Palladium-catalyzed C-H olefination of uracils and caffeines using molecular oxygen as the sole oxidant

Article abstract of DOI:10.1039/c7ob00616k

The palladium-catalyzed oxidative C-H olefination of uracils or caffeines with alkenes using an atmospheric pressure of molecular oxygen as the sole oxidant has been disclosed. This novel strategy offers an efficient and environmentally friendly method to

Full text of DOI:10.1039/c7ob00616k

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Palladium-catalyzed C-H olefination of uracils and caffeines using
molecular oxygen as the sole oxidant
Received 00th January 20xx,
Accepted 00th January 20xx
Xinyu Zhang, Lv Su, Lin Qiu, Zhenwei Fan, Xiaofeng Zhang, Shen Lin and Qiufeng Huang*
The palladium-catalyzed oxidative C-H olefination of uracils or caffeines with alkenes using atmospheric pressure of
molecular oxygen as the sole oxidant has been disclosed. This novel strategy offers an efficient and environmentally
friendly way to biologically important C5-alkene uracils derivatives or C8-alkene caffeines derivatives.
DOI: 10.1039/x0xx00000x
www.rsc.org/
examples , to name a few, include Pd(II)-catalyzed olefination
of electron-deficient arenes using 2,6-dialkylpyridine ligands
with molecular oxygen as the sole oxidant,15 regioselective
Introduction
There has been great interest in caffeines or uracil-scaffold-
containing compounds because of their potential biological
activity and pharmaceutical significance.1 Besides, their
derivatives have numerous applications as fluorescent
biological probes,2 organic light emitting diodes (OLEDs),3
advance materials,4 heavy metal sensor,5 and nucleobase
functionalized π-conjugated oligomers.6 Therefore, the
development of efficient and clean methodologies for the
synthesis of caffeine or uracil derivatives is highly desirable.7
Since Fujiwara and Moritani’s pioneering work,8 transition-
metal-catalyzed oxidative aryl C-H olefination has drawn
considerable attention.9 Various transition-metal complexes
such as palladium, rhodium, and ruthenium can be applied for
oxidative Heck reaction, and a variety of substrates such as
simple arene with directing groups, O-heteroarenes, N-
heteroarenes, and S-heteroarenes were successfully coupled
with olefin for delivering arylalkenes. However, most these
methods required stoichiometric amounts of the oxidants such
as copper(II) salt,10 silver (I) salt,11 HFIP,12 benzoquinone,13 etc
to drive the reaction forward. In order to fulfill the
requirements of green chemistry, there is an increasing
demand to use ecologically benign oxidants such as molecular
oxygen. Recent developments of our group and others have
demonstrated that the catalytic amount of polyoxometalates
(POMs) can act as relay species in oxidative Heck reactions in
which O2 serves as the terminal oxidant.14 Nevertheless,
copious POMs need to be added in the reaction system due to
its large molecular weights. Hence, using molecular oxygen as
the sole oxidant is considered as the ideal alternative because
the formation of C-C bond via oxidative Heck reaction occurs
with only the generation of water as a by-product. Typical
palladium-catalyzed olefination of coumarins,16 palladium-
catalyzed C3 alkenylation of indoles,17 enantioselective
metal/organo-catalyzed aerobic oxidative sp3 C-H olefination
of tertiary amines,18 aerobic dehydrogenative Heck reaction of
ferrocene with a Pd(OAc)2/4,5-diazafluoren-9-one catalyst,19
palladium-catalyzed oxidative olefination of phenol
derivatives,20 Rh(III)-catalyzed C-H olefination of N-
pentafluoroaryl benzamides.21 In 2015, our group also
disclosed palladium-catalyzed cross-dehydrogenative-coupling
(CDC) reaction of polyfluoroarenes with alkenes and arenes
using atmospheric pressure of molecular oxygen as the sole
oxidant.22 Despite these advances, the transition-metal-
catalyzed oxidative Heck reaction using molecular oxygen as
the sole oxidant still in its infancy, and there is much new
territory such as larger substrate scope to be explored.
In 2012, You et al. reported a dehydrogenative Heck
coupling of caffeine with alkenes using Cu(OAc)2·H2O (1.5
equiv.) and CuCl2 (15 mol%) as the oxidants.23 In 2013, Yu et al.
reported
the
palladium-catalyzed
dehydrogenative
alkenylation of uracils using AgOAc (3 equiv.) as the oxidant.24
However, stoichiometric amounts of metal oxidants are still
required in reaction system. In our continuous interests in this
area, we herein describe the palladium-catalyzed oxidative
Heck reaction of uracils and caffeines with alkenes using the
atmospheric molecular oxygen as the sole oxidant.
Results and discussion
Our initial studies involved the oxidative Heck reaction of 1,3-
dimethyluracil (1a) with n-butyl acrylate (2a) employing the
conditions of Pd(OAc)2 (10 mol%), DL-pGlu-OH (10 mol%) and
o
PivOH (2 equiv.) in DMA at 100 C using O2 (1atm) as the sole
oxidant. As shown in Table 1, this leads to the generation of C-
5-alkenylated product 3a in 72% yield with completely E-
stereoselectivity. (Table 1, entry 1). Yu and co-workers have
discovered that mono-N-protected amino acids
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Table 1 Optimization of the reaction conditionsa
Table 2 Oxidative olefination of uracils with alkenesa
View Article Online
DOI: 10.1039/C7OB00616K
O
O
O
O
N
c
mo
l
%
Pd OA
Z Ph
10
(
(
)
(
)
)
2
H
c
mo
l
%
)
R1
O
H
R1
R3
Pd OA
10
mo
l
%
u
CO2B
(
)
(
(
2
-
e-
O
mo
10 l
%
N
N
N
N
R3
s
MPAA 10
)
v
e
.
q
-n-
CO2
u
B
Pi OH
2
(
DMA
,
)
N
R2
N
R2
O
v
e .
