Functionalisation of the uracil ring via palladium-catalysed aminocarbonylation

Article abstract of DOI:10.1016/j.tet.2019.07.008

Iodouracil derivatives (5-iodouracil, 5-iodo-1,3-dimethyluracil) were aminocarbonylated using a set of primary and secondary amines in the presence of in situ palladium(0) catalysts. The formation of carboxamides via single CO insertion was favoured at atmospheric CO pressure. The chemoselectivity toward double CO insertion can be increased by using 40 bar of CO pressure, in this way up to 60% selectivity toward 2-ketocarboxamide was achieved. In the case of 5-iodouracil the corresponding 5-glyoxylamido-uracil derivatives were exclusively formed at 40 bar CO pressure. The only exception is the less basic aniline nucleophile which provided the corresponding carboxamide exclusively. A typical side-reaction took place when 5-iodouracil was used as substrate: this heterocycle, existing in lactam-lactim tautomeric forms, underwent deiodination providing the parent uracil as side-product.

Full text of DOI:10.1016/j.tet.2019.07.008

Accepted Manuscript
Functionalisation of the uracil ring via palladium-catalysed aminocarbonylation
László Kollár, Márta Georgina Varga, Ágnes Dörnyei, Attila Takács
PII:
S0040-4020(19)30750-1
https://doi.org/10.1016/j.tet.2019.07.008
TET 30450
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 8 May 2019
Revised Date: 1 July 2019
Accepted Date: 5 July 2019
Please cite this article as: Kollár Láó, Varga MáGeorgina, Dörnyei Á, Takács A, Functionalisation of the
uracil ring via palladium-catalysed aminocarbonylation, Tetrahedron (2019), doi: https://doi.org/10.1016/
j.tet.2019.07.008.
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Functionalisation of the Uracil Ring via Palladium-Catalysed Aminocarbonylation.
ACCEPTED MANUSCRIPT
László Kollár, Márta Georgina Varga, Ágnes Dörnyei, Attila Takács *
Graphical abstract
O
O
O
O
O
R'
N
R
O
I
R
O
R'
R
O
R"
H
R'
Pd(OAc)2 / 2 PPh3
N
N
N
N
+
+
N
1 or 40 bar of CO
DMF, Et3N, 50 °C
- [Et3NH]I
R"
O
R"
N
R
N
R
N
R
R = H, CH3
1

Functionalisation of the Uracil Ring via Palladium-Catalysed
ACCEPTED MANUSCRIPT
Aminocarbonylation.
László Kollára,b), Márta Georgina Vargaa), Ágnes Dörnyeic), Attila Takácsb) *
a) Department of Inorganic Chemistry, University of Pécs and Szentágothai Research Centre, H-7624
Pécs, P.O. Box 266, Hungary
b) MTA-PTE Research Group for Selective Chemical Syntheses, H-7624 Pécs, Ifjúság u. 6., Hungary;
e-mail: takacsattila@gamma.ttk.pte.hu
c) Department of Analytical and Environmental Chemistry, University of Pécs, H-7624, Ifjúság u. 6.,
Hungary
Abstract: Iodouracil derivatives (5-iodouracil, 5-iodo-1,3-dimethyluracil) were
aminocarbonylated using a set of primary and secondary amines in the presence of in
situ palladium(0) catalysts. The formation of carboxamides via single CO insertion
was favoured at atmospheric CO pressure. The chemoselectivity toward double CO
insertion can be increased by using 40 bar of CO pressure, in this way up to 60%
selectivity toward 2-ketocarboxamide was achieved. In the case of 5-iodouracil the
corresponding 5-glyoxylamido-uracil derivatives were exclusively formed at 40 bar
CO pressure. The only exception is the less basic aniline nucleophile which provided
the corresponding carboxamide exclusively. A typical side-reaction took place when
5-iodouracil was used as substrate: this heterocycle, existing in lactam-lactim
tautomeric forms, underwent deiodination providing the parent uracil as side-product.
Key-words: palladium, uracil, carbonylation, carbon monoxide, carboxamide
2

1. Introduction
Pd-catalysed aminocarbonylation of aryl halides (preferablyIPiodides) was discovered more than four
ACCEPTED MANUSCR T
decades ago1 and had become one of the most investigated carbonylation reactions. The facile introduction of
the carboxamide functionality into various skeletons made this reaction of synthetic importance and
discussed in several review papers2 and book chapters.3
In spite of the aminocarbonylation of alkenyl halides (or their synthetic surrogates, enol triflates) which
gave generally carboxamides,4 the same reaction of aryl halides (or triflates) was always accompanied by the
formation of the corresponding 2-ketocarboxamides due to double CO insertion.5
Recently, our interest turned to the functionalisation of skeletons of biological importance, therefore,
the potential of using halouracil derivatives as substrate is reviewed here. The antimicrobial and anticancer
properties of N-substituted 5-iodouracils, as well as their development for practical applications was
discussed.6 5-Functionalised uracil derivatives were synthesised from 5-iodouracil using halogen-magnesium
exchange and consecutive reaction with various electrophiles.7 The same substrate underwent direct arylation
via photochemical reaction.8 In addition to conventional synthetic procedures, palladium-copper catalysed
coupling of terminal alkynes with protected 5-iodouracil nucleosides was carried out.9 Furthermore, the
large-scale preparation of 5-ethynyluracil, which is a potent inhibitor of dihydropyrimidine dehydrogenase
enzyme playing key role in the metabolism of 5-fluorouracil, using Sonogashira coupling of
trimethylsilylacetylene and 5-iodouracil followed by a simple deprotection was developed.10 Similarly, 5-
iodouracil peptide nucleic acid monomer was reacted with terminal alkynes in Sonogashira reaction.11
Palladium-dba precursors without adding further ligands were used for direct arylation of 5-halouracil
derivatives and 5-halouracil nucleosides.12 Catalytic amination of 5-iodouracil in the presence of Cu(I) or
Ni(0) complexes was carried out.13 5-Alkenyl-, 5-alkynyl- and 5-aryluracil derivatives were synthesised in
Stille-coupling.14 The reactivity of 5-bromo- and 5-iodouracil in Suzuki- and Stille-couplings was
compared.15
The synthesis of uridine-5-carboxamides was described by Matsuda and coworkers in the reaction
between 5-(2,2,2-trifluoroethoxycarbonyl)-2’-deoxyuridine and various primary amines in acetonitrile.16 5-
Carboxamidouracil derivatives were synthesised by using uracil-5-carboxylic acid and amines in the presence
of 1,1’-carbonyldiimidazole as a coupling agent.17 Although the palladium-catalysed aminocarbonylation
reaction has found wide application in synthetic chemistry providing an easy route for the functionalisation of
biologically important skeletons, to the best of our knowledge, no efforts were made for the synthesis of
carboxamides of nucleotide bases.
In this work, the aminocarbonylation of the parent 5-iodouracil and its dimethyl-substituted derivative
will be described. During the systematic catalytic investigations, the influence of the reaction conditions on
reactivity and selectivity was explored.
3

