Three-component one-pot synthesis of fused uracils - Pyrano[2,3-d]- pyrimidine-2,4-diones

Article abstract of DOI:10.1007/s00706-008-0935-z

5-Arylidene-N,N-dimethylbarbituric acids undergo smooth hetero-Diels-Alder reactions with enol ethers to afford cis and trans diastereoisomers of 7-alkoxy-5-aryl-2H-pyrano[2,3-d]pyrimidine-2,4-diones in excellent yields (84-95%). Cycloadducts with cis-configuration were the major products. Three-component one-pot reactions of N,N-dimethylbarbituric acid, aromatic and heteroaromatic aldehydes, and enol ethers in the presence of piperidine gave uracils also in very good yields (87-95%). The structure of the cycloadducts is discussed in terms of configuration and preferred conformation.

Full text of DOI:10.1007/s00706-008-0935-z

Monatsh Chem 139, 1397–1404 (2008)
DOI 10.1007/s00706-008-0935-z
Printed in The Netherlands
Three-component one-pot synthesis of fused uracils – pyrano[2,3-d]-
pyrimidine-2,4-diones
Aleksandra Pałasz
´
Department of Organic Chemistry, Jagiellonian University, Krakow, Poland
Received 10 March 2008; Accepted 16 March 2008; Published online 9 June 2008
# Springer-Verlag 2008
Abstract 5-Arylidene-N,N-dimethylbarbituric acids
undergo smooth hetero-Diels-Alder reactions with
enol ethers to afford cis and trans diastereoisomers
of 7-alkoxy-5-aryl-2H-pyrano[2,3-d]pyrimidine-2,4-
diones in excellent yields (84–95%). Cycloadducts
with cis-configuration were the major products.
Three-component one-pot reactions of N,N-dimethyl-
barbituric acid, aromatic and heteroaromatic alde-
hydes, and enol ethers in the presence of piperidine
gave uracils also in very good yields (87–95%). The
structure of the cycloadducts is discussed in terms of
configuration and preferred conformation.
synthetic challenges. The synthesis exploitation of
nucleophilic double bond of uracil is an important
strategy for the synthesis of a variety of potential
products [8–11]. The synthesis of fused uracils is
well described in literature [12–16], but the synthe-
sis methods usually require drastic conditions, long
reaction times, complex synthetic pathways and the
yields are poor. Recently, a novel approach to the
synthesis of fused uracils of biological importance
has been made. New synthesis methods rely on a
multicomponent reaction in the solid state [17],
a stereoselective intramolecular hetero-Diels-Alder
reaction (HDA) [18], an intermolecular [4 þ 2] cyclo-
addition reaction [19], or a photo-induced oxidative
cyclization [20]. In our recent work, we have
shown that intermolecular and intramolecular HDA
reactions are a powerful tool in 2H-pyrans and
policyclic 2H-pyran derivatives synthesis [21–26].
Among them, reactions 5-arylidene-N,N-dimethyl-
barbituric acids with styrenes [24] or N-vinyl-2-oxa-
zolidinone [26] afforded 2H-pyrano[2,3-d]pyrimidine-
2,4-diones with very good yields. It is well-known
that a Knoevenagel condensation followed by a
hetero-Diels-Alder reaction can be used in dihydro-
pyran synthesis [27–31]. In the present paper this
method was used for the synthesis of fused uracils –
pyrano[2,3-d]pyrimidine-2,4-dione.
Keywords Uracil; Hetero-Diels-Alder reaction; l-Oxa-1,3-
butadiene; Pyrano[2,3-d]pyrimidine-2,4-dione.
Introduction
Uracil [1] is one of the five nucleobases and there-
fore an important component of nucleic acids, thus
uracil and its fused derivatives, such as pyrano[2,3-
d]pyrimidines, pyrido[2,3-d]pyrimidines or pyri-
mido[4,5-d]pyrimidines are well recognized by
synthesis as well as biological chemists. Compounds
with this ring system have antiallergic [2], antihyper-
tensive [3], cardiotonic [4], bronchiodilator [5], anti-
bronchitic [6], or antitumour [7] activity.
The preparation of naturally occurring complex
molecules containing an uracil ring poses significant
Results and discussion
Correspondence: Aleksandra Pałasz, Department of Organic
The aim of the studies was the preparation of
fused uracils – pyrano[2,3-d]pyrimidine-2,4-diones
´
Chemistry, Jagiellonian University, Krakow, Poland. E-mail:
palasz@chemia.uj.edu.pl

1398
A. Pałasz
Scheme 1
in a three-component one-pot synthesis. First, it
was examined if 5-arylidene-N,N-dimethylbarbituric
acids 1a–1f can act as active heterodienes in HDA
reaction with enol ethers 2a–2c. Potential hetero-
dienes 1a–1f were synthesized according to the ge-
neral reaction protocol described in literature [32] by
condensation of N,N-dimethylbarbituric acids with
appropriate aromatic or heteroaromatic aldehydes in
anhydrous ethanol in the presence of piperidine. The
cycloaddition reactions of 1a–1f with a ten-fold ex-
cess of 2a–2c were performed with methylene chlo-
ride as the solvent at room temperature for 1–5 h and
the uracils 3a–3h were obtained in excellent 84–
95% yields (Scheme 1, Table 1).