DMA
,
q
)
Pi OH 2
a m
t
O2
1
(
N
O
O
R1
R1
100 oC 24 h
,
1
2
3
a m
t
1
O2
a
1
a
2
a
3
O
N
O
O
N
O
O
O
n r
s
b
E t
MPAA
y
e
i ld
72
78
41
80
67
60
35
70
%
y
(
)
N
N
N
N
N
O
O
O
-
p
u-
1
2
3
4
5
6
7
8
9
DL Gl OH
N
O
O
O
O
O
oc- eu-
OH
B
B
B
L
a
c
3
86%
3
3b
5
88%
O
8
%
oc- a -
V l OH
O
N
O
O
O
oc- a-
Al OH
O
N
N
N
N
moc- eu-
OH
F
F
F
A
L
N
N
O
O
O
O
b
b
moc- e-
Il OH
e
85
3d 85
3
3f 95
%
%
%
O
N
O
O
moc- a-
Al
O
H
c- - eu-
DL L OH
N
N
-
e-
Z Ph OH
92 88
(
)
b
b
b
3
g
2
3h
7
0%
3i
4
8
%
8%
10c
11d
12e
13f
-
e-
Z Ph OH
56
70
0
F
O
O
O
N
O
O
-
e-
Z Ph OH
O
N
N
N
-
e-
Z Ph OH
N
N
O
O
O
-
e-
Z Ph OH
0
b
b
b
3
j
71
3k
7
3l
4
9%
%
3%
NO2
N
C
a
O
N
O
N
Reaction conditions (unless otherwise specified): 1a (0.2 mmol, 1 equiv.), 2a
(0.4 mmol, 2 equiv.), solvent (1 mL), O2 (1 atm) at 100 °C for 24 h. DMA = N,N-
N
N
b
dimethylacetamide, PivOH = pivalic acid. Yield according to GC based on the
O
O
amount of 2a used. Number in parenthesis is isolated yield. c The reaction time is
d
e
b
n
3
2
8%
m
3
8 h. The reaction time is 16 h. The reaction was carried out in the absence of
34%
Pd(OAc)2. f The reaction was carried out under a nitrogen atmosphere.
O
O
O
N
O
N
e
e
Ph
Ph
CO2M
CO2M
N
N
N
N
+
+
N
N
O
O
O
O
(MPAAs) could enable the acceleration of Pd(II)-catalyzed
oxidative heck reactions.25 With this research in mind, the
effect of MPAAs was investigated intensively to further boost
the yield. Z-Phe-OH (92%; Table 1, entry 9) was found to be
superior to others such as Boc-Leu-OH (78%;Table 1, entry 2),
Boc-Val-OH (41%; Table 1, entry 3), Boc-Ala-OH (80%; Table 1,
entry 4), Fmoc-Leu-OH (67%; Table 1, entry 5), Fmoc-Lle-OH
(60%; Table 1, entry 6), Fmoc-Ala-OH (35%; Table 1, entry
7)and Ac-DL-Leu-OH (70%; Table 1, entry 8). Additionally,
shortening the reaction time led to a decreased conversion of
1a to some degree (Table 1, entries 10-11). Finally, Control
experiments revealed that no 3a was formed in the absence of
a palladium catalyst or molecular oxygen (Table 1, entries 12-
13).
o-
:
o-
=
:
b
3
1 3
2
1 2 5
0%
-
-
=
2
:
1
:
3
3
4 5 75
%
p
p
O
O
O
O
O
N
O
N
O
N
O
N
O
N
O
N
O
O
r
3
s
72
3
7
3
9
%
80%
%
q
O
N
O
O
O
O
O
N
N
O
O
HN
O
N
O
O
C
l
N
O
H
u
3
r
t
v
3
0%
ace
3t
68%
a Reaction conditions: 1 (0.2 mmol),2 (2 equiv.), Pd(OAc)2 (10 mol%), Z-Phe-OH
(10 mol%), DMA (1 mL), O2 (1 atm), 100 °C, 24 h; Isolated yields. 120 °C, K2CO3
b
With the identification of the optimal MPAA, the substrate
scope with respect to direct olefination of 1,3-dimethyluracil
was illustrated in Table 2 (see 3a-p). The present protocol was
successfully extended to other acrylate of various alcohols. n-
Butylacrylate, t-butyl acrylate, ethyl acrylate and 2-
methoxyethyl acrylate reacted efficiently with caffeine to give
corresponding products (see 3a-d) in 72%, 59%, 68% and 54%
yield, respectively. In addition, styrenes were also found to be
competent coupling partners. Whereas, the reaction required
higher temperature (120 °C) and external base (K2CO3). The
effect of substituents in different position of the styrene was
examined then. It is clear that the steric effect of the
substituents was very significant. Styrene, 3- methylstyrene
and 4-methylstyrene were good substrates, and delivered the
(40 mol%).
desired products in excellent yields (see 3e-g). The direct
olefination of 1,3-dimethyluracil with 2,-4-dimethylstyene also
occurred, but afforded relatively low yield of the product (see 3h).
In contrast, for 2,4,6- trimethylstyrene, the olefination reaction
is sluggish and 3i was isolated in 48% yield (see 3i). styrenes
bearing an electron-donating groups (alkyl, methoxy or
acetoxyl group) showed better reactivity compared with that
bearing an electron-withdrawing group (F, CN, NO2, see 3l-n).
α-substituted such as N-phthaloyl dehydroalanine was not
suitable for the process,26 since the desired product were not
isolated, and starting materials were recovered. However, the
reaction of 1,3-dimethyluracil with α-substituted olefines such
2 | J. Name., 2012, 00, 1-3
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as methyl methacrylate and α-methylstyrene could afforded a
mixture of olefinated products in mild to good yields. (see 3o
). 1,3-dialkyluracils could be olefinated to give the desired
products in good yields (see 3q ). Treatment of 1,3,6-
trimethyluracil also afforded the desired product 3t in good
yield. However, when using 6-chloro-1,3-dimethyluracil as the
substrate, the desired transformation did not occur and
starting materials were recovered (see 3u). It is presumed that
this low yield seems to be due to the decreased nucleophilicity
of the C(5)-H bond of uracil. Unfortunately, the free (NH)-uracil
was not suitable substrate for the reaction, since the desired
product was not isolated.
To demonstrate the versatility of this methodology for
oxidative Heck reaction using O2 as the sole oxidant, we
further investigated the direct C-H olefination of caffeines with
above-mentioned reaction conditions (Table 1, entry 9).