2. Results and discussion
2.1. Aminocarbonylation of 5-iodouracil with primary and secondary amines as N-nucleophiles
ACCEPTED MANUSCRIPT
5-Iodouracil (1) was reacted with various primary (tert-butylamine (a), aniline (b), methyl glycinate
(e), methyl alaninate (f)) and secondary (piperidine (c), morpholine (d), methyl prolinate (g)) amines under
carbon monoxide atmosphere (Scheme 1). A highly durable, low-ligated palladium(0) catalyst, prepared in
situ from palladium(II) acetate and triphenylphosphine, was used.18 Although the palladium(II)-palladium(0)
reduction might also occur upon action of amine or carbon monoxide as reducing agents, it has been proved
by cyclic voltammetry and NMR measurements that one of the two phosphine ligands acts as reducing agent
while it is oxidized to phosphine oxide. Using solvents with good donor properties such as DMF, the
formation of a highly active, coordinatively unsaturated Pd(0)(PPh3)(solvent)n catalyst was supposed.
O
O
O
O
O
O
I
NR'R"
+
Pd(OAc)2 / 2 PPh3
HN
HN
NR'R"
+
HN
HN
O
HNR'R"
1- 40 bar CO
DMF, Et3N, 50 °C
-[Et3NHI]
O
N
H
O
N
H
O
N
H
O
N
H
1
2a-g
3a-g
4
R'
R"
a
H
H
tBu
Ph
b
-(CH2)5-
-(CH2)2O(CH2)2-
c
d
e
f
CH2COOCH3
H
H
CH(CH3)COOCH3
g
-CH(COOCH3)(CH2)3-
Scheme 1. Aminocarbonylation of 5-iodouracil (1)
The aminocarbonylation of 1 in the presence of tert-butylamine (a) and piperidine (c) resulted in the
formation of the corresponding carboxamides (2a, 2c) in low yields (<30%) under atmospheric carbon
monoxide pressure (Table 1, entries 1 and 4). The carbonylation reactions are accompanied by deiodination
providing the parent uracil (4). It has to be noted that it was found as major product at atmospheric CO
pressure.
In order to achieve double carbonylation 40 bar of carbon monoxide pressure was needed. Under these
conditions 2-ketocarboxamides (3a-3g) were found as exclusive carbonylated products, i.e., no carboxamides
were formed. The only exception in this amine set was aniline, which gave carboxamide (2b) via single CO
insertion in highly selective reaction (Table 1, entry 3). The same phenomenon was observed recently with
various iodoaromatics19 and iodoheteroaromatics20 also in our laboratory. Longer reaction times (>40 h) were
4

needed to reach complete conversion. Not only unfunctionalised amines (a-d), but also amino acid methyl
ACCEPTED MANUSCRIPT
esters (e-g) have been easily converted to the corresponding 2-ketoamide (except b).
5

Table 1. Aminocarbonylation of 1 in the presence of various aminesa)
ACCEPTED MANUSCRIPT
Entry
Amine
R. time p(CO) Conv.
Ratio of the carbonylated productsb) [%]
[h]
[bar]
[%]
carboxamide
2-keto-
carboxamide
(3a-h)
uracil (4)
(2a-h)
1
2
3
4
5
6
7
8
9
t-BuNH2 (a)
t-BuNH2 (a)
aniline (b)
42
40
48
50
42
48
69
68
68
1
>98
>98
>98
90
30 (2a)
0 (2a)
70 (2b), 60c)
<5 (2c)
0 (2c)
0 (3a);
95 (3a), 73c)
0 (3b)
70 (4)
5 (4)
40
40
1
30 (4)
>95 (4)
24 (4)
28 (4)
<5 (4)
<5 (4)
<5 (4)
piperidine (c)
piperidine (c)
morpholine (d)
GlyOMe (e)
AlaOMe (f)
ProOMe (g)
0 (3c)
40
40
40
40
40
>98
>98
>98
>98
>98
76 (3c), 64c)
72 (3d), 65c)
>98 (3e), 52c)
>95 (3f), 68c)
>95 (3g), 63c)
0 (2d)
0 (2e)
0 (2f)
0 (2g)
a) Reaction conditions (unless otherwise stated): 1 mmol of substrate (1), amine nucleophile: 3 mmol of a or
2 mmol of b/1.5 mmol of c, d/1.1 mmol of e-g), 0.025 mmol of Pd(OAc)2, 0.05 mmol of PPh3, 0.5 mL of
Et3N, 10 mL of DMF, 50 oC.
b) Determined by 1H NMR.
c) Yields of the isolated target compounds (%), based on the substrate (1).
The formation of the double carbonylated (3) and the deiodinated products (4) can be rationalised on the
basis of the generally accepted reaction mechanism depicted in Scheme 2. The 5-iodouracil (1) is oxidatively
added to the in situ formed palladium(0) complex (Cycle ‘A’). The coordination of the carbon monoxide to
the palladium(II)-aryl complex (A) and its insertion into the Pd-C bond resulted in the formation of
palladium(II)-acyl complex (C). This catalytic intermediate is apt to coordinate the amine nucleophile
providing a palladium(II)-amido-acyl complex (D) accompanied by HX elimination in the presence of
triethylamine. The coordination of the second carbon monoxide (E) is followed by its insertion into the Pd-N
bond giving a palladium(II)-acyl-carbamoyl complex (F), which undergoes reductive elimination leading the
formation of 2-ketocarboxamide type product (3) while the coordinatively unsaturated palladium(0) complex
is re-formed. Deiodination has also been occurred, which can be explained on the basis of an earlier work of
our research group.21 The following plausible reaction mechanism (Cycle ‘B’), including of the OH moiety
formed in the lactim-lactam tautomerism of the uracil ring, is suggested for the deiodination. The
tautomerism of the uracil ring in palladium(II)-aryl complex (A) could be resulted in G catalytic intermediate
containing a 2-hydroxy-4-oxo-uracil moiety. Its deiodination in the presence of triethylamine leads to H
species, which activates the amine nucleophile by providing palladium(II)-amido complex (I). The activation
of carbon monoxide as a terminal ligand (J) is followed by its insertion into Pd-N bond forming the
corresponding palladium(II)-carbamoyl complex (K). This species reacts with the second primary or
6

secondary amine providing the ‘urea-type’ product and the palladium(II)-aryl-hydrido complex (L), which
undergoes reductive elimination for in acil (4 an lladium(0) complex. Consequently, the
hydrogen derived from the amine nucleophile is necessary to formal deiodination.
m g ur ) d the pa
ACCEPTED MANUSCRIPT
7

