An expeditious synthesis of β-pyrimidyl-α,β-didehydro-α-amino acid derivatives and pyrano[2,3-d]pyrimidines using microwave-assisted conditions

Article abstract of DOI:10.1016/j.tet.2009.07.072

An expeditious transformation of 5-acyl-2H-pyran-2-ones with various amidines as 1,3-binucleophiles into isomerically pure (E)-α,β-didehydro-α-amino acid derivatives (DDAAD) containing the 5-pyrimidyl moiety at the β-position is described. The method was

Full text of DOI:10.1016/j.tet.2009.07.072

Tetrahedron 65 (2009) 8216–8221
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An expeditious synthesis of
b-pyrimidyl-a,b-didehydro-a-amino acid derivatives
and pyrano[2,3-d]pyrimidines using microwave-assisted conditions
a
a
b
a
a,
*
ˇ a
ˇ
ꢀ
Jure Hren , Franc Pozgan , Alma Bunic , Vasile I. Parvulescu , Slovenko Polanc , Marijan Kocevar
a
ˇ
ˇ
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, SI-1000 Ljubljana, Slovenia
b Department of Chemical Technology and Catalysis, University of Bucharest, B-dul Regina Elisabeta 4-12, 030016 Bucharest, Romania
a r t i c l e i n f o
a b s t r a c t
Article history:
An expeditious transformation of 5-acyl-2H-pyran-2-ones with various amidines as 1,3-binucleophiles
into isomerically pure (E)- -didehydro- -amino acid derivatives (DDAAD) containing the 5-pyrimidyl
moiety at the -position is described. The method was performed in ethanolic (or ethanol/water) so-
lutions in the presence of Na2CO3 as a nontoxic base and under microwave-assisted conditions. When
starting from the 5-ethoxycarbonyl-2H-pyran-2-one derivative and in the presence of DBU as a base the
corresponding pyrano[2,3-d]pyrimidines were prepared.
Received 29 April 2009
Received in revised form 29 June 2009
Accepted 23 July 2009
a
,b
a
b
Available online 29 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
with binucleophilic reagents (hydrazine and its derivatives, hy-
droxylamine) into DDAAD bearing a pyrazolyl or isoxazolyl moiety
The significance of
a,
b
-didehydro-
a
-amino acid derivatives
at the b
-position.1d,7 Having in mind the above-mentioned con-
(DDAAD) is recognized as a result of their occurrence in the
structure of various natural products, their biological activity, and
version of 2H-pyran-2-one derivatives into pyrimidine deriva-
tives,6c we decided to check the possibility of transforming our
3-acylamino-2H-pyran-2-one derivatives 17b,8 with a series of
their synthetic potential.1,2 The hydrogenation of
b
-heteroaryl-a,b-
didehydroalanines is one of the most convenient ways to prepare
amidines 2 as binucleophilic reagents9 toward
b-(5-pyrimidyl)-
novel types of optically pure nonproteinogenic
a
-amino acid de-
DDAAD 3. The idea was to connect a binucleophilic amidine de-
rivative with the C-6 carbon atom of the 2H-pyran-2-one ring and
the carbonyl function at position 5 of the 2H-pyran-2-one ring,
leaving the 3-acylamino moiety unreacted. When starting from
differently substituted 2H-pyran-2-ones and amidines a large li-
brary of multifunctional products,10 diverse, small molecules con-
taining the didehydroamino acid unit and the pyrimidyl ring in
their structure, would be accessible.
rivatives.2 For this reason, the synthesis of novel types of DDAAD
opens up new possibilities for investigating this important class of
compounds.
Pyrimidines and their fused derivatives also constitute a very
important class of compounds including natural products, phar-
maceuticals, and functional materials. They are accessible by variety
of methods, including classical approaches and novel strategies.3
Recently, the preparation of some
the 2-pyrimidyl,4a 4-pyrimidyl4b or 5-pyrimidyl4c–e moiety at the
-position was published, mostly in connection with their biological
potential.
2H-Pyran-2-ones and fused pyran-2-ones are versatile synthons
b
-pyrimidyl-DDAAD4 containing
b
2. Results and discussion
To find the optimal conditions for the preparation of 3 we first
examined the reaction of 2H-pyran-2-one 1a with a slight excess of
acetamidine hydrochloride (1.1 equiv) in the presence of a base.
When applying an excess of triethylamine (4 equiv) in boiling
ethanol 9 h of conventional heating was required to complete the
reaction, and the product 3a was isolated after an acidic work-up in
a 76% yield. The relatively long reaction time and the need for an
excess of the organic base stimulated us to develop a less-time-
consuming and greener process. For this reason we turned, in our
test experiments, to reactions that take place under a variety of
conditions, from heterogeneous to homogeneous, in conjunction
with a microwave-accelerated reaction and the principles of green
chemistry.11,12
for the synthesis of different types of products.1d,5 It is well known,
for example, that several kinds of nucleophiles react with the pyran-
2-one nucleus at the C-2, C-4, andC-6 positionscausing an initial ring
opening, followed by a recyclization into a new heterocyclic ring.
Among them there are a few reports concerning the transformations
of pyran-2-one derivatives with amidines or related compounds
(urea, thiourea, guanidine) toward pyrimidine derivatives.6
As a part of our continuing interest in the transformations of 2H-
pyran-2-ones we have developed their efficient transformation
* Corresponding author. Tel.: þ386 1 2419230.
ˇ
E-mail address: marijan.kocevar@fkkt.uni-lj.si (M. Kocevar).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.07.072

J. Hren et al. / Tetrahedron 65 (2009) 8216–8221
8217
Me
R2
O
O
1) base, MW
100-115 ºC
25-120 min
2) HCl (10%)
NH
NH
Me
R2
O
O
R3
R3
+
×HX
NHCOR1
NH2
NH2
NHCOR1
O
2
O
1a: R1 = Ph, R2 = Me
1b: R1 = R2 = Me
X = Cl, I
1c: R1 = R2 = Ph
1d: R1 = Ph, R2 = OEt
R3
N
R3
N
Me
O
O
N
R3
N
HO
HO2C
N
HO2C
N
R2
PhCONH
Me
R1CONH
H
Me
5a-d
PhCONH
H
3a-l
4a-d
Scheme 1.
The test reactions were run on a 0.5-mmol scale with equimolar
amounts of 1a, acetamidine hydrochloride, and the base in 1.5 mL
of solvent in a closed-vessel microwave reactor (10 mL) at 100 ꢀC
and stopped after 15 min to find the combination with the highest
conversion. After irradiation the solvent was evaporated and the
remaining residue was acidified, filtered off, and analyzed by means
of 1H NMR spectroscopy. When using triethylamine, pyridine or
DABCO (1 equiv) no conversion to the final product 3a was ob-
served using the 1H NMR spectroscopy in any of the tested solvents
(toluene, DME, THF, MeCN, EtOH). Additionally, the screening
showed that the reaction in a nonpolar solvent (PhMe, DME) gives
no product 3a, even with sodium carbonate, which was finally
chosen as the most appropriate base for the desired transformation.
