A novel convenient synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones via 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

Article abstract of DOI:10.1016/j.tet.2009.11.099

A novel four-step methodology for the synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates of 1,3-diketones or β-oxoesters followed by heterocycliz

Full text of DOI:10.1016/j.tet.2009.11.099

Tetrahedron 66 (2010) 940–946
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Tetrahedron
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A novel convenient synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones via
4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones
*
Anastasia A. Fesenko, Pavel A. Solovyev, Anatoly D. Shutalev
Department of Organic Chemistry, Moscow State Academy of Fine Chemical Technology, 86 Vernadsky Avenue, 119571 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel four-step methodology for the synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones has been
Received 10 September 2009
Received in revised form 3 November 2009
Accepted 20 November 2009
Available online 27 November 2009
developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates
of 1,3-diketones or b-oxoesters followed by heterocyclization–dehydration of the oxoalkylureas formed
gave 5-acyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of NaH,
eliminate CHCl3 to give the target compounds.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
1,2,3,4-Tetrahydropyrimidin-2-ones
1,2-Dihydropyrimidin-2-ones
Ureidoalkylation
Aromatization
1. Introduction
functionalized pyrimidines8,9 has been reported for the synthesis of
pyrimidines 1b. However, the synthetic methods generallyefficientin
1,2-Dihydropyrimidin-2-ones 1a are of considerable interest due
to their wide range of biological activities.1 These compounds have
been extensively studied, and effective methods for their synthesis
have been developed.2 In contrast, 5-acyl-1,2-dihydropyrimidin-2-
ones (1b, Fig. 1) have been studied less widely. A number of methods
including condensations of (C–C–C–N–C–N)-,3 (C–C–C–NþC–N)-,4
and (C–C–CþN–C–N)-types,3b,5 dehydrogenation6 and oxidation7 of
corresponding 1,2,3,4-tetrahydropyrimidin-2-ones, catalytic acyla-
tionof5-trialkylstannylpyrimidines,8 andhydrolysisofappropriate2-
the preparation of 1a tend to give poor yields in the specific case of 1b.
The lack of reliable synthetic methods severely hampers studies of
their potentially diverse biological activities.
Taking into consideration the reported formation of imines from
a-trichloromethyl-substituted secondary amines and amides by
elimination of chloroform in the presence of bases,10 we hypothe-
sized that 4-unsubstituted 1,2-dihydropyrimidin-2-ones (1b R2¼H)
could be obtained starting from corresponding 5-acyl-4-tri-
chloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. Synthesis of the
latter is presented in our retrosynthetic plan (Scheme 1) and includes
the ureidoalkylation of sodium enolates of a
-substituted ketones.11a–c
Figure 1. Structures of 1,2-dihydropyrimidin-2-ones 1a and 5-acyl-1,2-dihydropyr-
imidin-2-ones 1b.
* Corresponding author. Tel.: þ7 495 936 8908; fax: þ7 495 936 8909.
E-mail address: shutalev@orc.ru (A.D. Shutalev).
Scheme 1. Retrosynthesis of 4-unsubstituted 5-acyl-1,2-dihydropyrimidin-2-ones.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.099

A.A. Fesenko et al. / Tetrahedron 66 (2010) 940–946
941
In this article we describe a novel convenient synthesis of
4-unsubstituted 1,2-dihydropyrimidin-2-ones via 5-acyl-4-tri-
chloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones as key inter-
mediates.
reactions of ureidoalkylation,14,15 we hypothesized that compounds
4 and 5 might also be used in the synthesis of compounds 7 under
the conditions similar to those applicable for ureidoalkylation of
a-substituted ketones with
a
-tosyl-substituted N-alkylureas.11a–c
Sodium enolates of 1,3-dicarbonyl compounds 6a,b and
b
-
oxoesters 6c,d generated in situ by treating the corresponding CH-
acids with an equivalent amount of NaH reacted with urea 4 for
2.7–4.3 h at rt to give the products of acetoxy group substitution, N-
oxoalkylureas 7a–d, in 70–95% yield (Scheme 3, Table 1). Anhy-
drous MeCN was used as a solvent for preparation of compounds
7a,c–d; however, for compound 7b anhydrous THF was used be-
cause the solubility of the enolate of 6b in MeCN was very low and
the resulting extremely dense suspension hampered the comple-
tion of reaction of NaH with 6b.
Following the same procedure, urea 5 reacted with the sodium
enolate of 6a and 6c in MeCN (rt, 4.2–4.4 h) to give oxoalkylureas 7e
and 7f in 82 and 69% yield, respectively (Scheme 3, Table 1).