The progress of the reactions was monitored by
TLC. The ratios of the cis=trans diastereoisomers of
the pyrano[2,3-d]pyrimidine-2,4-diones 3a–3h were
Table 1 Synthesis of pyrano[2,3-d]pyrimidine-2,4-diones
3a–3h by HDA reaction of 5-arylidene-N,N-dimethylbarbitu-
ric acids 1a–1f with enol ethers 2a–2c
Table 2 One-pot synthesis of pyrano[2,3-d]pyrimidine-2,4-
diones 3a–3h by reaction of N,N-dimethylbarbituric acid 4,
aldehydes 5a–5f, and enol ethers 2a–2c
1
2
3
Reaction
time=h
Yield=%a
Ratio of
cis=transb
5
2
3
Reaction
time=h
Yield=%a
Ratio of
cis=transb
1a
2a
3a
2
12c
3
3
2
1
5
5
5
94
92c
92
89
90
95
84
87
89
2.6:1
3.6:1c
2.6:1
2:1
1a
1a
1b
1c
1d
1e
1f
2b
2c
2a
2a
2a
2a
2a
3b
3c
3d
3e
3f
5a
5a
5a
5b
5c
5d
5e
5f
2a
2b
2c
2a
2a
2a
2a
2a
3a
3b
3c
3d
3e
3f
3
4
4
3
2
7
7
7
95
93
89
92
94
87
90
89
2.6:1
2.4:1
2.1:1
1.6:1
1.1:1
2.6:1
1.7:1
2.9:1
2:1
1.75:1
1.25:1
1.7:1
2.2:1
3g
3h
3g
3h
a
Isolated yields after column chromatography
Ratio based on 1H NMR (300MHz) spectra of crude products
The cycloaddition was performed at ꢀ35ꢁC
b
c
a
Isolated yields after column chromatography
Ratio based on 1H NMR (300MHz) spectra of crude products
b

One-pot synthesis of fused uracils
Table 3 Signals of proton 5-H and 7-H in H NMR spectra of products 3a–3h
1399
1
Compound
dd 5-H
ꢀ=ppm
J6ax,5=J6eq,5=Hz
dd 7-H
ꢀ=ppm
J6ax,7=J6eq,7=Hz
Compound
dd 5-H
ꢀ=ppm
J6ax,5=J6eq,5=Hz
dd 7-H
ꢀ=ppm
J6ax,7=J6eq,7=Hz
cis-3a
cis-3b
cis-3c
cis-3d
cis-3e
cis-3f
cis-3g
cis-3h
4.00
6.9=6.6
5.35
5.4=2.7
trans-3a
trans-3b
trans-3c
trans-3d
trans-3e
trans-3f
trans-3g
trans-3h
4.12
5.4=4.8
5.17
6.9=3.9
4.01
7.2=5.7
5.33
4.8=2.7
4.12
5.4=4.8
5.16
7.5=3.0
3.99
6.9=4.5
–
3.97
11.4=6.9
–
4.05
6.9=6.6
5.35
6.0=2.7
4.17
5.4=4.8
5.18
7.2=3.3
4.15
7.5=4.2
5.45
3.9=2.7
4.21
6.6=6.6
5.27
6.3=2.4
4.37
6.0=6.0
5.43
3.6=3.3
4.43
5.4=2.7
5.32
9.3=2.4
4.15
6.6=3.9
5.43
3.3=3.3
4.21
6.0=2.7
5.37
9.3=2.4
4.04
7.5=3.9
5.44
3.6=2.7
4.09
6.0=5.7
5.20
7.2=2.4
1
determined on the basis of H NMR spectra of
crude products, analyzing the signals of protons
5-H and 7-H. All diastereoisomers of 3a–3h were
very easily separated by column chromatography
using t-butyl-methyl ether as an eluent because the
difference between Rf (cis) and Rf (trans) was ap-
proximately 0.2.
and the ratio of cis=trans isomers of 3a was 3.6:1.
Decreasing the reaction temperature resulted in a
slight increase of the reaction diastereoselectivity
and the reaction needed longer time to be completed.
Compounds 3a–3h were characterized by 1H, 13
C
1
NMR, IR, mass spectra, and elemental analysis. H
and 13C signal assignments were confirmed by two-
dimensional NMR, COSY and HETCOR spectra.
The relative cis and trans configuration of the C-5,
In the next step of studies three-component one-
pot synthesis of uracils 3a–3h was investigated.
The experimental procedure was simple: equimolar
amounts of N,N-dimethylbarbituric acid 4 and aro-
matic or heteroaromatic aldehydes 5a–5f were mixed
with a ten-fold excess of enol ethers 2a–2c in meth-
ylene chloride in the presence of piperidine at room
temperature for 2–7 h and the pyrano[2,3-d]pyrimi-
dines 3a–3h were obtained in excellent 87–95%
yields (Scheme 1 and Table 2). The progress of the re-
actions was monitored by TLC. The ratios of the cis=
trans diastereoisomers of pyrano[2,3-d]pyrimidines
1
C-7 substituents were assigned on the basis of H
NMR spectra. They were deduced from the chemical
shift values and coupling constants of the protons at-
tached to C-5 and C-7 of the dihydropyran ring that
exists in a half-chair conformation [34] (Table 3). In
1
the H NMR spectra of the major diastereoisomers
cis-3a–3h the signal of 5-H appeared as a doublet of
doublets at ꢀ ¼ 3.99–4.37 ppm with coupling con-
stants (3J ¼ 6.0–7.5 and 3.9–6.6 Hz) due to coupling
with two protons at C-6 (Table 3). Thus, 5-H occu-
pies the pseudo-equatorial position, and the aroma-
1
3a–3h were determined on the basis of H NMR
spectra of crude products. Cycloadducts cis-3a–3h
were the major products in all reactions. The preferred
formation of the cis-diastereoisomers (Tables 1 and
2) results from the endo transition state interaction,
which is energetically more favorable than the exo
transition state. Thus, cis-products arise from a ki-
netically controlled process [33]. The cycloaddition
reaction of 1a with a ten-fold excess of 2a was
also performed at a temperature of ꢀ35ꢁC (Table 1)
Fig. 1 Preferred cis=trans configurations and conformations
of cycloadducts 3a–3h based on H NMR analysis
1

1400
A. Pałasz
Scheme 2
tic group adopts the pseudo-axial orientation (Fig. 1).
The 1H NMR spectra of cis-3a–3h reveal the signals
of proton 7-H as a doublet of doublets at ꢀ ¼ 5.33–
5.44 ppm with two small coupling constants (3J ¼
3.3–6.0 and 2.7–3.3 Hz). Thus, 7-H is in the equato-
rial position and the alkoxy group occupies the axial
position (Fig. 1).
dihydro-2H-pyrans derivatives undergo transforma-
tion to the thermodynamically more stable trans iso-
mers in the presence of Lewis acid or under heating
[35, 36]. These results corroborated that the cis and
trans configurations were correctly assigned to com-
pound 3a, 3f, and 3g.
In conclusion, fused uracils of potential biological
activity, the pyrano[2,3-d]pyrimidine-2,4-diones, were
obtained by a hetero-Diels-Alder reactions between
5-arylidene-N,N-dimethylbarbituric acids and enol
ethers or in a one-pot synthesis in which reagents were:
N,N-dimethylbarbituric acid, aromatic or heteroaro-
matic aldehydes, and enol ethers. The advantages of
the presented reactions are: the excellent yields, short
reactions times, and the fact that cycloadditions do not
require drastic conditions, but can be carried out at
room temperature. The described reactions give easy
and rapid access to both cis as trans diastereoisomers
of uracils and pure diastereoisomers can be very easily
isolated by column chromatography.
For the minor diastereoisomers trans-3a–3h, the
protons attached to C-5 give rise to a doublet of
3
doublets with coupling constants J ¼ 5.4–11.4 and
2.7–6.9 Hz at ꢀ ¼ 3.97–4.43 ppm. Thus, 5-H is pseu-
do-axial and the aryl moiety occupies the pseudo-
equatorial position (Fig. 1). The proton 7-H of
trans-3a–3h resonates at ꢀ ¼ 5.16–5.37 ppm as a
doublet of doublets with two coupling constants
(3J ¼ 6.3–9.3 and 2.4–3.9 Hz). This suggests that
for trans-3a–3h the conformation with an axial alk-
oxy group is preferred due to stabilization by the
anomeric effect.