This fact could be attributed to the low solubility of both the base
and the amidine salt. As the polarity of the solvent increased (using
THF, MeCN, EtOH), the conversion using sodium carbonate as a base
also increased. When we tried to perform the reaction toward 3a
under similar conditions, with Na2CO3 as a base in water, no
product formation was observed, most probably due to the faster
decomposition of the acetamidine (prior to the reaction with the
pyran-2-one 1a). Hence, the best combination seemed to be the
application of Na2CO3 in EtOH, in which most of the starting ma-
terial (1a) disappeared after 15 min and the 1H NMR spectrum of
the crude reaction mixture revealed, in addition to the product 3a,
a significant quantity of intermediates that disappeared after pro-
longed heating. We then tried to optimize the model reaction by
using other alkali carbonates (K2CO3, Cs2CO3) in an ethanolic mix-
ture. Cs2CO3 showed, probably due to the better solubility, the
highest conversion within 15 min, with no starting material
remaining and the smallest quantity of intermediates. Even with
only 1 equiv of Cs2CO3 the reaction toward 3a could be completed
within 30 min of microwave irradiation at 100 ꢀC and with 75% of
isolated yield. Surprisingly, Na2CO3 showed a higher conversion
than K2CO3; nevertheless, a reaction with only 1 equiv of Na2CO3
could not be completed after 150 min of irradiation at 100 ꢀC. Using
twice the amount of Na2CO3 and setting the reaction time to 90 min
increased the conversion to 100% and made it possible to isolate the
desired product 3a in an 85% yield (Table 1, run 1). In spite of the
fact that Cs2CO3 showed better features in the model conversion
than Na2CO3 we chose the latter in two-equivalent amounts for
other syntheses of the products 3 because of its lower price and
molecular mass.
Under the above, optimal conditions (with small changes to the
temperature and the reaction time), 3-acylamino-2H-pyran-2-
ones 1a–c reacted with an equimolar amount of amidines 2 in
ethanol and in the presence of Na2CO3 (2 equiv) to give the ap-
propriate 5-pyrimidyl moiety containing (E)-DDAAD 3a–l with
80–91% yields (Table 1, Scheme 1). The 1H NMR spectra of the
crude reaction mixtures under optimized conditions did not reveal
any signals that could be referred to the side products. As shown in
Table 1, these conditions are compatible with aliphatic and aro-
matic amidines, and even with guanidine. Additionally, in the re-
action of benzamidine hydrochloride with 1a and 1b we
successfully used water as the solvent and 1.5 equiv of K2CO3 or
Na2CO3. These reaction conditions reduced the reaction time sig-
nificantly and the yields of 3c and 3f were very high, especially
with Na2CO3 as a base (Table 1, runs 3 and 6). Unfortunately, water
cannot be used as a solvent for the reactions with aliphatic ami-
dines and formamidine, because they are not stable under these
conditions.
Table 1
Reaction conditions and yields of products 3, 4, and 5
Run
SM
Amidine 2
(R3¼)
Me
H
T (ꢀC), r.
time (min)
Product
Yielda
(%)
1
2
3
1a
1a
1a
100, 90b
3a
3b
3c
85
90
85
100, 60b
Ph
100, 60b
(27.5)c (30)d
(84)c
(91)d
90
4
5
6
1a
1a
1b
3-O2NC6H4
NH2
Ph
100, 60b
100, 30b
100, 45b
(25)c (30)d
3d
3e
3f
80
80
(75)c
(92)d
90b
91
7
8
9
1b
1c
1c
1c
1c
1c
1d
3-O2NC6H4
H
Me
Ph
3-O2NC6H4
NH2
Ph
100, 25b
115, 90b
115, 105b
100, 120b
100, 90b
110, 105b
100, 45e
110, 120f
100, 45e
110, 120f
100, 30e
110, 60f
3g
3h
3i
3j
3k
3l
4a
5a
4b
5b
4c
5c
4d
5d
86
82
90
88
85
56
81
54
80
52
81
50
10
11
12
13
14
15
16
17
18
19
20
1d
1d
1d
4-MeC6H4
4-ClC6H4
With the above results in hand we wanted to further extend this
transformation to the starting 5-ethoxycarbonyl-2H-pyran-2-one
derivative 1d. Surprisingly, all the preliminary experiments with
acetamidine hydrochloride were unsuccessful. For example, the
reaction of 1d with acetamidine hydrochloride on the 0.5-mmol
scale conducted in ethanol at room temperature, 60 ꢀC or 100 ꢀC for
1 h and with different bases (DBU, Na2CO3 and Cs2CO3; 1 equiv) did
not give any major product. On the other hand, when the
3-O2NC6H4
100, 20e
110, 120f
a
b
c
d
e
f
Yields of isolated products are given.
EtOH, Na2CO3 (2 equiv), 30 W.
H2O, K2CO3 (1.5 equiv), 30 W.
H2O, Na2CO3 (1.5 equiv), 30 W.
EtOH, H2O, Na2CO3 (2 equiv), 45 W.
EtOH, DBU (1.1 equiv), 45 W.

8218
J. Hren et al. / Tetrahedron 65 (2009) 8216–8221
suspension of 1d with 1 equiv of benzamidine hydrochloride and
1 equiv of Na2CO3 in ethanol was irradiated for 1 h at 100 ꢀC,
a mixture of the DDAAD 4a and the pyrano[2,3-d]pyrimidine 5a
was obtained. Surprisingly, applying DBU as a base instead of
Na2CO3 and under the above conditions 5a was obtained as an
exclusive product, albeit with a modest yield (35%). The yield of the
reaction increased to 56% as the reaction temperature and the time
were increased to 110 ꢀC and 120 min. A further increase in the
reaction temperature and the time did not result in any improve-
ment of the yield. However, all the aromatic amidines applied gave,
under similar reaction conditions, the corresponding pyrano[2,3-
d]pyrimidines 5a–d in reasonable yields (50–56%) (Table 1, runs 14,
16,18, 20). Having in mind the fact that the bicyclic derivatives 5 are
just the cyclized form of DDAAD 4 we then focused our in-
vestigation on the exclusive synthesis of 4. Adding water to the
reaction mixture proved beneficial to both the purity and the yield
of the reaction products 4. Thus, the reaction of equimolar amounts
of 1d and benzamidine hydrochloride with 2 equiv of Na2CO3 as
a base in an ethanol/water mixture (2:1) at 100 ꢀC led, after 45 min
of microwave irradiation and after an acidic work-up, exclusively to
the product 4a in a high yield (85%). These reaction conditions were
successfully applied to the syntheses of the products 4a–d (Table 1,
runs 13, 15, 17, 19). Recalling that the bicyclic derivatives 5 could be
formed by the cyclization of DDAAD 4, we decided to check the
possibility of preparing the pyrano[2,3-d]pyrimidines 5 from 4 in
a condensation reaction, including the elimination of water. We
were delighted to find that the transformation of 4a into the pyr-
ano[2,3-d]pyrimidine 5a could be accomplished in a 92% yield by
microwave irradiation of the derivative 4a in ethanol (in the ab-
sence of water) for 120 min at 110 ꢀC, followed by a simple filtration
of 5a from the reaction mixture (Table 2, run 1). In this way the
previous 56% yield of 5a, obtained directly from 1d in a single step,
here increased to 78% as a result of a two-step process starting from
1d. Similarly, we also successfully synthesized the products 5b–d in
higher yields than with the one-step process (Table 2) (Scheme 2).