ACCEPTED MANUSCRIPT
Scheme 2. Aminocarbonylation and deiodination of 5-iodouracil (1) rationalized by generally accepted
catalytic steps
8

2.2. Aminocarbonylation of 5-iodo-1,3-dimethyluracil with primary and secondary amines as N-nucleophiles
ACCEPTED MANUSCRIPT
Scheme 3. Aminocarbonylation of 5-iodo-1,3-dimethyluracil (5)
A strikingly different behaviour was observed using 5 as substrate. The aminocarbonylation of 5
resulted in the formation of carboxamides (6a-g) and 2-ketocarboxamides (7a-g) due to single and double CO
insertion, respectively (Scheme 3). That is, the formation of the deiodination product (1,3-dimethyluracil) was
not observed under various conditions. The mixture of mono and double carbonylated derivatives
(carboxamides and 2-ketocarboxamides, respectively) were formed depending on the CO pressure and amine
(Table 2).
Using simple primary (a, b) and secondary (c, d) amines practically full conversions were observed
both under atmospheric (entries 2, 5, 8) and high pressure conditions (entries 3, 4, 6, 10) after 24 hours.
As above, the use of aniline (b) as N-nucleophile resulted in the chemospecific formation of
carboxamide (6b) (entry 4). In general, the prevailed formation of carboxamides was observed at atmospheric
CO pressure. The chemoselectivity can be shifted toward 2-ketocarboxamides at 40 bar CO pressure.
Using amino acid methyl esters as nucleophile lower reactivity was observed under atmospheric
conditions: after 24 hours lower than 8% conversions were occurred (entries 12, 16). After longer reaction
time (120 h) full conversion was observed by using methyl alaninate (f) (entry 17), while the methyl prolinate
(g) has shown low reactivity (entry 14) under same conditions. Elevated carbon monoxide pressure had to be
used to reach full conversion after 24 hours (entries 11, 15, 18).
9

Table 2. Aminocarbonylation of 5-iodo-1,3-dimethyluracil (5) in the presence of various amines under
ACCEPTED MANUSCRIPT
atmospheric and 40 bar carbon monoxide pressure a)
Entry
Amine
R.
p(CO)
Conv.
[%]
Ratio of the carbonylated
productsb) [%]
time [bar]
[h]
carboxamide
2-
(6a-h)
ketocarboxamide
(7a-h)
1
2
t-BuNH2 (a)
t-BuNH2 (a)
t-BuNH2 (a)
aniline (b)
8
24
8
1
1
72
97
71 (6a)
83 (6a), 46c)
43 (6a)
100 (6b), 49c)
77 (6c); 45c)
43 (6c)
29 (7a)
17 (7a)
3
40
40
1
>98
>98
>98
>98
73
57 (7a), 38c)
0 (7b)
4
24
24
24
8
5
piperidine (c)
piperidine (c)
morpholine (d)
morpholine (d)
morpholine (d)
morpholine (d)
GlyOMe (e)
AlaOMe (f)
AlaOMe (f)
AlaOMe (f)
AlaOMe (f)
ProOMe (g)
ProOMe (g)
ProOMe (g)
23 (7c)
57 (7c); 49c)
6
40
1
7
82(6d)
82(6d); 43c)
18 (7d)
8
24
8
1
>98
94
18 (7d)
9
40
40
40
1
48(6d)
52 (7d)
10
11
12
13
14
15
16
17
18
24
24
24
48
120
24
24
120
24
>98
>98
8
52(6d)
40 (6e); 30c)
48 (7d); 28c)
60 (7e); 29c)
<1 (7f)
>99 (6f)
1
22
88 (6f)
90 (6f); 39c)
12 (7f)
1
>98
>98
<2%
13
10 (7f)
60 (7f); 34c)
40
1
40 (6f)
100 (6g)
0
1
100 (6g)
46 (6g); 25c)
0
40
>98
54 (7g); 21c)
a) Reaction conditions (unless otherwise stated): 1 mmol of substrate (1), amine nucleophile: 3 mmol of a or
2 mmol of b/1.5 mmol of c, d/1.1 mmol of e-g), 0.025 mmol of Pd(OAc)2, 0.05 mmol of PPh3, 0.5 mL of
Et3N, 10 mL of DMF, 50 oC.
b) Determined by GC-MS.
c) Yields of the isolated target compounds (%), based on the substrate (5). (n.i. = not isolated)
To compare the reactivity of a primary (a) and a secondary (d) amine both under atmospheric and high
pressure conditions, samples were taken from the reaction mixture after 1, 2, 4, 8, 24 hours. The influence of
the carbon monoxide pressure on the conversion can be clearly seen (Figure 1 and Figure 2): while 24 hours
was necessary to reach practically complete conversion under atmospheric conditions, very high conversion
(> 82%) was observed at 40 bar CO pressure after 4 hours. In spite of the quite higher basicity of the tert-
butylamine, there is no striking difference between the reactivity of a and d.
10

Figure 1. Conversion as a function of time in the aminocarbonylation of 5 with tert-butylamine (a)
ACCEPTED MANUSCRIPT
Figure 2. Conversion as a function of time in the aminocarbonylation of 5 with morpholine (d)
11

