Regioisomeric synthesis of dihydrofuro[2,3-d]pyrimidines in a diastereoselective manner involving nitrogen ylides in one-pot three-component reaction

Article abstract of DOI:10.1016/j.tet.2016.08.084

Synthesized some novel regioisomers of furo[2,3-d]pyrimidines in a diastereoselective manner via one-pot three-component reaction of barbituric acids, aryl aldehydes and pyridinium bromides in the presence of triethylamine as base. Both the isomers were obtained in comparable ratio with excellent overall yield.

Full text of DOI:10.1016/j.tet.2016.08.084

Accepted Manuscript
Regioisomeric synthesis of dihydrofuro[2,3-d]pyrimidines in a diastereoselective
manner involving nitrogen ylides in one-pot three-component reaction
Leema Dutta, Meenakshi Sharma, Pulak J. Bhuyan
PII:
S0040-4020(16)30879-1
10.1016/j.tet.2016.08.084
TET 28065
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 23 April 2016
Revised Date: 29 August 2016
Accepted Date: 30 August 2016
Please cite this article as: Dutta L, Sharma M, Bhuyan PJ, Regioisomeric synthesis of
dihydrofuro[2,3-d]pyrimidines in a diastereoselective manner involving nitrogen ylides in one-pot three-
component reaction, Tetrahedron (2016), doi: 10.1016/j.tet.2016.08.084.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Leave this area blank for abstract info.
Regioisomeric Synthesis of Dihydrofuro[2,3-d]-
pyrimidines in a Diastereoselective manner Involving
Nitrogen Ylides in One-pot Three-component Reaction
Leema Dutta, Meenakshi Sharmaa and Pulak J Bhuyan*
Medicinal Chemistry Division,CSIR-North East Institute of Science and Technology, Jorhat-785006, Assam, India.
aAcSIR, New Delhi
O
O
O
R2
Ar
R1
R1
O
Et3N
N
R1
O
N
N
ArCHO
Br
R2
Ar
N
O
N
CH3
1
O
O
O
CH3CN
reflux
N
CH3
N
CH3
R2
5
2
3
4

Tetrahedron
1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Regioisomeric Synthesis of Dihydrofuro[2,3-d]pyrimidines in a
Diastereoselective manner Involving Nitrogen Ylides in
One-pot Three-component Reaction
Leema Dutta, Meenakshi Sharmaa and Pulak J Bhuyan*
a
Medicinal Chemistry Division, CSIR-North-East Institute of Science & Technology, Jorhat 785006, Assam, India. AcSIR, New
Delhi
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Synthesized some novel regioisomers of furo[2,3-d]pyrimidines in a diastereoselective
manner via one-pot three-component reaction of barbituric acids, aryl aldehydes and
pyridinium bromides in the presence of triethylamine as base. Both the isomers were
obtained in comparable ratio with excellent overall yield.
Available online
Keywords:
Pyrimidine,
2015 Elsevier Ltd. All rights reserved
.
Furo[2,3-d]pyrimidines,
Aldehyde,
Pyridinium bromide
Pyridinium ylide
1. Introduction
application for the synthesis of dihydrofuran and its annelated
derivatives which produced the desired compounds in a
diastereosective manner.13
Furopyrimidines,
particularly
furo[2,3-d]pyrimidines
represent a very important class of compounds that possess
wide range of biological activities such as antibacterial,1
antifungal,2 antitumor,3 antiviral,4 antifolate5 and anti-human
cytomegalovirus activity.6 Compounds with this molecular
motif are also active on blood circulatory system7 and
stimulate the skin preparative regeneration.8 In view of the
vast biological activities and importance to pharmaceutical
discovery research, considerable attention has been diverted
towards the synthesis and molecular manipulation of furo[2,3-
d]pyrimidines. Furo[2,3-d]pyrimidines are usually prepared
either from suitably functionalized furan ring9 by generating
the pyrimidine ring on the parent furan ring or from a
pyrimidine derivative by constructing a furan ring on the
parent pyrimidine ring.10 Very recently, an excellent review
was published describing various synthetic routes for
furopyrimidines, particularly furo[2,3-d]pyrimidines.11
In continuation of our work on pyrimidines,14 in the present
paper, we report an unprecedented regioisomeric synthesis of
some highly functionalized dihydrofuro[2,3-d]pyrimidines 4
and 5 in diastereoselective manner from one-pot three-
components reaction of barbituric acids 1, aryl aldehydes 2
and pyridinium bromides 3 in the presence of triethylamine as
base (Scheme 1). During the reaction, nitrogen ylides were
formed and involved in [4+1] annulation as well as [2+1]
annulation processes which after intramolecular ring
transformation produced the two regioisomeric products.
Synthesis of dihydrofuro[2,3-d]pyrimidines 4 and 5
O
R1
N
ArCHO
Br
N
O
N
O
R2
3
2
CH3
1
Nitrogen ylides represent an important class of nucleophilic or
bifunctional reagents which can undergo cyclization,
olefination, rearrangement reactions etc, and hence have wide
application for the construction of diverse carbocyclic and
heterocyclic compounds of synthetic and biological
significance.12 In this regard, pyridinium ylides have extensive
CH3CN
reflux
Et3N
Ar
R2
O
O
R1
R1
N
N
Ar
R2
O
O
N
O
O
N
____________________
*Corresponding author.
E-mail: pulak_jyoti@yahoo.com
CH3
CH3
4a-o
5a-o
Scheme 1

2
Tetrahedron
ACCEPTED MANUSCRIPT
2. Results and Discussion
Increase in the load of the catalyst beyond 1.2 mmol did not
improve the yield of the products (Entry 7). The model
reaction was initiated with the preparation of
benzylpyridinium bromide 3 (R2 = COPh) from the reaction
of phenacyl bromide and pyridine in ethyl acetate at room
temperature following the existing reaction procedure.15
The study was initiated by performing the three-component
reaction of N,N-dimethylbarbituric acid 1 (R1 = Me),
benzaldehyde 2 (Ar = Ph) and benzylpyridinium bromide 3
(R2 = COPh) in various solvents and base to determine the
optimal condition for the model reaction. Among the solvents
viz water, ethanol, DMSO, dichloromethane and acetonitrile,
the acetonitrile was found to be most effective. The reaction
did not proceed in water as barbituric acid derivative 1 (R1 =
Me) was not soluble in the solvent. The model reaction was
also investigated employing different bases viz. Et3N, DBU
and K2CO3. The results were summarized in Table 1. It was
found that the reaction in acetonitrile and use of 1.2 mmol of
Et3N as base furnished the maximum yield of the two
products 4a and 5a in less time duration in comparison to
others (Entry 6). Therefore, all subsequent reactions were
carried out under this reaction condition only. While,
equimolar amount of the base is required just for the
formation of the ylide from pyridinium salt, we observed that,
the reaction proceeded in the presence of equimolar amount of
the base providing very low yield of the products (Entry 5),
and that indicated simultaneous formation of the ylide and the
products in the reaction process.