Delightedly, the current catalytic system was also effective for
the caffeines and the results are summarized in Table 3. Both
acrylates and styrenes took part in the alkenylation reaction
with good yields and excellent E-stereoselectivity. Similarly,
View Article Online
DOI: 10.1039/C7OB00616K
c
A
)
2
Pd
O
(
-
p
v
+
Pi H L
O
O
N
= - e-
L Z Ph
H
O
-s
N
c
A
H
O
H
2O
v
n
Pd Pi 2L
O
O
(
)
v
+
Pi
H
O
O2
v
Pi OH
n
PdL
O
N
O
N
v
n
L
Pd Pi
O
(
)
N
R
N
O
O
+
O
N
v
O
Pi
H
R
R
v
n
L
Pd Pi
O
(
)
N
O
Scheme 1 A plausible mechanism
the steric and electronic effect of the substituents on the
styrene is very significant. (see 4e ) 3-Ethyl or 3-propyl
substituted caffeines underwent olefination with n-butyl
acrylate to give the desired products in good yields (see 4
).However, moderate or low yield was observed in the
reaction of 7-ethyl, 7-propyl or 7-benzyl substituted caffeines
presumably due to steric reasons (see 4k ). Because of the
-j
Table 3. Oxidative olefination of caffeines with alkenesa
n
-
O
N
O
N
R1
N
R1
N
c
e-
mo
l
%
Pd OA
10
(
(
)
(
)
)
2
R2
O
R2
O
-
mo
Z Ph OH 10 l
N
%
N
o
R3
H
v
e
.
DMA
,
q
)
Pi OH
2
(
N
N
R3
a m
t
1
O2
-
m
1'
2
4
poor solubility of 3-NH caffeine in DMA, only 17% of the target
product 4p was obtained.
O
O
O
N
O
O
O
O
N
N
N
N
N
N
N
N
O
O
Base on the observed results and pioneering reports,27 the
mechanism for the direct C-H olefination of uracils with
alkenes was proposed in Scheme 1. It is thought that Pd(OAc)2
first coordinates with Ac-Gly-OH and PivOH to form the
activated palladium (II) catalyst, and then the reaction
mechanism involves the electrophilic attack of Pd(II) to uracil
or caffeine, followed by insertion into the olefin and the
subsequent reductive elimination to give product and Pd(0).
Finally, the reoxidation of Pd(0) to Pd(II) by molecular oxygen
to complete the catalytic cycle.
N
N
N
O
O
O
a
4
c
77
4b
6
4
4
7
3
%
%
%
O
N
O
N
O
O
O
N
N
N
N
N
N
N
N
N
N
O
O
O
O
b
b
e
4
4d
7
0
4f
50
N
58
%
%
%
O
O
N
N
N
N
N
N
N
N
O
O
O
O
b
b
4
g
4h
25
42
%
%
O
F
N
N
N
N
N
Conclusion
N
N
O
b
b
4i 7
5
4
38
j
%
%
In conclusion, we have developed the palladium-catalyzed
oxidative Heck reaction of uracil or caffeine using O2 as the
sole oxidant. This simple and efficient approach provides an
economical and environmentally benign process for the
O
N
O
O
O
N
O
N
O
O
N
N
N
N
N
N
N
N
N
O
O
O
O
O
preparation of
uracil/caffeine scaffolds.
a variety of vinyl or styryl-substituted
m
4
4k
4l
49
%
32
18
%
%
O
O
O
N
O
O
O
O
N
N
N
N
N
N
HN
O
O
N
N
N
N
O
O
O
Experimental section
Materials and methods
n
4
o
4
68%
4
p
69%
1
7
%
All reagents are analytically pure and used without further
purification, or prepared as described in the literature. 1H and
13C NMR spectra were recorded on a Bruker advance III 400
spectrometer at 400 MHz and 100 MHz, respectively. 1H
a Reaction conditions: 1’ (0.2 mmol), 2 (2 equiv.), Pd(OAc)2 (10 mol%), Z-Phe-OH
b
(10 mol%), DMA (1 mL), O2 (1 atm), 120 0C, 24 h; Isolated yields. 140 °C, K2CO3
(40 mol%).
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chemical shifts (δ) were referenced to TMS, and 13C NMR 59.2, 37.6, 28.3. HRMS: Calculated for C12H16N2NaO5+
View Article Online
DOI: 10.1039/C7OB00616K
chemical shifts (δ) were referenced to internal solvent [M+Na]+:291.0951; Found: 291.0953.
resonance. GC analyses of organic compounds were
performed on an Agilent Technologies 6890N GC (with a SGE-
(E)-1,3-dimethyl-5-styrylpyrimidine-2,4(1H,3H)-dione (3e)
:
24
1H NMR (400 MHz, Chloroform-d) δ 7.46 – 7.42 (m, 2H),
OV1701 25m capillary column) instrument. ESI-HRMS spectra 7.37 (d, J = 16.4 Hz, 1H), 7.35 – 7.30 (m, 3H), 7.26 – 7.23 (m,
were recorded on a Bruker micrOTO II equipment (ESI-QTOF). 1H), 6.82 (d, J = 16.4 Hz, 1H), 3.44 (s, 3H), 3.40 (s, 3H). 13C NMR
Column chromatography was performed using silica gel (230- (101 MHz, Chloroform-d) δ 162.3, 151.0, 139.3, 137.3, 129.3,
400 mesh). Thin layer chromatography (TLC) was performed 128.6, 127.6, 126.3, 120.0, 111.4, 37.2, 28.1.
using silica gel GF254, 0.25 mm thickness.
