Iron-catalyzed vinylogous aldol condensation of biginelli products and its application toward pyrido[4,3- d ]pyrimidinones

Article abstract of DOI:10.1021/jo402773r

A novel iron-catalyzed vinylogous aldol condensation of Biginelli products with aryl aldehydes has been developed for the syntheses of potential bioactive (E)-6-arylvinyl-dihydropyrimidin-2(1H)-ones. These materials are valuable synthetic precursors to drug-like pyrido[4,3-d]pyrimidine derivatives. The amide group at the 5-position of the dihydropyrimidin-2(1H)-ones played an important role in the vinylogous aldol condensation reaction.

Full text of DOI:10.1021/jo402773r

Note
pubs.acs.org/joc
Iron-Catalyzed Vinylogous Aldol Condensation of Biginelli Products
and Its Application toward Pyrido[4,3‑d]pyrimidinones
Lianqiang Zhang, Zhiguo Zhang,* Qingfeng Liu, Tongxin Liu, and Guisheng Zhang*
Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical
Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang,
Henan 453007, PR China
S
* Supporting Information
ABSTRACT: A novel iron-catalyzed vinylogous aldol condensation of Biginelli products with aryl aldehydes has been developed
for the syntheses of potential bioactive (E)-6-arylvinyl-dihydropyrimidin-2(1H)-ones. These materials are valuable synthetic
precursors to drug-like pyrido[4,3-d]pyrimidine derivatives. The amide group at the 5-position of the dihydropyrimidin-2(1H)-
ones played an important role in the vinylogous aldol condensation reaction.
ihydropyrimidin-2(1H)-ones (DHPMs) display a broad
products 1 should form the vinylogous conjugated systems A
in the presence of a suitable catalyst.13−15 Then, the vinylogous
enolate A would attack aldehyde 2 to afford the intermediates
B, subsequently leading to the products 3 via dehydration
(Scheme 2).21−28 In our efforts to develop highly efficient
methods for functional group transformations, we found that
iron salts are effective, reusable, operationally simple, and
environmentally benign catalysts.29−31 As a result, we selected
ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-
carboxylate 1a (1.0 equiv) and 5-acetyl-6-methyl-4-phenyl-3,4-
dihydropyrimidin-2(1H)-one 1b (1.0 equiv), respectively, to
react with 2a in the presence of FeCl3·6H2O (10 mol %) in
CH3CN at reflux (Scheme 3). Disappointingly, after 7 h, the
desired compounds 3a and 3b were not observed, and most of
the starting materials 1a (93%) and 1b (95%) were recovered.
Fortunately, 6-arylvinyl DHPM 3c was isolated in 15% yield
when 5-carboxamide substituted DHPM 1c32 was employed for
the reaction, but the yield of 3c could not be further increased
by prolonging the reaction time (Table 1, entry 9) (Scheme 3).
These results indicate that the amide moiety at the 5-position
of DHPMs 1 is very important for this vinylogous aldol
condensation reaction. We deduced that the nitrogen of the
amide moiety contributed its unpaired electrons to the
conjugated system A, which would enhance the nucleophilicity
of the alkene (Scheme 2).14,24,33−36 It is noteworthy that,
D
range of biological activities, such as antitumor,1
antihypertensive,2 anti-HIV,3 antioxidant,4 antimalarial,5 anti-
microbial, anti-inflammatory, antibacterial, antifungal, and
anthelmintic activities.6 To date, as the major method for the
synthesis of DHPMs, the Biginelli reaction has received much
attention. In the past decade, there have been nearly 500
publications concerning this reaction.7 However, these reports
have mostly focused on the improvement of the reaction
catalyst.7 Relatively, it is rare to focus on the derivatization of
DHPMs, especially on the functionalization of the C-6 methyl
group; in general, acetoacetates are employed in the Biginelli
reaction, and, therefore, in most cases, a methyl group is
introduced at the C-6 position of the pyrimidine ring.8 To the
best of our knowledge, very few reports have appeared in the
literature concerning the functionalization of the C-6 methyl
group, which is reported to proceed through (i) bromination
and a subsequent nucleophilic replacement reaction (Scheme 1,
eq 1),9−11 or (ii) electrophilic substitution reaction in the
presence of base (Scheme 1, eq 2).12 In contrast, vinylogous
aldol reaction of cyclic compounds has received much
attention,13−15 although vinylogous aldol reaction of Biginelli
products has not yet been achieved to date. We present here
the first report of vinylogous aldol reaction of Biginelli
products, an effective and practical Lewis acid-catalyzed
approach to 6-arylvinyl DHPMs 3 (Scheme 1, eq 3), and its
further application to generate additional drug-like complex
derivatives, including pyrido[4,3-d]pyrimidines 4 (Scheme 1).
In the course of our continuous research on the direct
syntheses of heterocyclic compounds from readily available
acyclic precursors,16−20 we note that there is a potential
vinylogous conjugated system in the Biginelli products
(Schemes 1 and 2). We hypothesized that the Biginelli
1
according to the H NMR data, the CC double bond at the
6-position was assigned as an E configuration on the basis of
the magnitude of the coupling constant (16.4 Hz).37
Received: December 14, 2013
Published: February 11, 2014
© 2014 American Chemical Society
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Note
Scheme 1. Functionalization of the C-6 Methyl Position of DHPMs 1
a
Scheme 2. Synthetic Hypothesis
Table 1. Survey of Reaction Conditions
2a
entry
1
cat. (equiv)
(equiv)
T (°C) time (h) yield (%)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.05)
FeCl3·6H2O (0.2)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.1)
FeCl3·6H2O (0.1)
FeCl3 (0.1)
2
2
2
2
2
2
2
2
2
1
1.5
3
2
2
2
2
reflux
reflux
reflux
80
18
24
10
10
10
30
10
38
18
4
88
30
0
Scheme 3. Initial Attempts to Synthesize 6-Arylvinyl DHPMs
3
b
2
c
3
d
4
0
e
5
f
reflux
60
0
6
50
0
g
7
40
8
9
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
80
84
15
51
88
77
86
82
trace
h
10
i
11
12
14
28
30
35
10
12
13
14
15
With these encouraging initial results in hand, a more
detailed screening of conditions was carried out immediately by
using a model compound of 5-carboxamide substituted DHPM
1c and benzaldehyde 2a. Some key results are summarized in
Table 1. It was found that the yield of 3c could reach 88% in
the presence of FeCl3·6H2O (10 mol %) in CH3CN (3.0 mL)
after reflux for 18 h when the ratio of 1c and 2a reached 1:2
(Table 1, entry 1). In EtOH, the yield of 3c reached only 30%
along with the recovered 1c (44%) and could not be increased
by prolonging the reaction time (entry 2). When the reaction
was performed in CH2Cl2 or DMSO, the desired product 3c
was not observed, and most of the 1c was recovered (entries 3
and 4). The efficacy of water as solvent for this reaction was
also investigated, given that it is very efficient in many similar
reactions.38 However, after using water under the optimized
conditions we found that the reaction of 1c with 2a did not
afford the desired compound 3c, and almost all of the starting
material 1c was recovered (98%). This result was observed
despite the use of 10 mmol % tetrabutylammonium bromide as
a phase-transfer catalyst to increase the solubility of 1c and 2a
(entry 5). It became obvious that acetonitrile achieved the best
conversion for this reaction,39 and we considered that an iron−
acetonitrile complex40,41 might be involved in the reaction and
promote the formation of the vinylogous conjugated systems.