IR-, 1H- and 13C NMR spectra indicated that compounds 7a–f
only existed in acyclic form both in solid state and in DMSO-d6
solution. Their cyclic isomers 8a–f (Scheme 3) were not detected by
any spectroscopic methods.
2. Results and discussion
In our previous experience,
a-tosyl-substituted N-alkylureas
proved very useful starting materials for the preparation of various
5-acyl-1,2,3,4-tetrahydropyrimidin-2-ones by ureidoalkylation of
a
-substituted ketones.11a–c However, the synthesis of tosyl de-
rivative 3 bearing a trichloromethyl group failed (Scheme 2) while
acetoxy derivatives 4 and 512 were conveniently prepared by
treatment of the readily available 213 with Ac2O in pyridine and
Ac2O in the presence of H2SO4, respectively. Based on the ability of
the acetoxy group to serve as a good leaving group in various
Compounds 7c,d, and f were formed as mixtures of two di-
astereomers (Table 1). The diastereoselectivity of the product for-
mation depended on the structures of both reagents and was
higher with 5 than with 4 (entry 3 vs entry 8) and with 6d than with
6c (entry 3 vs entry 4). The reaction time did not affect the ratio of
diastereomers (entry 5 vs entry 6). The use of a greater excess of
a nucleophile slightly reduced the stereoselectivity (entry 5 vs
entry 4), which indicated that these reactions were controlled by
both kinetic and thermodynamic factors.
Refluxing solutions of ureas 7a–f in the presence of TsOH
(Scheme 4) led to 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-
2-ones 9a–d. The dependence of the yields of 9a–d on the reaction
conditions is outlined in Table 2.
Scheme 2. Synthesis of ureidoalkylating agents 4 and 5. Reagents and conditions: (a)
H2O, rt; (b) 4-MeC6H4S(O)OH, H2O, rt or heating; (c) Ac2O, py, rt, 75%; (d) Ac2O, H2SO4,
rt, 79%.
Scheme 3. Synthesis of ureas 7a–f by reaction of sodium enolates of 1,3-diketones
Scheme 4. Synthesis of 5-acyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones
9a–d.
6a,b and b-oxoesters 6c,d with 4 and 5.
Table 1
Reaction of ureas 4 and 5 with sodium enolates of 6a–da
Entry
Starting material
Solvent
Reaction
time, h
Molar ratio
(4/6 or 5/6)
Product
Diastereomeric
ratiob
Yield,c
%
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6d
6d
6a
6c
4
4
4
4
4
4
5
5
MeCN
THF
3.3
4.3
4
2.7
5.75
9.3
4.4
4.2
1:1
1:1
1.1:1
1.1:1
1:1
1:1
1:1
1.1:1
7a
7b
7c
7d
7d
7d
7e
7f
d
70
89
86
95
91
90
82
69
d
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
57:43
72:28
83:17
84:16
d
75:25
a
At room temperature.
Established by 1H NMR data of crude product.
All yields refer to isolated material homogeneous spectroscopically and by TLC.
b
c

942
A.A. Fesenko et al. / Tetrahedron 66 (2010) 940–946
Table 2
Synthesis of pyrimidinones 9a–d from ureas 7a–fa
Entry Starting Solvent Molar ratio Reaction Product(s) Molar ratio Yield
material
of 7:TsOH time, h
of 9a:10b
of 9, %
1
2
3
4
5
6
7
8
7a
7a
7a
7a
7a
7a
7b
7c
7c
7d
7d
7e
7f
MeCN 1:0.3
PhMe 1:1.13
0.6
1.0
1.0
1.25
0.63
1.75
2.2
1.0
1.0
9a
d
95
d
d
d
d
d
91
93
84
81
75
d
77
9aþ10
9aþ10
9aþ10
9aþ10
9aþ10
9b
9c
9c
9d
9d
73:27
94:6
94:6
90:10
62:38
d
EtOH
EtOH
EtOH
1:1.13
1:0.5
1:0.3
MeOH 1:0.5
MeCN 1:1
MeCN 1:0.3
PhMe 1:1.1
MeCN 1:0.5
MeCN 1:3.0
d
9
d
10
11
12
13
33
14.2
2.0
d
d
Scheme 6. Synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones 13a–d.
EtOH
EtOH
1:1.5
1:2.0
9aþ10
79:21
d
3.0
9c
a
3. Conclusion
Boiling in the presence of TsOH.
b
Based on 1H NMR spectrum of crude product.