Table 2a: Synthesis of dihydrofuro[2,3-d]pyrimidines 4 and 5
O
O
R2
O
Ar
R1
O
R1
O
N
R1
O
Et3N
N
N
ArCHO
Br
R2
Ar
N
N
CH3
1
O
O
O
CH3CN
reflux
N
CH3
N
CH3
R2
5
2
3
4
Ent. R1
Ar
R2
Prod. Time Yieldb
(h)
%
1
2
3
4
5
6
7
8
9
CH3 C6H5
COPh
COPh
COPh
COPh
COPh
COPh
4a
5a
4b
5b
4c
5c
4d
5d
4e
5e
4f
4
40
38
36
33
45
42
43
40
42
40
35
32
40
36
32
28
36
34
44
40
42
39
41
39
33
30
37
34
38
35
CH3 p-CH3-C6H4
CH3 p-NO2-C6H4
CH3 p-Cl-C6H4
CH3 p-Br-C6H4
4.5
2.5
3.5
3.5
5
Table 1a: Optimisation of solvent and base
O
O
COPh
Ph
O
Ph
COPh
H3C
O
H3C
O
N
Base H3C
N
N
PhCHO
Br
N
N
CH3
1
O
O
O
N
CH3
Solvent
O
N
CH3
COPh
reflux,80oC
H
C6H5
4a
5a
2
3
5f
Entry
Solvent
Base
(1.20 mmol)
Time Product Yield%***
(h)
CH3 C6H5
COOEt 4g
5
5g
Water
Et3N
10
7
0
1
2
NR
4a
5a
4a
5a
4a
5a
4a
5a
4a
5a
4a
5a
4a
5a
4a
5a
CH3 p-OCH3-C6H4
CH3 p-CH3-C6H4
COOEt 4h
6
DMSO
Et3N
22
18
14
12
13
11
12
10
40
38
36
33
15
12
23
19
5h
COOEt 4i
6
C2H5OH
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Et3N
Et3N
8
5
3
4
5
6
7
8
9
5i
COOEt 4j
5j
10 CH3 p-NO2-C6H4
11 CH3 p-Cl-C6H4
12 CH3 p-Br-C6H4
3h
4
COOEt 4k
5k
Et3N*
Et3N
4
COOEt 4l
5l
4.5
6
4
13
H
C6H5
COOEt 4m
5m
Et3N**
K2CO3
DBU
4
14 CH3 C6H5
CN
4n
5n
4o
5o
3.5
3
10
8
15 CH3 p-Cl-C6H4
CN
Ent. = Entry, Prod. = Product,
aReaction conditions: Substituted Barbituric acid 1 (1mmol), Aryl
aldehyde 2 (1mmol), Pyridinium ylide 3 (1mmol), Et3N (1.20 mmol),
CH3CN (5ml), bisolated yield
aReaction conditions: N,N-dimethyl barbituric acid (1mmol),
benzaldehyde (1mmol), benzyl pyridinium bromide (1mmol)
*1 mmol; **1.5 mmol; *** isolated yield

Tetrahedron
3
ACCEPTED MANUSCRIPT
The benzylpyridinium bromide 3 (R2 = COPh) so obtained
was treated with N,N-dimethylbarbituric acid 1 (R1 = Me) and
benzaldehyde 2 (Ar = Ph) in one-pot three-component
reaction protocol in refluxing acetonitrle in the presence
of triethylamine as base. The progress of the reaction was
monitored by TLC which indicated the formation of two
products. The reaction was allowed to reflux for 4 hours till
the completion of the reaction. The solvent was removed
under reduced pressure and the compounds were separated by
chromatographic methods and isolated the expected
dihydrofuro[2,3-d]pyrimidines 4a (Ar = Ph, R2 = COPh)
along with unexpected regeoisomeric compound 5a (Ar = Ph,
R2 = COPh) in 40% & 38 % yield respectively in a
diastereoselective manner. The generality of the reaction was
established by synthesizing the compounds 4a-o and 5a-o by
utilizing various substituted barbituric acids 1, aryl aldehydes
2 and pyridinium salts 3 and characterizing them (Table 2).
The structures of the compounds were ascertained from the
spectroscopic data and elemental analysis. As for example, in
the 1H NMR spectra, the two protons at 2,3-positions of
dihydrofuran ring of compound 4a (Entry 1) display two
doublets at δ 4.04 and 4.19 with the vicinal coupling constant
J = 9.5 Hz. It is well recognized that stereochemical relations
among vicinal protons in fused dihydrofurans cannot be
reliably determined by simply measuring coupling constants
e.g. changing the size of the substituent at the dihydrofuran
Then we studied the effect of substituent of the substrates in
the reaction process. It was observed that the reaction requires
2-6 h in refluxing conditions depending upon the substituent
on aryl aldehyde and pyridinium ylide to afford the desired
compounds. Since aromatic aldehydes are more reactive than
aliphatic towards nucleophillic attack, hence more emphasis
was given on aryl aldehyde. The reactions were smooth and
easy in aldehydes having electron withdrawing substituent
(NO2, Cl, Br) in comparison to electron releasing substituent
(H, CH3) and also provide better yield of the products in less
reaction time.
Mechanism for the formation of dihydrofuro[2,3-d]-
pyrimidines 4a and 5a
O
Ph
O
O
H3C
O
H3C
O
Et3N
N
N
PhCHO
N
N
O
CH3
CH3
[A]
1
2
Et3N
CH3CN
Br
N
N
COPh
COPh
3
[B]
Ph
O
Ph
O
N
N
H3C
H3C
ring of benzodihydrofurans causes a reversal in the value of
N
N
16
COPh
Jcis and Jtrans
.
