds, and their structures were deduced
1 13
from elemental analyses and their IR, H NMR, and C NMR spectra.
The IR spectrum of 3a reveals the disappearance of NH group at
2
2
1
21
3390 cm
and two peaks at 1709 and 1660 cm
due to the carbonyl
1
groups of the pyrimidinone. The H NMR spectrum of 3a shows two
singlets at d 3.33 and 3.36 for the N-Me groups. The aliphatic methine
proton of the benzaldehyde moiety exhibits as a singlet at d 5.59. The
aromatic and NH protons were resonated in the regions d 7.08–7.22 and
2
1
.45, respectively, as multiplets. The H decoupled C NMR spectrum of
13
7
3a showed 11 distinct resonances, in agreement with the proposed
structure. The particularly distinct peak at d 86.40 readily related to C-5 of
pyrimidinone moiety, and the two carbonyl carbons exhibited two
separated peaks at d 154.69 and 163.46 ppm.
Scheme 1. Method A: ethanol, 808C, 4–5 h; method B: solvent-free, MW, 3 min.

Reactions of 6-Aminouracils
3633
Table 1. Synthesis of BAPMs by condensation reaction of 6-amino uracils and
aldehydes using thermal or microwave-assisted solvent-free methods
Method A
b
yield (%)
Method B
c
yield (%)
1
R
2
R
a
3
Time (h)
a
b
c
d
e
f
Me
Me
H
Ph-
4-NO -Ph-
5
70
75
71
77
72
72
70
90
93
88
92
92
90
92
4
2
Ph-
4-MeO
5
Me
Me
Me
Me
2
-Ph-
4
4-Me-Ph-
4-Cl-Ph-
4-EtO-2,6-dichloro-Ph-
4.5
4.5
4
g
a
b
c
Time for reactions based on method A.
Pure isolated yields of products 3 from method A.
Pure isolated yields of products 3 from method B.
The application of microwave technology in organic synthesis, particu-
larly under solvent-free conditions, is increasing rapidly because of reaction
simplicity, less pollution, minimum reaction times, and rapid access to large
[
18]
libraries of diverse small molecules.
interest in the use of microwave technology in synthetic organic
In the context of our general
[
19]
reactions, we have also considered the microwave-assisted reaction of
-aminouracils with aldehydes under solvent-free conditions (Scheme 1,
6
method B). When a homogenous mixture of 6-amino-1,3-dimethyluracil 1 and
aldehyde 2 was wetted with a few drops of dimethylsulfoide (DMSO) and then
irradiated in a microwave oven, the condensation reaction was completed in
less than 3 min. As one can see (Table 1, column 6), relative to method A, the
yields were significantly increased.
This work is a further example of the utility of microwaves in organic
synthesis. When conventional thermal procedures require considerable
reaction time, microwave irradiation can substitute for classical methods,
allowing easy and rapid access to new heterocycles, reducing the reaction
times, and improving yields.
These synthetic procedures are applicable to formaldehyde and aromatic
aldehydes, providing corresponding BAPMs 3 in varying yields (Table 1).
Although aromatic aldehydes produced corresponding products in uniformly
good to excellent yields, our attempts to carry the aliphatic ones under the
same reaction conditions were failed. In addition, with aliphatic and
aromatic ketones no reaction was observed.
In summary we have studied the condensation reaction of 6-aminouracils
with aldehydes and accordingly established the first green, fast, and highly
efficient procedure for preparation of BAPMs of biological interest. Further-
more, the results demonstrate that microwave-assisted reactions in the solid

3
634
J. Azizian et al.
state allow easy and rapid access to BAPMs and can reduce the reaction times
from many hours to a few minutes with improved yields.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus and are
uncorrected. IR spectra were measured on a Bomen FT-IR-MB 100 spec-
1
13
trometer. H and C NMR spectra were measured with a Bruker DRX-500
Avance spectrometer at 500.1 and 125.8 MHz using TMS as the internal
standard. Elemental analysis for C, H, and N were performed using a
Heraus CHN rapid analyzer. All chemicals were obtained from Merck or
Fluka and were used without further purification.
Preparation of 1-Phenyl-1-bis(6-amino-1,3-dimethyl-2,4-dioxo-
1,2,3,4-tetrahydropyrimid-5-yl)methane 3a as General Procedure
for Preparation of BAPMs 3
Method A
A mixture of 1,3-dimethyl-6-aminouracil 1a (0.310 g, 2 mmol) and benzal-
dehyde 2a (0.106 g, 1 mmol) in ethanol (20 mL) was refluxed for 5 h. The
reaction mixture was cooled to room temperature, filtered, and washed with
warm 80% ethanol (2 ꢀ 5 mL) to afford pure product 3a as a white solid
(
0.35 g, 70%).