Thus, we have developed a novel, more general synthesis of 5-
acyl-1,2-dihydropyrimidin-2-ones. The four-step procedure in-
volving 4-chloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones as key
compounds is very straightforward, giving the yields in a range of
69–95% per step, and uses very inexpensive starting materials. The
procedure is versatile in that, in addition to 5-acyl derivatives, it
allows one to obtain other 5-functionally substituted 1,2-dihy-
dropyrimidin-2-ones whose preparation will be disclosed in our
further publications.
Heterocyclization–dehydration of 7a–d proceeded smoothly in
MeCN as a solvent to give 9a–d in high yields (75–95%, Table 2,
entries 1, 7–11). Reaction of 7a,c was complete after 0.5–1 h in the
presence of TsOH (0.3 equiv, entries 1, 8). By comparison with
compounds 7a,c, their counterparts 7b,d, that possess a less elec-
trophilic carbonyl group, were converted into 9b,d (entries 7, 10–
11) using a greater amount of catalyst or/and longer reaction time.
Pyrimidine 9c was also readily synthesized from 7c using toluene as
a solvent (entry 9).
In contrast to the smooth conversion of 7a into 9a in MeCN,
refluxing 7a in EtOH, MeOH or toluene in the presence of TsOH led
to the formation of 9a plus the product of its deacetylation, py-
rimidine 10 (entries 2–6). Presumably,10 was obtained as a result of
the acid-promoted deacylation of 7a followed by heterocyclization
and dehydration of the intermediate formed. The data listed in
Table 2 indicates that the formation of 10 was favored in more polar
solvents (entry 4 vs entry 6), at higher reaction temperature (entry
2 vs entry 3), and in protic solvents (entry 1 vs entry 5). The amount
of catalyst had no appreciable effect on the ratio of 9a to 10 (entry 3
vs entry 4 vs entry 5).
The structure of 10 was confirmed by its independent synthesis
from 7a (Scheme 5). First, compound 7a was treated with aqueous
KOH (rt, 2 h) to give hydroxypyrimidine 11 in 73% yield as a single
(4R*,6S*)-diastereomer. In the next step, 11 was dehydrated by
heating in ethanolic TsOH to give pyrimidine 10 in 83% yield.
4. Experimental section
4.1. General
MeCN was dried by distillation from P2O5 and then from CaH2.
THF and DME were dried over Na-benzophenone followed by dis-
tillation. Ethyl acetoacetate and acetylacetone were dried over
MgSO4 followed by vacuum distillation. NaH (60% suspension in
mineral oil) was washed with dry hexane, and dried in a vacuum
desiccator prior to use. All other reagents and solvents were pur-
chased from commercial sources and used without further treat-
ment. IR spectra (in Nujol) were recorded either on a Bruker
Equinox 55/S spectrophotometer or on a Bruker Vector 22 spec-
trophotometer. Bands characteristics in the IR spectra are defined
as very strong (vs), strong (s), medium (m), shoulder (sh). NMR
spectra were recorded on a Bruker DPX 300 spectrometer at 300.13
(1H) and 75.48 (13C) MHz in DMSO-d6. 1H NMR chemical shifts are
referenced to the residual proton signal for DMSO-d6 (2.50 ppm).
13C NMR chemical shifts are reported to the carbon signal for
DMSO-d6 (39.50 ppm). Multiplicities are reported as singlet (s),
doublet (d), triplet (t), quartet (q), some combination of these,
multiplet (m). Thin layer chromatography (TLC) was performed on
silica gel plates Silufol UV 254 (Czech Republic) or Kieselgel 60 F254
(Merck) in chloroform–methanol (9:1, v/v) as a solvent system.
Plates were visualized with iodine vapor or UV light. All yields refer
to isolated, spectroscopically and TLC pure material.
Scheme 5. Synthesis of tetrahydropyrimidin-2-one 10.
Finally, aromatization of tetrahydropyrimidines 9a–d by NaH
(1.2–1.25 equiv) in an aprotic solvent at rt led to formation of the
corresponding 13a–d in good yields (Scheme 6). The reaction pro-
ceeded best in THF (for 13a,c,d) and, for 13b, in DME while the more
polar MeCN failed to give satisfactory yields even with a prolonged
reaction time (24 h) and a greater excess of NaH (up to 1.5 equiv).
The structure of compounds 13a–d was confirmed by 1H- and
13C NMR spectra and by comparing their constants with those
reported in literature.3a,3b,5a,7h 13C NMR spectra of the solutions of
these compounds in DMSO-d6 revealed an extremely large broad-
ening of the signals of C4, C6, and the carbon atom of group R1
directly bound to pyrimidine ring, which suggested that the com-
pounds existed as tautomeric mixtures of 13a–d and 14a–
d (Scheme 6).