configuration.13 In order to further confirm the observed configu-
ration, a NOESY experiment was carried out, which revealed the
spatial proximity between the NH proton of the benzamide group
(d 10.27) and the 3-H. Due to the large range of the 3-H chemical
shifts (6.78–7.21) of compounds 3, we decided to further confirm
the proposed configuration also in the case of compounds 3l (dH-3
6.78) and 3g (dH-3 7.21). The long-range coupling constant between
the C-1 and the H-3 was, in both cases, determined as 10.3 Hz (for
3l) and 10.5 Hz (3g), supporting the proposed (E)-configuration.
Since the H-3 chemical shift of compounds 4 has a very narrow
range (6.61–6.67) and is, in addition, shifted upfield from the mean
value of the H-3 chemical shifts for compounds 3, we again carried
out a NOESY experiment and determined the coupling constant
between the C-1 and the H-3 for 4a. Both experiments un-
equivocally confirmed the (E)-configuration of compounds 4 (the
coupling constant for 4a being 10.0 Hz).
3. Conclusions
We have developed a novel, convenient, and green methodology
for the synthesis of isomerically pure (E)-DDAAD 3 and 4 bearing
a highly substituted 5-pyrimidyl moiety at the
b-position. (E)-
DDAAD 3a–l were synthesized from 5-acyl-2H-pyran-2-ones 1a–c
and amidines 2 in ethanolic mixtures and in the presence of
Na2CO3. The 5-ethoxycarbonyl-2H-pyran-2-one 1d exhibited a dif-
ferent reactivity pattern than the 2H-pyran-2-ones 1a–c. Namely,
with aromatic amidines from 1d in ethanolic mixtures in the
presence of DBU as the base pyrano[2,3-d]pyrimidines 5 were
obtained as the final products. When Na2CO3 was used as the base
and a mixture of EtOH and water (2:1) was applied as a solvent the
corresponding
b-(4-hydroxypyrimidyl)-DDAAD 4 were isolated.
The utilization of microwaves, green solvents (ethanol, water), and
nontoxic carbonate bases combined with acceptable reaction times
and an easy work-up renders this synthesis environmentally be-
nign and user friendly.
Table 2
4. Experimental
4.1. General
Reaction conditions and yields of products 5 from 4
Run
SM
R3
Product 5a
Yieldb
(%)
Melting points were determined on a Kofler micro hot stage. 1H
NMR spectra were recorded with a Bruker Avance DPX 300 spec-
trometer at 29 ꢀC (unless otherwise stated) and 300 MHz using
TMS as an internal standard, with the exception of compounds 5,
where the spectra are referenced against the solvent signal
1
2
3
4
4a
4b
4c
4d
Ph
5a
5b
5c
5d
92
81
80
75
4-MeC6H4
4-ClC6H4
3-O2NC6H4
a
EtOH, MW, 110 ꢀC, 120 min, 45 W.
Yields of isolated products are given.
b
(CF3CO2D residual solvent singlet at
d
¼11.5 ppm). 13C NMR spectra
were recorded on the same instrument at 75.5 MHz and are ref-
erenced against the central line of the solvent signal (DMSO-d6
R3
N
O
O
N
R3
septet at
quartet at
d
¼39.5 ppm, pyridine-d5 triplet at
d
¼149.9 ppm, CF3CO2D
HO
HO2C
N
EtOH, MW
d
¼164.2 ppm). The coupling constants (J) are given in
N
PhCONH
Me
110 ºC
120 min
hertz. IR spectra were obtained with a Bio-Rad FTS 3000MX (KBr
pellets for all products). MS spectra were recorded with a VG-An-
alytical AutoSpec Q (EI and FAB) or a Q-TOF Premier instrument
(ESI). Elemental analyses (C, H, N) were performed with a Perkin
Elmer 2400 Series II CHNS/O Analyzer. TLC was carried out on Fluka
silica-gel TLC-cards. Microwave reactions were conducted in air
using a focused microwave unit (Discover by CEM Corporation,
Matthews, NC). The machine consists of a continuous, focused
microwave power-delivery system with an operator-selectable
power output from 0 to 300 W. Reactions were performed in glass
vessels (capacity 10 mL) sealed with a septum. The pressure was
controlled by a load cell connected to the vessel via the septum. The
temperature of the contents of the vessel was monitored using
a calibrated infrared temperature controller mounted under the
reaction vessel. All the mixtures were stirred with a Teflon-coated
magnetic stirring bar in the vessel. Temperature, pressure, and
Me
5a-d
PhCONH
H
4a-d
Scheme 2.
The most obvious pathway of the reaction from 1 into DDAAD
3 (or 4) is an attack of the amidine derivative as a 1,3-binucleophile
at the carbonyl moiety of the 5-acyl (or ethoxycarbonyl) group and
at the C-6 of the pyran-2-one ring (Scheme 1) followed by the ring
opening and the elimination of the water (or ethanol) molecule to
yield the product 3 (or 4). This reaction pathway supports the (E)-
configuration7 of the products 3 (or 4), which was proven in the
case of compound 3b using the 2D NMR technique. Namely, for the
product 3b the long-range coupling constant between the C-1
(d
164.8) and the H-3 (
d 7.00) was 10.5 Hz, which is consistent with
the literature data for related systems having the (E)-

J. Hren et al. / Tetrahedron 65 (2009) 8216–8221
8219
power profiles were recorded using commercially available soft-
ware provided by the manufacturer of the microwave unit. The
starting compounds 1a–d were prepared as described pre-
viously.7b,8 All other reagents and solvents were used as received
from commercial suppliers. Amidines were used in the form of
hydrochlorides, with the exception of 4-chlorobenzamidine, which
was used as a hydroiodide.