It is worth to note that trace amounts of com-
pounds 6a–6g created by a trans-diaxial-elimination
of the appropriate alcohol were obtained in the
above described reactions (1H NMR analysis of
crude products, Scheme 1). Only products 6a, 6e,
and 6f were isolated in small amounts after column
chromatography. Fused uracils 6e and 6f are not yet
described in literature. Compounds 6a, 6c, and 6d
were also obtained in earlier examined reactions of
5-arylidene-N,N-dimethyl-barbituric acids and N-
vinyl-2-oxazolidinone [26]. The cycloadditions were
conducted in boiling toluene and uracils 6a, 6c, and
6d created as products of 2-oxazolidinone elimina-
tion. Taking into account this fact, the cis-3a, cis-3f,
and cis-3g diastereoisomers were heated in boiling
toluene for 12 h. The mixture of cis and trans
isomers and small amounts of compounds 1a, 1d,
and 1e formed in a retro-Diels-Alder reaction, were
obtained (Scheme 2). Elimination products 6a, 6e,
and 6f were absent in reaction mixtures after 12 h of
heating. It is known that cis diastereoisomers of 3,4-
Experimental
Melting points were determined on a Boetius hot stage ap-
paratus. IR spectra: Bruker IFS 48 in KBr pellets. NMR spec-
tra: Bruker Avance II 300 (1H: 300.18MHz, 13C: 75.48 MHz)
in CDCl3 with TMS as an internal standard. Mass spectra:
Finningan Mat 95 (70 eV). Microanalyses were performed
with Euro EA 3000 Elemental Analyzer, their results agreed
satisfactorily with the calculated values. 5-Arylidene-N,N-
dimethylbarbituric acids 1a–1f were obtained according to
the general procedure described in Ref. [32]. Enol ethers
2a–2c were commercially available.
N,N-Dimethyl-5-(2-thienylidene)pyrimidine-2,4,6-trione
(1d, C11H10 N2O3S)
To a stirred solution of 1.56 g N,N-dimethylbarbituric acid 4
(10 mmol) in 30 cm3 anhydrous ethanol, 1 cm3 tiophene-2-car-
baldehyde (10 mmol) and two drops of piperidine were added
at room temperature. The mixture was allowed to stir at room
temperature for 1 h, then the precipitated light-yellow solid
was filtered off and washed with ethanol. Crystallization from
methanol gave 2.4g pale yellow crystals; mp 203ꢁC; yield

One-pot synthesis of fused uracils
1401
96%; IR (KBr): ꢁꢀ¼ 3103, 3077, 3058, 2953 (CH), 1704, 1667,
1652 (C¼O), 1560 (C¼C) cmꢀ1; 1H NMR (300 MHz, CDCl3):
ꢀ ¼ 3.42 (s, 3 N–CH3), 3.43 (s, 3 N–CH3), 7.29 (dd, J ¼ 3.9,
5.1 Hz, 1 thienyl-H), 7.90 (dd, J ¼ 0.9, 3.9 Hz, 1 thienyl-H), 8.00
(ddd, J ¼ 1.3, 5.1 Hz, 1 thienyl-H), 8.75 (d, J ¼ 0.6 Hz, 1 ¼C–
H)ppm;13C NMR(75.5 MHz, CDCl3):ꢀ ¼ 28.1(N–CH3), 28.9
(N–CH3), 110.6 (¼C–H), 128.2, 136.9, 141.8, 145.4 (thienyl-
C), 151.3 (C¼O), 161.7 (C¼O), 162.6 (C¼O) ppm; MS (EI,
70eV): m=z (%) ¼ 250 (100) [M]þ, 143 (27), 108 (13).
7.05Hz, 3OCH2CH3), 2.14 (m, 2 6-H), 3.30 (s, 3N–CH3),
3.43 (s, 3N–CH3), 3.64 (dq, J ¼ 7.05, 9.6 Hz, 1OCH2CH3),
3.77 (s, 3OCH3), 3.97 (dq, J ¼ 7.05, 9.5 Hz, 1OCH2CH3),
4.12 (dd, J ¼ 4.8, 5.4Hz, 1 5-H), 5.17 (dd, J ¼ 3.9, 6.9 Hz, 1
7-H), 6.84 (ddd, J ¼ 1.8, 3.0, 8.7 Hz, 2ArH), 7.08 (ddd, J ¼ 1.8,
3.0, 8.4 Hz, 2ArH) ppm; 13C NMR (75.5 MHz, CDCl3): ꢀ ¼
15.1 (OCH2CH3), 27.9 (N–CH3), 28.6 (N–CH3), 33.3 (C-6),
36.0 (C-5), 55.2 (OCH3), 65.9 (OCH2CH3), 88.7 (C-4a), 101.5
(C-7), 114.1, 128.1, 135.6, 151.3 (ArC), 155.2 (C-8a), 158.3
(C¼O), 162.1 (C¼O) ppm; MS (EI, 70eV): m=z (%) ¼ 346
(95) [M]þ, 300 (63), 273 (100), 243 (10), 134 (14), 73 (17).
Procedures for the synthesis of pyrano[2,3-d]pyrimidine-2,4-
diones 3a–3h
A solution of 4 mmol 1a–1f in 50cm3 anh. CH2Cl2 and
40mmol enol ethers 2a–2c (10 equivalents) was kept at room
temperature for the time given in Table 1. The progress of the
reactions was monitored by TLC. The solvent and excess of
ethers were evaporated and the mixture was separated and
purified by column chromatography on silica gel using t-butyl
methyl ether (3a–3g) or t-butyl methyl ether=methanol ¼
3=1 (3h) as an eluent. Recrystallization from t-butyl methyl
ether (3a–3g) or t-butyl-methyl ether=methanol¼ 4=1 (3h)
gave 3a–3h with yields listed in Table 1.
One-pot synthesis: Equimolar amounts (4mmol) of N,N-
dimethylbarbituric acid (4) and aromatic aldehydes 5a–5f
were mixed with a ten-fold excess of enol ethers 2a–2c
(40 mmol) in 50 cm3 anh. CH2Cl2 in the presence of 2 drops
of piperidine at room temperature for the time given in Table 2.
The progress of the reactions was monitored by TLC. The
solvent and excess of ethers were evaporated and the mixture
was separated and purified by column chromatography on
silica gel and recrystallized. Products 3a–3h were obtained
with yields listed in Table 2.