4.2. N-[(1-Acetoxy-2,2,2-trichloro)ethyl]urea (4)
To a stirred and cooled on cold-water bath mixture of compound
213 (2.020 g, 9.74 mmol) and anhydrous pyridine (4.5 mL) was
added Ac2O (1.511 g, 14.80 mmol). The reaction mixture was stirred
for 4 h at rt, the solvent was removed in vacuo, the syrupy residue
was triturated with cold H2O (20 mL) until crystallization, the
precipitate was filtered, washed with ice-cold water, ice-cold HCl
(3.6%, 15 mL), ice-cold water, and dried to give compound 4
(1.810 g, 74.5%), which was used without further purification. An
analytically pure sample was obtained by crystallization from
EtOH–benzene (1:6, v/v). Mp 150.5–151.5 ꢀC (decomp., EtOH–

A.A. Fesenko et al. / Tetrahedron 66 (2010) 940–946
943
benzene). 1H NMR
d
: 7.46 (1H, d, 3JNH,CH¼10.2 Hz, NH), 6.88 (1H, d,
liquids were decanted, H2O (5 mL) was added, and the residue was
triturated upon cooling to 0 ꢀC until crystallization. The pre-
cipitate was filtered, washed with ice-cold water, light petrol,
a mixture of Et2O–light petrol (1:1 v/v; 3ꢂ6 mL), and dried to give
compound 7b (2.645 g, 89.0%). Mp 122.5–125.5 ꢀC (decomp., ac-
3JCH,NH¼10.2 Hz, CH), 6.10 (2H, br s, NH2), 2.13 ppm (3H, s, CH3). 13
C
NMR d: 168.26 (C]O in Ac), 155.96 [N–C(O)–N], 99.10 (CCl3), 80.61
(N–CH), 20.49 (CH3). IR
1734 (vs) ( C]O in OAc), 1677 (vs) (amide-I), 1624 (s), 1525 (vs)
(amide-II), 1249 (vs), 1201 (s), 1021 (s) ( C–O). Anal. Calcd for
n n NH),
, cmꢁ1: 3473 (s), 3341 (s), 3211 (m) (
n
n
etone–H2O, 1:1 v/v). 1H NMR
d: 7.95–8.04 (4H, m, C(2)H and C(6)H
C5H7Cl3N2O3: C, 24.07; H, 2.83; N, 11.23%. Found: C, 24.32; H, 2.37;
N, 11.58%.
in Ph), 7.62–7.71 (2H, m, C(4)H in Ph), 7.48–7.58 (4H, m, C(3)H and
3
C(5)H in Ph), 6.74 (1H, d, JNH,CH¼10.5 Hz, NH), 6.10 (1H, d,
3JCH,CH¼6.4 Hz, CH–C]O), 6.01 (1H, dd, 3JCH,NH¼10.5,
4.3. N-[(1-Acetoxy-2,2,2-trichloro)ethyl]-N0-acetylurea (5)
3JCH,CH¼6.4 Hz, CH–N), 5.89 (2H, br s, NH2). 13C NMR
d: 192.61,
191.96 (C]O in Bz), 156.91 (N–C]O), 135.89, 135.11 (C(1) in Ph),
134.19, 134.10 (C(4) in Ph), 129.27, 129.19 (C(2) and C(6) in Ph),
128.77, 128.44 (C(3) and C(5) in Ph), 103.10 (CCl3), 62.52 (CH–N),
Compound 5 was prepared by the procedure briefly described in
reference12 and here we report our detailed method. To a mixture
of urea 213 (11.982 g, 57.8 mmol) and Ac2O (30.075 g, 294.6 mmol)
was added three drops of conc. H2SO4, and the solid substance
rapidly dissolved with heating upon stirring. The resulted solution
was cooled to 0 ꢀC until precipitation was complete, then the pre-
cipitate was filtered, thoroughly washed with light petrol, and dried
to give compound 5 (13.248 g, 78.7%), which was used further
without additional purification. Mp 165.5–166 ꢀC (decomp.,
56.44 (CH in CHBz2). IR
1700 (vs) ( C]O in Bz), 1675 (s) (amide-I), 1595 (m) (
1555 (s), 1523 (s) (amide-II), 761 (s), 690 cmꢁ1 (s) (
n
, cmꢁ1: 3466 (s), 3357 (s), 3199 (s) (
n
NH),
CC in Ph),
CH in Ph).
n
n
d
Anal. Calcd for C18H15Cl3N2O3: C, 52.26; H, 3.66; N, 6.77%. Found:
C, 52.06; H, 3.52; N, 6.41%.