In view of that, the NOESY NMR spectra of
O
Ph
O
[A]
N
CH3
O
[B]
O
N
CH3
O
the compound was studied properly where the two protons
showed no corelation, and hence it was concluded that the
product 4a was trans dihydrofuro[2,3-d]pyrimidines. In
[C]
Path II
-Py
Path I
1
contrary, H NMR spectra of the other compound (Entry 1)
Base
O
Ph
showed two protons of the dihydrofuran ring as two doublets
at δ 5.16 (J = 5.5) and 6.04 (J = 5.5) ppm respectively which
indicates the formation of isomeric dihydrofuro[2,3-
d]pyrimidine compound 5a. The study of the NOESY NMR
spectra confirmed the formation of the cis form of the
compound 5a as the two protons showed strong correlation in
the spectra. The formation of these cis and trans forms of
regioisomeric compounds are in contrary to many other
reactions which produced exclusively one regioisomer of the
fused dihydrofuran derivatives, and usually the trans form
with coupling constants in the range of J = 4-6 Hz.18 In our
present case, it might be because of the unique nonplanner
structure of the substituted uracil moiety. In IR spectrum,
stretching frequencies at 1687.2, 1557.6 cm-1 of 4a and
1685.4, 1560.2 cm-1 of 5a confirmed the presence of the furan
ring and amide C=O functional groups in both the
O
O
Ph
H
H3C
H3C
O
N
N
N
N
COPh
O
N
O
O
N
Ph
CH3
CH3 [C]
[D]
-Py
Ph
O
Ph
O
H3C
O
H3C
O
N
O
COPh
O
N
CH3
4a
N
CH3
O Ph
[E]
Ph
Ph
O
O
O
H3C
O
O
H3C
O
N
N
Ph
Ph
compounds. The mass spectrum shows,
a
sharp
N
O
N
O
distinguishable peak of compound 4a and 5a at 363.41
[M+H]+ and 363.32 [M+H]+ respectively. Interestingly, even
though we considered the formation of the compound 5 as
unexpected, a literature survey revealed one example which
reported the formation of exclusively this type of isomeric
compounds (two compounds only) by using sulfur ylides, and
our product 5h was found to be comparable in all respect to
one of that compounds.17 Again, although the compound 4a
was the usual expected product from the reaction of nitrogen
ylides, the formation of the unexpected product 5a in a
comparable ratio might be because of the typical nonplanner
structure of pyrimidinedione moiety.
CH3
CH3
[F]
Scheme 2
5a
To expand the scope of the reaction, different pyridinium
ylides were generated from various pyridinium salts viz.
phenacyl pyridinium bromide, 1-ethoxy carbonyl methyl
pyridinium iodide19 and 1-cyanomethyl pyridinium bromide,20
and utilized during the course of the study. Benzylpyridinium
ylide obtained from benzylpyridinium bromide was most
effective which may be accounted from the mechanism that
interprets the resonance stabilization of enolate ion by phenyl

4
Tetrahedron
ACCEPTED MANUSCRIPT
group. The reaction with 1-cyanomethyl pyridinium ylide was
not smooth, and provided less yields even on increasing the
reaction time, hence we have limited our experiment with this
ylide.
performed on Perkin-Elmer 2400 spectrometer at the
Analytical Chemistry Division, CSIR-NEIST, Jorhat.
General Procedure for preparation of dihydrofuro[2,3-
d]pyrimidines 4 & 5: A mixture of N,N-dimethylbarbituric
acid 1 (R1 = Me, 156 mg, 1mmol), benzaldehyde 2 (Ar = Ph,
106 mg, 1mmol) and benzylpyridinium 3 (R2 = COPh, 278
mg, 1mmol) in acetonitrile (5 mL) were taken in round
bottom flask. Triethyl amine (121 mg, 1.20 mmol) were
added to the reaction mixture and allowed to reflux for 4 h at
80 ˚C. The solvent was removed under reduced pressure, and
the crude products were purified by column chromatography
(silica gel 100-200#, petroleum ether/ethyl acetate, 9:1 ratio),
which afforded the desired dihydrofuro[2,3-d]pyrimidine
derivatives 4a and 5a in 40% (144 mg) and 38% (137 mg)
respectively.
The effect of substituents in barbituric acids was also studied
properly and observed that N,N-dimethylbarbituric acid was
more reactive than N-methylbarbituric acid and products were
obtained in better yield in less reaction time. Moreover, in
case of N-methylbarbituric acid, selectively the more favoured
N-methyl amidic carbonyl group involved in the cyclization
process to produce only the two regioisomeric
dihydrofuro[2,3-d]pyrimidines (Entry 6 & 13, Table 2) as
expected, and such selectivity is well precedented.21
A
reasonable mechanism for the formation of the
regioisomers is depicted in the scheme 2 taking the formation
of 4a and 5a as example. The reaction occurred via initial
formation of the knoevenagel condensed product [A] from the
reaction of N,N-dimethylbarbituric acid 1 (R1 = Me) and
benzaldehyde 2 (Ar = Ph), and the ylide [B] from the
benzylpyridinium bromide 3 (R2 = COPh) in the presence of
triethyl amine (Scheme 2). The intermediates [A] and [B] then
reacted to produce the intermediate [C] which followed two
different reaction path to afford the product 4a & 5a
respectively. In path I, the intermediate [C] produced the
compound 4a by a direct cyclization process by eliminating
pyridine. But in path II, first, intermediate [D] with the
cyclopropane ring was formed, which underwent an
intramolecular ring transformation, and proceeded through the
intermediates [E] and [F] in the presence of base to produce
the product 5a. The mechanism for the formation of both
types of compounds from ylides is well documented.13c,17
Similarly, compounds 4b-o and 5b-o were synthesized and
characterized.
6-Benzoyl-1,3-dimethyl-5-phenyl-5,6-dihydrofuro[2,3-d]-
pyrimidine-2,4(1H,3H)-dione (4a): Yield: 144 mg (40%);
Yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2) 0.50; mp.
1
134.0-135.8 ˚C; H NMR (CDCl3, 500 MHz) δ 3.22 (s, 3H),
3.24 (s, 3H), 4.17 (d, J = 9.5 Hz, 1H), 4.26 (d, J = 9.5 Hz,
1H), 7.24-8.24 (m, 10H); 13C NMR (CDCl3, 125 MHz) δ 28.8,
29.0, 47.9, 87.4, 90.6, 128.1 (2C ), 128.3 (2C), 128.6 (2C),
128.8, 129.5 (2C), 131.0, 133.7, 136.0, 151.3, 163.4, 165.7,
191.2; IR (KBr, cm-1) νmax:1180.7, 1451.9, 1679.1, 2960.4;
MS (ESI): 363.4 [M+H]+; Anal. Cald. For C21H18N2O4: C,
69.60; H, 5.01; N, 7.73%. Found: C, 69.72; H, 5.02; N,
7.75%.
5-Benzoyl-1,3-dimethyl-6-phenyl-5,6-dihydrofuro-[2,3-d]-
pyrimidine-2,4(1H,3H)-dione (5a): Yield: 137 mg (38%);
Yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2) 0.32; mp.