(5RS,7SR)-1,5,6,7-Tetrahydro-7-isobutoxy-5-(4-methoxy-
phenyl)-1,3-dimethyl-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-
dione (cis-3b, C20H26N2O5)
Colorless crystals; mp 121ꢁC; yield 67%; IR (KBr): ꢁꢀ¼ 2956,
2911, 2876 (CH), 1707, 1641 (C¼O), 1240, 1175, 1128 (C–O)
cmꢀ1; 1H NMR (300MHz, CDCl3): ꢀ ¼ 0.80 (d, J ¼ 6.6 Hz, 6
OCH2CH(CH3)2), 1.75 (m, J ¼ 6.6Hz, 1OCH2CH(CH3)2),
2.18 (ddd, J ¼ 5.4, 5.4, 14.1 Hz, 1 6-H), 2.33 (ddd, J ¼ 2.7,
7.2, 14.1Hz, 1 6-H), 3.28 (s, 3N–CH3), 3.29 (dd, J ¼ 6.6,
9.0 Hz, 1OCH2CH(CH3)2), 3.42 (s, 3N–CH3), 3.60 (dd,
J ¼ 6.6, 9.0 Hz, 1OCH2CH(CH3)2), 3.76 (s, 3OCH3), 4.01
(dd, J ¼ 5.7, 7.2Hz, 1 5-H), 5.33 (dd, J ¼ 2.7, 4.8 Hz, 1 7-H),
6.77 (ddd, J ¼ 2.1, 3.0, 8.7 Hz, 2ArH), 7.09 (ddd, J ¼ 1.8, 3.0,
8.4 Hz, 2ArH) ppm; 13C NMR (75.5 MHz, CDCl3): ꢀ ¼ 19.0
(OCH2CH(CH3)2), 27.9 (N–CH3), 28.3 (OCH2CH(CH3)2),
28.6 (N–CH3), 33.2 (C-6), 35.9 (C-5), 55.2 (OCH3), 77.2
(OCH2CH(CH3)2), 89.7 (C-4a), 102.8 (C-7), 113.5, 128.0,
135.6, 151.3 (ArC), 154.9 (C-8a), 157.8 (C¼O), 162.1
(C¼O) ppm; MS (EI, 70 eV): m=z (%) ¼ 374 (75) [M]þ, 300
(69), 289 (19), 274 (100), 243 (8), 134 (14), 73 (64).
(5RS,7SR)-7-Ethoxy-1,5,6,7-tetrahydro-5-(4-methoxyphenyl)-
1,3-dimethyl-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(cis-3a, C18H22N2O5)
(5RS,7RS)-1,5,6,7-Tetrahydro-7-isobutoxy-5-(4-methoxy-
phenyl)-1,3-dimethyl-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-
dione (trans-3b, C20H26N2O5)
Colorless crystals; mp 120ꢁC; yield 68%; IR (KBr): ꢁꢀ¼ 2974,
Colorless crystals; mp 143ꢁC; yield 26%; IR (KBr): ꢁꢀ¼ 2955,
2940, 2888 (CH), 1707, 1652 (C¼O), 1247, 1177, 1131 (C–O)
2899, 2870, 2831 (CH), 1708, 1648 (C¼O), 1252, 1158, 1106
1
cmꢀ1; H NMR (300MHz, CDCl3): ꢀ ¼ 1.17 (t, J ¼ 7.05Hz,
(C–O) cmꢀ1
;
1H NMR (300MHz, CDCl3): ꢀ ¼ 0.90 (d,
3H, OCH2CH3), 2.13 (ddd, J ¼ 5.7, 6.0, 14.1Hz, 1H, 6-H), 2.34
(ddd, J ¼ 2.7, 7.2, 14.1Hz, 1H, 6-H), 3.27 (s, 3H, N–CH3), 3.43
(s, 3H, N–CH3), 3.61 (dq, J ¼ 7.2, 9.3 Hz, 1H, OCH2CH3), 3.76
(s, 3H, OCH3), 3.89 (dq, J ¼ 7.2, 9.3 Hz, 1H, OCH2CH3), 4.00
(dd J ¼ 6.6, 6.9Hz, 1H, 5-H), 5.35 (dd, J ¼ 2.7, 5.4Hz, 1H, 7-
H), 6.78 (ddd, J ¼ 1.8, 3.0, 9.0 Hz, 2H, ArH), 7.10 (ddd, J ¼ 1.8,
3.0, 8.4 H, 2H, ArH) ppm; 13C NMR (75.5 MHz, CDCl3):
ꢀ ¼ 14.9 (OCH2CH3), 27.9 (N–CH3), 28.7 (N–CH3), 33.7 (C-
6), 36.3 (C-5), 55.2 (OCH3), 65.5 (OCH2CH3), 90.0 (C-4a),
102.4 (C-7), 113.5, 128.2, 135.7, 151.3 (ArC), 154.9 (C-8a),
157.9 (C¼O), 162.1 (C¼O) ppm; MS (EI, 70 eV): m=z (%) ¼
300 (10) [M]þ, 300 (5), 273 (10), 134 (2), 73 (100).
J ¼ 6.6Hz, 6OCH2CH(CH3)2), 1.88 (m, J ¼ 6.6 Hz, 1OCH2-
CH(CH3)2), 2.15 (m, 2 6-H), 3.30 (s, 3N–CH3), 3.34 (dd,
J ¼ 6.6, 9.0 Hz, 1OCH2CH(CH3)2), 3.42 (s, 3N–CH3), 3.66
(dd, J ¼ 6.6, 9.3 Hz, 1OCH2CH(CH3)2), 3.77 (s, 3OCH3),
4.12 (dd, J ¼ 4.8, 5.4 Hz, 1 5-H), 5.16 (dd, J ¼ 3.0, 7.5 Hz, 1
7-H), 6.84 (d, J ¼ 8.7 Hz, 2ArH), 7.08 (d, J ¼ 8.7 Hz, 2ArH)
ppm; 13C NMR (75.5 MHz, CDCl3): ꢀ ¼ 19.1 (OCH2-
CH(CH3)2), 27.9 (N–CH3), 28.4 (OCH2CH(CH3)2), 28.6
(N–CH3), 33.2 (C-6), 36.0 (C-5), 55.2 (OCH3), 77.3
(OCH2CH(CH3)2), 88.7 (C-4a), 101.8 (C-7), 114.1, 128.1,
135.6, 151.4 (ArC), 155.2 (C-8a), 158.3 (C¼O), 162.1 (C¼O)
ppm; MS (EI, 70eV): m=z (%) ¼ 374 (79) [M]þ, 300 (74),
289 (21), 274 (100), 243 (9), 134 (14), 73 (31).
(5RS,7RS)-7-Ethoxy-1,5,6,7-tetrahydro-5-(4-methoxyphenyl)-
1,3-dimethyl-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(trans-3a, C18H22N2O5)
(5RS,7SR)-1,5,6,7-Tetrahydro-7-methoxy-5-(4-methoxy-
phenyl)-1,3,7-trimethyl-2H-pyrano[2,3-d]pyrimidine-
2,4(3H)-dione (cis-3c, C18H22N2O5)
Colorless crystals; mp 141ꢁC; yield 26%; IR (KBr): ꢁꢀ¼ 2982,
2944, 2906, 2890 (CH), 1699, 1646 (C¼O), 1243, 1190, 1150
Colorless crystals; mp 170ꢁC; yield 59%; IR (KBr): ꢁꢀ¼ 2999,
1
(C–O) cmꢀ1; H NMR (300 MHz, CDCl3): ꢀ ¼ 1.25 (t, J ¼
2946, 2872, 2836 (CH), 1699, 1639 (C¼O), 1248, 1182, 1055

1402
A. Pałasz
1
(C–O) cmꢀ1; H NMR (300MHz, CDCl3): ꢀ ¼ 1.56 (s, 3 7-
CH3), 2.17 (dd, J ¼ 7.2, 14.1 Hz, 1 6-H), 2.28 (dd, J ¼ 4.5,
14.1Hz, 1 6-H), 3.25 (s, 3 7-OCH3), 3.25 (s, 3N–CH3), 3.44
(s, 3N–CH3), 3.76 (s, 3 4-CH3O–C6H4), 3.99 (dd, J ¼ 4.5,
6.9 Hz, 1 5-H), 6.79 (d, J ¼ 8.7 Hz, 2ArH), 7.08 (d, J ¼
8.4 Hz, 2ArH) ppm; 13C NMR (75.5MHz, CDCl3): ꢀ ¼ 22.3
(7-CH3), 28.0 (N–CH3), 28.6 (N–CH3), 33.9 (C-6), 40.1 (C-
5), 49.6 (7-OCH3), 55.1 (4-CH3O–C6H4), 89.1 (C-4a), 105.5
(C-7), 113.5, 128.1, 135.7, 151.4 (ArC), 155.1 (C-8a), 157.8
(C¼O), 162.3 (C¼O) ppm; MS (EI, 70eV): m=z (%) ¼ 346
(28) [M]þ, 314 (9), 274 (100), 273 (79), 191 (19), 159 (9),
72 (8).