2.3. Conclusions
In summary, the uracil ring can be efficiently functionalisedIPby carboxamido and 2-ketocarboxamido
ACCEPTED MANUSCR T
substituents under aminocarbonylation conditions in the presence of Pd(OAc)2 / PPh3 catalysts.
In the aminocarbonylation of 5-iodouracil under atmospheric carbon monoxide the deiodination
process dominates. Increasing the carbon monoxide pressure (40 bar) the double carbon monoxide insertion,
resulting in the 5-glyoxylamido-uracil derivatives, is highly favoured over deiodination side reaction. The
formation of deiodinated products can be rationalised by a reaction mechanism based on generally accepted
elementary steps. In our suggestion, the OH moiety of the 5-iodouracil formed in tautomerization has an
important role in the deiodination resulting in the uracil as a side product.
A strikingly different behaviour can be observed in the aminocarbonylation of 1,3-dimethyl-5-
iodouracil. A mixture of carbonylated products was observed both at low (1 bar) and high (40 bar) carbon
monoxide pressure. The product formation can be shifted toward the corresponding 5-glyoxylamido-1,3-
dimethyluracil derivatives by using 40 bar of carbon monoxide pressure. Deiodination did not occur due to
the lack of the lactim-lactam tautomerism. It has to be added, that the isolation procedures in case of 1,3-
dimethyl-5-iodouracil were not optimized, i.e. the yields added in Table 2. were obtained under these
conditions.
12

3. Experimental
3.1. General procedures
ACCEPTED MANUSCRIPT
1H and 13C NMR spectra were recorded in CDCl3 or DMSO on a Bruker Avance III 500 spectrometer
at 500 and 125.7 MHz, respectively. Chemical shifts δ are reported in ppm relative to CHCl3 (7.26 and 77.00
1
13
1
13
ppm for H and C, respectively) or to DMSO (2.50 and 39.50 ppm for H and C, respectively). Mass
spectrometry data have been obtained using either a GC-MS system consisting of a Perkin Elmer
AutoSystem XL gas-chromatograph or an Agilent 6300 Series Ion Trap LC/MSD XCT Plus mass
spectrometer (Agilent Technologies, Germany) equipped with an electrospray ion source and controlled with
the Agilent LC/MSD Trap software 5.3 (in case of the isolated compounds of the catalytic reactions of 5-
iodouracil). Elemental analyses were measured on a 1108 Carlo Erba apparatus. The FT-IR spectra were
taken in KBr pellets using an IMPACT 400 spectrometer (Nicolet) applying a DTGS detector in the region of
400-4000 cm-1, the resolution was 4 cm-1. The amount of the samples was ca. 0.5 mg. Melting points are
uncorrected and were measured with a Büchi apparatus. TLC plates (silica gel on TLC aluminium foil with
fluorescence indicator 254 nm) were purchased from Sigma-Aldrich. The eluents used in thin-layer
chromatography are specified below.
5-Iodouracil (1), 5-iodo-1,3-dimethyluracil (5) substrates and amine nucleophiles (a-g) were purchased
from Sigma-Aldrich and were used without further purification.
3.2. Aminocarbonylation of iodouracil derivatives (1, 5) under atmospheric pressure of carbon monoxide.
In a typical experiment Pd(OAc)2 (5.6 mg, 0.025 mmol), triphenylphosphine (13.2 mg, 0.05 mmol), 5-
iodouracil (1) or 5-iodo-1,3-dimethyluracil (5) substrates (1 mmol), amine nucleophiles (see above in tables)
and triethylamine (0.5 mL) were dissolved in DMF (10 mL) under argon in a 100 mL three-necked flask
equipped with reflux condenser connected to a balloon filled with argon. The atmosphere was changed to
carbon monoxide. The reaction was conducted for the given reaction time upon stirring at 50 °C and analysed
by GC and GC-MS. The cooled reaction mixture was then concentrated and evaporated to dryness under
reduced pressure.
Method A. (2b, 3a, 3c-3g): Chloroform (10 mL) was added to the residue and the insoluble material
(product) was filtered, washed with absolute ethanol and dried.
Method B. (6a-6g, 7a-3g): The residue was dissolved in chloroform (15 mL) and washed twice with
water (15 mL). The organic phase was dried over Na2SO4, filtered and evaporated under reduced pressure to
a solid material. All compounds were subjected to column chromatography (Silicagel 60 (Sigma), 0.063-
0.200 mm), CHCl3/EtOAc/MeOH or hexane/EtOAc/MeOH eluent mixtures (the exact ratios are specified in
Characterization (3.4) for each compound).
3.3. Aminocarbonylation of iodouracil derivatives under high carbon monoxide pressure (a general synthetic
methodology for the synthesis of 3a-3g and 7a-7g).
13