132.0, 132.4, 133.2, 155.7, 163.3, 164.8, 165.4. MS (EI): m/z 297 (Mþ,
6.6%), 105 (100). Anal. Calcd for C16H15N3O3: C, 64.64; H, 5.09; N,
14.13. Found: C, 64.68; H, 5.19; N, 13.85.
4.5.3. (E)-2-(Benzoylamino)-3-(4,6-dimethyl-2-phenylpyrimidin-5-
yl)propenoic acid (3c). Yield: 158.7 mg (85%); off-white powder;
mp 109–111 ꢀC (H2O/EtOH). IR (KBr): 3388, 1673, 1637, 1541, 1516,
1485 cmꢁ1. 1H NMR14 (DMSO-d6)
d
2.48 (s, 6H, two Me), 7.04 (s, 1H,
3-H), 7.57 (m, 6H, Ph), 7.98 (m, 2H, Ph), 8.40 (m, 2H, Ph),10.27 (s,1H,
NH), 12.89 (br s, 1H, OH). 13C NMR14 (DMSO-d6)
22.8, 120.5, 125.9,
4.2. Microwave-assisted synthesis of 3
d
A suspension of the starting 3-benzoylamino-2H-pyran-2-ones
1a–c (0.5 mmol), amidine (guanidine) hydrochloride 2 (0.5 mmol),
sodium carbonate (1 mmol, 106 mg) in ethanol (1.5 mL) was irra-
diated in the focused MW equipment (for the reaction time and
temperature, see Table 1, Scheme 1). After irradiation, ethanol was
removed under a reduced pressure and 2 mL of water was added
and acidified with 10% aq HCl to pHw2. The resulting precipitated
solid was filtered off, washed with water, and dried.
127.5, 127.6, 128.5, 130.4, 132.0, 132.4, 133.3, 137.2, 160.5, 163.8,
164.8, 165.4 (one signal is hidden). MS (EI): m/z 373 (Mþ, 27%), 105
(100). Anal. Calcd for C22H19N3O3$1/3H2O: C, 69.64; H, 5.22; N,
11.07. Found: C, 69.58; H, 5.39; N, 10.77.
4.5.4. (E)-2-(Benzoylamino)-3-[4,6-dimethyl-2-(3-nitro-
phenyl)pyrimidin-5-yl]propenoic acid (3d). Yield: 188.3 mg (90%);
off-white powder; mp 209–213 ꢀC (H2O/EtOH). IR (KBr): 3389,
1736, 1645, 1526 cmꢁ1. 1H NMR (DMSO-d6)
d 2.50 (s, 6H, two Me),
4.3. Microwave-assisted synthesis of 4
7.19 (s, 1H, 3-H), 7.60 (m, 3H, Ph), 7.83 (m, 1H, C6H4), 7.96 (m, 2H,
Ph), 8.37 (m, 1H, C6H4), 8.81 (m, 1H, C6H4), 9.13 (m, 1H, C6H4), 10.27
A suspension of the starting 5-ethoxycarbonyl-6-methyl-3-
benzoylamino-2H-pyran-2-one 1d (0.5 mmol, 150 mg), amidine
hydrochloride or hydroiodide 2 (0.5 mmol), Na2CO3 (1 mmol,
106 mg) in a mixture of ethanol and water (2:1, 1.5 mL) was irra-
diated in the focused MW equipment at 100 ꢀC (see Table 1, Scheme 1).
After irradiation, ethanol was removed under a reduced pressure
and 2 mL of water was added and acidified with 10% aq HCl to
pHw2. The resulting precipitated solid was filtered off, washed
with water, and dried.
(s, 1H, NH), 12.96 (br s, 1H, OH). 13C NMR (DMSO-d6)
d 22.8, 120.1,
121.7, 125.0, 127.1, 127.6, 128.5, 130.4, 132.0, 132.6, 133.2, 133.5,
138.8, 148.3, 158.4, 164.3, 164.8, 165.4. MS (EI): m/z 418 (Mþ, 7.5%),
105 (100). Anal. Calcd for C22H18N4O5: C, 63.15; H, 4.34; N, 13.39.
Found: C, 63.16; H, 4.49; N, 13.28.
4.5.5. (E)-2-(Benzoylamino)-3-(2-amino-4,6-dimethylpyrimidin-5-
yl)propenoic acid (3e). Yield: 124.9 mg (80%); brown powder; mp
268–271 ꢀC (with decay) (H2O/EtOH). IR (KBr): 3348, 1704, 1665,
1518, 1385 cmꢁ1. 1H NMR (DMSO-d6)
d
2.17 (s, 6H, two Me), 6.35 (s,
2H, NH2), 6.78 (s, 1H, 3-H), 7.52 (m, 3H, Ph), 7.95 (m, 2H, Ph), 10.15
(s, 1H, NH), 12.58 (br s, 1H, OH). 13C NMR (DMSO-d6)
22.4, 115.7,
4.4. Microwave-assisted synthesis of 5
d
4.4.1. Synthesis of
5
from 1d. A suspension of the starting
122.0, 127.6, 128.4, 131.5, 131.8, 133.4, 161.5, 164.1, 165.2. MS (EI) m/z
312 (Mþ, 36%), 105 (100). HRMS (EI) calcd for C16H16N4O3: 312.1222,
found: 312.1226.
5-ethoxycarbonyl-2H-pyran-2-one 1d (0.5 mmol,150 mg), amidine
hydrochloride or hydroiodide (0.5 mmol), DBU (0.55 mmol, 84 mg)
in ethanol (1.5 mL) was irradiated in the focused MW equipment at
110 ꢀC (see Table 1, Scheme 1). The resulting precipitated solid was
filtered off, washed with ethanol, and dried.
4.5.6. (E)-2-(Acetylamino)-3-(4,6-dimethyl-2-phenylpyrimidin-5-
yl)propenoic acid (3f). Yield: 124.5 mg (80%); pale-brown powder;
mp 209–212 ꢀC (H2O/EtOH). IR (KBr): 3229, 3182, 3028, 1721, 1657,
4.4.2. Synthesis of 5 from 4a–d. A suspension of (E)-2-[(benzoyl-
amino)-3-(4-hydroxy-6-methylpyrimidin-5-yl)]propenoic acid de-
rivative 4 (0.5 mmol) in EtOH (1.5 mL) was irradiated in the focused
MW equipment (see Table 2, Scheme 2). After irradiation, the re-
action mixture was cooled and the resulting precipitated product
was filtered off and dried.