4.6. N-[(1,1,1-Trichloro-3-ethoxycarbonyl-4-oxo)-
pent-2-yl]urea (7c)
i-PrOH) [Lit.12 mp 160 ꢀC (decomp.; EtOH–H2O)]. 1H NMR
d: 10.93
3
(1H, s, NH in NHAc), 9.67 (1H, d, JNH,CH¼10.0 Hz, NH in NH–CH),
6.96 (1H, d, 3JCH,NH¼10.0 Hz, CH), 2.18 (3H, s, CH3 in OAc), 2.07 (3H,
Compound 7c (2.827 g, 85.8%) as
a mixture of two di-
s, CH3 in N–Ac). 13C NMR
d: 173.74 (C]O in NHAc), 168.23 (C]O in
astereomers (57:43) was prepared (analogously to 7a) from 4
(2.572 g, 10.31 mmol), 6c (1.487 g, 11.43 mmol) and NaH (0.272 g,
11.33 mmol) in MeCN (20 mL) (rt, 4 h). Mp 169.5–170 ꢀC (decomp.,
AcOEt) (rate of heating 1 ꢀC per 4–11 s) and >250 ꢀC (decomp.
without melting) (rate of heating 1 ꢀC per more than 25 s). 1H NMR
OAc), 152.12 [N–C(O)–N], 97.86 (CCl3), 78.95 (N–CH), 23.69 (CH3 in
NHAc), 20.34 ppm (CH3 in OAc). IR NH),
, cmꢁ1: 3235 (s), 3137 (s) (
1775 (vs), w1723 (sh), 1718 (s), 1693 (vs) [ C]O in OAc, C]O in
C(O)–NH–C(O)–NH],1541 (s), 1510 (m) (amide-II),1258 (s), 1206 (s),
1026 (s) ( C–O).
n
n
n
n
n
of major diastereomer
d
: 6.71 (1H, d, 3JNH,CH¼10.5 Hz, NH), 6.07 (2H,
3
3
br s, NH2), 5.53 (1H, dd, JCH,NH¼10.5, JCH,CH¼5.1 Hz, CH–N), 4.26
(1H, d, 3JCH,CH¼5.1 Hz, CH–C]O), 4.06–4.23 (2H, m, signals overlap
with signals of analogous protons of minor diastereomer, OCH2),
4.4. N-[(3-Acetyl-1,1,1-trichloro-4-oxo)pent-2-yl]urea (7a)
To a stirred and cooled in ice bath suspension of NaH (0.296 g,
12.33 mmol) in anhydrous MeCN (13.5 mL) was added dropwise
the solution of acetylacetone (6a) (1.244 g, 12.43 mmol) in MeCN
(9 mL) and the resulting suspension was stirred for 16 min. To the
formed suspension of the sodium enolate of acetylacetone was
added compound 4 (3.079 g, 12.34 mmol). The reaction mixture
was stirred for 3 h 20 min at rt and the solvent was removed in
vacuo. To the residue was added saturated aqueous solution of
NaHCO3 (5 mL), and the obtained suspension was left in a water
bath (bath temperature 35 ꢀC) for 30 min. Upon cooling to 0 ꢀC, the
precipitate was filtered, washed with ice-cold water, light petrol,
cold Et2O (3ꢂ10 mL), and dried to give compound 7a (2.498 g,
2.27 (3H, s, CH3 in Ac), 1.21 (3H, t, 3JCH3,CH2¼7.1 Hz, CH3 in OEt). 1H
3
NMR of minor diastereomer
d
: 6.84 (1H, d, JNH,CH¼10.6 Hz, NH),
5.98 (2H, br s, NH2), 5.53 (1H, dd, 3JCH,NH¼10.6, 3JCH,CH¼8.2 Hz, CH–
N), 3.93 (1H, d, 3JCH,CH¼8.2 Hz, CH–C]O), 4.06–4.23 (2H, m, signals
overlap with signals of analogous protons of major diastereomer,
3
OCH2), 2.17 (3H, s, CH3 in Ac), 1.19 (3H, t, JCH3,CH2¼7.1 Hz, CH3 in
OEt). 13C NMR of major diastereomer
d: 199.13 (C]O in Ac), 166.58
(C]O in COOEt), 156.92 (N–C]O), 102.66 (CCl3), 61.55 (OCH2),
61.42 (CH–N), 59.96 (CH in CH–Ac), 28.92 (CH3 in Ac), 13.75 (CH3 in
OEt). 13C NMR of minor diastereomer
d: 199.33 (C]O in Ac), 167.08
(C]O in COOEt), 157.04 (N–C]O), 102.35 (CCl3), 62.32 (CH–N),
61.95 (OCH2), 61.14 (CH in CH–Ac), 28.68 (CH3 in Ac), 13.73 (CH3 in
70.0%). Mp >300 ꢀC (decomp., AcOEt). 1H NMR
d
: 6.80 (1H, d,
OEt). IR
(vs) ( C]O in Ac and COOEt), 1663 (vs) (amide-I), 1622 (s), 1597 (s),
1546 (vs) (amide-II), 1231 (vs), 1162 (s), 1025 cmꢁ1 (s) (
C–O). Anal.