We found that temperature also had a significant influence on
the transformation, because the yield of 3c decreased
Fe2(SO4)3·xH2O (0.1)
FeSO4·7H2O (0.1)
Fe(NO3)3·9H2O (0.1)
j
16
a
Unless otherwise indicated, all reactions were carried out with 1c (0.5
mmol), 2a (1.0 mmol), and FeCl3·6H2O (10 mol %) in CH3CN (3.0
mL) at reflux. Reaction was performed in EtOH, and 44% 1c was
recovered. Reaction was performed in CH2Cl2, and 95% 1c was
recovered. Reaction was performed in DMSO, and 90% 1c was
recovered. Reaction was performed in water, and 98% 1c was
recovered. 44% 1c was recovered. 95% 1c was recovered. The yield
of 3c could not be increased by prolonging the reaction time, and 80%
1c was recovered. The yield of 3c could not be increased by
prolonging the reaction time, and 43% 1c was recovered. 79% 1c was
b
c
d
e
f
g
h
i
j
recovered.
significantly with decreasing temperature (entries 6 and 7).
These results suggest that temperature influences the formation
of the enolate of the Biginelli products, essentially affecting the
formation of the vinylogous conjugated systems. In contrast,
the amount of FeCl3·6H2O had little effect on the yield of
product 3c, with different amounts of the catalyst leading to
negligible changes in yield (entries 8 and 9). It was noted that
the amount of 2a had an obvious influence on the reaction. 3c
was obtained in 51% yield when 1.5 equiv of 2a was used (43%
1c was recovered) and the yield of 3c was not increased by
prolonging the reaction time (entry 1 vs 11). Similarly, the yield
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a
Table 2. Synthesis of 3
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Note
Table 2. continued
a
b
Unless otherwise indicated, all reactions were carried out with 1 (0.5 mmol), 2 (1.0 mmol), and FeCl3·6H2O (10 mol %) in CH3CN (3.0 mL). 3.0
c
d
equiv of 2 was used. Unidentified complex mixture was observed. 10 mol % Fe2(SO4)3·xH2O was used, and the yield was based on the conversion
of 1m, and 42% substrate 1m was recovered. 50 mol % Fe2(SO4)3·xH2O was used, and some unidentified complex mixture was obtained. 56%
substrate 1 was recovered, and the yield of 3w could not be increased by prolonging the reaction time. 93% substrate 1 was recovered. 95%
e
f
g
h
I
j
substrate 1 was recovered. 56% substrate 1 was recovered, and the yield of 3aa would decrease by prolonging the reaction time. 87% substrate 1
was recovered.
of 3c did not improve when the amount of 2a was increased
from 2.0 to 3.0 equiv, although an increased amount of 2a
appeared beneficial for the conversion (entry 1 vs 12). The
effectiveness of other iron salts such as anhydrous FeCl3,
Fe2(SO4)3·xH2O, FeSO4·7H2O, and Fe(NO3)3·9H2O varied
between slightly less effective and near ineffective (entries 13−
16).
antitumor, and antimicrobial properties,42 while some com-
pounds have also been discovered as EGFr-TK inhibitors43 or
DHFR inhibitors.44 Commonly, compounds 4 can be obtained
by intramolecular cyclization of the side chain of pyridines or
pyrimidines.45−47 However, sometimes this requires a multistep
process, relatively strict reaction conditions, and/or long
reaction time. Thus, we became interested in developing a
more facile and flexible synthetic approach to a wide range of
structurally different pyrido[4,3-d]pyrimidinones 4. Some
compounds 3 were randomly selected as substrates to prepare
compounds 4. As a result, we found that pyrido[4,3-
d]pyrimidines 4a−4e could be successfully produced in good
to excellent yields via intramolecular cyclocondensation of
corresponding 3 in the presence of NaOH in EtOH at reflux.
Compared with known procedures, the present methodology
allows ready access to multisubstituted pyrido[4,3-d]-
pyrimidines 4 via two reactions and is much more concise
and practical (Scheme 4).
Using the optimized reaction conditions (Table 1, entry 1),
the scope of this protocol was investigated (Table 2). First, the
reactions of benzaldehyde 2a with a series of DHPMs 1d−1j
bearing different substituents [such as an electron-donating
group (OMe) or an electron-withdrawing group (Cl, CO2Et) at
ortho-, meta-, or para-position] on the benzene ring of N-aryl
group at the 5-position were performed. As expected, these
reactions worked well and gave the target products 3d−3j in
good to excellent yields (75−94%) regardless of the electronic
nature and the position of the diverse substituents. The
variation in yields of the products 3g, 3h, 3i, and 3d, 3e, 3f is
likely the result of the electronic effect of the substituent on the
aryl ring, which affects the electron density of the amide
nitrogen atom, and thereby affects the formation of the
vinylogous conjugated systems. In addition, the reactions of 2a
with N-aliphatic substituted DHPMs 1k and 1l resulted in the
yields of 3k and 3l of 80 and 35%, respectively. When 4-phenyl-
3,4-dihydropyrimidin-2(1H)-thione 1m was employed for the
condensation, 3m was obtained in 81% yield based on the
conversion of 1m after 30 h in the presence of 10 mol %
Fe2(SO4)3·xH2O, while 42% substrate 1m was recovered. The
yield of 3m was not improved by increasing the amount of
Fe2(SO4)3·xH2O. Next, to enlarge the available drug-like library
of the diverse 3 for bioactive screening, several DHPMs 1 and
aldehydes 2 (commonly different from the aldehydes being
used in the preparation of Biginelli products 1) were selected
randomly to prepare 3n−3u. These products, featuring a
variety of substituents with different electronic properties, were
smoothly prepared in good to excellent yields (73−91%) under
the optimized conditions. Subsequently, the condensations of
1c with heterocyclic aldehydes and aliphatic aldehyde were
investigated. The reaction of 2-furaldehyde with 1c gave 3w in
11% yield, while 2-thienaldehyde reacted with 1c to give 3v in
45% yield along with some unidentified complex mixture by
using 0.5 equiv of Fe2(SO4)3·xH2O. However, when 2-
pyrrolaldehyde, 4-pyridylaldehyde, and pivaldehyde were
subjected to the optimized reaction conditions, the desired
products 3x−3z were not obtained, and most of the starting
materials were recovered. In further experiments, the
thiophene-substituted Biginelli product 1aa gave the desired
product 3aa in 32% yield, while no reaction occurred using 4-t-
butyl-substituted DHPM 1ab.