5.4 Hz, 1 5-H), 5.18 (dd, J ¼ 3.3, 7.2 Hz, 1 7-H), 7.16–7.34
(m, 5PhH) ppm; 13C NMR (75.5MHz, CDCl3): ꢀ ¼ 15.1
(OCH2CH3), 28.0 (N–CH3), 28.7 (N–CH3), 34.1 (C-6), 35.9
(C-5), 66.0 (OCH2CH3), 88.5 (C-4a), 101.5 (C-7), 126.7,
127.2, 128.7, 143.6 (PhC), 151.4 (C-8a), 155.3 (C¼O),
162.1 (C¼O) ppm; MS (EI, 70eV): m=z (%) ¼ 316 (100)
[M]þ, 287 (13), 270 (40), 259 (40), 243 (93), 186 (14), 161
(14), 115 (17), 72 (30).
(5RS,7SR)-7-Ethoxy-1,5,6,7-tetrahydro-1,3-dimethyl-5-(4-
nitrophenyl)-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(cis-3e, C17H19N3O6)
Colorless crystals; mp 141ꢁC; yield 60%; IR (KBr): ꢁꢀ¼ 2987,
(5RS,7RS)-1,5,6,7-Tetrahydro-7-methoxy-5-(4-methoxy-
phenyl)-1,3,7-trimethyl-2H-pyrano[2,3-d]pyrimidine-
2,4(3H)-dione (trans-3c, C18H22N2O5)
2956, 2893 (CH), 1707, 1639 (C¼O), 1516, 1343 (NO2),
1175, 1130, 1108 (C–O) cmꢀ1
;
1H NMR (300 MHz,
CDCl3): ꢀ ¼ 1.08 (t, J ¼ 7.05Hz, 3 OCH2CH3), 2.23 (ddd,
J ¼ 3.9, 4.2, 14.1Hz, 1 6-H), 2.39 (ddd, J ¼ 2.7, 7.5, 14.1Hz,
1 6-H), 3.30 (s, 3N–CH3), 3.45 (s, 3N–CH3), 3.56 (dq,
J ¼ 7.05, 9.3Hz, 1OCH2CH3), 3.83 (dq, J ¼ 7.05, 9.3Hz,
1OCH2CH3), 4.15 (dd, J ¼ 4.2, 7.5 Hz, 1 5-H), 5.45 (dd,
J ¼ 2.7, 3.9 Hz, 1 7-H), 7.35 (ddd, J ¼ 1.8, 2.4, 8.7 Hz,
2ArH), 8.11 (ddd, J ¼ 1.8, 2.4, 8.7Hz, 2ArH) ppm; 13C NMR
(75.5 MHz, CDCl3): ꢀ ¼ 14.8 (OCH2CH3), 28.0 (N–CH3),
28.8 (N–CH3), 33.4 (C-6), 34.6 (C-5), 65.6 (OCH2CH3),
88.1 (C-4a), 101.5 (C-7), 123.3, 128.4, 146.4, 151.1 (ArC),
151.6 (C-8a), 155.3 (C¼O), 162.2 (C¼O) ppm; MS (EI,
70eV): m=z (%) ¼ 361 (85) [M]þ, 332 (15), 304 (37), 288
(5), 206 (14), 84 (100), 72 (44).
Colorless crystals; mp 143ꢁC; yield 29%; IR (KBr): ꢁꢀ¼ 2999,
2947, 2872, 2836 (CH), 1699, 1639 (C¼O), 1247, 1182, 1055
1
(C–O) cmꢀ1; H NMR (300MHz, CDCl3): ꢀ ¼ 1.59 (s, 3 7-
CH3), 1.83 (dd, J ¼ 11.4, 14.1Hz, 1 6-H), 2.34 (dd, J ¼ 6.9,
14.1Hz, 1 6-H), 3.24 (s, 3 7-OCH3), 3.33 (s, 3N–CH3), 3.42
(s, 3N–CH3), 3.77 (s, 3 4-CH3O–C6H4), 3.97 (dd J ¼ 6.9,
11.4Hz, 1 5-H), 6.82 (d, J ¼ 8.4 Hz, 2ArH), 7.10 (d, J ¼
8.4 Hz, 2ArH) ppm; 13C NMR (75.5MHz, CDCl3): ꢀ ¼ 22.2
(7-CH3), 27.9 (N–CH3), 28.5 (N–CH3), 33.8 (C-6), 43.5 (C-
5), 50.0 (7-OCH3), 55.1 (4-CH3O–C6H4), 91.2 (C-4a), 104.0
(C-7), 114.0, 127.8, 136.0, 151.4 (ArC), 154.6 (C-8a), 158.0
(C¼O), 161.9 (C¼O) ppm; MS (EI, 70eV): m=z (%) ¼ 346
(30) [M]þ, 314 (8), 274 (100), 273 (80), 191 (19), 159 (10), 72 (6).