In conclusion, we have reported an unprecedented
1
131.0.-132.1 ˚C; H NMR (CDCl3, 500 MHz) δ 3.19 (s, 3H),
regioisomeric synthesis of some
highly functionalized
3.32 (s, 3H), 5.16 (d, J = 5.5 Hz, 1H), 6.04 (d, J = 5.5 Hz,
1H), 7.18-8.02 (m, 10H); 13C NMR (CDCl3, 125 MHz) δ 27.9,
29.2, 53.9, 87.4, 89.7, 125.6 (2C), 128.9 (2C), 129.2 (2C),
129.2 (2C), 129.6, 133.1, 133.9, 135.7, 149.4, 159.4, 162.2,
191.5; IR (KBr, cm-1) νmax:1180.5, 1451.4, 1678.3, 2960.2;
MS (ESI): 363.3 [M+H]+; Anal. Cald. For C21H18N2O4: C,
69.60; H, 5.01; N, 7.73%. Found: C, 69.55; H, 5.03; N,
7.74%.
dihydrofuro[2,3-d]pyrimidines by generating nitrogen ylides
in an one-pot three-components reaction barbituric acids, aryl
aldehydes and pyridinium bromides in the presence of
triethylamine as base. The products were formed in a
diastereoselective manner and overall good yields. A suitable
mechanism is given for the reaction process which shows that
nitrogen ylides involve in [4+1] annulations as well as [2+1]
annulation followed by intramolecular ring transformation in
the presence of base to afford two isomeric products.
6-Benzoyl-1,3-dimethyl-5-(p-tolyl)-5,6-dihydrofuro-[2,3-d-
]pyrimidine-2,4(1H,3H)-dione (4b): Yield: 135 mg (36%);
Light yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2) 0.52;
4. Experimental Section
1
mp. 131.1.-133.6 ˚C; H NMR (CDCl3, 500 MHz) δ 2.17 (s,
All chemicals were purchased from Merck and Aldrich
chemical companies. The reagents and solvents were used
without drying. The IR spectra were recorded on Perkin
3H), 3.21 (s, 3H), 3.24 (s, 3H), 4.03 (d, J = 9.5 Hz, 1H), 4.20
(d, J = 9.5 Hz, 1H), 7.21-7.64 (m, 9H); 13C NMR (CDCl3, 125
MHz) δ 21.1, 28.8, 28.9, 46.7, 86.3, 90.1, 122.9, 128.1 (2C),
128.8 (2C),130.1, 131.1 (2C), 131.5 (2C), 133.8, 135.8, 151.1,
163.3, 165.4, 190.7; IR (KBr, cm-1) νmax: 1180.9, 1452.2,
1678.8, 2960.5; MS (ESI): 377.1 [M+H]+; Anal. Cald. For
C22H20N2O4: C, 70.20; H, 5.36; N, 7.44%. Found: C, 70.32;
H, 5.37; N, 7.42%.
1
Elmer system 2000 FTIR spectrometer. H NMR and 13C
NMR Spectra were recorded on Bruker AV500 Avance – III
500 MHz and 125 MHz FT NMR in CDCl3 using TMS as an
internal standard. Chemical shifts (δ units) are given from
TMS (0 ppm). Chemical shifts for CDCl3 were reported at
7.26 ppm (δ units). Mass spectra were recorded in Bruker
Daltonics ESQUIRE 3000 LC ESI ion trap mass
spectrometer. Analytical thin layer chromatography (TLC)
was performed using E-Merck aluminium-backed silica gel
plates coated with 0.2 mm thickness of silica gel. Melting
points (uncorrected) were determined in open capillary tubes
on a Buchi B-540 apparatus. Elemental analyses were
5-Benzoyl-1,3-dimethyl-6-(p-tolyl)-5,6-dihydrofuro-[2,3-d]-
pyrimidine-2,4(1H,3H)-dione (5b): Yield: 124 mg (33%);
Light yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2) 0.33;
1
mp. 130.2.-130.9 ˚C; H NMR (CDCl3, 500 MHz) δ 2.17 (s,
3H), 3.20 (s, 3H), 3.25 (s, 3H), 4.95 (d, J = 6 Hz, 1H), 5.82 (d,
J = 6 Hz, 1H), 7.18-7.62 (m, 9H); 13C NMR (CDCl3, 125

Tetrahedron
5
ACCEPTED MANUSCRIPT
MHz) δ 21.1, 28.7, 28.8, 45.6, 87.2, 90.3, 123.4, 128.2 (2C),
129.3 (2C),130.4, 131.0 (2C), 131.7 (2C), 133.8, 136.2, 150.4,
164.1, 165.2, 191.2; IR (KBr, cm-1) νmax: 1181.6, 1451.8,
1678.7, 2960.9; MS (EI): 377.3 [M+H]+; Anal. Cald. For
C22H20N2O4: C, 70.20; H, 5.36; N, 7.44%. Found: C, 70.18;
H, 5.34; N, 7.45%.
(s, 3H), 3.16 (s, 3H), 3.94 (d, J = 10.5 Hz, 1H), 4.15 (d, J =
10.5 Hz, 1H), 7.12-7.89 (m, 9H); 13C NMR (CDCl3, 125
MHz) δ 28.8, 28.9, 46.7, 87.3, 89.8, 122.9, 128.1 (2C), 128.8
(2C), 130.1, 131.1 (2C), 131.5 (2C), 133.8, 135.8, 151.2,
163.3, 165.4, 190.8; IR (KBr, cm-1) νmax: 1180.4, 1451.9,
1678.9, 2960.7; MS (ESI): 442.2 [M+H]+; Anal. Cald. For
C21H17BrN2O4: C, 57.16; H, 3.88; N, 6.35%. Found: C, 57.35;
H, 3.89; N, 6.33%.
6-Benzoyl-1,3-dimethyl-5-(p-nitro-phenyl)-5,6-dihydrofuro-
[2,3-d]pyrimidine-2,4(1H,3H)-dione (4c): Yield: 183.2 mg
(45%); Orange solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2) 0.47;
5-Benzoyl-1,3-dimethyl-6-(p-bromo-phenyl)-5,6-dihydrofuro-
[2,3-d]pyrimidine-2,4(1H,3H)-dione (5e): Yield: 176 mg
(40%); Light yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2)
0.32; mp. 137.2-138.8 ˚C; 1H NMR (CDCl3, 500 MHz) δ 3.12
(s, 3H), 3.28 (s, 3H), 4.72 (d, J = 6 Hz, 1H), 5.97 (d, J = 6 Hz,
1H), 7.08-7.88 (m, 9H); 13C NMR (CDCl3, 125 MHz) δ 29.5,
29.7, 53.7, 87.2, 89.7, 123.6, 127.4 (2C), 128.3 (2C), 128.7
(2C), 132.5 (2C), 134.2, 135.7, 136.9, 151.3, 159.4, 162.2,
197.7; IR (KBr, cm-1) νmax: 1180.2, 1452.0, 1678.4, 2960.8 ;
MS (ESI): 442.5 [M+H]+; Anal. Cald. For C21H17BrN2O4: C,
57.16; H, 3.88; N, 6.35%. Found: C, 57.25; H, 3.87; N,
6.36%.