Scheme 4. Synthesis of Pyrido[4,3-d]pyrimidine-2,5-diones
4
In summary, we developed an iron-catalyzed intermolecular
vinylogous aldol condensation of DHPMs 1 and aldehydes 2
for the synthesis of useful 6-arylvinyl DHPMs 3 in good to
excellent yields. It is noteworthy that the amide group at the 5-
position of the DHPMs played an important role in the
vinylogous aldol condensation reaction. Advantages of the
present method include the variety of cheap and readily
available reactants, a wide range of substrates with dense or
flexible substitution patterns, and the important synthetic
potential of the products. As one of the important applications
of 6-arylvinyl DHPMs 3, multisubstituted pyrido[4,3-d]-
pyrimidines 4 were easily prepared in good yields via
intramolecular addition.
We reasoned that an important application of vinylogous
reaction products 3 could be the conversion via an intra-
molecular addition reaction to give pyrido[4,3-d]pyrimidine
derivatives 4, which possess various remarkable biological
activities including fungicidal, antiviral, anti-inflammatory,
EXPERIMENTAL SECTION
General Information. All reagents were purchased from
■
commercial sources and used without further treatment. All reactions
were carried out under air atmosphere. H NMR and 13C{1H} NMR
1
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Note
spectra were recorded on a 400 MHz NMR spectrometer (1H: 400
MHz, 13C{1H}: 100 MHz at 25 °C) and TMS as internal standard.
Data are represented as follows: chemical shift, integration, multiplicity
(br = broad, s = singlet, d = doublet, dd = double doublet, t = triplet, q
= quartet, m = multiplet), coupling constants in Hertz (Hz). All high-
resolution mass spectra (HRMS) were measured on a mass
spectrometer by using electrospray ionization (ESI), and the purity
= 80/1) as a white solid (180.6 mg, 85%): mp 242−244 °C; 1H NMR
(400 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.77 (s, 1H), 7.71 (s, 1H), 7.47
(d, J = 8.4 Hz, 2H), 7.42−7.24 (m, 11H), 7.21 (d, J = 16.4 Hz, 1H),
6.85 (d, J = 8.0 Hz, 2H), 5.48 (s, 1H), 3.71 (s, 3H); 13C{1H} NMR
(100 MHz, DMSO-d6) δ 164.4, 155.5, 152.9, 143.6, 136.3, 135.8,
132.1, 131.2, 128.9, 128.5, 128.4, 127.5, 126.6, 126.4, 121.5, 119.4,
113.7, 110.2, 55.7, 55.2; HRMS (ESI), m/z calcd. for C26H23N3O3 ([M
+ Na]+) 448.1634, found 448.1631.
1
of all samples used for HRMS (>95%) were confirmed by H and
13C{1H} NMR spectroscopic analysis. Melting points were measured
(E)-N-(3-Methoxyphenyl)-2-oxo-4-phenyl-6-styryl-1,2,3,4-
tetrahydropyrimidine-5-carboxamide (3e). The product was
isolated by flash chromatography (eluent: dichloromethane/methanol
on a melting point apparatus equipped with a thermometer and were
uncorrected. All reactions were monitored by TLC with GF254 silica
gel coated plates. Flash chromatography was carried out on SiO2 (silica
gel 200−300 mesh).
1
= 100/1) as a white solid (167.8 mg, 79%): mp 212−214 °C; H
NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.82 (s, 1H), 7.75 (s,
1H), 7.42−7.38 (m, 3H), 7.37−7.26 (m, 9H), 7.20−7.15 (m, 3H),
6.63 (dd, J1 = 7.2 Hz, J2 = 2.0 Hz, 1H), 5.47 (d, J = 2.4 Hz, 1H), 3.70
(s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 164.9, 159.4, 152.8,
143.6, 140.2, 136.9, 136.3, 131.6, 129.4, 129.3, 128.9, 128.6, 127.6,
126.7, 126.4, 119.3, 112.2, 110.0, 108.8, 105.7, 55.7, 55.0; HRMS
(ESI), m/z calcd. for C26H23N3O3 ([M + H]+) 426.1812, found
426.1822.