n n NH), 1711
, cmꢁ1: 3465 (s), 3354 (s), 3281 (s), 3206 (s) (
3JNH,CH¼10.6 Hz, NH), 5.97 (2H, br s, NH2), 5.58 (1H, dd,
n
3
3
3JCH,NH¼10.6, JCH,CH¼7.5 Hz, CH–N), 4.37 (1H, d, JCH,CH¼7.5 Hz,
n
CH–C]O), 2.24 (3H, s, CH3), 2.13 (3H, s, CH3). 13C NMR
d
: 200.71,
Calcd for C9H13Cl3N2O4: C, 33.83; H, 4.10; N, 8.77%. Found: C, 33.85;
H, 3.71; N, 8.53%.
200.59 (C]O in Ac), 157.08 (N–C]O), 102.65 (CCl3), 67.99 (CH in
CHAc2), 61.86 (CH–N), 30.22, 29.43 (CH3). IR
n
, cmꢁ1: 3476 (m), 3372
(m), 3214 (s), 3087 (s) (
n
NH), 1720 (s) (
n
C]O in Ac), 1685 (s)
4.7. N-[(1,1,1-Trichloro-3-ethoxycarbonyl-4-oxo-4-
phenyl)but-2-yl]urea (7d)
(amide-I), 1618 cmꢁ1 (s) (amide-II). Anal. Calcd for C8H11Cl3N2O3: C,
33.19; H, 3.83; N, 9.68%. Found: C, 33.25; H, 3.45; N, 9.33%.
Compound 7d (1.913 g, 94.5%) as
a mixture of two di-
4.5. N-[(3-Benzoyl-1,1,1-tricloromethyl-4-oxo-4-phenyl)but-
2-yl]urea (7b)
astereomers (72:28) was prepared (analogously to 7a with the
exception that it was washed with Et2O–light petrol, 1:1, instead of
Et2O) from 4 (1.323 g, 5.30 mmol), 6d (1.122 g, 5.84 mmol), and NaH
(0.139 g, 5.79 mmol) in MeCN (10 mL) (rt, 2 h 40 min). Mp 82.5–
To a stirred and cooled in ice bath suspension of NaH (0.173 g,
7.21 mmol) in anhydrous THF (8 mL) was subsequently added
dibenzoylmethane (6b) (1.618 g, 7.21 mmol) and THF (3 mL). After
10 min, to the resulting solution was added compound 4 (1.792 g,
7.18 mmol) and then THF (4 mL). The obtained suspension was
stirred for 4 h 20 min at rt and solvent was removed in vacuo. The
residue was triturated with light petrol, saturated aqueous solu-
tion of NaHCO3 (2.5 mL) was added and the obtained mixture was
left in a water bath (bath temperature 35 ꢀC) for 30 min. The
85 ꢀC (EtOH–H2O, 1:1 v/v). 1H NMR of major diastereomer
d: 7.54–
8.02 (5H, m, signals overlap with signals of analogous protons of
minor diastereomer, Ph), 6.83 (1H, d, 3JNH,CH¼10.7 Hz, NH), 6.03 (br
s, 2H, NH2), 5.87 (1H, dd, 3JCH,NH¼10.7, 3JCH,CH¼6.7 Hz, CH–N), 4.97
(1H, d, 3JCH,CH¼6.7 Hz, CH–C]O), 3.95–4.17 (2H, m, signals overlap
with signals of analogous protons of minor diastereomer, OCH2),
3
1.10 (3H, t, JCH3,CH2¼7.1 Hz, CH3 in OEt). 1H NMR of minor di-
astereomer d: 7.54–8.02 (5H, m, signals overlap with signals of

944
A.A. Fesenko et al. / Tetrahedron 66 (2010) 940–946
analogous protons of major diastereomer, Ph), 6.81 (1H, d,
3JNH,CH¼10.2 Hz, NH), 5.94 (2H, br s, NH2), 5.65 (1H, dd,
3JCH,NH¼10.2, 3JCH,CH¼6.1 Hz, CH–N), 5.15 (1H, d, 3JCH,CH¼6.1 Hz, CH–
C]O), 3.95–4.17 (2H, m, signals overlap with signals of analogous
protons of major diastereomer, OCH2), 1.05 (3H, t, 3JCH3,CH2¼7.1 Hz,
(s), 1147 (s), 1033 cmꢁ1 (s) (
n C–O). Anal. Calcd for C11H15Cl3N2O5: C,
36.54; H, 4.18; N, 7.75%. Found: C, 36.47; H, 3.91; N, 7.85%.