1
mp. 151.5-153.8 ˚C; H NMR (CDCl3, 500 MHz) δ 3.20 (s,
3H), 3.22 (s, 3H), 4.15 (d, J = 9.5 Hz, 1H), 4.25 (d, J = 9.5
Hz, 1H), 7.22-8.28 (m, 9H); 13C NMR (CDCl3, 125 MHz) δ
29.0, 29.2, 41.1, 87.4, 90.3, 123.5 (2C), 127.9 (2C), 128.9
(2C), 130.5 (2C), 134.0, 135.6, 138.6, 147.8, 150.9, 163.3,
164.9, 190.1; IR (KBr, cm-1) νmax: 1180.6, 1451.4, 1678.1,
2960.3; MS (ESI): 408.3 [M+H]+; Anal. Cald. For
C21H17N3O6: C, 61.91; H, 4.21; N, 10.31%. Found: C, 62.00;
H, 4.22; N, 10.29%.
5-Benzoyl-1,3-dimethyl-6-(p-nitro-phenyl)-5,6-dihydrofuro-
[2,3-d]pyrimidine-2,4(1H,3H)-dione (5c): Yield: 171 mg
(42%); Orange solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2) 0.29;
6-Benzoyl-3-methyl-5-phenyl-5,6-dihydrofuro[2,3-d]-
1
mp. 149.2-150.9 ˚C; H NMR (CDCl3, 500 MHz) δ 3.24 (s,
pyrimidine-2,4(1H,3H)-dione (4f): Yield: 122 mg (35%);
Yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2) 0.49;
3H), 3.35 (s, 3H), 5.01 (d, J = 6 Hz, 1H), 6.01 (d, J = 6 Hz,
1H), 7.03-8.20 (m, 9H); 13C NMR (CDCl3, 125 MHz) δ 28.9,
29.5, 53.0, 80.3, 85.8, 123.5 (2C), 128.0 (2C), 128.9 (2C),
130.5 (2C), 133.9, 135.7, 138.6, 147.8, 151.5, 162.9, 164.9,
190.0; IR (KBr, cm-1) νmax: 1180.7, 1451.3, 1678.0, 2960.2;
MS (ESI): 408.5 [M+H]+; Anal. Cald. For C21H17N3O6: C,
61.91; H, 4.21; N, 10.31%. Found: C, 61.90; H, 4.20; N,
10.32%.
1
mp.137.5-138.1 ˚C; H NMR (CDCl3, 500 MHz) δ 3.13 (s,
3H), 4.03 (d, J = 9.5 Hz, 1H), 4.17 (d, J = 9.5 Hz, 1H), 7.12-
7.90 (m, 10H), 10.33 (s, 1H, NH); 13C NMR (CDCl3, 125
MHz) δ 28.7, 47.8, 87.2, 91.4, 128.3 (2C), 128.6 (2C), 129.1,
129.4 (2C), 129.6 (2C), 131.1, 133.4, 134.0, 152.4, 162.3,
165.8, 190.3; IR (KBr, cm-1) νmax: 1191.0, 1681.2, 1744.3,
2924.9; MS (ESI): 349.4 [M+H]+; Anal. Cald. For
C20H16N2O4: C, 68.96; H, 4.63; N, 8.04%. Found: C, 68.92;
H, 4.64; N, 8.05%.
6-Benzoyl-1,3-dimethyl-5-(p-chloro-phenyl)-5,6-dihydrofuro-
[2,3-d]pyrimidine-2,4(1H,3H)-dione (4d): Yield: 170.3 mg
(43%); Light yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2)
0.48; mp. 146.7-148.9 ˚C; 1H NMR (CDCl3, 500 MHz) δ 3.14
(s, 3H), 3.18 (s, 3H), 3.98 (d, J = 9.5 Hz, 1H), 4.15 (d, J = 9.5
Hz, 1H), 7.09-7.85 (m, 9H); 13C NMR (CDCl3, 125 MHz) δ
28.8, 28.9, 41.4, 86.7, 90.2, 128.1 (2C), 128.6 (2C), 128.8
(2C), 129.3. 131.2 (2C), 133.8, 134.6, 135.8, 151.2, 163.3,
165.4, 190.7; IR (KBr, cm-1) νmax: 1181.0, 1451.8, 1680.1,
2960.7; MS (ESI): 397.1 [M+H]+; Anal. Cald. For
C21H17ClN2O4: C, 63.56; H, 4.32; N, 7.06%. Found: C, 63.71;
H, 4.31; N, 7.07%.
5-Benzoyl-3-methyl-6-phenyl-5,6-dihydrofuro[2,3-d]-
pyrimidine-2,4(1H,3H)-dione (5f) : Yield: 112 mg (32%);
Yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2) 0.30; mp.
1
135.2-135.8 ˚C; H NMR (CDCl3, 500 MHz) δ 3.18 (s, 3H),
5.19 (d, J = 5.5 Hz, 1H), 6.03 (d, J = 5.5 Hz, 1H), 7.15-8.01
(m, 10H), 10.21 (s, 1H, NH); 13C NMR (CDCl3, 125 MHz) δ
27.8, 55.4, 87.3, 89.8, 125.6 (2C), 128.8 (2C), 129.0 (2C),
129.2 (2C), 129.7, 133.2, 133.9, 135.6, 149.5, 158.3, 162.3,
191.3; IR (KBr, cm-1) νmax:1191.6, 1680.8, 1743.6, 2925.5;
MS (ESI): 349.3 [M+H]+; Anal. Cald. For C20H16N2O4: C,
68.96; H, 4.63; N, 8.04%. Found: C, 68.99; H, 4.62; N,
8.03%.
5-Benzoyl-1,3-dimethyl-6-(p-chloro-phenyl)-5,6-dihydrofuro-
[2,3-d]pyrimidine-2,4(1H,3H)-dione (5d): Yield: 158 mg
(40%); Light Yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2)
0.31; mp. 139.9-142.8 ˚C; 1H NMR (CDCl3, 500 MHz) δ 3.27
(s, 3H), 3.41 (s, 3H), 5.18 (d, J = 5.5 Hz, 1H), 6.11 (d, J = 5.5
Hz, 1H), 7.21-7.62 (m, 9H); 13C NMR (CDCl3, 125 MHz) δ
28.0, 29.7, 53.8, 87.3, 89.8, 127.2 (2C), 128.7 (2C), 129.3
(2C), 129.4 (2C), 134.1, 135.6, 135.6, 136.3, 151.3, 159.3,
162.0, 197.8 ; IR (KBr, cm-1) νmax: 1180.5, 1450.7, 1679.8,
2960.5; MS (ESI): 397.3 [M+H]+; Anal. Cald. For
C21H17ClN2O4: C, 63.56; H, 4.32; N, 7.06%. Found: C, 63.78;
H, 4.33; N, 7.05%.