Typical Experimental Procedure for the Synthesis of 3 (3c as
an Example). To a round-bottom flask (25 mL) equipped with a
spherical condenser (40 cm length) were added 6-methyl-2-oxo-N,4-
diphenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamide 1c (153.5 mg,
0.5 mmol), benzaldehyde 2a (106.0 mg, 1.00 mmol), FeCl3·6H2O
(13.5 mg, 0.05 mmol), CH3CN (3.0 mL). Then the mixture was well
stirred under reflux for 18 h (the whole process was closely monitored
by TLC). After the mixture cooled off, water was added (3.0 mL), the
mixture was filtered, and then the filter cake was purified by a short
flash silica gel column chromatography (eluent: dichloromethane/
methanol = 80/1) to give (E)-2-oxo-N,4-diphenyl-6-styryl-1,2,3,4-
tetrahydropyrimidine-5-carboxamide 3c as white solid (173.8 mg,
(E)-N-(2-Methoxyphenyl)-2-oxo-4-phenyl-6-styryl-1,2,3,4-
tetrahydropyrimidine-5-carboxamide (3f). The product was
isolated by flash chromatography (eluent: dichloromethane/methanol
1
= 100/1) as a yellow solid (187.3 mg, 88%): mp 234−236 °C; H
NMR (400 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.77 (s, 1H), 7.74 (d, J =
7.2 Hz, 2H), 7.51−7.31 (m, 12H), 7.07 (t, J = 7.6 Hz, 1H), 6.98 (d, J =
8.4 Hz, 1H), 6.88 (t, J = 7.2 Hz, 1H), 5.39 (s, 1H), 3.60 (s, 3H);
13C{1H} NMR (100 MHz, DMSO-d6) δ 164.9, 153.2, 150.7, 143.9,
1
88%): mp 221−223 °C; H NMR (400 MHz, DMSO-d6) δ 10.03 (s,
1H), 8.84 (s, 1H), 7.76 (s, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.45−7.25
(m, 13H), 7.22 (d, J = 16.8 Hz, 1H), 7.04 (t, J = 7.6 Hz, 1H), 5.51 (d, J
= 2.0 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 164.88,
152.84, 143.62, 139.06, 136.29, 136.19, 131.50, 128.94, 128.61, 127.58,
126.70, 126.41, 123.48, 119.93, 119.35, 110.03, 106.61, 55.75; HRMS
(ESI), m/z calcd. for C25H21N3O2 ([M + H]+) 396.1707, found
396.1704.
138.3, 136.7, 133.0, 129.3, 129.1, 128.2, 127.5, 127.4, 127.1, 125.3,
123.0, 120.7, 120.0, 111.5, 109.2, 56.0, 55.9; HRMS (ESI), m/z calcd.
for C26H23N3O3 ([M + H]+) 426.1812, found 426.1810.
(E)-N-(4-Chlorophenyl)-2-oxo-4-phenyl-6-styryl-1,2,3,4-tet-
rahydropyrimidine-5-carboxamide (3g). The product was iso-
lated by flash chromatography (eluent: dichloromethane/methanol =
Typical Experimental Procedure for the Synthesis of 4 (4a as
an Example). To a round-bottom flask (25 mL) equipped with a
spherical condenser (40 cm length) were added (E)-2-oxo-N,4-
diphenyl-6-styryl-1,2,3,4-tetrahydropyrimidine-5-carboxamide 3c
(197.5 mg, 0.5 mmol), NaOH (24.0 mg, 0.6 mmol), EtOH (3.0
mL). Then the mixture was well stirred under reflux for 8 h (the whole
process was closely monitored by TLC). After cooling off, the mixture
was treated with saturated aqueous NH4Cl solution (30 mL), and the
aqueous phase was extracted with ethyl acetate (20 mL × 3). The
combined organic layer was washed with brine (3.0 mL) and dried
over MgSO4. The solvent was evaporated, and the residue was purified
by a short flash silica gel column chromatography (eluent: dichloro-
methane/methanol = 100/1) to give 4,6,7-triphenyl-3,4,7,8-
tetrahydropyrido[4,3-d]pyrimidine-2,5(1H,6H)-dione 4a as white
solid (163.9 mg, 83%): mp 302−304 °C; 1H NMR (400 MHz,
DMSO-d6) δ 9.26 (s, 1H), 7.74 (s, 1H), 7.40−7.14 (m, 12H), 7.10 (d,
J = 7.6 Hz, 2H), 7.03 (t, J = 7.2 Hz, 1H), 5.33 (t, J = 5.2 Hz, 1H), 5.22
(s, 1H), 3.28 (dd, J1 = 16.4 Hz, J2 = 5.6 Hz, 1H), 2.72 (dd, J1 = 16.4
Hz, J2 = 4.0 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 163.73,
152.11, 144.94, 143.45, 141.84, 141.06, 128.52, 128.37, 128.09, 127.47,
127.19, 126.85, 126.67, 126.54, 125.25, 100.94, 59.91, 53.33, 33.33;
HRMS (ESI), m/z calcd. for C25H21N3O2 ([M + H]+) 396.1707,
found 396.1706.
1
80/1) as a white solid (186.6 mg, 87%): mp 252−254 °C; H NMR
(400 MHz, DMSO-d6) δ 10.15 (s, 1H), 8.86 (s, 1H), 7.78 (s, 1H),
7.61 (d, J = 8.8 Hz, 2H), 7.42−7.26 (m, 13H), 7.19 (d, J = 16.8 Hz,
1H), 5.48 (d, J = 2.4 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6)
δ 165.6, 153.4, 143.5, 138.0, 136.8, 136.3, 132.4, 129.4, 129.3, 129.1,
129.0, 128.3, 128.0, 127.2, 126.9, 122.1, 119.4, 110.0, 56.2; HRMS
(ESI), m/z calcd. for C25H20ClN3O2 ([M + H]+) 430.1317, found
430.1316.
(E)-N-(3-Chlorophenyl)-2-oxo-4-phenyl-6-styryl-1,2,3,4-tet-
rahydropyrimidine-5-carboxamide (3h). The product was iso-
lated by flash chromatography (eluent: dichloromethane/methanol =
1
80/1) as a white solid (165.2 mg, 77%): mp 225−227 °C; H NMR
(400 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.89 (s, 1H), 7.80 (s, 2H),
7.49 (d, J = 8.4 Hz, 1H), 7.45−7.36 (m, 6H), 7.34−7.27 (m, 6H), 7.22
(d, J = 16.4 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 5.52 (d, J = 2.4 Hz,
1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 165.6, 153.2, 144.0,
141.0, 137.4, 136.7, 133.4, 132.5, 130.7, 129.4, 129.1, 128.1, 127.2,
126.9, 123.6, 119.7, 118.6, 109.9, 107.1, 56.1; HRMS (ESI), m/z calcd.
for C25H20ClN3O2 ([M + H]+) 430.1317, found 430.1314.
(E)-N-(2-Chlorophenyl)-2-oxo-4-phenyl-6-styryl-1,2,3,4-tet-
rahydropyrimidine-5-carboxamide (3i). The product was isolated
by flash chromatography (eluent: dichloromethane/methanol = 100/
1) as a white solid (201.6 mg, 94%): mp 225−227 °C; 1H NMR (400
MHz, DMSO-d6) δ 9.55 (s, 1H), 8.87 (s, 1H), 7.76 (s, 1H), 7.48
−7.39 (m, 12H), 7.30 (t, J = 7.2 Hz, 3H), 7.20 (t, J = 7.6 Hz, 1H), 5.46
(s, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 165.5, 153.2, 143.9,
137.7, 136.7, 135.5, 132.5, 129.9, 129.3, 129.1, 129.0, 128.7, 128.1,
127.9, 127.6, 127.4, 127.3, 127.1, 120.0, 109.3, 56.1; HRMS (ESI), m/z
calcd. for C25H20ClN3O2 ([M + H]+) 430.1317, found 430.1304.