Method B
A homogeneous mixture of 1,3-dimethyl-6-aminouracil 1a (0.310 g, 2 mmol)
and benzaldehyde 2a (0.106 g, 1 mmol) in a test tube was wetted with 2–4
drops of DMSO and allowed to irradiated in a 300-W microwave oven for
3
min. The reaction mixture was cooled to room temperature, ethanol (5 mL)
was added, and the obtained precipitate was filtered and washed with warm
0% ethanol (2 ꢀ 5 mL) to afford pure compound 3a (0.45 g, 90%).
8
Physical, Spectral, and Microanalysis Data for Compounds 3a–g
1
-Phenyl-1-bis(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimid-5-yl)
2
1 1
methane 3a: mp . 3008C; IR n 3445, 3195, 2990, 1691, 1659 cm ; H NMR
DMSO-d , 300 MHz) d 3.33 (s, 3H, N-CH ), 3.36 (s, 3H, N-CH ), 5.59 (s, 1H,
(
6
3
3
1
3
methine proton), 7.08–7.22 (m, 5H, arom), 7.45 (br s, 4H, 2 ꢀ NH ); C
NMR (DMSO-d , 300 MHz) d 28.4, 30.4, 35.8, 86.4, 125.3, 127.0, 128.1,
2
6
1
5
40.1, 150.9, 154.7, 163.4. Microanalysis C H N O (398.2), calcd. %: C,
19 22 6 4
7.28; H, 5.57; N, 21.09; found %: C, 57.33; H, 5.43; N, 21.02.

Reactions of 6-Aminouracils
3635
1
-(4-Nitrophenyl)-1-bis(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyri-
21
mid-5-yl)methane 3b: mp . 3008C; IR n 3445, 3325, 3100, 1687, 1663 cm
;
1
H NMR (DMSO-d , 300 MHz) d 3.34 (br s, 6H, 2 ꢀ N-CH ), 5.66 (s, 1H,
6
3
13
methine proton), 7.40 (m, 6H, arom and 2 ꢀ NH ), 8.06 (br m, 2H, arom); C
NMR (DMSO-d , 300 MHz) d 28.5, 30.5, 36.3, 86.3, 123.3, 128.4, 145.7,
2
6
148.3, 149.4, 151.9; 162.5.6. Microanalysis C H N O (443.2), calcd. %: C,
19 21 7 6
51.47; H, 4.77; N, 22.11; found %: C, 51.49; H, 4.61; N, 22.18.
1
-Phenyl-1-bis(6-amino-2,4-dioxo-1,2,3,4-tetrahydropyrimid-5-yl)methane 3c:
1
21
; H NMR (DMSO-d6,
00 MHz) d 5.31 (s, 1H, methine proton), 6.72 (br m, 3H, arom), 7.10–7.31 (br
mp . 3008C; IR n 3345, 3145, 1704, 1659 cm
3
m, 6H, arom and 2 ꢀ NH ), 10.31 (br s, 2H, pyrimidinone NH), 10.50 (br s,
2
13
2H, pyrimidinone NH); C NMR (DMSO-d , 300 MHz) d 32.8, 86.5, 125.4,
6
127.0, 128.1, 139.9, 150.2, 154.7, 165.8. Microanalysis C H N O (342.1),
calcd. %: C, 52.63; H, 4.12; N, 24.55; found %: C, 52.56; H, 4.20; N, 24.59.
15 14 6 4
Methyl 4-(1,1-bis(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimid-5-
21
yl)methyl)benzoate 3d: mp . 3008C; IR n 3340, 3215, 3060, 1691, 1659 cm
;
H NMR (DMSO-d , 300 MHz) d 3.33 (s, 3H, N-CH ), 3.35 (s, 3H, N-CH ),
1
6
3
3
3
.82 (s, 3H, O-CH ), 5.63 (s, 1H, methine proton), 7.25 (d, J ¼ 9 Hz, 2H,
3
13
arom), 7.43 (br, 4H, 2 ꢀ NH ), 7.80 (d, J ¼ 9 Hz, 2H, arom); C NMR
2
(DMSO-d , 300 MHz) d 25.9, 27.9, 33.6, 49.7, 84.6, 124.4, 124.8, 126.6,
6
1
44.0, 148.3, 152.5, 162.1, 164.2. Microanalysis C H N O (456.2), calcd.
2
1 24 6 6
%: C, 55.26; H, 5.30; N, 18.41; found %: C, 55.20; H, 5.22; N, 18.48.