(5RS,7RS)-7-Ethoxy-1,5,6,7-tetrahydro-1,3-dimethyl-5-(4-
nitrophenyl)-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(trans-3e, C17H19N3O6)
(5RS,7SR)-7-Ethoxy-1,5,6,7-tetrahydro-1,3-dimethyl-5-
phenyl-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(cis-3d, C17H20N2O4)
Colorless crystals; mp 141ꢁC; yield 35%; IR (KBr): ꢁꢀ¼ 2987,
Colorless crystals; mp 164ꢁC; yield 60%; IR (KBr): ꢁꢀ¼ 3057,
2958, 2893 (CH), 1702, 1637 (C¼O), 1518, 1346 (NO2),
3021, 2978, 2887 (CH), 1702, 1631 (C¼O), 1178, 1132 (C–
1159, 1092 (C–O) cmꢀ1 1H NMR (300MHz, CDCl3):
;
O) cmꢀ1
;
1H NMR (300MHz, CDCl3): ꢀ ¼ 1.15 (t, J ¼
ꢀ ¼ 1.27 (t, J ¼ 7.05Hz, 3OCH2CH3), 2.05 (ddd, J ¼ 2.4,
6.6, 14.1 Hz, 1 6-H), 2.29 (ddd, J ¼ 6.3, 6.3, 14.1Hz, 1 6-
H), 3.27 (s, 3N–CH3), 3.44 (s, 3N–CH3), 3.68 (dq, J ¼ 7.05,
9.3 Hz, 1OCH2CH3), 3.94 (dq, J ¼ 7.05, 9.3Hz, 1OCH2CH3),
4.21 (t, J ¼ 6.6 Hz, 1 5-H), 5.27 (dd, J ¼ 2.4, 6.3Hz, 1 7-H),
7.37 (ddd, J ¼ 1.8, 2.4, 8.4 Hz, 2ArH), 8.17 (ddd, J ¼ 1.8, 2.4,
8.7 Hz, 2ArH) ppm; 13C NMR (75.5 MHz, CDCl3): ꢀ ¼ 15.0
(OCH2CH3), 28.0 (N–CH3), 28.8 (N–CH3), 33.9 (C-6), 35.9
(C-5), 66.0 (OCH2CH3), 88.2 (C-4a), 100.7 (C-7), 124.0,
128.0, 146.8, 151.2 (ArC), 151.7 (C-8a), 155.5 (C¼O),
162.0 (C¼O) ppm; MS (EI, 70eV): m=z (%) ¼ 361 (100)
[M]þ, 332 (17), 304 (42), 288 (6), 206 (16), 84 (20), 72 (53).
7.05Hz, 3OCH2CH3), 2.16 (ddd, J ¼ 6.0, 6.6, 14.1 Hz, 1 6-
H), 2.36 (ddd, J ¼ 2.7, 7.5, 14.1Hz, 1 6-H), 3.27 (s, 3N–CH3),
3.43 (s, 3N–CH3), 3.60 (dq, J ¼ 6.9, 9.3 Hz, 1OCH2CH3), 3.88
(dq, J ¼ 6.9, 9.6Hz, 1OCH2CH3), 4.05 (dd, J ¼ 6.6, 6.9Hz, 1
5-H), 5.35 (dd, J ¼ 2.7, 6.0 Hz, 1 7-H), 7.13–7.27 (m, 5PhH)
ppm; 13C NMR (75.5 MHz, CDCl3): ꢀ ¼ 14.9 (OCH2CH3),
27.9 (N–CH3), 28.7 (N–CH3), 34.4 (C-6), 36.1 (C-5), 65.5
(OCH2CH3), 89.7 (C-4a), 102.3 (C-7), 126.2, 127.3, 128.1,
143.5 (PhC), 151.3 (C-8a), 155.0 (C¼O), 162.1 (C¼O)
ppm; MS (EI, 70 eV): m=z (%) ¼ 316 (96) [M]þ, 287 (14),
270 (41), 259 (47), 243 (100), 186 (15), 161 (16), 115 (25),
72 (30).
(5RS,7SR)-7-Ethoxy-1,5,6,7-tetrahydro-1,3-dimethyl-5-(2-
thienyl)-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(cis-3f, C15H18N2O4S)
(5RS,7RS)-7-Ethoxy-1,5,6,7-tetrahydro-1,3-dimethyl-5-
phenyl-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione (trans-
3d, C17H20N2O4)
Colorless crystals; mp 120ꢁC; yield 47%; IR (KBr): ꢁꢀ¼ 2972,
Colorless crystals; mp 162ꢁC; yield 30%; IR (KBr): ꢁꢀ¼ 3057,
2930, 2893 (CH), 1704, 1633 (C¼O), 1490 (C¼C), 1272,
1
3019, 2977, 2891 (CH), 1700, 1629 (C¼O), 1177, 1149
1180, 1116 (C–O) cmꢀ1; H NMR (300MHz, CDCl3): ꢀ ¼
1
(C–O) cmꢀ1; H NMR (300 MHz, CDCl3): ꢀ ¼ 1.25 (t, J ¼
1.16 (t, J ¼ 7.05 Hz, 3OCH2CH3), 2.35 (dd, J ¼ 3.3, 6.0 Hz, 2
6-H), 3.31 (s, 3N–CH3), 3.41 (s, 3N–CH3), 3.61 (dq, J ¼ 7.05,
9.3 Hz, 1OCH2CH3), 3.86 (dq, J ¼ 7.05, 9.3Hz, 1OCH2CH3),
4.37 (t, J ¼ 6.0 Hz, 1 5-H), 5.43 (t, J ¼ 3.3 Hz, 1 7-H), 6.87 (m,
7.05Hz, 3OCH2CH3), 2.16 (m, 2 6-H), 3.30 (s, 3N–CH3),
3.43 (s, 3N–CH3), 3.64 (dq, J ¼ 7.05, 9.6 Hz, 1OCH2CH3),
3.97 (dq, J ¼ 7.05, 9.6 Hz, 1OCH2CH3), 4.17 (dd J ¼ 4.8,

One-pot synthesis of fused uracils
1403
2 thienyl-H), 7.07 (dd, J ¼ 1.8, 4.2 Hz, 1 thienyl-H) ppm;
13C NMR (75.5MHz, CDCl3): ꢀ ¼ 14.8 (OCH2CH3), 28.0
(N–CH3), 28.7 (N–CH3), 29.0 (C-6), 35.5 (C-5), 65.5
(OCH2CH3), 90.0 (C-4a), 101.6 (C-7), 122.9, 124.4, 126.2,
147.8 (thienyl-C), 151.2 (C-8a), 154.5 (C¼O), 162.1 (C¼O)
ppm; MS (EI, 70 eV): m=z (%) ¼ 322 (100) [M]þ, 276 (27),
265 (24), 250 (95), 167 (17), 136 (26), 108 (15), 73 (13).
(dd J ¼ 2.7, 6.0 Hz, 1 5-H), 5.37 (dd, J ¼ 2.4, 9.3 Hz, 1 7-
H), 6.07 (d, J ¼ 3.3 Hz, 1 furyl-H), 6.28 (dd, J ¼ 1.8, 3.3 Hz,
1 furyl-H), 7.31 (d, J ¼ 1.8 Hz, 1 furyl-H) ppm; 13C NMR
(75.5 MHz, CDCl3): ꢀ ¼ 15.1 (OCH2CH3), 27.9 (N–CH3),
28.4 (N–CH3), 28.6 (C-6), 32.4 (C-5), 66.1 (OCH2CH3),
86.8 (C-4a), 102.4 (C-7), 106.4, 110.4, 141.4, 151.2 (furyl-
C), 155.1 (C-8a), 155.6 (C¼O), 162.0 (C¼O) ppm; MS (EI,
70eV): m=z (%) ¼ 306 (100) [M]þ, 249 (23), 234 (52), 206
(29), 151 (13), 120 (19), 92 (12), 73 (9).