Ethyl-1,3-dimethyl-2,4-dioxo-5-phenyl-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-6-carboxylate (4g): Yield:
132 mg (40%); Dark yellow solid; Rf (Pet. Ether. 60-
1
80/EtOAc, 8:2) 0.49; mp. 182.5-183.9 ˚C; H NMR (CDCl3,
500 MHz) δ 1.25 (t, 3H), 3.25 (s, 3H), 3.32 (s, 3H), 4.04 (d, J
= 9.5 Hz, 1H), 4.18-4.25 (m, 3H), 7.18-7.47 (m, 5H); 13C
NMR (CDCl3, 125 MHz) δ 14.0, 28.0, 29.4, 52.5, 62.0, 88.7,
90.0, 125.6 (2C), 126.7, 128.7 (2C), 137.4, 151.4, 159.2,
161.9, 171.1; IR (KBr, cm-1) νmax: 1192.0, 1681.3, 1734.9,
2925.0; MS (ESI): 331.2 [M+H]+; Anal. Cald. For
C17H18N2O5: C, 61.81; H, 5.49; N, 8.48%. Found: C, 61.59;
H, 5.50; N, 8.45%.
6-Benzoyl-1,3-dimethyl-5-(p-bromo-phenyl)-5,6-dihydrofuro-
[2,3-d]pyrimidine-2,4(1H,3H)-dione (4e): Yield: 185 mg
(42%); Light yellow solid; Rf (Pet. Ether. 60-80/EtOAc, 8:2)
0.48; mp. 143.1-144.5 ˚C; 1H NMR (CDCl3, 500 MHz) δ 3.12
Ethyl-1,3-dimethyl-2,4-dioxo-6-phenyl-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-5-carboxylate (5g): Yield:

6
Tetrahedron
ACCEPTED MANUSCRIPT
119.1 mg (36%); Dark yellow solid; Rf (Pet. Ether. 60-
80/EtOAc, 8:2) 0.26; mp. 178.7-179.2 ˚C; H NMR (CDCl3,
Ethyl-1,3-dimethyl-5-(p-nitrophenyl)-2,4-dioxo-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-6-carboxylate (4j): Yield:
165 mg (44%); Dark orange solid; Rf (Pet. Ether. 60-
1
500 MHz) δ 1.18 (t, 3H), 3.21 (s, 3H), 3.32 (s, 3H), 4.15-4.22
(m, 3H), 5.96 (d, J = 6 Hz, 1H), 7.18-7.37 (m, 5H); 13C NMR
(CDCl3, 125 MHz) δ 14.0, 28.3, 29.5, 52.5, 62.0, 85.9, 90.0,
125.5 (2C), 128.5 (2C), 129.0, 137.5, 151.4, 159.3, 161.8,
171.4; IR (KBr, cm-1) νmax: 1191.4, 1681.1, 1735.2, 2925.2;
MS (ESI): 331.4 [M+H]+; Anal. Cald. For C17H18N2O5: C,
61.81; H, 5.49; N, 8.48%. Found: C, 61.93; H, 5.47; N,
8.50%.
1
80/EtOAc, 8:2) 0.44; mp. 204.3- 207.8 ˚C; H NMR (CDCl3,
500 MHz) δ 1.21 (t, 3H), 3.13 (s, 3H), 3.31 (s, 3H), 3.65 (d, J
= 9.5 Hz, 1H), 3.91 (d, J = 9.5 Hz, 1H), 4.22 (m, 2H), 7.38 (d,
J = 11.5 Hz, 2H), 8.11 (d, J = 8.5 Hz, 2H); 13C NMR (CDCl3,
125 MHz) δ 13.9, 28.8, 28.9, 44.6, 62.1, 87.1, 89.1, 123.4
(2C), 124.2, 130.4 (2C), 138.5, 147.7, 150.9, 163.2, 165.4; IR
(KBr, cm-1) νmax: 1191.2, 1515.5, 1734.0, 2925.9; MS (ESI):
376.3 [M+H]+; Anal. Cald. For C17H17N3O7: C, 54.40; H,
4.57; N, 11.20%. Found: C, 54.59; H, 4.58; N, 11.18%.
Ethyl-5-(p-methoxyphenyl)-1,3-dimethyl-2,4-dioxo-
1,2,3,4,5,6-hexahydrofuro-[2,3-d]pyrimidine-6-carboxylate
(4h): Yield: 115 mg (32%); Colourless solid; Rf (Pet. Ether.
60-80/EtOAc, 8:2) 0.50; mp. 173.4-175.2 ˚C; 1H NMR
(CDCl3, 500 MHz) δ 0.97 (t, 3H), 3.13 (s, 3H), 3.27 (s, 3H),
3.79(s, 3H,OMe), 3.94(d, J = 9.5 Hz, 1H), 4.08 (d, J = 9.5 Hz,
1H), 4.38 (m, 2H), 6.84-7.25 (m, 4H); 13C NMR (CDCl3, 125
MHz) δ 14.0, 28.5, 29.6, 52.5, 60.2, 62.4, 87.7, 89.2, 123.6,
127.2 (2C), 132.0(2C), 151.4, 159.2, 161.8, 16,1.9 169.4; IR
(KBr, cm-1) νmax: 1190.1, 1683.1, 1734.0, 2923.7; MS (ESI):
361.2 [M+H]+; Anal. Cald. For C18H20N2O6: C, 59.99; H,
5.59; N, 7.77%. Found: C, 59.97; H, 5.58; N, 7.75%.
Ethyl-1,3-dimethyl-6-(p-nitrophenyl)-2,4-dioxo-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-5-carboxylate (5j): Yield:
150 mg (40%); Orange solid; Rf (Pet. Ether. 60-80/EtOAc,
8:2) 0.22; mp. 200.9-202.1 ˚C; 1H NMR (CDCl3, 500 MHz) δ
1.41 (t, 3H), 3.21 (s, 3H), 3.40 (s, 3H), 4.09 (d, J = 6 Hz, 1H),
4.45 (m, 2H), 6.00 (d, J = 6 Hz, 1H), 7.20-8.20 (m, 4H); 13C
NMR (CDCl3, 125 MHz) δ 14.1, 28.9, 29.0, 52.3, 62.2, 88.2,
89.0, 123.3 (2C), 125.3, 130.5 (2C), 138.4, 147.6, 151.0,
163.1, 166.3; IR (KBr, cm-1) νmax: 1191.1, 1515.4, 1680.3,
1734.1, 2925.8 ; MS (ESI): 376.6 [M+H]+; Anal. Cald. For
C17H17N3O7: C, 54.40; H, 4.57; N, 11.20%. Found: C, 54.49;
H, 4.55; N, 11.17%.
Ethyl-6-(p-methoxyphenyl)-1,3-dimethyl-2,4-dioxo-
1,2,3,4,5,6-hexahydrofuro-[2,3-d]pyrimidine-5-carboxylate
(5h): Yield: 101 mg (28%); Colourless solid; Rf (Pet. Ether.