(E)-Ethyl 4-(2-oxo-4-phenyl-6-styryl-1,2,3,4-tetrahydropyri-
midine-5-carboxamido)benzoate (3j). The product was isolated
by flash chromatography (eluent: dichloromethane/methanol = 80/1)
(E)-2-Oxo-N,4-diphenyl-6-styryl-1,2,3,4-tetrahydropyrimi-
dine-5-carboxamide (3c). The product was isolated by flash
chromatography (eluent: dichloromethane/methanol = 80/1) as a
1
white solid (173.8 mg, 88%): mp 221−223 °C; H NMR (400 MHz,
DMSO-d6) δ 10.03 (s, 1H), 8.84 (s, 1H), 7.76 (s, 1H), 7.58 (d, J = 8.0
Hz, 2H), 7.43−7.26 (m, 13H), 7.22 (d, J = 16.8 Hz, 1H), 7.04 (t, J =
7.6 Hz, 1H), 5.51 (d, J = 2.0 Hz, 1H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 164.9, 152.8, 143.6, 139.1, 136.3, 136.2, 131.5, 128.9,
128.6, 127.6, 126.7, 126.4, 123.5, 119.9, 119.4, 110.0, 106.6, 55.8;
HRMS (ESI), m/z calcd. for C25H21N3O2 ([M + H]+) 396.1707,
found 396.1704.
1
as a white solid (175.1 mg, 75%): mp 211−213 °C; H NMR (400
MHz, DMSO-d6) δ 10.34 (s, 1H), 8.90 (s, 1H), 7.88 (d, J = 8.4 Hz,
2H), 7.80 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.42−7.26 (m, 11H), 7.21
(d, J = 16.4 Hz, 1H), 5.51 (d, J = 2.4 Hz, 1H), 4.28 (q, J = 7.2 Hz,
(E)-N-(4-Methoxyphenyl)-2-oxo-4-phenyl-6-styryl-1,2,3,4-
tetrahydropyrimidine-5-carboxamide (3d). The product was
isolated by flash chromatography (eluent: dichloromethane/methanol
2285
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The Journal of Organic Chemistry
Note
2H), 1.30 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ
165.4, 165.3, 152.8, 143.6, 143.5, 137.3, 136.2, 132.1, 130.1, 129.0,
128.7, 127.6, 126.8, 126.4, 124.3, 119.2, 119.1, 109.3, 60.4, 55.6, 14.2;
One carbon was not observed; HRMS (ESI), m/z calcd. for
C28H25N3O4 ([M + Na]+) 490.1737, found 490.1710.
5.50 (s, 1H), 3.83 (s, 3H), 3.71 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 165.9, 164.7, 158.8, 152.7, 141.0, 139.0, 135.8, 135.6,
130.1, 129.9, 129.1, 128.6, 127.7, 126.9, 123.6, 122.0, 120.0, 114.0,
111.5, 55.3, 55.1, 52.2; HRMS (ESI), m/z calcd. for C28H25N3O5 ([M
+ Na]+) 506.1686, found 506.1664.
(E)-N-Benzyl-2-oxo-4-phenyl-6-styryl-1,2,3,4-tetrahydropyri-
midine-5-carboxamide (3k). The product was isolated by flash
chromatography (eluent: dichloromethane/methanol = 60/1) as a
(E)-Methyl 4-(2-(2-oxo-6-phenyl-5-(phenylcarbamoyl)-
1,2,3,6-tetrahydropyrimidin-4-yl)vinyl)benzoate (3q). The
product was isolated by flash chromatography (eluent: dichloro-
methane/methanol = 80/1) as a white solid (165.3 mg, 73%): mp
1
white solid (163.6 mg, 80%): mp 228−230 °C; H NMR (400 MHz,
1
270−272 °C; H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.87
DMSO-d6) δ 8.69 (s, 1H), 8.60 (s, 1H), 7.66 (s, 1H), 7.36−7.24 (m,
14H), 7.20 (d, J = 16.8 Hz, 1H), 7.14−7.12 (m, 2H), 5.37 (d, J = 2.8
Hz, 1H), 4.39 (dd, J1 = 14.8 Hz, J2 = 6.0 Hz, 1H), 4.20 (dd, J1 = 14.8
Hz, J2 = 6.0 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.0,
152.9, 143.5, 139.6, 136.4, 135.1, 130.8, 128.9, 128.6, 128.5, 128.3,
127.6, 127.4, 126.74, 126.69, 119.4, 110.1, 55.7, 42.4; One carbon was
not observed; HRMS (ESI), m/z calcd. for C26H23N3O2 ([M + Na]+)
432.1682, found 432.1648.
(s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.79 (s, 1H), 7.56 (t, J = 8.0 Hz,
4H), 7.45 (d, J = 16.8 Hz, 1H), 7.37−7.27 (m, 8H), 7.05 (t, J = 7.2 Hz,
1H), 5.55 (d, J = 2.0 Hz, 1H), 3.84 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 165.8, 164.6, 152.7, 143.4, 140.9, 138.9, 135.9, 130.2,
129.8, 129.1, 128.6, 127.6, 126.8, 126.4, 123.5, 121.9, 120.0, 111.1,
55.8, 52.1; HRMS (ESI), m/z calcd. for C27H23N3O4 ([M + H]+)
454.1761, found 454.1747.
(E)-Methyl 4-(2-(6-(4-fluorophenyl)-2-oxo-5-(phenylcarba-
moyl)-1,2,3,6-tetrahydropyrimidin-4-yl)vinyl)benzoate (3r).
The product was isolated by flash chromatography (eluent: dichloro-
methane/methanol = 80/1) as a white solid (204.8 mg, 87%): mp
(E)-N-Methyl-2-oxo-4-phenyl-6-styryl-1,2,3,4-tetrahydropyr-
imidine-5-carboxamide (3l). The product was isolated by flash
chromatography (eluent: dichloromethane/methanol = 40/1) as a
yellow solid (58.3 mg, 35%): mp 250−252 °C; H NMR (400 MHz,
DMSO-d6) δ 8.67 (s, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.45−7.26 (m,
12H), 5.32 (d, J = 2.4 Hz, 1H), 2.60 (d, J = 4.0 Hz, 3H); 13C{1H}
NMR (100 MHz, DMSO-d6) δ 166.4, 153.0, 143.6, 136.5, 135.6,
130.9, 128.9, 128.5, 128.4, 127.5, 126.8, 126.4, 119.7, 109.8, 55.3, 26.1;
HRMS (ESI), m/z calcd. for C20H19N3O2 ([M + Na]+) 356.1369,
found 356.1368.