4.10. 5-Acetyl-4-(trichloromethyl)-6-methyl-1,2,3,4-
tetrahydropyrimidin-2-one (9a)
CH3 in OEt). 13C NMR of major diastereomer
d: 190.48 (C]O in Bz),
165.90 (C]O in COOEt), 156.86 (N–C]O), 134.96 (C(1) in Ph), 134.35
(C(4) in Ph), 129.35 (C(2) and C(6) in Ph), 128.29 (C(3) and C(5) in Ph),
102.72 (CCl3), 61.87 (OCH2), 61.13 (CH–N), 56.27 (CH in CH–Bz),
A suspension of compound 7a (2.377 g, 8.21 mmol) and
TsOH$H2O (0.461 g, 2.42 mmol) in MeCN (20 mL) was refluxed for
36 min under stirring and then the solvent was removed in vacuo.
To the dry residue was added saturated aqueous solution of
NaHCO3 (5 mL), and the mixture was triturated until crystallization.
Upon cooling to 0 ꢀC, the precipitate was filtered, washed with ice-
cold water, light petrol, and dried to give compound 9a (2.115 g,
13.69 (CH3 in OEt). 13C NMR of minor diastereomer
d: 192.94 (C]O
in Bz), 166.99 (C]O in COOEt), 156.92 (N–C]O), 136.28 (C(1) in Ph),
134.09 (C(4) in Ph), 129.09 (C(2) and C(6) in Ph), 128.61 (C(3) and C(5)
in Ph), 102.89 (CCl3), 63.61 (CH–N), 61.87 (OCH2), 53.22 (CH in CH–
Bz),13.67 (CH3 in OEt). IR
1734 (s) ( C]O in COOEt), 1670 (vs) (amide-I and
1596 (m) ( CC in Ph), 1511 (s) (amide-II), 1223 (s), 1169 (s), 1023 (s)
C–O), 728 (s), 687 cmꢁ1 (s) (
CH in Ph). Anal. Calcd for
n
, cmꢁ1: 3442 (s), 3383 (s), 3196 (s) (
n
NH),
94.9%). Mp >300 ꢀC (decomp., EtOH). 1H NMR
d: 9.66 (1H, d,
n
n
C]O in Bz),
4JN(1)H,N(3)H¼1.7 Hz, N(1)H), 8.57 (1H, dd, 3JN(3)H,4-H¼4.7,
n
4JN(3)H,N(1)H¼1.7 Hz, N(3)H), 5.07 (1H, d, 3J4-H,N(3)H¼4.7 Hz, 4-H), 2.31
(n
d
(3H, s, CH3 in Ac), 2.21 (3H, s, 6-CH3). 13C NMR
d: 195.33 (C]O in
C14H15Cl3N2O4: C, 44.06; H, 3.96; N, 7.34%. Found: C, 44.02; H, 3.75;
N, 7.46%.
Ac), 151.70 (C(2)), 149.34 (C(6)), 105.96 (CCl3), 105.01 (C(5)), 65.95
(C(4)), 30.12 (CH3 in Ac), 18.56 (6-CH3). IR
, cmꢁ1: 3206 (s), 3106 (s)
NH), 1710 (vs) (
C]O in Ac), 1663 (s) (amide-I), 1601 cmꢁ1 (s) (
n
(n
n
n
4.8. N-Acetyl-N0-[(3-acetyl-1,1,1-trichloro-4-oxo)
C]C). Anal. Calcd for C8H9Cl3N2O2: C, 35.39; H, 3.34; N, 10.32%.
pent-2-yl]urea (7e)
Found: C, 35.51; H, 2.97; N, 10.51%.