In a typical experiment Pd(OAc)2, triphenylphosphine, iodouracil derivatives (1, 5), amine nucleophiles
(a-g) and triethylamine were used in the amEDoun as ab e a ere dissolved in 10 mL of DMF under
A
C
s
C
a
E
m
P
e
T
t ov nd w
MANUSCRIPT
argon in a 100 mL autoclave. The atmosphere was changed to carbon dioxide and the autoclave was
pressurized to the given pressure with carbon monoxide. (Caution: High pressure carbon monoxide should
only be used with adequate ventilation (hood) using CO sensors as well.) The reaction was conducted for the
°
given reaction time upon stirring at 50 C. After the given reaction time the reaction mixture was cooled to
room temperature and the autoclave was carefully depressurized in a well-ventilated hood. The product
mixture was analysed by GC and GC-MS. The work-up of the reaction mixture was identical to that
discussed for the atmospheric experiments.
3.4. Characterisation of the products
3.4.1. 5-(N-tert-Butylglyoxylamido)uracil (3a)
Yield: 175 mg (73%), Off white powder, m.p. 270-271 °C; Rf (15% MeOH/CHCl3) 0.65. δH (500 MHz,
DMSO-d6) 11.82 (1H, br s, NH), 11.42 (1H, br s, NH), 8.20 (1H, s, NHCH), 7.98 (1H, s, CONH), 1.31 (9H,
3 x (CH)3). δC NMR (125.7 MHz) 186.6, 165.7, 161.3, 150.9, 150.6, 108.8, 51.1, 28.7. IR (KBr, ν (cm-1)):
3375 (NH), 1734, 1700, 1669 (CO), 1653 (Amide I.), 1616 (C=C), 1499 (Amide II.); MS m/z (rel. int.): 238
(100, [M–H]–), MS/MS (rel. int.) 238 (19), 223 (10), 195 (32), 123 (8), 111 (100).
3.4.2. 5-(N-Phenylcarboxamido)-uracil (2b)
Yield: 140 mg (60%), Beige powder, m.p. > 300 °; Rf (15% MeOH/CHCl3) 0.65. δH (500 MHz,
DMSO-d6) 11.86 (2H, br s, 2 x NH), 10.91 (1H, s, CONH), 8.26 (1H, s, NHCH), 7.64 (2H, s, Ph (ortho)),
7.35 (2H, s, Ph (meta)), 7.10 (1H, s, Ph (para)). δC NMR (125.7 MHz) 165.0, 160.7, 150.8, 149.0, 138.6,
129.5, 124.2, 120.9, 104.6. IR (KBr, ν (cm-1)): 3221 (NH), 1718, 1696 (CO), 1653 (Amide I.), 1617 (C=C),
1553 (Amide II.); MS m/z (rel. int.): 229.9 (100, [M–H]–), MS/MS (rel. int.) 186.9 (46), 143.0 (100).
3.4.3. 5-(N,N-Pentane-1’,5’-diylglyoxylamido)-uracil (3c)
Yield: 160 mg (64%), Off white powder, m.p. 281-282 °C; Rf (15% MeOH/CHCl3) 0.50. δH (500 MHz,
DMSO-d6) 12.05 (1H, br s, NH), 11.52 (1H, s, NH), 8.22 (1H, s, NHCH), 3.43 (2H, s, CH2), 3.15 (2H, s,
CH2), 1.66-1.42 (6H, br m, 3 x CH2). δC NMR (125.7 MHz) 188.1, 166.0, 161.8, 151.0, 150.8, 108.7, 46.3,
41.6, 25.4, 24.9, 24.4. IR (KBr, ν (cm-1)): 1768, 1728, 1680 (CO), 1660 (Amide I.), 1626 (C=C); MS m/z
(rel. int.): 250.0 (100, [M–H]–), MS/MS (rel. int.) 250.0 (56), 222.0 (20), 206.9 (100), 205.9 (61), 179.0 (10),
163.0 (19), 139.0 (32), 121.1 (8).
3.4.4. 5-(N,N-Penta-3’-oxa-1’,5’-diylglyoxylamido)-uracil (3d)
Yield: 165 mg (65%), Pale brown powder, m.p. 248-249 °C; Rf (15% MeOH/CHCl3) 0.44. δH (500
MHz, DMSO-d6) 12.05 (1H, br s, NH), 11.57 (1H, s, NH), 8.26 (1H, s, NHCH), 3.68-3.60 (2H, m, CH2),
3.58-3.52 (2H, m, CH2), 3.50-3.44 (2H, m, CH2), 3.25-3.17 (2H, m, CH2). δC NMR (125.7 MHz) 187.7,
166.4, 162.0, 151.0, 150.9, 108.7, 66.0, 65.9, 48.8, 41.3. IR (KBr, ν (cm-1)): 1772, 1727, 1679 (CO), 1663
14

(Amide I.), 1624 (C=C), 1114 (COC); MS m/z (rel. int.): 251.9 (100, [M–H]–), MS/MS (rel. int.) 252.0
(26.4), 208.9 (100), 207.9 (89), 181.9 (13)
.
ACCEPTED MANUSCRIPT
3.4.5. 5-(N-(Methoxycarbonylmethyl)-glyoxylamido)-uracil (3e)
Yield: 132 mg (52%), Brown powder, m.p. 135-136 °C; Rf (15% MeOH/CHCl3) 0.35. δH (500 MHz,
DMSO-d6) 11.86 (1H, br s, NH), 11.44 (1H, s, NH), 9.00 (1H, br s, CONH), 8.39 (1H, s, NHCH), 3.95 (2H,
s, CH2), 3.67 (3H, s, OCH3). δC NMR (125.7 MHz) 185.1, 170.1, 165.3, 161.0, 152.0, 150.7, 108.2, 52.4,
40.9. IR (KBr, ν (cm-1)): 3114 (NH), 1735 (ester CO), 1726, 1699, 1668 (CO), 1648 (Amide I.), 1610 (C=C),
1506 (Amide II.); MS m/z (rel. int.): 253.9 (100, [M–H]–), MS/MS (rel. int.) 221.9 (7), 210.9 (100), 196.9
(4), 178.9 (9), 177.9 (11), 111.1 (3).
3.4.6. 5-(N-(1’-Methoxycarbonylethyl)-glyoxylamido)-uracil (3f)
Yield: 183 mg (68%), Off white powder, m.p. 223-224 °C; Rf (15% MeOH/CHCl3) 0.49. δH (500 MHz,
DMSO-d6) 11.85 (1H, br s, NH), 11.45 (1H, s, NH), 8.99 (1H, br s, CONH), 8.30 (1H, s, NHCH), 4.39 (1H,
s, CHCH3), 3.66 (3H, s, OCH3), 1.35 (3H, s, CHCH3). δC NMR (125.7 MHz) 1885.8, 172.8, 165.2, 161.1,
151.7, 150.8, 108.73, 52.5, 47.8, 17.1 IR (KBr, ν (cm-1)): 3327 (NH), 1735 (ester CO), 1720, 1685, 1678
(CO), 1654 (Amide I.), 1634 (C=C), 1527 (Amide II.); MS m/z (rel. int.): 268 (100, [M–H]–), MS/MS (rel.
int.) 235.9 (6) 224.9 (100), 192.9 (31), 191.9 (49), 149.0 (7), 111.0 (15).
3.4.7 5-(N-(1’-Methoxycarbonyl-butan-1’,4’-diyl)-glyoxylamido)-uracil (3g) (ca.1/3 mixture of two C(O)N
rotamers)
Yield: 185 mg (63%), White solid material, m.p. 245-246 °C; Rf (15% MeOH/CHCl3) 0.56. δH (500
MHz, DMSO-d6) 12.08 (1H, br s, NH), 11.54/12.52 (major/minor) (1H, s, NH), 8.23/8.21 (major/minor)
(1H, s CCH), 4.41-4.37/4.36-4.32 (major/minor) (1H, m, NCH), 3.68/3.61 (major/minor) (3H, s, OCH3), 3.58
(2H, m, NCH2, overlapping with the water content of DMSO-d6), 2.31-2.20/2.19-2.12 (major/minor) (2H, m,
CH2), 2.00-1.99/1.97-1.83 (minor/major) (2H, m, CH2). δC NMR (125.7 MHz) 187.2/187.0 (major/minor),
172.3/172.2 (minor/major), 165.7/165.5 (major/minor), 161.6/161.5 (minor/major), 151.7/151.3
(major/minor), 150.8/150.6 (major/minor), 108.4/108.1 (minor/major), 59.2/58.2 (minor/major), 52.6/52.5
(minor/major), 47.0/46.1 (major/minor), 30.8/29.2 (minor/major), 24.9/22.4 (major/minor). IR (KBr, ν (cm-
1)): 1738 (ester CO), 1728, 1695, 1682 (CO), 1640 (Amide I.), 1605 (C=C); MS m/z (rel. int.): 294.0 (100,
[M–H]–), MS/MS (rel int) 261.9 (31), 251.0 (22), 237.0 (6), 233.9 (5), 218.9 (8), 217.9 (100), 205.9 (10),
174.9 (66).
3.4.8. 1,3-Dimethyl-5-(N-tert-butylcarboxamido)uracil (6a)
Yield: 110 mg (46%), White solid, m.p. 184-185 °C; [Anal. Calcd. for C11H17N3O3:C, 55.22; H, 7.16;
N, 17.56. Found: C, 55.98; H, 6.57; N, 16.78]; Rf (5% MeOH, 35% EtOAc, 60% hexane) 0.64. δH (500 MHz,
CHCl3) 8.80 (1H, br s, CONH), 8.36 (1H, s, CH), 3.51 (3H, s, NCH3), 3.38 (3H, s, NCH3), 1.43 (9H, 3 x
(CH)3). δC NMR (125.7 MHz), 163.1, 160.8, 151.0, 148.3, 106.0, 51.1, 37.7, 28.8, 28.2. IR (KBr, ν (cm-1)):
3292 (NH), 1699 (br, CO + Amide I.), 1620 (C=C), 1554 (Amide II.); MS m/z (rel. int.): 239 (2, M+), 224
(46), 182 (8), 167 (100), 140 (2), 110 (4), 82 (4), 53 (4).
15