1
1
283−285 °C; H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.91
(s, 1H), 7.94 (d, J = 7.6 Hz, 2H), 7.81 (s, 1H), 7.55 (s??, 4H), 7.44 (d,
J = 16.4 Hz, 1H), 7.37−7.26 (m, 5H), 7.19 (t, J = 8.4 Hz, 2H), 7.04 (d,
J = 6.8 Hz, 1H), 5.53 (s, 1H), 3.83 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 165.9, 164.6, 152.6, 140.9, 139.7, 138.9, 136.1, 130.4,
129.9, 129.1, 128.7, 128.5 (d, J = 8.4 Hz), 126.9, 123.6, 121.9, 120.1,
115.4 (d, J = 21.2 Hz), 110.9, 55.2, 52.2; One carbon was not
observed; HRMS (ESI), m/z calcd. for C27H22FN3O4 ([M + H]+)
472.1667, found 472.1665.
(E)-N,4-Diphenyl-6-styryl-2-thioxo-1,2,3,4-tetrahydropyrimi-
dine-5-carboxamide (3m). The product was isolated by flash
chromatography (eluent: dichloromethane/methanol = 500/1) as a
1
yellow solid (96.6 mg, 47%): mp 237−239 °C; H NMR (400 MHz,
(E)-N-(4-Chlorophenyl)-6-(4-methoxystyryl)-2-oxo-4-phenyl-
1,2,3,4-tetrahydropyrimidine-5-carboxamide (3s). The product
was isolated by flash chromatography (eluent: dichloromethane/
methanol = 80/1) as a white solid (208.8 mg, 91%): mp 236−238 °C;
1H NMR (400 MHz, DMSO-d6) δ 10.07 (s, 1H), 8.76 (s, 1H), 7.72 (s,
1H), 7.61 (d, J = 8.4 Hz, 2H), 7.36−7.26 (m, 10H), 7.07 (d, J = 16.4
Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), 5.47 (s, 1H), 3.76 (s, 3H); 13C{1H}
NMR (100 MHz, DMSO-d6) δ 165.6, 160.2, 153.3, 144.2, 138.6,
137.5, 132.0, 129.3, 129.0, 128.9, 128.6, 128.0, 127.4, 126.8, 121.8,
117.4, 114.9, 109.1, 56.0, 55.7; HRMS (ESI), m/z calcd. for
C26H22ClN3O3 ([M + H]+) 460.1422, found 460.1422.
(E)-4-(4-Fluorophenyl)-6-(4-methoxystyryl)-2-oxo-N-phenyl-
1,2,3,4-tetrahydropyrimidine-5-carboxamide (3t). The product
was isolated by flash chromatography (eluent: dichloromethane/
methanol = 80/1) as a white solid (188.3 mg, 85%): mp 248−250 °C;
1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.82 (s, 1H), 7.77 (s,
1H), 7.57 (d, J = 8.0 Hz, 2H), 7.37−7.34 (m, 4H), 7.28 (dd, J1 = 14.8
Hz, J2 = 7.6 Hz, 3H), 7.19 (t, J = 8.8 Hz, 2H), 7.09−7.02 (m, 2H),
6.94 (d, J = 8.4 Hz, 2H), 5.48 (d, J = 2.8 Hz, 1H), 3.74 (s, 3H);
13C{1H} NMR (100 MHz, DMSO-d6) δ 165.0, 161.5 (d, J = 241.8
DMSO-d6) δ 10.20 (s, 1H), 9.98 (s, 1H), 9.69 (s, 1H), 7.60 (d, J = 8.0
Hz, 2H), 7.50−7.27 (m, 13H), 7.17 (d, J = 16.4 Hz, 1H), 7.06 (t, J =
7.2 Hz, 1H), 5.50 (d, J = 2.8 Hz, 1H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 174.9, 164.6, 142.4, 138.9, 136.2, 134.0, 132.7, 129.0,
128.8, 128.7, 127.9, 126.8, 126.5, 123.7, 120.0, 118.4, 111.0, 55.7; One
carbon was not observed; HRMS (ESI), m/z calcd. for C25H21N3OS
([M + Na]+) 434.1298, found 434.1286.
(E)-4-(4-Fluorophenyl)-N-(4-methoxyphenyl)-2-oxo-6-styryl-
1,2,3,4-tetrahydropyrimidine-5-carboxamide (3n). The product
was isolated by flash chromatography (eluent: dichloromethane/
methanol = 80/1) as a white solid (192.7 mg, 87%): mp 248−250 °C;
1H NMR (400 MHz, DMSO-d6) δ 9.91 (s, 1H), 8.85 (s, 1H), 7.77 (s,
1H), 7.47 (d, J = 8.8 Hz, 2H), 7.43−7.35 (m, 7H), 7.29 (t, J = 7.2 Hz,
1H), 7.23−7.17 (m, 3H), 6.86 (d, J = 8.8 Hz, 2H), 5.49 (s, 1H), 3.70
(s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 164.4, 161.6 (d, J =
241.3 Hz), 155.5, 152.8, 139.9 (d, J = 2.5 Hz), 136.3, 136.0, 132.1,
131.5, 129.0, 128.6, 128.5, 126.7, 121.6, 119.4, 115.4 (d, J = 21.1 Hz),
113.8, 110.1, 55.2, 55.1; HRMS (ESI), m/z calcd. for C26H22FN3O3
([M + Na]+) 466.1537, found 466.1524.