1631, 1545 cmꢁ1. 1H NMR (DMSO-d6)
d
2.04 (s, 3H, Me), 2.41 (s, 6H,
two Me), 7.14 (s, 1H, 3-H), 7.50 (m, 3H, Ph), 8.38 (m, 2H, Ph), 9.67
(s, 1H, NH), 12.96 (br s, 1H, OH). 13C NMR (DMSO-d6)
22.8, 23.1,
d
117.9, 126.3, 127.5, 128.5, 130.3, 131.6, 137.2, 160.3, 163.6, 164.8,
168.9. MS (EI) m/z 311 (Mþ, 82), 269 (100). Anal. Calcd for
C17H17N3O3: C, 65.58; H, 5.50; N, 13.50. Found: C, 65.45; H, 5.62; N,
13.31.
4.5. Analytical and spectroscopic data of products
4.5.7. (E)-2-(Acetylamino)-3-[4,6-dimethyl-2-(3-nitro-
phenyl)pyrimidin-5-yl]propenoic acid (3g). Yield: 160.3 mg (90%);
off-white powder; mp 244–247 ꢀC (H2O/EtOH). IR (KBr): 3372,
4.5.1. (E)-2-(Benzoylamino)-3-(2,4,6-trimethylpyrimidin-5-yl)prope-
noic acid (3a). Yield: 132.3 mg (85%); brown powder; mp 198–
200 ꢀC (from H2O/EtOH). IR (KBr): 3385, 3348, 1670, 1512,
1705, 1524 cmꢁ1 1H NMR (DMSO-d6)
. d 2.07 (s, 3H, Me), 2.45 (s,
1485 cmꢁ1
.
1H NMR14 (DMSO-d6)
d
2.34 (s, 6H, two Me), 2.51 (s,
3H, Me), 6.94 (s, 1H, 3-H), 7.58 (m, 3H, Ph), 7.96 (m, 2H, Ph), 10.23
(s, 1H, NH), 12.83 (br s, 1H, OH). 13C NMR14 (DMSO-d6)
22.4, 25.1,
6H, two Me), 7.21 (s, 1H, 3-H), 7.79 (m, 1H, C6H4), 8.34 (m, 1H,
C6H4), 8.76 (m, 1H, C6H4), 9.08 (m, 1H, C6H4), 9.69 (s, 1H, NH),
d
13.07 (br s, 1H, OH). 13C NMR (DMSO-d6)
d 22.7, 23.2, 117.5, 121.7,
120.4, 124.4, 127.6, 128.5, 132.0, 132.3, 133.2, 163.2, 164.3, 164.8,
165.4. MS (EI): m/z 311 (Mþ, 6.2%), 105 (100). Anal. Calcd for
C17H17N3O3: C, 65.58; H, 5.50; N, 13.50. Found: C, 65.42; H, 5.66; N,
13.24.
124.9, 127.5, 130.3, 131.7, 133.5, 138.8, 148.2, 158.2, 164.1, 164.7,
169.0. MS (EI) m/z 356 (Mþ, 41%), 314 (100). Anal. Calcd for
C17H16N4O5: C, 57.30; H, 4.53; N, 15.72. Found: C, 57.23; H, 4.47; N,
15.63.
4.5.2. (E)-2-(Benzoylamino)-3-(4,6-dimethylpyrimidin-5-yl)prope-
noic acid (3b). Yield: 133.8 mg (90%); white powder; mp 213–
216 ꢀC (H2O/EtOH). IR (KBr): 3389, 1668, 1578, 1518, 1487 cmꢁ1. 1H
4.5.8. (E)-2-(Benzoylamino)-3-(4-methyl-6-phenylpyrimidin-5-yl)-
propenoic acid (3h). Yield: 163.5 mg (91%); pale-brown poꢁw1der;
mp 225–228 ꢀC (H2O/EtOH). IR (KBr): 3376, 1660, 1530 cm
.
1H
NMR (DMSO-d6)
3H, Ph), 7.97 (m, 2H, Ph), 8.78 (s, 1H, 20-H), 10.25 (s, 1H, NH), 12.89
(br s, 1H, OH). 13C NMR (DMSO-d6)
22.5, 120.1, 127.6, 127.8, 128.5,
d
2.39 (s, 6H, two Me), 7.00 (s, 1H, 3-H), 7.58 (m,
NMR (DMSO-d6)
7.75 (m, 2H, Ph), 7.93 (m, 2H, Ph), 9.01 (s,1H, 20-H),10.08 (s,1H, NH),
12.83 (br s, 1H, OH). 13C NMR (DMSO-d6)
22.9, 121.2, 126.3, 126.7,
d 2.50 (s, 3H, Me), 7.11 (s,1H, 3-H), 7.52 (m, 6H, Ph),
d
d

8220
J. Hren et al. / Tetrahedron 65 (2009) 8216–8221
127.6, 128.0, 128.5, 129.2, 129.4, 131.95, 131.98, 133.2, 137.9, 156.1,
161.9, 163.4, 164.6. MS (EI) m/z 360 (MHþ, 0.7%), 105 (100). Anal.
Calcd for C21H17N3O3: C, 70.18; H, 4.77; N, 11.69. Found: C, 70.22; H,
4.87; N, 11.40.
1663, 1620 (br), 1551, 1511, 1465 cmꢁ1. 1H NMR (DMSO-d6)
d 2.29 (s,
3H, Me), 2.39 (s, 3H, Me), 6.61 (s, 1H, 3-H), 7.34 and 8.04 (AA0XX0,
J¼8.1 Hz, 4H, C6H4), 7.61 (m, 3H, Ph), 7.94 (m, 2H, Ph), 10.17 (s, 1H,
NH), 12.60 (br s, 2H, 2ꢂOH). 13C NMR (pyridine-d5)
d 21.4, 23.4,
117.3, 120.0, 128.1, 128.5, 129.1, 129.9, 131.3, 132.2, 133.3, 135.7, 142.1,
155.6, 161.5, 163.6, 166.7, 167.9. MS (ESIꢁ): m/z 388 (MHꢁ), 344.
Anal. Calcd for C22H19N3O4: C, 67.86; H, 4.92; N, 10.79. Found: C,
68.00; H, 4.83; N, 10.42.