1
-(4-Methylphenyl)-1-bis(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-
pyrimid-5-yl)methane 3e: mp . 3008C; IR n 3475, 3355, 3150, 1691,
21 1
1
668 cm ; H NMR (DMSO-d , 300 MHz) d 2.24 (s, 3H, CH ), 3.32 (br s,
6 3
6
H, 2 ꢀ N-CH ), 5.54 (s, 1H, methine proton), 6.98 (br s, 4H, arom), 7.43
3
1
3
(br, 4H, 2 ꢀ NH ); C NMR (DMSO-d , 300 MHz) d 20.9, 28.46, 30.4,
2
6
35.4, 84.6, 126.6, 128.2, 134.0, 136.8, 150.9, 153.3, 159.4. Microanalysis
C H N O (412.2), calcd. %: C, 58.24; H, 5.87; N, 20.38; found %:
2
0 24 6 4
C, 58.19; H, 5.87; N, 20.31.
1
-(4-Chlorophenyl)-1-bis(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-
21 1
pyrimid-5-yl)methane 3f: mp . 3008C; IR n 3335, 3155, 1696, 1673 cm ; H
NMR (DMSO-d , 300 MHz) d 3.33 (s, 3H, N-CH ), 3.35 (s, 3H, N-CH ), 5.56
6
3
3
(
s, 1H, methine proton), 7.12 (d, J ¼ 9 Hz, 2H, arom), 7.22 (d, J ¼ 9 Hz, 2H,
1
3
arom), 7.44 (br, 4H, 2 ꢀ NH ); C NMR (DMSO-d , 300 MHz) d 29.9, 31.9,
2 6
36.84, 87.2, 129.4, 130.5, 131.3, 140.7, 152.3, 155.9, 165.0. Microanalysis
C H ClN O (432.1), calcd. %: C, 52.72; H, 4.89; N, 19.42; found %: C,
1
9
21
6 4
5
1
2.78; H, 4.97; N, 19.5.
-(4-Ethoxy-2,6-dichlorophenyl)-1-bis(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4
-tetrahydropyrimid-5-yl)methane 3 g: mp . 3008C; IR n 3465, 3340, 1684,

3
636
J. Azizian et al.
21 1
1
625 cm ; H NMR (DMSO-d , 300 MHz) d 1.11 (br t, 3H, -OCH CH ), 3.33
6
2
3
(
br s, 6H, 2 ꢀ N-CH ), 3.41 (br q, 2H, O-CH Me), 6.18 (s, 1H, methine proton),
3
2
1
3
6
1
.93 (s, 2H, arom), 7.35 (br, 4H, 2 ꢀ NH ); C NMR (DMSO-d , 300 MHz) d
2
6
8.5, 27.0, 29.3, 36.4, 56.0, 83.4, 127.2, 128.7, 128.8, 134.6, 135.1, 152.4, 159.9.
Microanalysis, C H C N O (510.1), calcd. %: C, 49.32; H, 4.73; N, 16.43;
1 24 l2 6 5
2
found %: C, 49.38; H, 4.65; N, 16.38.
ACKNOWLEDGMENT
We are thankful to the Shahid Beheshti University Research Council for the
partial support of this work.
REFERENCES
1
. (a) Figueroa-Villar, J. D.; Carneiro, C. L.; Cruz, E. R. Synthesis of 6-phenylami-
nofuro [2,3-d]pyrimidine-2,4(1H,3H)-diones from barbiturylbenzylidenes and iso-
nitriles. Heterocycles 1992, 34, 891–894; (b) Nugent, R. A.; Schlachter, S. T.;
Murphy, M. J.; Cleek, G. J.; Poel, T. J.; Wishka, D. G.; Graber, D. R.; Yogi, Y.;
Kaiser, B. J.; Olmsted, R. A.; Kopta, L. A.; Swaney, S. M.; Poppe, S. M.;
Morris, J.; Tarpley, W. G.; Thomas, R. C. Pyrimidine thioethers: A novel class
of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant
HIV. J. Med. Chem. 1998, 41, 3793–3803; (c) Campaigne, E.; Ellis, R. L.;
Bradford, M.; Ho, J. Synthesis of some ureidodihydrofurans and related pyrimi-
dones as potential antimalarials. J. Med. Chem. 1996, 12, 339–342.
2
3
4
. Singh, K.; Singh, S.; Mahajan, A. Metalation of Biginelli compounds: A general
unprecedented route to C-6 functionalized 4-aryl-3,4-dihydropyrimidinones.