3.4.9. 1,3-Dimethyl-5-(N-tert-butylglyoxylamido)uracil (7a)
ACCEPTED MANU RIPTalcd. for C12H17N3O4:C, 53.92; H, 6.41;
Yield: 101 mg (38%), White solid, m.p. 142-143 °C; [ASCnal. C
N, 15.72. Found: C, 53.28; H, 6.17; N, 15.25]; Rf (5% MeOH, 35% EtOAc, 60% hexane) 0.41. δH (500 MHz,
CHCl3) 9.21 (1H, s, CH), 7.08 (1H, br s, CONH), 3.56 (3H, s, NCH3), 3.39 (3H, s, NCH3), 1.44 (9H, 3 x
(CH)3). δC NMR (125.7 MHz), 182.1, 160.8, 159.6, 152.9, 150.4, 108.0, 51.7, 38.72, 28.3, 28.1. IR (KBr, ν
(cm-1)): 3329 (NH), 1718, 1688, 1670 (CO), 1661 (Amide I.), 1626 (C=C), 1552 (Amide II.); MS m/z (rel.
int.): 167 (70, M+-100), 140 (100), 110 (6), 82 (12), 57 (22).
3.4.10. 1,3-Dimethyl-5-(N-tert-phenylcarboxamido)uracil (6b)
Yield: 126 mg (49%), White solid, m.p. 216-217 °C; [Anal. Calcd. for C13H13N3O3:C, 60.23; H, 5.05;
N, 16.21. Found: C, 59.60; H, 4.79; N, 15.67.]; Rf (30% EtOAcH/CHCl3) 0.44. δH (500 MHz, CDCl3) 10.94
(1H, s, CONH), 8.52 (1H, s, CH), 7.70 (2H, d, 7.4 Hz, Ph (ortho)), 7.39 (2H, t, 7.4 Hz, Ph (meta)), 7.16 (1H,
t, 7.4 Hz, Ph (para)) 3.50 (3H, s, NCH3), 3.28 (3H, s, NCH3). δC NMR (125.7 MHz) 163.2, 160.0, 150.9,
149.2, 137.9, 129.0, 124.3, 120.4, 105.2, 38.0, 28.4. IR (KBr, ν (cm-1)): 3265 (NH), 1705, 1695 (CO), 1622
(Amide I.), 1596 (C=C), 1527 (Amide II.); MS m/z (rel. int.): 259 (65, M+), 167 (100), 140 (1), 110 (6), 82
(2), 65 (6), 53 (5).
3.4.11. 1,3-Dimethyl-5-(N-pentane-1’,5’-diylcarboxamido)uracil (6c)
Yield: 119 mg (45%), Off white solid, m.p. 123-124 °C; [Anal. Calcd. for C12H17N3O3:C, 57.36; H,
6.82; N, 16.72. Found: C, 57.36; H, 6.35; N, 16.23.]; Rf (10% MeOH, 45% EtOAc, 45% hexane) 0.46. δH
(500 MHz, CHCl3) 7.56 (1H, s, NHCH), 3.64 (2H, br s, CH2), 3.43 (3H, s, NCH3), 3.35 (3H, s, NCH3), 3.28
(2H, br s, CH2), 1.71-1.54 (6H, br m, 3 x CH2). δC NMR (125.7 MHz) 162.8, 159.9, 151. 3, 144.8, 111.4,
48.7, 43.4, 37.3, 28.1, 26.3, 25.4, 24.4. IR (KBr, ν (cm-1)): 1703, 1655 (CO), 1645 (Amide I.), 1620 (C=C);
MS m/z (rel. int.): 251 (91, M+), 167 (23), 140 (9), 112 (2), 84 (100), 82 (2), 56 (7).
3.4.12. 1,3-Dimethyl-5-(N-pentane-1’,5’-diylglyoxylamido)uracil (7c)
Yield: 135 mg (49%), White solid, m.p. 190-191 °C; [Anal. Calcd. for C13H17N3O4:C, 575.91; H, 6.14;
N, 15.05. Found: C, 56.08; H, 5.89; N, 14.40.]; Rf (10% MeOH, 45% EtOAc, 45% hexane) 0.69. δH (500
MHz, CHCl3) 8.24 (1H, s, NHCH), 3.63 (2H, br s, CH2), 3.53 (3H, s, NCH3), 3.34 (3H, s, NCH3), 3.28 (2H,
br s, CH2), 1.69 (4H, br s, 2 x CH2), 1.61 (2H, br s, CH2). δC NMR (125.7 MHz) 187.3, 165.8, 160.4, 150.9,
150.0, 109.3, 46.8, 42.1, 38.1, 28.0, 25.5, 24.9, 24.5. IR (KBr, ν (cm-1)): 1722, 1683, 1654 (CO), 1634
(Amide I.), 1612 (C=C); MS m/z (rel. int.): 279 (40, M+), 207 (1), 167 (82), 140 (4), 112 (100), 84 (30), 69
(73), 56 (15).
3.4.13. 1,3-Dimethyl-5-(N-penta-3’-oxa-1’,5’-diylcarboxamido)uracil (6d)
Yield: 86 mg (43%), Off white solid, m.p. 216-217 °C; [Anal. Calcd. for C11H15N3O4:C, 52.17; H,
5.97; N, 16.59. Found: C, 51.80; H, 5.66; N, 16.27.]; Rf (5% MeOH, 10% EtOAc, 85% CHCl3) 0.38. δH (500
MHz, CHCl3) 7.66 (1H, s, NHCH), 3.73 (6H, br s, 3 x CH2), 3.45 (3H, s, NCH3), 3.35 (5H, br s, overlapping
of NCH3 and CH2). δC NMR (125.7 MHz) 163.2, 159.9, 151. 1, 146.3, 110.2, 66.9, 66.6, 48.1, 43.1, 37.5,
16