(E)-1,3-dimethyl-5-(3-methylstyryl)pyrimidine-2,4(1H,3H)-
dione (3f): 1H NMR (400 MHz, Chloroform-d) δ 7.32 (d, J = 16.3
A Representative Procedure for the oxidative coupling of 1,3- Hz, 1H), 7.32 (s, 1H), 7.28 (s, 1H), 7.26 – 7.19 (m, 3H), 7.06 (d, J
dimethyluracil (1a) with n-butyl acrylate (2a)
= 6.9 Hz, 1H), 6.83 (d, J = 16.3 Hz, 1H), 3.46 (s, 3H), 3.41 (s, 3H),
2.35 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 162.4, 151.2,
139.2, 138.3, 137.4, 129.5, 128.7, 128.6, 127.2, 123.7, 119.8,
Formation of (E)-butyl 3-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)acrylate 3a: 1,3-dimethyluracil 1a (28
mg, 0.2 mmol), n-butyl acrylate 2a (58 µl, 0.4 mmol), Pd(OAc)2
(4.5 mg, 0.02 mmol), Z-Phe-OH (6.0 mg, 0.02 mmol), PivOH (41
mg, 0.4 mmol) and DMA (1 mL) were placed in a 50 mL Schlenk
tube. The reaction solution was degassed twice and refilled
with O2 (1.0 atm).The mixture was heated in oil bath at 100 oC
with stirring for 24 h. After the reaction vessel was cooled to
room temperature, the crude reaction mixture was diluted
with CH2Cl2 to 5 mL and C28H58 (0.2 mmol) was added as an
internal standard for GC analysis. After GC analysis of the
reaction mixture, volatiles were removed under reduced
pressure, and the residue was subjected to silica gel column
chromatography [eluting with petroleum ether/ethyl
acetate=2:1] to afford 3a in 88% yield. The GC analyses of the
reaction mixture disclosed the formation of 3a in 92% yield.
+
111.7, 37.3, 28.3, 21.5. HRMS: Calculated for C15H17N2O2
[M+H]+:257.1285; Found: 257.1280.
(E)-1,3-dimethyl-5-(4-methylstyryl)pyrimidine-2,4(1H,3H)-
dione (3g): 1H NMR (400 MHz, Chloroform-d) δ 7.37 – 7.30 (m,
4H), 7.14 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 16.4 Hz, 1H), 3.45 (s,
3H), 3.40 (s, 3H), 2.34 (s, 3H). 13C NMR (101 MHz, Chloroform-d)
δ 162.4, 151.2, 139.0, 137.7, 134.6, 129.5, 129.3, 126.4, 119.0,
+
111.8, 37.3, 28.3, 21.4. HRMS: Calculated for C15H17N2O2
[M+H]+:257.1285; Found: 257.1287.
(E)-5-(2,4-dimethylstyryl)-1,3-dimethylpyrimidine-
2,4(1H,3H)-dione (3h): 1H NMR (400 MHz, Chloroform-d) δ
7.61 (d, J = 16.1 Hz, 1H), 7.41 (d, J = 7.7 Hz, 1H), 7.29 (s, 1H),
6.99 (d, J = 7.7 Hz, 1H), 6.98 (s, 1H), 6.67 (d, J = 16.1 Hz, 1H),
3.46 (s, 3H), 3.41 (s, 3H), 2.37 (s, 3H), 2.31 (s, 3H). 13C NMR
(101 MHz, Chloroform-d) δ 162.5, 151.2, 139.3, 137.5, 135.8,
133.7, 131.3, 127.5, 127.0, 125.1, 120.4, 112.1, 37.28, 28.2,
21.2, 20.0. HRMS: Calculated for C16H19N2O2+ [M+H]+:271.1441;
Found: 271.1424.
(E)-butyl
3-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)acrylate (3a) 24
:
1H NMR (400 MHz,
Chloroform-d) δ 7.42 (s, 1H), 7.27 (d, J = 15.8 Hz, 1H), 6.97 (d, J
= 15.8 Hz, 1H), 4.15 (t, J = 6.6 Hz, 2H), 3.47 (s, 3H), 3.37 (s, 3H),
1.68 – 1.59 (m, 2H), 1.45 – 1.34 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H).
13C NMR (101 MHz, Chloroform-d) δ 167.8, 161.4, 150.8, 144.8,
136.3, 119.3, 109.0, 64.4, 37.6, 30.86, 28.2, 19.3, 13.8.
(E)-1,3-dimethyl-5-(2,4,6-trimethylstyryl)pyrimidine-
2,4(1H,3H)-dione (3i): 1H NMR (400 MHz, Chloroform-d) δ 7.36
(d, J = 16.6 Hz, 1H), 6.88 (s, 2H), 6.30 (d, J = 16.6 Hz, 1H), 3.47
(s, 3H), 3.41 (s, 3H), 2.31 (s, 6H), 2.27 (s, 3H). 13C NMR (101
MHz, Chloroform-d) δ 162.5, 151.3, 139.0, 136.5, 136.1, 134.2,
128.9, 128.3, 125.1, 111.9, 37.3, 28.2, 21.2, 21.1. HRMS:
Calculated for C17H21N2O2+ [M+H]+:285.1598; Found: 285.1596.
(E)-ethyl
3-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)acrylate (3b): 1H NMR (400 MHz,
Chloroform-d) δ 7.43 (s, 1H), 7.30 (d, J = 15.8 Hz, 1H), 6.98 (d, J
= 15.8 Hz, 1H), 4.22 (q, J = 7.1 Hz, 2H), 3.48 (s, 3H), 3.39 (s, 3H),
1.31 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, Chloroform-d) δ
167.6, 161.4, 150.8, 144.8, 136.3, 119.3, 109.0, 60.5, 37.6, 28.2,
14.4. HRMS: Calculated for C11H15N2O4+ [M+H]+:239.1026;
Found: 239.1030.
(E)-4-(2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)vinyl)phenyl acetate (3j)
24
:
1H NMR
(400 MHz, Chloroform-d) δ 7.47 – 7.43 (m, 2H), 7.39 (d, J =
16.3 Hz, 1H), 7.33 (s, 1H), 7.09 – 7.03 (m, 2H), 6.78 (d, J = 16.3
Hz, 1H), 3.47 (s, 3H), 3.41 (s, 3H), 2.30 (s, 3H). 13C NMR (101
MHz, Chloroform-d) δ 169.6, 162.4, 151.2, 150.2, 139.5, 135.4,
128.5, 127.4, 121.9, 120.4, 111.5, 37.4, 28.3, 21.3. HRMS:
Calculated for C16H17N2O4+ [M+H]+:301.1183; Found: 301.1176.
(E)-5-(4-methoxystyryl)-1,3-dimethylpyrimidine-2,4(1H,3H)-
dione (3k): 1H NMR (400 MHz, Chloroform-d) δ 7.42 – 7.36 (m,
2H), 7.30 (d, J = 16.3 Hz, 1H), 7.30 (s, 1H), 6.90 – 6.85 (m, 2H),
6.71 (d, J = 16.3 Hz, 1H), 3.82 (s, 3H), 3.46 (s, 3H), 3.41 (s, 3H).