(5RS,7RS)-7-Ethoxy-1,5,6,7-tetrahydro-1,3-dimethyl-5-(2-
thienyl)-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(trans-3f, C15H18N2O4S)
(5RS,7SR)-7-Ethoxy-1,5,6,7-tetrahydro-1,3-dimethyl-5-(4-
pyridinyl)-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(cis-3h, C16H19N3O4)
Colorless crystals; mp 125ꢁC; yield 37%; IR (KBr): ꢁꢀ¼ 2973,
2943, 2904 (CH), 1705, 1630 (C¼O), 1501 (C¼C), 1165,
1
1094 (C–O) cmꢀ1; H NMR (300MHz, CDCl3): ꢀ ¼ 1.30 (t,
Colorless crystals; mp 152ꢁC; yield 61%; IR (KBr): ꢁꢀ¼ 3032,
J ¼ 7.05Hz, 3OCH2CH3), 2.14 (ddd, J ¼ 5.7, 9.3, 13.8Hz, 1 6-
H), 2.31 (ddd, J ¼ 2.7, 2.7, 13.8Hz, 1 6-H), 3.33 (s, 3N–CH3),
3.41 (s, 3N–CH3), 3.70 (dq, J ¼ 7.05, 9.6 Hz, 1OCH2CH3),
4.01 (dq, J ¼ 7.05, 9.3 Hz, 1OCH2CH3), 4.43 (dd J ¼ 2.7,
5.4 Hz, 1 5-H), 5.32 (dd, J ¼ 2.4, 9.3Hz, 1 7-H), 6.83 (dd,
J ¼ 1.2, 3.3 Hz, 1 thienyl-H), 6.93 (dd, J ¼ 3.6, 5.1 Hz, 1 thie-
nyl-H), 7.14 (dd, J ¼ 1.2, 5.1 Hz, 1 thienyl-H) ppm; 13C NMR
(75.5MHz, CDCl3): ꢀ ¼ 15.1 (OCH2CH3), 28.0 (N–CH3),
28.6 (N–CH3), 29.8 (C-6), 35.8 (C-5), 66.2 (OCH2CH3),
89.1 (C-4a), 102.0 (C-7), 123.7, 124.4, 127.0, 147.8 (thie-
nyl-C), 151.2 (C-8a), 155.0 (C¼O), 162.1 (C¼O) ppm; MS
(EI, 70eV): m=z (%) ¼ 322 (100) [M]þ, 276 (23), 265 (20),
250 (97), 167 (15), 136 (22), 108 (11), 73 (26).
2977, 2943, 2886 (CH), 1701, 1640 (C¼O), 1598 (C¼C),
1200, 1056 (C–O) cmꢀ1 1H NMR (300MHz, CDCl3):
;
ꢀ ¼ 1.03 (t, J ¼ 7.05Hz, 3OCH2CH3), 2.36 (ddd, J ¼ 2.7,
7.5, 14.4 Hz, 1 6-H), 2.26 (ddd, J ¼ 3.6, 3.9, 13.8Hz, 1 6-
H), 3.27 (s, 3N-CH3), 3.44 (s, 3N–CH3), 3.54 (dq, J ¼ 7.05,
9.3 Hz, 1OCH2CH3), 3.81 (dq, J ¼ 7.05, 9.3Hz, 1OCH2CH3),
4.04 (dd, J ¼ 3.9, 7.5 Hz, 1 5-H), 5.44 (dd, J ¼ 2.7, 3.6 Hz, 1 7-
H), 7.13 (dd, J ¼ 1.5, 4.5Hz, 2 pyridinyl-H), 8.46 (dd, J ¼ 1.5,
4.5 Hz, 2 pyridinyl-H) ppm; 13C NMR (75.5 MHz, CDCl3):
ꢀ ¼ 15.0 (OCH2CH3), 27.9 (N–CH3), 28.7 (N–CH3), 33.4
(C-6), 35.3 (C-5), 66.0 (OCH2CH3), 87.4 (C-4a), 100.9
(C-7), 122.4, 150.0, 151.1 (pyridinyl-C), 152.7 (C-8a), 155.5
(C¼O), 161.9 (C¼O) ppm; MS (EI, 70eV): m=z (%) ¼ 317
(100) [M]þ, 260 (20), 245 (16), 217 (24), 131 (12), 103 (14),
72 (5).
(5RS,7SR)-7-Ethoxy-5-(2-furyl)-1,5,6,7-tetrahydro-1,3-
dimethyl-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(cis-3g, C15H18N2O5)
(5RS,7RS)-7-Ethoxy-1,5,6,7-tetrahydro-1,3-dimethyl-5-(4-
pyridinyl)-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(trans-3h, C16H19N3O4)
Colorless crystals; mp 141ꢁC; yield 55%; IR (KBr): ꢁꢀ¼ 2977,
2949, 2901 (CH), 1705, 1642 (C¼O), 1485 (C¼C), 1179,
1
1056 (C–O) cmꢀ1; H NMR (300 MHz, CDCl3): ꢀ ¼ 1.19.(t,
Colorless crystals; mp 131ꢁC; yield 28%; IR (KBr): ꢁꢀ¼ 3031,
J ¼ 7.05Hz, 3OCH2CH3), 2.15 (ddd, J ¼ 3.0, 6.9, 14.1 Hz,
1 6-H), 2.51 (ddd, J ¼ 3.6, 3.9, 14.1Hz, 1 6-H), 3.33 (s,
3N–CH3), 3.39 (s, 3N–CH3), 3.55 (dq, J ¼ 7.05, 9.3 Hz,
1OCH2CH3), 3.80 (dq, J ¼ 7.05, 9.3 Hz, 1OCH2CH3), 4.15
(dd, J ¼ 3.9, 6.6 Hz, 1 5-H), 5.43 (t, J ¼ 3.3 Hz, 1 7-H), 5.93
(d, J ¼ 3.0Hz, 1 furyl-H), 6.25 (dd, J ¼ 1.8, 3.3Hz, 1 furyl-H),
7.26 (d, J ¼ 1.8 Hz, 1 furyl-H) ppm; 13C NMR (75.5 MHz,
CDCl3): ꢀ ¼ 14.7 (OCH2CH3), 26.9 (N–CH3), 28.0 (N–
CH3), 28.6 (C-6), 31.4 (C-5), 65.2 (OCH2CH3), 87.7 (C-4a),
101.3 (C-7), 105.0, 110.3, 140.2, 151.2 (furyl-C), 154.6 (C-
8a), 155.6 (C¼O), 162.2 (C¼O) ppm; MS (EI, 70eV): m=z
(%) ¼ 306 (100) [M]þ, 249 (21), 234 (46), 206 (27), 151 (12),
120 (16), 92 (10), 72 (5).