(E)-4-(4-Fluorophenyl)-2-oxo-N-phenyl-6-styryl-1,2,3,4-tet-
rahydropyrimidine-5-carboxamide (3o). The product was iso-
lated by flash chromatography (eluent: dichloromethane/methanol =
80/1) as a white solid (173.4 mg, 84%): mp 238−240 °C; H NMR
(400 MHz, DMSO-d6) δ 9.99 (s, 1H), 8.85 (s, 1H), 7.75 (s, 1H), 7.58
(d, J = 7.6 Hz, 2H), 7.44−7.26 (m, 10H), 7.20 (dd, J1 = 17.2 Hz, J2 =
8.8 Hz, 3H), 7.04 (t, J = 7.2 Hz, 1H), 5.52 (d, J = 1.6 Hz, 1H);
13C{1H} NMR (100 MHz, DMSO-d6) δ 165.3, 162.0 (d, J = 242.3
Hz), 153.2, 140.3 (d, J = 2.3 Hz), 139.5, 136.8, 136.7, 132.2, 129.4,
129.0, 128.9, 127.2, 124.0, 120.5, 119.8, 115.8 (d, J = 21.4 Hz), 110.3,
55.6; HRMS (ESI), m/z calcd. for C25H20FN3O2 ([M + H]+)
414.1612, found 414.1618.
Hz), 159.7, 152.7, 140.0 (d, J = 2.8 Hz), 139.1, 136.7, 131.4, 128.8,
128.6, 128.5 (d, J = 8.3 Hz), 128.2, 123.5, 119.9, 116.9, 115.3 (d, J =
21.5 Hz), 114.5, 108.8, 55.2, 55.0; HRMS (ESI), m/z calcd. for
C26H22FN3O3 ([M + H]+) 444.1718, found 444.1715.
1
(E)-4-(4-Methoxyphenyl)-6-(4-methoxystyryl)-2-oxo-N-phe-
nyl-1,2,3,4-tetrahydropyrimidine-5-carboxamide (3u). The
product was isolated by flash chromatography (eluent: dichloro-
methane/methanol = 60/1) as a white solid (166.1 mg, 73%): mp
240−242 °C; 1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.74 (s,
1H), 7.67 (s, 1H), 7.59 (d, J = 7.6 Hz, 2H), 7.37−7.24 (m, 7H), 7.10
(d, J = 16.4 Hz, 1H), 7.03 (t, J = 7.2 Hz, 1H), 6.92 (dd, J1 = 14.4 Hz, J2
= 8.4 Hz, 4H), 5.45 (s, 1H), 3.75 (s, 3H), 3.71 (s, 3H); 13C{1H} NMR
(100 MHz, DMSO-d6) δ 165.1, 159.6, 158.7, 152.8, 139.2, 136.4,
135.9, 131.1, 128.9, 128.6, 128.1, 127.7, 123.4, 119.9, 117.1, 114.4,
113.9, 109.3, 55.2, 55.14, 55.08; HRMS (ESI), m/z calcd. for
C27H25N3O4 ([M + Na]+) 478.1737, found 478.1731.
(E)-Methyl 4-(2-(6-(4-methoxyphenyl)-2-oxo-5-(phenylcar-
bamoyl)-1,2,3,6-tetrahydropyrimidin-4-yl)vinyl)benzoate (3p).
The product was isolated by flash chromatography (eluent: dichloro-
methane/methanol = 80/1) as a white solid (205.3 mg, 85%): mp
1
269−271 °C; H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.88
(E)-2-Oxo-N,4-diphenyl-6-(2-(thiophen-2-yl)vinyl)-1,2,3,4-
tetrahydropyrimidine-5-carboxamide (3v). The product was
isolated by flash chromatography (eluent: dichloromethane/methanol
= 100/1) as a white solid (90.2 mg, 45%): mp 236−238 °C; 1H NMR
(s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.76 (s, 1H), 7.56 (dd, J1 = 12.0 Hz,
J2 = 8.4 Hz, 4H), 7.44 (d, J = 16.4 Hz, 1H), 7.36 (d, J = 16.8 Hz, 1H),
7.30−7.23 (m, 4H), 7.04 (t, J = 7.2 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H),
2286
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The Journal of Organic Chemistry
Note
(400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.80 (s, 1H), 7.75 (s, 1H),
7.57 (dd, J1 = 12.4 Hz, J2 = 3.6 Hz, 3H), 7.50 (d, J = 4.8 Hz, 1H),
7.37−7.26 (m, 7H), 7.13 (d, J = 3.2 Hz, 1H), 7.07−7.04 (m, 2H), 7.01
(d, J = 16.0 Hz, 1H), 5.48 (d, J = 2.4 Hz, 1H); 13C{1H} NMR (100
MHz, DMSO-d6) δ 164.8, 152.8, 143.6, 141.5, 139.0, 136.0, 128.62,
128.60, 128.3, 128.2, 127.6, 126.9, 126.4, 125.1, 123.5, 119.9, 118.4,
109.8, 55.7; HRMS (ESI), m/z calcd. for C23H19N3O2S ([M + H]+)
402.1271, found 402.1272.
= 80/1) as a white solid (216.2 mg, 95%): mp 278−280 °C; 1H NMR
(400 MHz, DMSO-d6) δ 9.20 (s, 1H), 7.65 (s, 1H), 7.25−7.16 (m,
6H), 7.08−7.03 (m, 3H), 6.87 (dd, J1 = 12.8 Hz, J2 = 8.4 Hz, 4H), 5.24
(br, 1H), 5.15 (s, 1H), 3.72 (s, 3H), 3.69 (s, 3H), 3.19 (dd, J1 = 16.4
Hz, J2 = 4.8 Hz, 1H), 2.68 (dd, J1 = 16.0 Hz, J2 = 2.4 Hz, 1H);
13C{1H} NMR (100 MHz, DMSO-d6) δ 163.8, 158.4, 152.1, 143.2,
141.9, 137.2, 132.8, 128.0, 127.6, 126.7, 125.2, 113.8, 113.6, 101.2,
59.4, 55.1, 55.0, 52.7, 33.5; HRMS (ESI), m/z calcd. for C27H25N3O4
([M + Na]+) 478.1737, found 478.1734.