4.5.9. (E)-2-(Benzoylamino)-3-(2,4-dimethyl-6-phenylpyrimidin-5-
yl)propenoic acid (3i). Yield: 160.6 mg (86%); white powder; mp
202–204 ꢀC (H2O/EtOH). IR (KBr): 3353, 1671, 1640, 1542,
1440 cmꢁ1. 1H NMR (DMSO-d6)
d 2.44 (s, 3H, Me), 2.61 (s, 3H, Me),
7.01 (s, 1H, 3-H), 7.42 (m, 3H, Ph), 7.55 (m, 3H, Ph), 7.70 (m, 2H, Ph),
4.5.15. (E)-2-(Benzoylamino)-3-[2-(4-chlorophenyl)-4-hydroxy-6-
methylpyrimidin-5-yl]propenoic acid (4c). Yield: 163.9 mg (80%);
yellow powder; mp 318–323 ꢀC (H2O/EtOH). IR (KBr): 3409, 1667,
7.91 (m, 2H, Ph), 10.05 (s, 1H, NH), 12.73 (br s, 1H, OH). 13C NMR
(DMSO-d6) d 23.7, 26.3, 122.4, 124.4, 128.5, 128.8, 129.4, 130.0, 130.3,
132.8, 132.9, 134.1, 139.1, 163.0, 165.59, 165.62, 165.9, 166.2. MS (EI)
m/z 374 (MHþ, 0.6%), 105 (100). Anal. Calcd for C22H19N3O3: C,
70.76; H, 5.13; N, 11.25. Found: C, 70.99; H, 5.17; N, 11.09.
1622, 1551, 1521, 1490 cmꢁ1. 1H NMR (DMSO-d6)
d 2.31 (s, 3H, Me),
6.64 (s, 1H, 3-H), 7.57 (m, 3H, Ph), 7.60 and 8.14 (AA0XX0, J¼8.6 Hz,
4H, C6H4), 7.94 (m, 2H, Ph),10.16 (s, 1H, NH), 12.70 (br s, 2H, 2 x OH).
13C NMR (pyridine-d5)
d 23.6, 117.2, 121.0, 128.9, 130.0, 130.1, 130.9,
4.5.10. (E)-2-(Benzoylamino)-3-(4-methyl-2,6-diphenylpyrimidin-5-
yl)propenꢀoic acid (3j). Yield: 178.5 mg (82%); off-white powder; mp
125–128 C (H2O/EtOH). IR (KBr): 3386, 1709, 1670, 1530,
133.2, 135.3, 135.7, 138.3, 155.7, 161.8, 165.1, 167.8, 169.3 (one signal
is hidden). MS (ESIꢁ) m/z 408 (MHꢁ), 364. Anal. Calcd for
C21H16ClN3O4: C, 61.54; H, 3.94; N,10.25. Found: C, 61.35; H, 3.91; N,
10.47.
1489 cmꢁ1. 1H NMR (DMSO-d6)
d 2.58 (s, 3H, Me), 7.13 (s, 1H, 3-H),
7.37 (m, 3H, Ph), 7.55 (m, 9H, Ph), 7.84 (m, 2H, Ph), 7.93 (m, 2H, Ph),
8.47 (m, 2H, Ph), 10.10 (s, 1H, NH), 12.80 (br s, 1H, OH). 13C NMR
4.5.16. (E)-2-(Benzoylamino)-3-[4-hydroxy-6-methyl-2-(3-nitro-
phenyl)pyrimidin-5-yl]propenoic acid (4d). Yield: 170.3 mg (81%);
yellow powder; mp 267–270 ꢀC (H2O/EtOH). IR (KBr): 3406, 1667,
(DMSO-d6)
d 23.3, 119.3, 125.7, 127.4, 127.6, 127.9, 128.53, 128.56,
129.1, 129.5, 130.5, 131.9, 132.7, 133.5, 137.3, 138.5, 160.5, 162.0,
164.8, 165.0, 165.6. MS (EI) m/z 453 (Mþ, 1.6%), 105 (100). HRMS (EI)
calcd for C27H21N3O (Mþ): 435.1583, found: 435.1591. Anal. Calcd
for C27H21N3O3$1⁄2 EtOH: C, 73.35; H, 5.28; N, 9.16. Found: C, 73.29;
H, 5.15; N, 9.11.
1620, 1600, 1522 cmꢁ1. 1H NMR (DMSO-d6)
d 2.36 (s, 3H, Me), 6.69
(s, 1H, 3-H), 7.56 (m, 3H, Ph), 7.84 (m, 1H, C6H4), 7.95 (m, 2H, Ph),
8.41 (m, 1H, C6H4), 8.60 (m, 1H, C6H4), 9.00 (m, 1H, C6H4), 10.19 (s,
1H, NH), 12.80 (br s, 2H). 13C NMR (pyridine-d5)
d 23.3, 117.0, 118.4,
123.2, 125.4, 128.1, 129.2, 130.2, 132.3, 133.3, 134.2, 135.7, 138.3,
149.0,156.8,163.5,166.4,166.7,167.8. MS (ESIꢁ) m/z 419 (MHꢁ), 375.
Anal. Calcd for C21H16N4O6: C, 60.00; H, 3.84; N, 13.33. Found: C,
60.05; H, 3.96; N, 13.18.
4.5.11. (E)-2-(Benzoylamino)-3-[4-methyl-2-(3-nitrophenyl)-6-phenyl
pyrimidin-5-yl]propenoic acid (3k). Yield: 216.2 mg (90%); brown
powder; mp 243–246 ꢀC (H2O/EtOH). IR (KBr): 3367, 1733, 1643,
1534, 1341 cmꢁ1. 1H NMR (DMSO-d6)
d 2.63 (s, 3H, Me), 7.17 (s, 1H,
3-H), 7.55 (m, 6H, Ar), 7.85 (m, 3H, Ar), 7.94 (m, 2H, Ph), 8.40 (m, 1H,
Ar), 8.88 (m, 1H, Ar), 9.18 (m, 1H, Ar), 10.14 (s, 1H, NH), 12.66 (br s,
4.5.17. N-(4-Methyl-7-oxo-2-phenyl-7H-pyrano[2,3-d]pyrimidin-6-
yl)benzamide (5a). Yield: from 1d 100.1 mg (56%), from 4a
164.4 mg (92%); light-brown powder; mp 279–281 ꢀC (DMF/EtOH).