13C NMR (101 MHz, Chloroform-d) δ 162.5, 159.5, 151.2, 138.6,
130.3, 129.1, 127.8, 117.9, 114.3, 112.0, 55.5, 37.3, 28.3.
(E)-tert-butyl
tetrahydropyrimidin-5-yl)acrylate (3c)
3-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
24
:
1H NMR (400 MHz,
Chloroform-d) δ 7.39 (s, 1H), 7.20 (d, J = 15.8 Hz, 1H), 6.89 (d, J
= 15.8 Hz, 1H), 3.47 (s, 3H), 3.39 (s, 3H), 1.50 (s, 9H). 13C NMR
(101 MHz, Chloroform-d) δ 166.9, 161.5, 150.9, 144.3, 135.1,
121.4, 109.2, 80.5, 37.6, 28.3, 28.2.
(E)-2-methoxyethyl
3-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)acrylate (3d): 1H NMR (400 MHz,
Chloroform-d) δ 7.42 (s, 1H), 7.31 (d, J = 15.8 Hz, 1H), 7.03 (d, J
= 15.8 Hz, 1H), 4.34 – 4.29 (m, 2H), 3.66 – 3.62 (m, 2H), 3.47 (s,
3H), 3.40 (s, 3H), 3.37 (s, 3H). 13C NMR (101 MHz, Chloroform-
d) δ 167.6, 161.4, 150.8, 144.9, 136.9, 118.9, 109.0, 70.7, 63.7,
+
HRMS: Calculated for C15H17N2O3 [M+H]+:273.1234; Found:
273.1240.
(E)-5-(4-fluorostyryl)-1,3-dimethylpyrimidine-2,4(1H,3H)-
dione (3l): 1H NMR (400 MHz, Chloroform-d) δ 7.44 – 7.39 (m,
4 | J. Name., 2012, 00, 1-3
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2H), 7.36 (d, J = 16.3 Hz, 1H), 7.32 (s, 1H), 7.06 – 6.98 (m, 2H), Chloroform-d) δ 7.38 (s, 1H), 7.29 (d, J = 15.8 Hz, 1H), 7.00 (d, J
View Article Online
6.73 (d, J = 16.3 Hz, 1H), 3.47 (s, 3H), 3.41 (s, 3H). 13C NMR (101 = 15.8 Hz, 1H), 4.17 (t, J = 6.6 Hz, 2H), 3.97 – 3.91 (m, 2H), 3.80
DOI: 10.1039/C7OB00616K
1
MHz, Chloroform-d) δ 162.5 (d, J C-F= 247.4 Hz), 162.4, 151.1, – 3.75 (m, 2H), 1.81 – 1.71 (m, 2H), 1.70 – 1.61 (m, 4H), 1.47 –
3
3
139.4, 133.7 (d, JC-F = 3.2 Hz), 128.4, 128.0 (d, JC-F = 7.9 Hz), 1.36 (m, 2H), 1.00 – 0.92 (m, 9H). 13C NMR (101 MHz,
3
2
119.9 (d, J C-F= 1.9 Hz), 115.7 (d, JC-F = 21.7 Hz), 111.5, 37.3, Chloroform-d) δ 167.9, 161.2, 150.4, 144.4, 136.5, 119.2, 109.1,
28.3. HRMS: Calculated for C14H14FN2O2 [M+H]+:261.1034; 64.4, 52.0, 43.3, 30.9, 22.5, 20.9, 19.3, 13.8, 11.4, 11.0. HRMS:
+
Found: 261.1043.
Calculated for C17H27N2O4+ [M+H]+:323.1965; Found: 323.1962.
(E)-1,3-dimethyl-5-(4-nitrostyryl)pyrimidine-2,4(1H,3H)-
(E)-butyl
3-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-
dione (3m): 1H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 8.7 tetrahydropyrimidin-5-yl)acrylate (3s): 1H NMR (400 MHz,
Hz, 2H), 7.63 – 7.52 (m, 3H), 7.41 (s, 1H), 6.94 (d, J = 16.2 Hz, Chloroform-d) δ 7.50 – 7.46 (m, 2H), 7.41 – 7.34 (m, 4H), 7.34
1H), 3.50 (s, 3H), 3.42 (s, 3H). 13C NMR (101 MHz, Chloroform-d) – 7.25 (m, 5H), 7.21 (d, J = 15.8 Hz, 1H), 6.98 (d, J = 15.8 Hz,
δ 162.1, 150.9, 146.8, 144.2, 141.5, 127.2, 126.8, 124.9, 124.3, 1H), 5.17 (s, 2H), 4.96 (s, 2H), 4.13 (t, J = 6.6 Hz, 2H), 1.68 –
+
110.6, 37.6, 28.3. HRMS: Calculated for C14H14N3O4
1.57 (m, 2H), 1.45 – 1.33 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13C
NMR (101 MHz, Chloroform-d) δ 167.7, 160.9, 150.7, 143.9,
136.5, 136.3, 134.7, 129.4, 129.2, 128.9, 128.6, 128.3, 127.9,
[M+H]+:288.0979; Found: 288.0975.
(E)-4-(2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)vinyl)benzonitrile (3n)
: 1H NMR 119.5, 109.6, 64.4, 52.8, 45.0, 30.8, 19.2, 13.8. HRMS:
(400 MHz, Chloroform-d) δ 7.62 – 7.58 (m, 2H), 7.54 – 7.48 (m, Calculated for C25H27N2O4+ [M+H]+:419.1965; Found: 419.1965.
3H), 7.39 (s, 1H), 6.89 (d, J = 16.3 Hz, 1H), 3.49 (s, 3H), 3.42 (s,
(E)-butyl
3-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-
3H). 13C NMR (101 MHz, Chloroform-d) δ 162.1, 151.0, 142.2, tetrahydropyrimidin-5-yl)acrylate (3t): 1H NMR (400 MHz,
141.12, 132.6, 127.7, 126.8, 124.0, 119.2, 110.7, 110.7, 37.52, Chloroform-d) δ 7.56 (d, J = 15.6 Hz, 1H), 7.11 (d, J = 15.6 Hz,
+
28.33. HRMS: Calculated for C15H14N3O2 [M+H]+: 268.1081; 1H), 4.18 (t, J = 6.6 Hz, 2H), 3.54 (s, 3H), 3.39 (s, 3H), 2.47 (s,
Found: 268.1083.