Ethyl 4-(2,5-dioxo-4,6-diphenyl-1,2,3,4,5,6,7,8-octahydro-
pyrido[4,3-d]pyrimidin-7-yl)benzoate (4e). The product was
isolated by flash chromatography (eluent: dichloromethane/methanol
= 60/1) as a white solid (191.5 mg, 82%): mp 265−267 °C; 1H NMR
(400 MHz, DMSO-d6) δ 10.22 (s, 1H), 7.79 (d, J = 8.0 Hz, 2H),
7.58−7.52 (m, 3H), 7.43 (t, J = 8.0 Hz, 2H), 7.13 (dd, J1 = 17.6 Hz, J2
= 7.2 Hz, 2H), 7.01 (t, J = 8.0 Hz, 4H), 6.53 (d, J = 7.6 Hz, 2H), 5.44
(br, 1H), 5.02 (s, 1H), 4.35 (q, J = 7.2 Hz, 2H), 3.38 (dd, J1 = 14.4 Hz,
J2 = 3.2 Hz, 1H), 3.13 (dd, J1 = 14.4 Hz, J2 = 3.2 Hz, 1H), 1.35 (t, J =
7.2 Hz, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.3, 165.7,
152.2, 151.3, 142.5, 140.1, 137.1, 129.8, 129.0, 128.9, 128.5, 127.8,
127.2, 126.6, 123.5, 121.4, 103.3, 60.6, 56.5, 52.9, 32.2, 14.3; HRMS
(ESI), m/z calcd. for C28H25N3O4 ([M + Na]+) 490.1737, found
490.1761.
(E)-6-(2-(Furan-2-yl)vinyl)-2-oxo-N,4-diphenyl-1,2,3,4-tetra-
hydropyrimidine-5-carboxamide (3w). The product was isolated
by flash chromatography (eluent: dichloromethane/methanol = 100/
1
1) as a white solid (21.3 mg, 11%): mp 173−175 °C; H NMR (400
MHz, DMSO-d6) δ 10.03 (s, 1H), 8.80 (s, 1H), 7.72 (s, 1H), 7.67 (s,
1H), 7.56 (d, J = 8.0 Hz, 2H), 7.34−7.21 (m, 8H), 7.04 (t, J = 8.0 Hz,
2H), 6.52 (d, J = 2.0 Hz, 2H), 5.47 (s, 1H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 164.9, 152.8, 151.8, 144.1, 143.6, 139.1, 135.8, 128.60,
128.58, 127.6, 126.4, 123.5, 119.8, 119.4, 117.0, 112.3, 111.4, 110.2,
55.8; HRMS (ESI), m/z calcd. for C23H19N3O3 ([M + H]+) 386.1499,
found 386.1494.
(E)-2-Oxo-N-phenyl-6-styryl-4-(thiophen-2-yl)-1,2,3,4-tetra-
hydropyrimidine-5-carboxamide (3aa). The product was isolated
by flash chromatography (eluent: dichloromethane/methanol = 60/1)
1
as a white solid (64.2 mg, 32%): mp 240−242 °C; H NMR (400
MHz, DMSO-d6) δ 10.03 (s, 1H), 8.96 (s, 1H), 7.96 (s, 1H), 7.61 (d, J
= 8.4 Hz, 2H), 7.43−7.35 (m, 6H), 7.29 (dd, J1 = 16.0 Hz, J2 = 6.8 Hz,
4H), 7.05 (t, J = 7.2 Hz, 1H), 6.97−6.95 (m, 2H), 5.77 (d, J = 2.8 Hz,
1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 164.5, 152.7, 147.8,
139.1, 137.1, 136.2, 132.1, 128.9, 128.6, 126.8, 125.4, 123.9, 123.5,
120.0, 119.4, 109.4, 51.2; Two carbons were not observed; HRMS
(ESI), m/z calcd. for C23H19N3O2S ([M + Na]+) 424.1090, found
424.1093.
ASSOCIATED CONTENT
■
S
* Supporting Information
General experimental methods and H NMR and 13C{1H}
1
NMR spectra of compounds 3 and 4. This material is available
free of charge via the Internet at http://pubs.acs.org.
4,6,7-Triphenyl-3,4,7,8-tetrahydropyrido[4,3-d]pyrimidine-
2,5(1H,6H)-dione (4a). The product was isolated by flash
chromatography (eluent: dichloromethane/methanol = 80/1) as a
AUTHOR INFORMATION
■
Corresponding Authors
*Fax: (+86) 373-3325250. E-mail: zhangzg@htu.edu.cn.
*E-mail: zgs6668@yahoo.com.
1
white solid (163.9 mg, 83%): mp 302−304 °C; H NMR (400 MHz,
DMSO-d6) δ 9.26 (s, 1H), 7.74 (s, 1H), 7.35−7.16 (m, 12H), 7.10 (d,
J = 7.6 Hz, 2H), 7.03 (t, J = 7.2 Hz, 1H), 5.33 (t, J = 5.2 Hz, 1H), 5.22
(s, 1H), 3.28 (dd, J1 = 16.4 Hz, J2 = 5.6 Hz, 1H), 2.72 (dd, J1 = 16.4
Hz, J2 = 4.0 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 163.7,
152.1, 144.9, 143.5, 141.8, 141.1, 128.5, 128.4, 128.1, 127.5, 127.2,
126.9, 126.7, 126.5, 125.3, 100.9, 59.9, 53.3, 33.3; HRMS (ESI), m/z
calcd. for C25H21N3O2 ([M + H]+) 396.1707, found 396.1714.
6-(3-Methoxyphenyl)-4,7-diphenyl-3,4,7,8-tetrahydro-
pyrido[4,3-d]pyrimidine-2,5(1H,6H)-dione (4b). The product was
isolated by flash chromatography (eluent: dichloromethane/methanol
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the NSFC (21002051, 21172056, 21272057, and
21372065), PCSIRT (IRT1061), China Postdoctoral Science
Foundation funded project (2012M521397, 2013T60701, and
2013M530339), and Key Project of Henan Educational
Committee (13A150546) for financial support of this research.
1
= 100/1) as a white solid (148.7 mg, 70%): mp 303−305 °C; H
NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.70 (s, 1H), 7.34−7.21
(m, 10H), 7.07 (t, J = 8.0 Hz, 1H), 6.69−6.66 (m, 2H), 6.61 (dd, J1 =
8.4 Hz, J2 = 1.6 Hz, 1H), 5.31 (t, J = 6.0 Hz, 1H), 5.20 (d, J = 3.2 Hz,
1H), 3.61 (s, 3H), 3.25 (dd, J1 = 16.8 Hz, J2 = 6.8 Hz, 1H), 2.70 (dd, J1
= 16.8 Hz, J2 = 5.6 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ
163.7, 159.0, 152.1, 144.9, 143.5, 142.9, 141.1, 128.7, 128.5, 128.3,
127.5, 127.2, 126.8, 126.5, 119.2, 113.0, 110.5, 100.9, 59.9, 55.0, 53.3,
33.3; HRMS (ESI), m/z calcd. for C26H23N3O3 ([M + H]+) 426.1812,
found 426.1816.
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