IR (KBr): 3352, 1723, 1671, 1624, 1576, 1528 cmꢁ1. 1H NMR (DMSO-
1H, OH). 13C NMR (DMSO-d6)
d 23.3, 118.7, 121.8, 125.0, 126.9, 127.5,
128.0, 128.5, 129.4, 129.6, 130.4, 131.9, 133.0, 133.4, 133.6, 138.1,
138.9, 148.3, 158.4, 162.3, 164.8, 165.0, 166.2. MS (FAB) m/z 481
(MHþ, 2%), 154 (100). Anal. Calcd for C27H20N4O5: C, 67.49; H, 4.20;
N, 11.37. Found: C, 67.26; H, 4.34; N, 11.37.
d6, 100 ꢀC)
(m, 2H, Ph), 8.73 (s, 1H, 5-H), 9.57 (s, 1H, NH). 13C NMR (DMSO-d6,
100 ꢀC)
20.43, 109.3, 120.3, 124.9, 127.0, 127.7, 128.11, 128.15, 130.9,
131.8, 133.0, 135.7, 156.8, 160.8, 161.3, 165.6, 166.1. 1H NMR
(CF3CO2D) 3.13 (s, 3H, Me), 7.47 (m, 2H, Ph), 7.58 (m, 3H, Ph), 7.70
(m, 1H, Ph), 7.81 (m, 2H, Ph), 8.20 (m, 2H, Ph), 9.10 (s, 1H, 5-H). 13C
NMR (CF3CO2D) 19.5,115.3, 119.1,130.13, 130.19,130.5, 131.8, 132.3,
d 2.79 (s, 3H, Me), 7.57 (m, 6H, Ph), 7.97 (m, 2H, Ph), 8.42
d
4.5.12. (E)-3-(2-Amino-4-methyl-6-phenylpyrimidin-5-yl)-2-(ben-
zoylamino)propenoic acid (3l). Yield: 164.7 mg (88%); brown pow-
der; mp 264–266 ꢀC (H2O/EtOH). IR (KBr): 3368, 1703, 1669, 1600,
d
d
1507 cmꢁ1. 1H NMR (DMSO-d6)
d
2.27 (s, 3H, Me), 6.56 (s, 2H, NH2),
6.78 (s, 1H, 3-H), 7.37 (m, 3H, Ph), 7.57 (m, 5H, Ph), 7.90 (m, 3H, Ph),
9.97 (s, 1H, NH), 12.56 (br s, 1H, OH). 13C NMR (DMSO-d6)
22.7,
132.9, 134.0, 137.4, 139.0, 159.5, 162.2, 165.97, 166.00, 173.7. MS (EI)
m/z 357 (Mþ, 38%), 105 (100). Anal. Calcd for C21H15N3O3: C, 70.58;
H, 4.23; N, 11.76. Found: C, 70.51; H, 4.35; N, 11.54.
d
114.9, 123.1, 127.5, 127.6, 128.4, 128.7, 129.1, 131.0, 131.8, 133.3, 138.9,
161.8, 163.6, 165.10, 165.11, 165.7. MS (EI) m/z 374 (Mþ, 1.6), 105
(100). Anal. Calcd for C21H18N4O3: C, 67.37; H, 4.85; N, 14.96. Found:
C, 67.02; H, 4.70; N, 14.81.
4.5.18. N-[4-Methyl-2-(4-methylphenyl)-7-oxo-7H-pyrano[2,3-
d]pyrimidin-6-yl]benzamide (5b). Yield: from 1d 100.3 mg (54%),
from 4b 150.4 mg (81%); pale-yellow crystals; mp 324–327 ꢀC
(DMF/MeOH). IR (KBr): 3378, 1720, 1668, 1626, 1579, 1526
4.5.13. (E)-2-(Benzoylamino)-3-(4-hydroxy-6-methyl-2-phenyl-
pyrimidin-5-yl)propenoic acid (4a). Yield: 159.8 mg (85%); yellow
powder; mp 285–287 ꢀC (H2O/EtOH). IR: 3417, 1663, 1599, 1561,
(br) cmꢁ1 1H NMR (CF3CO2D)
. d 2.47 (s, 3H, Me), 3.17 (s, 3H, Me),
7.47 and 8.18 (AA0XX0, J¼8.3 Hz, 4H, C6H4), 7.56 (m, 2H, Ph), 7.69 (m,
1H, Ph), 7.89 (m, 2H, Ph), 9.16 (s, 1H, 5-H). 13C NMR (CF3CO2D)
d 19.1,
1526 cmꢁ1. 1H NMR (DMSO-d6)
d
2.30 (s, 3H, Me), 6.62 (s, 1H, 3-H),
22.9, 114.4, 127.2, 129.6, 129.8, 131.5, 132.0, 133.4, 133.7, 137.1, 152.0,
159.4,161.9,165.4,165.6,173.5 (one signal is missing). MS (ESIþ) m/z
372 (MHþ). Anal. Calcd for C22H17N3O3: C, 71.15; H, 4.61; N, 11.31.
Found: C, 70.88; H, 4.61; N, 11.30.
7.55 (m, 6H, Ph), 7.96 (m, 2H, Ph), 8.13 (m, 2H, Ph), 10.20 (s, 1H, NH),
12.75 (br s, 2H, 2ꢂOH). 13C NMR (pyridine-d5)
d 23.4, 117.3, 120.2,
128.2, 128.6, 129.18, 129.21, 131.8, 132.2, 133.5, 134.3, 135.7, 155.9,
161.6, 163.8, 166.8, 168.0. MS (ESIþ) m/z 376 (MHþ). Anal. Calcd for
C21H17N3O4: C, 67.19; H, 4.56; N, 11.19. Found: C, 66.89; H, 4.57; N,
11.08.
4.5.19. N-[2-(4-Chlorophenyl)-4-methyl-7-oxo-7H-pyrano[2,3-
d]pyrimidin-6-yl]benzamide (5c). Yield: from 1d 101.9 mg (52%),
from 4c 156.7 mg (80%); pale-yellow powder; mp 301–303 ꢀC
(DMF/MeOH). IR (KBr): 3386, 1725, 1674, 1622, 1569, 1518 cmꢁ1. 1H
4.5.14. (E)-2-(Benzoylamino)-3-[4-hydroxy-6-methyl-2-(4-methyl-
phenyl)pyrimidin-5-yl]propenoic acid (4b). Yield: 157.7 mg (81%);
pale-yellow powder; mp 321–323 ꢀC (H2O/EtOH). IR (KBr): 3405,
NMR (CF3CO2D)
d 3.00 (s, 3H, Me), 7.42 (m, 5H, 3H of Ph and 2H of
C6H4), 7.70 (m, 2H, Ph), 8.05 (AA0XX0, J¼8.7 Hz, 2H of C6H4), 8.97 (s,

J. Hren et al. / Tetrahedron 65 (2009) 8216–8221
8221
1H, 5-H). 13C NMR (CF3CO2D)
d 19.45, 115.4,118.9,128.9, 130.1,130.2,
132.2, 133.0, 133.3, 133.9, 137.4, 146.7, 159.3, 161.0, 165.8, 166.0,
173.6. MS (ESIþ) m/z 392 (MHþ), 372. Anal. Calcd for C21H14ClN3O3:
C, 64.38; H, 3.60; N, 10.72. Found: C, 64.35; H, 3.51; N, 10.78.