(E)-methyl
3H), 1.70 – 1.64 (m, 2H), 1.46 – 1.38 (m, 2H), 0.95 (t, J = 7.4 Hz,
3-(1,3-dimethyl-2,4-dioxo-1,2,3,4- 3H). 13C NMR (101 MHz, Chloroform-d) δ 168.4, 161.0, 152.8,
tetrahydropyrimidin-5-yl)-2-methylacrylate (3o-1) and methyl 151.3, 135.5, 121.5, 107.3, 64.4, 32.9, 30.9, 28.5, 19.3, 17.0,
+
2-((1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-
yl)methyl)acrylate (3o-2): H NMR (400 MHz, Chloroform-d) δ Found: 281.1509.
13.9. HRMS: Calculated for C14H21N2O4 [M+H]+:281.1496;
1
7.54 (s, 1H, 3o-1), 7.36 (s, 1H, 3o-1), 7.15 (s, 1H, 3o-2), 6.27 (s,
1H, 3o-2), 5.82 (s, 1H, 3o-2), 3.79 (s, 3H, 3o-1), 3.75 (s, 3H, 3o- 1H-purin-8-yl)acrylate (4a)
(E)-butyl 3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-
23
:
1H NMR (400 MHz, Chloroform-
2
), 3.49 (s, 3H, 3o-1), 3.39 (s, 6H, 3o-1+3o-2), 3.34 (s, 5H, 3o-2), d) δ 7.51 (d, J = 15.3 Hz, 1H), 7.04 (d, J = 15.3 Hz, 1H), 4.25 (t, J
2.05 (s, 3H, 3o-1). 13C NMR (101 MHz, Chloroform-d) δ 168.3, = 6.6 Hz, 2H), 4.09 (s, 3H), 3.59 (s, 3H), 3.41 (s, 3H), 1.74 – 1.66
167.2, 163.4, 162.4, 151.8, 151.1, 142.4, 141.1, 136.8, 129.7, (m, 2H), 1.47 – 1.40 (m, 2H), 0.97 (t, J = 7.3 Hz, 3H). 13C NMR
128.1, 128.0, 110.5, 109.8, 52.2, 52.0, 37.7, 37.0, 29.7, 28.3, (101 MHz, Chloroform-d) δ 166.1, 155.4, 151.7, 148.5, 146.9,
28.0, 14.8. HRMS: Calculated for C11H15N2O4+ [M+H]+: 239.1026; 126.5, 126.5, 109.4, 65.2, 32.0, 30.8, 29.9, 28.2, 19.3, 13.8.
Found: 239.1033.
(E)-tert-butyl
tetrahydro-1H-purin-8-yl)acrylate (4b)
3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-
23
(E)-1,3-dimethyl-5-(2-phenylprop-1-en-1-yl)pyrimidine-
:
1H NMR (400 MHz,
2,4(1H,3H)-dione
(3p-1)
and
1,3-dimethyl-5-(2- Chloroform-d) δ 7.43 (d, J = 15.3 Hz, 1H), 6.97 (d, J = 15.3 Hz,
1
phenylallyl)pyrimidine-2,4(1H,3H)-dione (3p-2): H NMR (400 1H), 4.07 (s, 3H), 3.58 (s, 3H), 3.41 (s, 3H), 1.54 (s, 9H). 13C
MHz, Chloroform-d) δ 7.52 – 7.41 (m, 2H, 3p-1; 2H, 3p-2), 7.38 NMR (101 MHz, Chloroform-d) δ 165.2, 155.4, 151.6, 148.5,
– 7.26 (m, 4H, 3p-1; 3H, 3p-2 ), 6.84 (s, 1H, 3p-2), 6.58 (s, 1H, 147.1, 128.6, 125.6, 109.2, 81.7, 31.9, 29.8, 28.2, 28.1.
3p-1), 5.57 (s, 1H, 3p-2), 5.17 (s, 1H, 3p-2), 3.59 (s, 2H, 3p-2),
(E)-ethyl
3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-
3.47 (s, 3H, 3p-1), 3.40 (s, 3H, 3p-1), 3.37 (s, 3H, 3p-3), 3.28 (s, 1H-purin-8-yl)acrylate (4c): 1H NMR (400 MHz, Chloroform-d)
3H, 3p-2), 2.21 (s, 3H, 3p-2). 13C NMR (101 MHz, Chloroform-d) δ 7.51 (d, J = 15.3 Hz, 1H), 7.03 (d, J = 15.3 Hz, 1H), 4.30 (q, J =
δ 163.6, 163.3, 151.7, 151.4, 144.3, 143.1, 140.5, 140.3, 139.5, 7.2 Hz, 2H), 4.09 (s, 3H), 3.59 (s, 3H), 3.41 (s, 3H), 1.35 (t, J =
138.3, 128.6, 128.4, 128.0, 127.6, 126.1, 126.0, 118.2, 115.3, 7.2 Hz, 3H). 13C NMR (101 MHz, Chloroform-d) δ 166.0, 155.4,
111.6, 111.5, 37.4, 37.0, 32.2, 28.3, 28.2, 18.0. HRMS: 151.7, 148.5, 146.9, 126.5, 126.5, 109.4, 61.3, 32.0, 29.9, 28.2,
Calculated for C15H17N2O2+ [M+H]+: 257.1285; Found: 257.1289. 14.4. HRMS: Calculated for C13H17N4O4 [M+H]+:293.1244;
+
Found: 293.1250.