J. Org. Chem. 2005, 70, 6114–6117.
. Petricci, E.; Radi, M.; Corelli, F.; Botta, M. Microwave-enhanced Sonogashira
coupling reaction of substituted pyrimidinones and pyrimidine nucleosides. Tetra-
hedron Lett. 2003, 44, 9181–9184.
. Makarov, V. A.; Riabova, O. B.; Granik, V. G.; Dahse, H. M.; Stelzner, A.;
Wutzlerc, P.; Schmidtke, M. Anti-coxsackievirus B3 activity of 2-amino-3-nitro-
pyrazolo[1,5-a]pyrimidines and their analogs. Bioorg. Med. Chem. Lett. 2005, 15,
3
7–39.
5
6
. Sharma, P.; Kumar, A.; Rane, N.; Gurram, V. Hetero Diels–Alder reaction: A
novel strategy to regioselective synthesis of pyrimido[4,5-d]pyrimidine
analogues from Biginelli derivative. Tetrahedron 2005, 61, 4237–4248.
. (a) Nobuaki Matsumoto, N.; Takahashi, M. Synthesis of pyrrolo[2,3-d]pyrimidine-
2
,4-diones by sunlight photolysis of N-(5-vinyluracil-6-yl)sulfilimines. Tetrahe-
dron Lett. 2005, 46, 5551–5554; (b) Wang, S.; Folkes, A.; Chuckowree, I.;
Cockcroft, X.; Sohal, S.; Miller, W.; Milton, S. J.; Wren, S. P.; Vicker, N.;
Depledge, P.; Scott, J.; Smith, L.; Jones, H.; Mistry, P.; Faint, R. F.;
Thompson, D.; Cocks, S. Studies on pyrrolopyrimidines as selective inhibitors
of multidrug-resistance-associated protein in multidrug resistance. J. Med.
Chem. 2004, 47, 1329–1338.
7
. Agarwal, A.; Goyal, N.; Chauhana, P. M.S.; Gupta, S. Dihydropyrido[2,3-d]pyri-
midines as a new class of antileishmanial agents. Bioorg. Med. Chem. 2005, 13,
6
678–6684.

Reactions of 6-Aminouracils
3637
8
. Pontillo, J.; Chen, C. Efficient synthesis of bicyclic oxazolino- and thiazolino[3,2-
c]pyrimidine-5,7-diones and its application to the synthesis of GnRH antagonists.
Bioorg. Med. Chem. Lett. 2005, 15, 1407–1411.
9
. Alberti, M. J.; Auten, E. P.; Lackey, K. E.; McDonald, O. B.; Wood, E. R.;
Preugschat, F.; Cutler, G. J.; Kane-Carson, L.; Liu, W.; Jung, D. K. Discovery
and in vitro evaluation of potent kinase inhibitors: Pyrido[10,20:1,5]pyra-
zolo[3,4-d]pyrimidines. Bioorg. Med. Chem. Lett. 2005, 15, 3778–3781.
1
1
0. Baraldi, P. G.; El-Kashef, H.; Farghaly, A. R.; Vanellec, P.; Fruttaroloa, F.
Synthesis of new pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines and related
heterocycles. Tetrahedron 2004, 60, 5093–5104.
1. Naya, S. I.; Miyagawa, M.; Nitta, M. Novel photo-induced oxidative cyclization
of 1,3-dimethyl-5-(1-arylmethylidene)pyrimidine-2,4,6(1,3,5H)-triones: Synthesis
and properties of areno[5,6]pyrano[2,3-d]pyrimidine-2,4(1,3H)-dionylium ions
and their photo-induced autorecycling oxidizing reaction toward some amines.
Tetrahedron 2005, 61, 4919–4930.
1
1
2. Waelchli, R.; Bollbuck, B.; Bruns, C.; Buhl, T.; Eder, J.; Feifel, R.; Hersperger, R.;
Janser, P.; Revesz, L.; Zerwes, H.; Schlapbach, A. Design and preparation of
2-benzamido-pyrimidines as inhibitors of IKK. Bioorg. Med. Chem. Lett. 2006,
16, 108–112.
3. (a) Zhi, C.; Long, Z. Y.; Gambino, J.; Xu, W. C.; Brown, N. C.; Barnes, M.;
Butler, M.; LaMarr, W.; Wright, G. E. Synthesis of substituted 6-anilinouracils
and their inhibition of DNA, polymerase IIIC and gram-positive bacterial
growth. J. Med. Chem. 2003, 46, 2731–2739; (b) Devi, I.; Bhuyan, P. J. An
expedient method for the synthesis of 6-substituted uracils under microwave
irradiation in a solvent-free medium. Tetrahedron Lett. 2005, 46, 5727–5729.