28.3. IR (KBr, ν (cm-1)): 1722, 1683, 1669 (CO), 1653 (Amide I.), 1634 (C=C), 1111 (COC); MS m/z (rel.
+
ACCEPTED MANUSCRIPT
int.): 253 (2, M ), 207 (9), 167 (100), 154 (10), 140 (17), 86 (68), 74 (22), 56 (15).
3.4.14. 1,3-Dimethyl-5-(N-penta-3’-oxa-1’,5’-diylglyoxylamido)uracil (7d)
Yield: 78 mg (28%), Off white solid, m.p. 156-157 °C; [Anal. Calcd. for C12H15N3O5:C, 52.24; H,
5.38; N, 14.94. Found: C, 51.53; H, 5.34; N, 14.23.]; Rf (5% MeOH, 10% EtOAc, 85% CHCl3) 0.49. δH (500
MHz, CHCl3) 8.24 (1H, s, NHCH), 3.85-3.80 (2H, m, CH2), 3.74-3.70 (2H, m, CH2), 3.57 (3H, s, NCH3),
3.49-3.44 (2H, m, CH2), 3.38 (5H, br s, overlapping of NCH3 and CH2). δC NMR (125.7 MHz) 186.9, 166.0,
160.6, 150. 8, 150.0, 109.2, 66.8, 66.5, 46.5, 41.5, 38.2, 28.1. IR (KBr, ν (cm-1)): 1707, 1653, (CO), 1634
(Amide I.), 1627 (C=C), 1111 (COC); MS m/z (rel. int.): 281 (18, M+), 253 (1), 224 (1), 196 (2), 167 (100),
140 (2), 114 (21), 86 (5), 70 (32), 56 (5).
3.4.15. 1,3-Dimethyl-5-(N-(methoxycarbonylmethyl)-carboxamido)-uracil (6e)
Yield: 75 mg (30%), Pale y ellow solid, m.p. 131-132 °C; [Anal. Calcd. for C10H13N3O5:C, 47.06; H,
5.13; N, 16.46. Found: C, 46.93; H, 4.79; N, 15.97.]; Rf (5% MeOH, 10% EtOAc, 85% CHCl3) 0.55. δH (500
MHz, CHCl3) 9.32 (1H, br s, CONH), 8.43 (1H, s, NHCH), 4.19 (2H, d, 5.4 Hz, NHCH2), 3.78 (3H, s,
OCH3), 3.54 (3H, s, NCH3), 3.40 (3H, s, NCH3). δC NMR (125.7 MHz) 170.0, 162.8, 162.6, 150.9, 149.2,
104.5, 52.4, 41.3, 37.9, 28.3. IR (KBr, ν (cm-1)): 3301 (NH), 1737 (ester CO), 1710, 1671 (CO), 1626
(Amide I.), 1618 (C=C), 1538 (Amide II.); MS m/z (rel. int.): 255 (7, M+), 223 (11), 196 (38), 167 (100), 140
(4), 110 (4), 82 (4), 53 (6).
3.4.16. 1,3-Dimethyl -5-(N-(methoxycarbonylmethyl)-glyoxylamido)-uracil (7e)
Yield: 81 mg (29%), Beige solid, m.p. 145-146 °C; [Anal. Calcd. for C11H13N3O6:C, 46.65; H, 4.63; N,
14.84. Found: C, 45.53; H, 4.35; N, 14.01.]; Rf (5% MeOH, 10% EtOAc, 85% CHCl3) 0.40. δH (500 MHz,
CHCl3) 9.12 (1H, s, NHCH), 7.76 (1H, br s, CONH), 4.15 (2H, d, 5.4 Hz, NHCH2), 3.80 (3H, s, OCH3), 3.56
(3H, s, NCH3), 3.38 (3H, s, NCH3). δC NMR (125.7 MHz) 181.0, 169.2, 162.2, 159.6, 153.3, 150.5, 107.9,
52.6, 41.1, 38.3, 28.1. IR (KBr, ν (cm-1)): 3261 (NH), 1757 (ester CO), 1711, 1684, 1674 (CO), 1651 (Amide
I.), 1616 (C=C), 1543 (Amide II.); MS m/z (rel. int.): 195 (2, M+-88), 167 (100), 140 (49), 110 (7), 83 (11),
53 (11).
3.4.17. 1,3-Dimethyl 5-(N-(1’-methoxycarbonylethyl)-carboxamido)-uracil (6f)
Yield: 105 mg (39%), White solid, m.p. 152-153 °C; [Anal. Calcd. for C11H15N3O5:C, 49.07; H, 5.62;
N, 15.61. Found: C, 49.23; H, 5.13; N, 15.50.]; Rf (5% MeOH, 10% EtOAc, 85% CHCl3) 0.74. δH (500 MHz,
CHCl3) 9.32 (1H, d, 7.2 Hz, CONH), 8.40 (1H, s, NHCH), 4.71 (1H, qi, 7.2 Hz, NHCH), 3.78 (3H, s, OCH3),
3.54 (3H, s, NCH3), 3.42 (3H, s, NCH3), 1.52 (3H, d, 7.2 Hz, CH3). δC NMR (125.7 MHz) 173.0, 162.8,
161.7, 150.9, 148.9, 104.7, 52.4, 48.2, 37.9, 28.3, 18.2. IR (KBr, ν (cm-1)): 3288 (NH), 1731 (ester CO),
1716, 1684 (CO), 1630 (Amide I.), 1617 (C=C), 1533 (Amide II.); MS m/z (rel. int.): 269 (1, M+), 238 (1),
210 (64), 167 (100), 140 (3), 110 (3), 82 (2), 53 (3).
3.4.18. 1,3-Dimethyl 5-(N-(1’-methoxycarbonylethyl)-glyoxylamido)-uracil (7f)
17