(E)-butyl
3-(1,3-diethyl-2,4-dioxo-1,2,3,4-
(E)-2-methoxyethyl
3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-
tetrahydropyrimidin-5-yl)acrylate (3q): 1H NMR (400 MHz, tetrahydro-1H-purin-8-yl)acrylate (4d): 1H NMR (400 MHz,
Chloroform-d) δ 7.43 (s, 1H), 7.29 (d, J = 15.8 Hz, 1H), 6.99 (d, J Chloroform-d) δ 7.51 (d, J = 15.3 Hz, 1H), 7.06 (d, J = 15.3 Hz,
= 15.8 Hz, 1H), 4.17 (t, J = 6.6 Hz, 2H), 3.48 (s, 3H), 3.39 (s, 3H), 1H), 4.40 – 4.35 (m, 2H), 4.06 (s, 3H), 3.68 – 3.63 (m, 2H), 3.55
1.69 – 1.62 (m, 2H), 1.48 – 1.35 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). (s, 3H), 3.42 – 3.38 (m, 6H). 13C NMR (101 MHz, Chloroform-d)
13C NMR (101 MHz, Chloroform-d) δ 167.8, 161.4, 150.8, 144.8, δ 165.9, 155.3, 151.6, 148.4, 146.7, 126.9, 126.0, 109.3, 70.4,
+
136.3, 119.3, 109.0, 64.4, 37.6, 30.9, 28.2, 19.3, 13.9. HRMS: 64.2, 59.1, 31.9, 29.8, 28.1. HRMS: Calculated for C14H19N4O5
Calculated for C15H23N2O4+ [M+H]+:295.1652; Found: 295.1650. [M+H]+:323.1350; Found: 323.1333.
(E)-butyl
3-(2,4-dioxo-1,3-dipropyl-1,2,3,4-
(E)-1,3,7-trimethyl-8-styryl-1H-purine-2,6(3H,7H)-dione (4e)
:
23
tetrahydropyrimidin-5-yl)acrylate (3r): 1H NMR (400 MHz,
1H NMR (400 MHz, Chloroform-d) δ 7.81 (d, J = 15.8 Hz, 1H),
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ARTICLE
Journal Name
7.58 (d, J = 7.0 Hz, 2H), 7.45 – 7.34 (m, 3H), 6.92 (d, J = 15.8 Hz, 1H), 4.34 (t, J = 7.4 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H)V,i3ew.5A2rtic(lse,O3nHlin)e,
1H), 4.07 (s, 3H), 3.63 (s, 3H), 3.42 (s, 3H). 13C NMR (101 MHz, 3.34 (s, 3H), 1.86 – 1.71 (m, 2H), 1.69 – 1.57 (m, 2H), 1.42 –
DOI: 10.1039/C7OB00616K
Chloroform-d) δ 155.4, 151.8, 150.1, 148.7, 138.5, 135.6, 129.7, 1.30 (m, 2H), 0.93 – 0.84 (m, 6H). 13C NMR (101 MHz,
129.1, 127.5, 111.3, 108.1, 31.7, 29.9, 28.1.
Chloroform-d) δ 166.2, 155.0, 151.7, 148.6, 146.5, 126.7, 126.4,
(E)-1,3,7-trimethyl-8-(3-methylstyryl)-1H-purine-
108.9, 65.2, 46.8, 30.7, 29.8, 28.2, 25.0, 19.2, 13.8, 10.9. HRMS:
2,6(3H,7H)-dione (4f): 1H NMR (400 MHz, Chloroform-d) δ 7.79 Calculated for C17H25N4O4+ [M+H]+:349.1870; Found: 349.1863.
(d, J = 15.8 Hz, 1H), 7.40 (s, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.30 (t,
(E)-butyl
3-(7-benzyl-1,3-dimethyl-2,6-dioxo-2,3,6,7-
J = 7.5 Hz, 1H), 7.19 (d, J = 7.5 Hz, 1H), 6.91 (d, J = 15.8 Hz, 1H), tetrahydro-1H-purin-8-yl)acrylate (4m): 1H NMR (400 MHz,
4.07 (s, 3H), 3.63 (s, 3H), 3.42 (s, 3H), 2.40 (s, 3H). 13C NMR Chloroform-d) δ 7.55 (d, J = 15.3 Hz, 1H), 7.37 – 7.27 (m, 3H),
(101 MHz, Chloroform-d) δ 155.5, 151.8, 149.2, 148.3, 139.7, 7.26 – 7.19 (m, 2H), 7.04 (d, J = 15.3 Hz, 1H), 5.69 (s, 2H), 4.22
138.3, 135.3, 130.0, 128.6, 128.1, 125.9, 114.4, 107.5, 32.6, (t, J = 6.6 Hz, 2H), 3.60 (s, 3H), 3.41 (s, 3H), 1.72 – 1.64 (m, 2H),
+
29.9, 28.1, 21.5. HRMS: Calculated for C17H19N4O2
1.49 – 1.35 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz,
Chloroform-d) δ 166.0, 155.2, 151.6, 148.7, 146.9, 135.7, 129.3,
128.6, 127.2, 126.9, 126.8, 108.8, 65.2, 48.4, 30.8, 29.9, 28.3,
[M+H]+:311.1503; Found: 311.1498.
(E)-8-(2,4-dimethylstyryl)-1,3,7-trimethyl-1H-purine-
2,6(3H,7H)-dione (4g): 1H NMR (400 MHz, Chloroform-d) δ 19.3, 13.8. HRMS: Calculated for C21H25N4O4+ [M+H]+:397.1870;
8.02 (d, J = 15.6 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 8.4 Found: 397.1870.
Hz, 1H), 7.04 (s,1H), 6.79 (d, J = 15.6 Hz, 1H), 4.04 (s, 3H), 3.63
(E)-butyl
3-(1-ethyl-3,7-dimethyl-2,6-dioxo-2,3,6,7-
(s, 3H), 3.41 (s, 3H), 2.46 (s, 3H), 2.34 (s, 3H). 13C NMR (101 tetrahydro-1H-purin-8-yl)acrylate (4n): 1H NMR (400 MHz,
MHz, Chloroform-d) δ 155.4, 151.9, 150.5, 148.7, 139.7, 137.2, Chloroform-d) δ 7.51 (d, J = 15.3 Hz, 1H), 7.03 (d, J = 15.3 Hz,
136.2, 131.8, 131.8, 127.3, 125.7, 111.5, 107.9, 31.6, 29.9, 28.1, 1H), 4.25 (t, J = 6.6 Hz, 2H), 4.13 – 4.03 (m, 5H), 3.58 (s, 3H),
21.4, 20.0. HRMS: Calculated for C18H21N4O2+ [M+H]+:325.1659; 1.73 – 1.66 (m, 2H), 1.49 – 1.39 (m, 2H), 1.25 (t, J = 7.0 Hz, 3H),
Found: 325.1659.