4. (a) Waynebills, C. W.; Gebura, S. E.; Meek, J. S.; Sweeti, O. J. New synthesis of
uric acid and dimethyluric acid. J. Org. Chem. 1962, 27, 4633–4635;
1
(
b) Muller, C. E.; Shi, D.; Manning, M.; Daly, J. W. Synthesis of paraxanthine
analogs (1,7-disubstituted xanthines) and other xanthines unsubstituted at the
-position: Structure–activity relationships at adenosine receptors. J. Med.
3
Chem. 1993, 36, 3341–3349.
1
5. (a) Lee, Y.; Kim, S. Y.; Lee, J. Y.; Yu, C. M.; Lee, D. H.; Gong, Y. D. Solution-
phase parallel synthesis of new 2H-pyrimido-[4,5-e][1,2,4]triazin-3-ylidenecyana-
mides. Tetrahedron Lett. 2004, 45, 9319–9322; (b) Langen, P.; Etzold, G.;
B a¨ rwolff, D.; Preussel, B. Inhibition of thymidine phosphorylase by 6-aminothy-
mine and derivatives of 6-aminouracil. Biochem. Pharmacol. 1967, 16,
1833–1837; (c) Ali, A.; Taylor, G. E.; Ellsworth, K.; Harris, G.; Painter, R.;
Silver, L. 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; (d) Baraldi, P. G.; Preti, D.;
Tabrizi, M. A.; Fruttarolo, F.; Romagnoli, R.; Zaid, N. A.; Moorman, A. R.;
Merighi, S.; Varani, K.; Borea, P. A. New pyrrolo[2,1-f]purine-2,4-dione and
imidazo[2,1-f]purine-2,4-dione derivatives as potent and selective human A3
adenosine receptor antagonists. J. Med. Chem. 2005, 48, 4697–4701.
1
6. (a) Devi, I.; Kumar, B. S.D.; Bhuyana, P. J. A novel three-component one-pot
synthesis of pyrano[2,3-d]pyrimidines and pyrido[2,3-d]pyrimidines using
microwave heating in the solid state. Tetrahedron Lett. 2003, 44, 8307–8310;
(
b) Bagley, M. C.; Singh, N. Microwave-assisted synthesis of 5-deaza-5,8-dihy-
dropterins. Synlett 2002, 1718–1720; (c) Agarwal, A.; Chauhan, P. M. S. Solid
supported synthesis of structurally diverse dihydropyrido[2,3-d]pyrimidines
using microwave irradiation. Tetrahedron Lett. 2005, 46, 1345–1348.

3
638
J. Azizian et al.
1
7. Azizian, J.; Mohammadizadeh, M. R.; Mohammadi, A. A.; Karimi, A. R.;
Teimouri, F. A novel one-pot procedure for preparation of some new condensed
pyrido[2,3-d]pyrimidine(1H,3H)-2,4-diones. Heteroatom. Chem. (in press).
8. (a) Pourashraf, M.; Delair, P.; Rasmaissen, M. O.; Greene, A. E. Highly
enantioselective approach to indolizidines: Preparation of (þ)-(1S,8aS)-1-hydro-
xyindolizidine and (2)-slaframine. J. Org. Chem. 2000, 65, 6966–6972;
1
(
b) Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J. Microwave assisted
organic synthesis—a review. Tetrahedron 2001, 57, 9225–9283;
c) Bougrin, K.; Loupy, A.; Soufiaoui, M. J. Microwave-assisted solvent-free
(
heterocyclic synthesis. J. Photochem. Photobiol. C 2005, 6, 139–167.
9. (a) Azizian, J.; Karimi, A. R.; Kazemizadeh, Z.; Mohammadi, A. A.;
Mohammadizadeh, M. R. A synthetic route to 11-(1H-pyrrol-1-yl)-11H-
indeno[1,2-b]quinoxaline derivatives exploiting a three-component coupling
strategy under microwave irradiation. Tetrahedron Lett. 2005, 46, 6155–6157;
1
(b) Azizian, J.; Karimi, A. R.; Mohammadi, A. A. An efficient one-pot
procedure for preparation of 2,4(1H,3H)-quinazolinediones and 2-thioxoquinazo-
linone derivatives under microwave irradiation. Synth. Commun. 2003, 33,
415–420; (c) Azizian, J.; Karimi, A. R.; Kazemizadeh, Z.; Mohammadi, A. A.;
Mohammadizadeh, M. R. A novel one-pot synthesis of some new interesting
pyrrole derivatives. J. Org. Chem. 2005, 70, 1471–1473.