60-80/EtOAc, 8:2) 0.28; mp. 170.1-172.3˚C; 1H NMR
(CDCl3, 500 MHz) δ 1.24 (t, 3H), 3.26 (s, 3H), 3.33 (s, 3H),
3.76 (s, 3H, OMe), 4.16-4.26 (m,3H), 5.98 (d, J = 6 Hz, 1H),
7.19-7.38 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ 14.0, 28.0,
29.5, 52.4, 56.0, 61.9, 86.0, 90.3, 114.2, 127.8 (2C),129.5
Ethyl-1,3-dimethyl-5-(p-chlorophenyl)-2,4-dioxo-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-6-carboxylate (4k): Yield:
153 mg (42%); Light yellow solid; Rf (Pet. Ether. 60-
1
80/EtOAc, 8:2) 0.46; mp. 198.1- 199.5 ˚C; H NMR (CDCl3,
500 MHz) δ 1.21 (t, 3H), 3.13 (s, 3H), 3.28 (s, 3H), 3.63 (d, J
= 9.5 Hz, 1H), 3.81 (d, J = 9.5 Hz, 1H), 4.20 (m, 2H), 7.09-
7.75 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ 13.9, 28.8, 28.8,
46.2, 61.9, 87.4, 89.9, 128.4 (2C), 129.3, 130.7 (2C), 134.5,
151.2, 163.1, 165.8, 165.9; IR (KBr, cm-1) νmax: 1192.5,
1680.7, 1735.1, 2925.4; MS (ESI): 365.3 [M+H]+; Anal. Cald.
For C17H17ClN2O5: C, 55.97; H, 4.70; N, 7.68%. Found: C,
56.08; H, 4.69; N, 7.71%.
(2C), 151.4, 159.2, 161.7, 161.9, 171.5; IR (KBr, cm-1) νmax
:
1190.7, 1684.1, 1733.7, 2924.5; MS (ESI): 361.1 [M+H]+;
Anal. Cald. For C18H20N2O6: C, 59.99; H, 5.59; N, 7.77%.
Found: C, 60.01; H, 5.60; N, 7.79%.
Ethyl-1,3-dimethyl-2,4-dioxo-5-(p-tolyl)-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-6-carboxylate (4i): Yield:
123 mg (36%); Yellow solid; Rf (Pet. Ether. 60-80/EtOAc,
8:2) 0.51; mp. 175.4-177.6 ˚C; 1H NMR (CDCl3, 500 MHz) δ
1.19 (t, 3H), 2.24 (s, 3H), 3.08 (s, 3H), 3.11 (s, 3H), 3.67 (d, J
= 9.5 Hz, 1H), 3.84 (d, J = 9.5 Hz, 1H), 4.19 (m, 2H),7.01-
7.23 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ 14.0, 20.9, 28.8,
29.5, 46.0, 62.2, 86.0, 88.2, 126.6 (2C), 129.3 (2C), 134.4,
139.6, 151.5, 161.9, 162.8, 171.5; IR (KBr, cm-1) νmax: 1190.9,
1680.1, 1735.1, 2925.5; MS (ESI): 345.5 [M+H]+; Anal. Cald.
For C18H20N2O5: C, 62.78; H, 5.85; N, 8.13%. Found: C,
63.00; H, 5.87; N, 8.10%.
Ethyl-1,3-dimethyl-6-(p-chlorophenyl)-2,4-dioxo-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-5-carboxylate (5k): Yield:
142.1 mg (39%); Light yellow solid; Rf (Pet. Ether. 60-
1
80/EtOAc, 8:2) 0.23; mp. 195.7-197.4 ˚C; H NMR (CDCl3,
500 MHz) δ 1.29 (t, 3H), 3.25 (s, 3H), 3.30 (s, 3H), 4.10 (d, J
= 6 Hz, 1H), 4.20 (m, 2H), 5.93 (d, J = 6 Hz, 1H), 7.13-7.34
(m, 4H); 13C NMR (CDCl3, 125 MHz) δ 14.1, 29.3, 29.7,
52.7, 62.2, 85.9, 88.4, 127.1 (2C), 128.3, 129.2 (2C), 130.6,
151.4, 159.2, 161.9, 171.3; IR (KBr, cm-1) νmax: 1191.3,
1680.5, 1734.9, 2925.8; MS (ESI): 365.1 [M+H]+; Anal. Cald.
For C17H17ClN2O5: C, 55.97; H, 4.70; N, 7.68%. Found: C,
56.10; H, 4.71; N, 7.70%.
Ethyl-1,3-dimethyl-2,4-dioxo-6-(p-tolyl)-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-5-carboxylate (5i): Yield:
116 mg (34%); Yellow solid; Rf (Pet. Ether. 60-80/EtOAc,
8:2) 0.28; mp. 169.9-172.4 ˚C; 1H NMR (CDCl3, 500 MHz) δ
1.23 (t, 3H), 2.32 (s, 3H), 3.30 (s, 3H), 3.39 (s, 3H), 4.22-4.30
(m, 3H), 5.99 (d, J = 6 Hz, 1H),6.84-7.38 (m, 4H); 13C NMR
(CDCl3, 125 MHz) δ 14.0, 21.1, 28.0, 29.2, 52.4, 61.9, 86.0,
88.9, 125.8 (2C), 128.9, 129.6 (2C), 139.6, 151.4, 159.2,
161.7, 169.6; IR (KBr, cm-1) νmax: 1190.8, 1680.0, 1734.8,
2925.6; MS (ESI): 345.1 [M+H]+; Anal. Cald. For
C18H20N2O5: C, 62.78; H, 5.85; N, 8.13%. Found: C, 62.93;
H, 5.86; N, 8.15%.
Ehyl-1,3-dimethyl-5-(p-bromophenyl)-2,4-dioxo-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-6-carboxylate (4l): Yield:
167 mg (41%); Light orange solid; Rf (Pet. Ether. 60-
80/EtOAc, 8:2) 0.46; mp. 193.2-194.6.2 ˚C; 1H NMR (CDCl3,
500 MHz) δ 1.28 (t, 3H), 3.13 (s, 3H), 3.32 (s, 3H), 3.62 (d, J
= 9.5 Hz, 1H), 3.79 (d, J = 9.5 Hz, 1H), 4.20 (m, 2H), 7.05-
7.43 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ 13.9, 28.8, 29.5,
46.1, 61.9, 85.0, 86.8, 122.7, 130.0, 131.0 (2C), 131.4 (2C),
151.2, 163.1, 165.7, 165.8; IR (KBr, cm-1) νmax: 1190.8,
1681.1, 1734.7, 2925.6; MS (ESI): 410.1 [M+H]+; Anal. Cald.

Tetrahedron
7
ACCEPTED MANUSCRIPT
For C17H17BrN2O5: C, 49.89; H, 4.19; N, 6.85%. Found: C,
50.03; H, 4.20; N, 6.83%.