Yield: 100 mg (34%), off white solid, m.p. 138-139 °C; [Anal. Calcd. for C12H15N3O6:C, 48.49; H,
5.09; N, 14.14. Found: C, 48.19; H, 4.92 13.8 .]; Rf (5 10% EtOAc, 85% CHCl3) 0.56. δH (500
SCeO
; N, 0 % M H,
ACCEPTED MANU RIPT
MHz, CHCl3) 9.12 (1H, s, NHCH), 8.40 (1H, d, 7.2 Hz, CONH), 4.59 (1H, qi, 7.2 Hz, NHCH), 3.80 (3H, s,
OCH3), 3.56 (3H, s, NCH3), 3.38 (3H, s, NCH3), 1.52 (3H, d, 7.2 Hz, CH3). δC NMR (125.7 MHz) 181.0,
172.2, 161.3, 159.5, 153.1, 150.5, 108.0, 52.7, 48.3, 38.3, 28.1, 17.9. IR (KBr, ν (cm-1)): 3278 (NH), 1751
(ester CO), 1721, 1676, 1657 (CO), 1641 (Amide I.), 1612 (C=C), 1539 (Amide II.); MS m/z (rel. int.): 238
(2, M+-59), 167 (100), 140 (76), 110 (6), 83 (12), 53 (9).
3.4.19. 1,3-Dimethyl 5-(N-(1’-methoxycarbonyl-butan-1’,4’-diyl)-carboxamido)-uracil (6g) (ca.1/3 mixture
of two C(O)N rotamers)
Yield: 71 mg (25%), Yellow viscous material; [Anal. Calcd. for C11H13N3O5:C, 49.44; H, 4.90; N,
15.72. Found: C, 50.08; H, 5.20; N, 15.29.]; Rf (5% MeOH, 10% EtOAc, 85% CHCl3) 0.58. δH (500 MHz,
CHCl3) 7.71/7.61 (major/minor) (1H, s CCH), 4.58/4.51 (minor/major) (1H, br s, NCH), 3.73/3.71
(minor/major) (3H, s, OCH3), 3.69-3.63 (2H, br s, NCH2), 3.43/3.41 (minor/major) (3H, s, NCH3), 3.32 (3H,
s, NCH3), 2.32-2.19/2.05-1.91 (minor/major) (4H, br s, 2 x CH2). δC NMR (125.7 MHz) 173.0/172.5
(minor/major), 163.8/163.5 (minor/major), 159.8/159.5 (minor/major), 151.2/151.4 (minor/major),
146.1/143.7 (major/minor), 110.9/110.8 (minor/major), 59.7/59.5 (minor/major), 52.4/52.2 (minor/major),
48.1/47.0 (major/minor), 37.4/37.2 (major/minor), 31.1/29.2 (minor/major), 28.4/28.1 (minor/major),
24.6/22.5 (major/minor). IR (KBr, ν (cm-1)): 1745 (ester CO), 1710, 1661 (CO), 1654 (Amide I.), 1616
(C=C); MS m/z (rel. int.): 295 (4, M+), 236 (12), 167 (100), 140 (3), 128 (69), 110 (4), 82 (2), 68 (8), 53 (4).
3.4.20. 1,3-Dimethyl 5-(N-(1’-methoxycarbonyl-butan-1’,4’-diyl)-glyoxylamido)-uracil (7g) (ca.1/2 mixture
of two C(O)N rotamers)
Yield: 68 mg (21%), Yellow viscous material; Rf (5% MeOH, 10% EtOAc, 85% CHCl3) 0.68. δH (500 MHz,
CHCl3) 8.51/8.34 (major/minor) (1H, s, CCH), 4.64-4.56/4.55-4.50 (minor/major) (1H, m, NCH), 3.7/3.74
(minor/major) (3H, s, OCH3), 3.65 (2H, br s, NCH2), 3.44/3.41 (minor/major) (3H, s, NCH3), 3.33 (3H, s,
NCH3), 2.35-2.22/2.07-1.96 (minor/major) (4H, m, 2 x CH2). δC NMR (125.7 MHz) 186.3/186.0
(major/minor), 172.2/172.0 (minor/major), 165.3/165.1 (major/minor), 163.6/163.4 (major/minor),
151.7/151.4 (minor/major), 143.3/143.0 (minor/major), 101.1, 59.5/58.4 (minor/major), 52.5/52.4
(major/minor), 47.0/46.4 (major/minor), 38.3/38.2 (major/minor), 30.8/29.1 (minor/major), 28.4/ 28.0
(major/minor), 24.6/22.5 (major/minor). IR (KBr, ν (cm-1)): 1740 (ester CO), 1706, 1685, 1662 (CO), 1634
(Amide I.), 1615 (C=C); MS m/z (rel. int.): 323 (1, M+), 295 (8), 264 (12), 236 (1), 207 (1) 167 (82), 128
(100), 110 (3), 82 (7), 68 (4), 53 (6).
Acknowledgement: The authors thank the Hungarian Scientific Research Fund (K113177) and GINOP-
2.3.2-15-2016-00049 grant for the financial support and Johnson Matthey for the generous gift of
palladium(II) acetate. The project has been supported by the European Union, co-financed by the European
Social Fund Grant no.: EFOP-3.6.1.-16-2016-00004 entitled by Comprehensive Development for
Implementing Smart Specialization Strategies at the University of Pécs. This paper was supported by the
18

János Bolyai Research Scholarship of the Hungarian Academy of Sciences. The present scientific
contribution is dedicated to the 650th a
nn vers ry f th foun atio the University of Pécs, Hungary.
i a o e d n of
ACCEPTED MANUSCRIPT
19

References
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ACCEPTED MANUSCRIPT
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Organic Synthesis (Vol. I-II.), Wiley-VCH, Weinheim, 1998.; (c) Colquhoun, H. M.; Thompson, D. J.;
Twigg, M. V. Carbonylation. Direct Synthesis of Carbonyl Compounds. Plenum Press, New York and
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ACCEPTED MANUSCRIPT
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Functionalisation of the uracil ring via palladium-catalysed aminocarbonyaltion
Selective synthesis of 5-glyoxylamidouracil derivatives at high CO pressure
Describing a proposed mechanism of deiodination side reaction
Synthesis of uracil derivatives bearing amide moiety with biological importance