0.97 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, Chloroform-d) δ
(E)-1,3,7-trimethyl-8-(2,4,6-trimethylstyryl)-1H-purine-
166.2, 155.2, 151.3, 148.5, 146.8, 126.5, 126.4, 109.5, 65.2,
2,6(3H,7H)-dione (4h): 1H NMR (400 MHz, Chloroform-d) δ 36.7, 32.0, 30.8, 29.8, 19.3, 13.8, 13.4. HRMS: Calculated for
7.89 (d, J = 16.0 Hz, 1H), 6.93 (s, 2H), 6.53 (d, J = 16.0 Hz, 1H), C16H23N4O4+ [M+H]+:335.1714; Found: 335.1708.
3.99 (s, 3H), 3.64 (s, 3H), 3.42 (s, 3H), 2.40 (s, 6H), 2.31 (s, 3H).
(E)-butyl
3-(3,7-dimethyl-2,6-dioxo-1-propyl-2,3,6,7-
13C NMR (101 MHz, Chloroform-d) δ 155.5, 151.7, 149.4, 148.5, tetrahydro-1H-purin-8-yl)acrylate (4o): 1H NMR (400 MHz,
138.3, 137.5, 135.5, 132.7, 128.5, 117.2, 107.5, 32.3, 29.6, 28.0, Chloroform-d) δ 7.51 (d, J = 15.3 Hz, 1H), 7.03 (d, J = 15.3 Hz,
21.1, 20.4. HRMS: Calculated for C19H23N4O2+ [M+H]+:339.1816; 1H), 4.25 (t, J = 6.7 Hz, 2H), 4.09 (s, 3H), 4.02 – 3.91 (m, 2H),
Found: 339.1816.
(E)-8-(4-(tert-butyl)styryl)-1,3,7-trimethyl-1H-purine-
3.58 (s, 3H), 1.75 – 1.61 (m, 4H), 1.44 (dq, J = 14.7, 7.4 Hz, 2H),
0.97 (t, J = 7.4 Hz, 6H). 13C NMR (101 MHz, Chloroform-d) δ
2,6(3H,7H)-dione (4i): 1H NMR (400 MHz, Chloroform-d) δ 7.79 166.1, 155.3, 151.4, 148.5, 146.8, 126.5, 126.4, 109.4, 65.2,
(d, J = 15.7 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 43.1, 31.9, 30.7, 29.7, 21.4, 19.2, 13.8, 11.4. HRMS: Calculated
2H), 6.87 (d, J = 15.7 Hz, 1H), 4.05 (s, 3H), 3.63 (s, 3H), 3.41 (s, for C17H25N4O4+ [M+H]+:349.1870; Found: 349.1872.
3H), 1.35 (s, 9H). 13C NMR (101 MHz, Chloroform-d) δ 155.3,
(E)-butyl 3-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-
153.2, 151.8, 150.3, 148.7, 138.4, 132.9, 127.3, 126.0, 110.5, purin-8-yl)acrylate (4p): 1H NMR (400 MHz, Chloroform-d) δ
107.9, 35.0, 31.6, 31.3, 29.9, 28.0. HRMS: Calculated for 8.46 (s, 1H), 7.50 (d, J = 15.3 Hz, 1H), 7.05 (d, J = 15.3 Hz, 1H),
C20H25N4O2+ [M+H]+:353.1972; Found: 353.1971.
4.25 (t, J = 6.7 Hz, 2H), 4.07 (s, 3H), 3.55 (s, 3H), 1.74 – 1.67 (m,
(E)-8-(4-fluorostyryl)-1,3,7-trimethyl-1H-purine-2,6(3H,7H)- 2H), 1.44 (dq, J = 14.7, 7.4 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H).
23
+
dione (4j)
:
1H NMR (400 MHz, Chloroform-d) δ 7.77 (d, J = HRMS: Calculated for C14H19N4O4 [M+H]+:307.1401; Found:
15.7 Hz, 1H), 7.60 – 7.53 (m, 2H), 7.14 – 7.06 (m, 2H), 6.83 (d, J 307.1400.
= 15.7 Hz, 1H), 4.06 (s, 3H), 3.62 (s, 3H), 3.41 (s, 3H). 13C NMR
1
(101 MHz, Chloroform-d) δ 163.5 (d, JC-F = 250.6 Hz), 155.4,
151.8, 149.9, 148.7, 137.2, 131.9, 129.2 (d, 3JC-F = 8.3 Hz), 116.2
Acknowledgements
(d, 2JC-F = 21.9 Hz), 111.1, 108.1, 31.6, 29. 9, 28.1.
We are grateful to the National Natural Science Foundation of
China (Grant No. 21103022 and 61520106015), Natural
Science Foundation of Fujian Province, China (Grant No.
2017J01572), the Foundation of Fujian Educational Committee
(Grant No. JK2014010 and JZ160424), and the Fujian Province
University Fund for New Century Excellent Talents for financial
support.
(E)-butyl
3-(7-ethyl-1,3-dimethyl-2,6-dioxo-2,3,6,7-
tetrahydro-1H-purin-8-yl)acrylate (4k): 1H NMR (400 MHz,
Chloroform-d) δ 7.50 (d, J = 15.3 Hz, 1H), 7.06 (d, J = 15.3 Hz,
1H), 4.52 (q, J = 7.1 Hz, 2H), 4.25 (t, J = 6.6 Hz, 2H), 3.59 (s, 3H),
3.42 (s, 3H), 1.70 (p, J = 6.9 Hz, 2H), 1.53 – 1.41 (m, 5H), 0.97 (t,
J = 7.4 Hz, 3H). 13C NMR (101 MHz, Chloroform-d) δ 166.2,
155.0, 151.7, 148.7, 146.0, 126.6, 126.5, 108.6, 65.2, 40.6, 30.7,
29.8, 28.2, 19.2, 17.1, 13.8. HRMS: Calculated for
C16H23N4O4+ [M+H]+:335.1714; Found: 335.1706.
Notes and references
(E)-butyl
3-(1,3-dimethyl-2,6-dioxo-7-propyl-2,3,6,7-
1
(a) J. Kakish, K. J. H. Allen, T. A. Harkness, E. S. Krol and J. S.
tetrahydro-1H-purin-8-yl)acrylate (4l): 1H NMR (400 MHz,
Chloroform-d) δ 7.42 (d, J = 15.3 Hz, 1H), 6.98 (d, J = 15.3 Hz,
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