For C15H13N3O3: C, 63.60; H, 4.63; N, 14.83%. Found: C,
63.58; H, 4.62; N, 14.82%.
Ethyl-1,3-dimethyl-6-(p-bromo-phenyl)-2,4-dioxo-1,2,3,4,5,6-
hexahydrofuro-[2,3-d]pyrimidine-5-carboxylate (5l): Yield:
143 mg (35%); Light orange solid; Rf (Pet. Ether. 60-
5-(p-Chlorophenyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-6-carbonitrile (4o): Yield:
120.2 mg (38%); Light yellow solid; Rf (Pet. Ether. 60-
1
1
80/EtOAc, 8:2) 0.24; mp. 190.7-192.3 ˚C; H NMR (CDCl3,
80/EtOAc, 8:2) 0.42; mp. 100.7-101.2 ˚C; H NMR (CDCl3,
500 MHz) δ 1.32 (t, 3H), 3.32 (s, 3H), 3.39 (s, 3H), 4.17 (d, J
= 6 Hz, 1H), 4.30 (m, 2H), 5.98 (d, J = 6 Hz, 1H), 7.14-7.61
(m, 4H); 13C NMR (CDCl3, 125 MHz) δ 14.0, 28.5, 29.5,
52.5, 62.4, 85.7, 87.7, 123.6, 127.2 (2C), 132.0 (2C), 136.4,
151.3, 159.1, 161.8, 171.0; IR (KBr, cm-1) νmax: 1191.7,
1681.2, 1734.1, 2925.8 ; MS (ESI): 410.3 [M+H]+; Anal.
Cald. For C17H17BrN2O5: C, 49.89; H, 4.19; N, 6.85%. Found:
C, 50.05; H, 4.20; N, 6.86%.
500 MHz) δ 3.28 (s, 3H), 3.35 (s, 3H), 4.29 (d, J = 9.5 Hz,
1H), 5.60 (d, J = 9.5 Hz, 1H), 7.15-7.55 (m, 5H); 13C NMR
(CDCl3, 125 MHz) δ 28.1, 29.5, 45.1, 80.1, 87.0, 119.5, 128.0
(2C), 129.8 (2C), 134.0, 139.5, 151.0, 160.1, 161.7; IR (KBr,
cm-1) νmax: 1681.8, 2251.3, 2925.7, 1194.3; MS (ESI): 318.2
[M+H]+; Anal. Cald. For C15H12ClN3O3: C, 56.70; H, 3.81; N,
13.23%. Found: C, 56.73; H, 3.82; N, 13.25%.
6-(p-Chlorophenyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-5-carbonitrile (5o): Yield:
111 mg (35%);Light yellow solid; Rf (Pet. Ether. 60-
80/EtOAc, 8:2) 0.18; mp. 98.2-99.5 ˚C; 1H NMR (CDCl3, 500
MHz) δ 3.20 (s, 3H), 3.24 (s, 3H), 4.79 (d, J = 6 Hz, 1H)),
4.93 (d, J = 6 Hz, 1H), 7.09-7.39 (m, 4H); 13C NMR (CDCl3,
125 MHz) δ 29.5, 29.7, 38.1, 82.4, 88.8, 116.6, 126.8 (2C),
129.7 (2C), 134.1, 136.5, 150.9, 158.3, 161.8; IR (KBr, cm-1)
νmax: 2253.1, 1680.2, 1194.6, 2925.3; MS (ESI): 318.5
[M+H]+- Anal. Cald. For C15H12ClN3O3: C, 56.70; H, 3.81; N,
13.23%. Found: C, 56.84; H, 3.79; N, 13.27%.
Ethyl-3-methyl-2,4-dioxo-5-phenyl-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-6-carboxylate (4m): Yield:
105 mg (33%); Yellow solid; Rf (Pet. Ether. 60-80/EtOAc,
1
8:2) 0.47; mp. 186.6-188.40 ˚C; H NMR (CDCl3, 500 MHz)
δ 1.24 (t, 3H), 3.25 (s, 3H), 4.01 (d, J = 9.5 Hz, 1H), 4.15-
4.22 (m, 3H), 7.15-7.37 (m, 5H), 10.31 (s, 1H, NH); 13C
NMR (CDCl3, 125 MHz) δ 14.1, 28.0, 53.2, 62.1, 88.8, 91.2,
125.6 (2C), 126.8, 128.6 (2C), 137.5, 151.3, 158.3, 162.9,
172.3; IR (KBr, cm-1) νmax:1191.2, 1680.5, 1743.4, 2925.3;
MS (ESI): 317.3 [M+H]+; Anal. Cald. For C16H16N2O5: C,
60.75; H, 5.10; N, 8.86%. Found: C, 60.79; H, 5.09; N,
8.85%.
Acknowledgements
We thank DST, New Delhi and CSIR, New Delhi for
financial assistance (CAAF-NE Project).
Ethyl-3-methyl-2,4-dioxo-6-phenyl-1,2,3,4,5,6-
hexahydrofuro[2,3-d]pyrimidine-5-carboxylate (5m): Yield:
95.35 mg (30%); Yellow solid; Rf (Pet. Ether. 60-80/EtOAc,
8:2) 0.25; mp. 185.1-186.7 ˚C; 1H NMR (CDCl3, 500 MHz) δ
1.17 (t, 3H), 3.22 (s, 3H), 4.14-4.26 (m, 3H), 5.92 (d, J = 6
Hz, 1H), 7.17-7.36 (m, 5H), 10.33 (s, 1H, NH); 13C NMR
(CDCl3, 125 MHz) δ 14.1, 28.5, 53.6, 62.1, 86.9, 90.0, 125.6
(2C), 128.4 (2C), 129.1, 137.6, 151.3, 159.4, 162.3, 172.3; IR
(KBr, cm-1) νmax:1191.4, 1680.9, 1743,0, 2925.1; MS (ESI):
317.5 [M+H]+; Anal. Cald. For C16H16N2O5: C, 60.75; H,
5.10; N, 8.86%. Found: C, 60.77; H, 5.11; N, 8.87%.
5. References and notes
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105 mg (37%); Dark yellow solid; Rf (Pet. Ether. 60-
80/EtOAc, 8:2) 0.44; mp. 96.4-96.8 ˚C; 1H NMR (CDCl3, 500
MHz) δ 3.20 (s, 3H), 3.48 (s, 3H), 4.21 (d, J = 9 Hz, 1H), 5.30
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1
0.20; mp. 94.2-95.1 ˚C; H NMR (CDCl3, 500 MHz) δ 3.19
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(s, 3H), 3.27 (s, 3H), 4.82 (d, J = 6 Hz, 1H), 4.94 (d, J = 6 Hz,
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29.3, 39.0, 80.1, 87.5, 115.1, 123.3, 128.1, 130.5 (2C), 131.8
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8
Tetrahedron
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