4. (a) Arai, H.; Hagmann, W. K.; Suguna, H.; Hecht, S. M. J. Am. Chem. Soc. 1980, 102,
ˇ
6631–6633; (b) Zupet, R.; Tisler, M. J. Org. Chem. 1994, 59, 507–508; (c) Fotouhi,
N.; Gillespie, P.; Guthrie, R.W.; Pietranico-Cole, S. L.; Yun, W. PCT Int. Appl. WO
58,853, 2001; Chem. Abstr. 2001, 135, 180944y; (d) Kubota, H.; Nakamura, Y.;
Tojima, T.; Yamamoto, Y.; Oka, K.; Igarashi, S. Jpn. Kokai Tokkyo Koho JP 119,451,
2007; Chem. Abstr. 2007, 146, 501029d; (e) Chen, L.; Chaturvedula, P. V.; Civiello,
R.; Degnan, A. P.; Dubowchik, G. M.; Han, X.; Jiang, X. J. J.; Karageorge, G. N.; Luo,
G.; Macor, J. E.; Poindexter, G. S.; Tora, G. O. U.S. Pat. Appl. Publ. US 232,600,
4.5.20. N-[4-Methyl-2-(3-nitrophenyl)-7-oxo-7H-pyrano[2,3-d]pyr-
imidin-6-yl]benzamide (5d). Yield: from 1d 100.6 mg (50%), from
4d 150.9 mg (75%); light-brown needles; mp 268–270 ꢀC (DMF/
2007; Chem. Abstr. 20
07, 147, 406845d.
5. (a) Ellis, G. P. In Comprehensive Heterocyclic Chemistry: Pyrans and Fused Pyrans:
(ii) Reactivity; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984; Vol. 3,
pp 647–736; (b) Ram, V. J.; Srivastava, P. Curr. Org. Chem. 2001, 5, 571–599; (c)
Afarinkia, K.; Vinader, M. V. In Science of Synthesis; Thomas, E. J., Ed.; Thieme:
MeOH). IR (KBr): 3389, 1743, 1677, 1626, 1530 (br) cmꢁ1 1H NMR
.
(CF3CO2D)
7.93 (m, 3H, Ph), 8.64 (m, 1H, C6H4), 8.78 (m, 1H, C6H4), 9.25 (m, 2H,
5-H and 1H of C6H4). 13C NMR (CF3CO2D)
19.3, 116.2, 118.2, 126.4,
d 3.28 (s, 3H, Me), 7.60 (m, 2H, Ph), 7.73 (m, 1H, C6H4),
ˇ
Stuttgart, 2006; Vol. 14, pp 275–346; (d) Hren, J.; Polanc, S.; Kocevar, M. Arkivoc
2008, i, 209–231.
d
6. (a) Lemaitre, P.; Bastian, G.; Hubert-Habart, M.; Royer, R. Eur. J. Med. Chem.1976,11,
381–384; (b) Morita, H.; Tanaka, M.; Takagi, K. Chem. Pharm. Bull. 1983, 31, 3728–
3731; (c) Kvita, V.; Sauter, H.; Tuck, B. Helv. Chim. Acta 1988, 71, 1467–1473.
129.8, 130.5, 131.97, 132.04, 132.4, 133.5, 134.1, 137.2, 137.6, 151.3,
158.7, 159.2, 165.5, 166.4, 173.5. MS (ESIþ) m/z 403 (MHþ), 372. Anal.
Calcd for C21H14N4O5: C, 62.69; H, 3.51; N, 13.92. Found: C, 62.50; H,
3.37; N, 13.38.
ˇ
ˇ
ˇ
ˇ
7. (a) Trebse, P.; Polanc, S.; Kocevar, M.; Solmajer, T.; Golic Grdadolnik, S. Tetra-
ˇ
ˇ
hedron 1997, 53, 1383–1390; (b) Vranicar, L.; Polanc, S.; Kocevar, M. Tetrahedron
ˇ
ˇ
1999, 55, 271–278; (c) Vranicar, L.; Meden, A.; Polanc, S.; Kocevar, M. J. Chem.
ˇ
ˇ
Soc., Perkin Trans. 1 2002, 675–681; (d) Vranicar, L.; Polanc, S.; Kocevar, M.
ꢀ
ˇ
ˇ
Heterocycles 2003, 61, 105–112; (e) Vranicar, L.; Pozgan, F.; Polanc, S.; Kocevar,
Acknowledgements
M. Amino Acids 2003, 24, 273–280.
ˇ
ˇ
ˇ
8. (a) Kepe, V.; Kocevar, M.; Polanc, S.; Vercek, B.; Tisler,
M. Tetrahedron 1990, 46,
ꢀ
ˇ
2081–2088; (b) Pozgan, F.; Krejan, M.; Polanc, S.; Kocevar, M. Heterocycles 2006,
69, 123–132.
We thank the Ministry of Higher Education, Science and Tech-
nology of the Republic of Slovenia and the Slovenian Research
Agency for financial support (P1-0230-0103; BI-RO/08-09-006). Dr.
9. (a) Dunn, P. J. In Comprehensive Organic Functional Group Transformations:
Amidines and N-Substituted Amidines; Katritzky, A. R., Meth-Cohn, O., Rees, C. W.,
Eds.; Pergamon: Oxford, 1995; Vol. 5, pp 741–782; (b) Dunn, P. J. In Compre-
hensive Organic Functional Group Transformations II: Amidines and N-Substituted
Amidines; Katritzky, A. R., Taylor, R. J. K., Eds.; Pergamon: Oxford, 2005; Vol. 5,
pp 655–699.
ˇ
ꢀ
B. Kralj and Dr. D. Zigon (Center for Mass Spectroscopy, ‘Jozef Stefan’
Institute, Ljubljana, Slovenia) are gratefully acknowledged for the
mass measurement.
10. Burke, M. D.; Schreiber, S. L. Angew. Chem., Int. Ed. 2004, 43, 46–58.
11. For some selected recent books and reviews about microwave assisted re-
actions see, for example: (a) Microwaves in Organic Synthesis; Loupy, A., Ed.;
Wiley-VCH: Weinheim, 2002; (b) Hayes, B. L. Microwave Synthesis: Chemistry at
the Speed of Light; CEM: Matthews, NC, 2002; (c) Dallinger, D.; Kappe, C. O.
Chem. Rev. 2007, 107, 2563–2591; (d) Kappe, C. O. Chem. Soc. Rev. 2008, 37, 1127–
1139; (e) Polshettiwar, V.; Varma, R. S. Chem. Soc. Rev. 2008, 37, 1546–1557; (f)
Polshettiwar, V.; Varma, R. S. Acc. Chem. Res. 2008, 41, 629–639.
12. For some of our recent selected microwave investigations under different
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