2979, 2943, 2888 (CH), 1702, 1645 (C¼O), 1593 (C¼C),
1
1196, 1056 (C–O) cmꢀ1; H NMR (300MHz, CDCl3): ꢀ ¼
1.27 (t, J ¼ 7.05Hz, 3OCH2CH3), 2.08 (ddd, J ¼ 2.4, 5.7,
13.8Hz, 1 6-H), 2.25 (ddd, J ¼ 6.0, 7.2, 13.8Hz, 1 6-H),
3.32 (s, 3N–CH3), 3.44 (s, 3N–CH3), 3.67 (dq, J ¼ 7.05,
9.3 Hz, 1OCH2CH3), 3.96 (dq, J ¼ 7.05, 9.3 Hz, 1OCH2CH3),
4.12 (dd, J ¼ 5.7, 6.0 Hz, 1 5-H), 5.20 (dd, J ¼ 2.4, 7.2 Hz, 1 7-
H), 7.12 (dd, J ¼ 1.5, 4.5Hz, 2 pyridinyl-H), 8.54 (dd, J ¼ 1.5,
4.5 Hz, 2 pyridinyl-H) ppm; 13C NMR (75.5 MHz, CDCl3):
ꢀ ¼ 14.7 (OCH2CH3), 27.9 (N–CH3), 28.7 (N–CH3), 32.6 (C-
6), 34.1 (C-5), 65.4 (OCH2CH3), 87.6 (C-4a), 101.3 (C-7),
122.7, 149.3, 151.1 (pyridyl-C), 152.6 (C-8a), 155.2 (C¼O),
162.1 (C¼O) ppm; MS (EI, 70eV): m=z (%) ¼ 317 (100)
[M]þ, 260 (27), 245 (23), 217 (15), 131 (17), 103 (21), 72 (14).
(5RS,7RS)-7-Ethoxy-5-(2-furyl)-1,5,6,7-tetrahydro-1,3-
dimethyl-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione
(trans-3g, C15H18N2O5)
1,5-Dihydro-1,3-dimethyl-5-thienyl-2H-pyrano[2,3-d]-
pyrimidine-2,4(3H)-dione (6e, C13H12N2O3S)
Colorless crystals; mp 125ꢁC; yield 32%; IR (KBr): ꢁꢀ¼ 2979,
Orange crystals; mp 195ꢁC; 21mg (2%); IR (KBr): ꢁꢀ¼ 2973,
2951, 2824 (CH), 1706, 1648 (C¼O), 1504 (C¼C), 1177,
2932, 2899 (CH), 1705, 1639 (C¼O), 1600, 1489 (C¼C)
1
1
1095 (C–O) cmꢀ1; H NMR (300MHz, CDCl3): ꢀ ¼ 1.30 (t,
cmꢀ1; H NMR (300MHz, CDCl3): ꢀ ¼ 3.34 (s, 3N–CH3),
J ¼ 7.05Hz, 3OCH2CH3), 2.03 (ddd, J ¼ 5.7, 9.3, 13.8 Hz,
1 6-H), 2.37 (ddd, J ¼ 2.4, 2.7, 13.8Hz, 1 6-H), 3.32 (s,
3N–CH3), 3.40 (s, 3N–CH3), 3.73 (dq, J ¼ 7.05, 9.6 Hz,
1OCH2CH3), 4.03 (dq, J ¼ 7.05, 9.3 Hz, 1OCH2CH3), 4.21
3.41 (s, 3N–CH3), 7.12 (d, J ¼ 15.0Hz, 1 5-H), 7.21 (dd, J ¼
3.9, 5.0 Hz, 1 thienyl-H), 7.77 (dd, J ¼ 1.2, 5.1 Hz, 1 thienyl-
H), 7.78 (dd, J ¼ 1.2, 3.9 Hz, 1 thienyl-H), 8.13 (d, J ¼
12.3Hz, 1 7-H), 8.36 (dd, J ¼ 12.0, 15.0 Hz, 1 6-H) ppm;

1404
A. Pałasz
13C NMR (75.5 MHz, CDCl3): ꢀ ¼ 28.0 (CH3), 28.5 (CH3),
98.7 (C-5), 117.7, 123.4, 123.9, 124.4, 127.5, 138.7, 148.0,
156.6 (C-4a, C-6, C-7, C-8a, thienyl-C), 159.0 (C-4), 160.2
(C-2) ppm; MS (EI, 70 eV): m=z (%) ¼ 267 (100) [M]þ, 161
(32), 115 (19).
12. Ahluvalia VK, Sharma HR, Tyagi R (1986) Tetrahdron
42:4045
13. Wamhoff H, Muhr J (1988) Synthesis:919
14. Ahluwalia VK, Kumar R, Khurana K, Batla R (1990)
Tetrahedon 46:3953
15. Hirota K, Kuki H, Maki Y (1994) Heterocycles 37:563
16. Srivastava P, Saxena AS, Ram VJ (2000) Synthesis:541
17. Devi I, Kumar BSD, Bhuyan PJ (2003) Tetrahedron Lett
44:8307
18. Devi I, Bhuyan PJ (2004) Tetrahedron Lett 45:7727
19. Devi I, Borah HN, Bhuyan PJ (2004) Tetrahedron Lett
45:2405
20. Naya S, Miyagawa M, Nitta M (2005) Tetrahedron
61:4919
21. Bogdanowicz-Szwed K, Pałasz A (1995) Monatsh Chem
126:1341
5-Furyl-1,5-dihydro-1,3-dimethyl-2H-pyrano[2,3-d]-
pyrimidine-2,4(3H)-dione (6f, C13H12N2O4)
Orange crystals; mp 199ꢁC; 19 mg (2%); IR (KBr): ꢁꢀ¼ 2978,
2951, 2903 (CH), 1706, 1645 (C¼O), 1599, 1485 (C¼C)
1
cmꢀ1; H NMR (300 MHz, CDCl3): ꢀ ¼ 3.38 (s, 3N–CH3),
3.39 (s, 3N–CH3), 6.56 (dd, J ¼ 1.5, 3.6 Hz, 1 furyl-H), 6.83
(d, J ¼ 3.6 Hz, 1 furyl-H), 7.17 (d, J ¼ 15.3Hz, 1 5-H), 7.61
(d, J ¼ 1.5 Hz, 1 furyl-H), 8.13 (d, J ¼ 12.3Hz, 1 7-H), 8.41
(dd, J ¼ 12.3, 15.3Hz, 1 6-H) ppm; 13C NMR (75.5 MHz,
CDCl3): ꢀ ¼ 28.0 (CH3), 28.4 (CH3), 96.8 (C-5), 102.4,
113.4, 117.7, 123.4, 138.7, 146.8, 156.5, 156.6 (C-4a, C-6,
C-7, C-8a, furyl-C), 158.5 (C-4), 160.0 (C-2) ppm; MS (EI,
70eV): m=z (%) ¼ 260 (100) [M]þ, 145 (29), 115 (21).
22. Bogdanowicz-Szwed K, Pałasz A (1997) Monatsh Chem
128:1157
23. Bogdanowicz-Szwed K, Pałasz A (1999) Monatsh Chem
130:795
24. Bogdanowicz-Szwed K, Pałasz A (2001) Z Naturforsch
56b:416
25. Bogdanowicz-Szwed K, Pałasz A (2001) Monatsh Chem
132:393
26. Pałasz A (2005) Org Biomol Chem 3:3207
27. Tietze LF, Meier H, Nutt H (1989) Chem Ber 122:643
28. Tietze LF, Stegelmeier H, Harms K, Brumby T (1982)
Angew Chem Int Ed Engl 21:863
29. Tietze LF, Brumby T, Brand S, Bratz M (1988) Chem Ber
121:499
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