Compound 7e (1.826 g, 82.1%) was prepared (analogously to 7a)
from 5 (1.956 g, 6.71 mmol), 6a (0.690 g, 6.89 mmol), and NaH
(0.161 g, 6.71 mmol) in MeCN (8 mL) (rt, 4 h 25 min). Mp 162.5–
4.11. 5-Benzoyl-4-(trichloromethyl)-6-phenyl-1,2,3,4-
tetrahydropyrimidin-2-one (9b)
164 ꢀC (BuOH). 1H NMR
d
: 10.72 (1H, s, NH in NHAc), 9.41 (1H, d,
Compound 9b (2.291 g, 90.7%) was prepared (analogously to 9a)
from 7b (2.641 g, 6.38 mmol) and TsOH$H2O (1.213 g, 6.38 mmol)
3
3JNH,CH¼10.5 Hz, NH in NH–CH), 5.66 (1H, dd, JCH,NH¼10.5,
3JCH,CH¼6.2 Hz, CH–N), 4.67 (1H, d, JCH,CH¼6.2 Hz, CH–C]O), 2.26
in MeCN (18 mL) (reflux, 2 h 10 min). Mp 222–223 ꢀC (MeCN). 1H
3
3
(3H, s, CH3 in CHAc2), 2.25 (3H, s, CH3 in CHAc2), 2.04 (3H, s, CH3 in
NMR
d
: 9.77 (1H, s, N(1)H), 8.68 (1H, d, JN(3)H,4-H¼4.5 Hz, N(3)H),
N–Ac). 13C NMR
d
: 201.24, 199.91 (C]O in CHAc2), 173.11 (C]O in
NHAc), 152.92 [N–C(O)–N],101.32 (CCl3), 65.75 (CH in CHAc2), 61.60
(CH–N), 31.32, 29.91 (CH3 in CHAc2), 23.57 (CH3 in NHAc). IR
7.41–7.46 (2H, m, C(2)H and C(6)H in Bz), 7.20–7.26 (2H, m, C(4)H in
Bz), 7.03–7.15 (7H, m, C(3)H and C(5)H in Bz, CH in 6-Ph), 5.22 (1H, d,
n
,
3J4-H,N(3)H¼4.5 Hz, 4-H). 13C NMR
d: 194.42 (C]O in Bz), 152.04
cmꢁ1: 3240 (s), 3127 (s) (
n
NH),1734 (s),1710 (s) (
n
C]O in Ac), 1690
(C(2)), 149.08 (C(6)), 138.11 (C(1) in Bz), 132.99 (C(1) in 6-Ph), 131.55
(C(4) in Bz), 129.21 (C(4) in 6-Ph), 129.06 (C(2) and C(6) in Bz), 128.59
(C(2) and C(6) in 6-Ph), 127.74 (C(3) and C(5) in Bz), 127.62 (C(3) and
(vs) (amide-I), 1529 (vs), 1501 cmꢁ1 (s) (amide-II). Anal. Calcd for
C10H13Cl3N2O4: C, 36.22; H, 3.95; N, 8.45%. Found: C, 36.35; H, 3.73;
N, 8.34%.
C(5) in 6-Ph), 105.36 (CCl3), 105.00 (C(5)), 67.74 (C(4)). IR
n
, cmꢁ1
C]O
CC in Ph),
:
3212 (s), 3134 (s) (
n
NH), 1711 (vs), w1694 (sh) (amide-I and n
4.9. N-Acetyl-N0-[(1,1,1-trichloro-3-ethoxycarbonyl-4-
oxo)pent-2-yl]urea (7f)
in Bz), 1627 (s) (
n
C]C), 1597 (m), 1578 (m), 1496 (m) (
n
732 (s), 699 cmꢁ1 (s) (
d CH in Ph). Anal. Calcd for C18H13Cl3N2O2: C,
54.64; H, 3.31; N, 7.08%. Found: C, 54.60; H, 3.12; N, 7.18%.
Compound 7f (1.258 g, 68.8%) as a mixture of two diastereomers
(75:25) was prepared (analogously to 9a) from
5.06 mmol), 6c (0.738 g, 5.67 mmol), and NaH (0.134 g, 5.57 mmol)
in MeCN (16 mL) (rt, 4 h 14 min). Mp 123–129 ꢀC (EtOH–H2O, 1:1
5
(1.475 g,
4.12. Ethyl 4-(trichloromethyl)-6-methyl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (9c)
v/v). 1H NMR of major diastereomer
d
: 10.72 (1H, s, NH in NHAc),
Method A: Compound 9c (2.423 g, 93.4%) was prepared (analo-
gously to 9a) from 7c (2.749 g, 8.60 mmol) and TsOH$H2O (0.491 g,
2.58 mmol) in MeCN (16 mL) (reflux, 58 min).
Method B: Compound 9c (0.335 g, 76.7%) was prepared (analo-
gously to 9a) from 7f (0.524 g, 1.45 mmol) and TsOH$H2O (0.557 g,
2.93 mmol) in EtOH (5 mL) (reflux, 3 h). Mp 257.5–258 ꢀC
(decomp., toluene) (rate of heating 1 ꢀC per 12–32 s) and Mp
>258 ꢀC (decomp. without melting) (rate of heating 1 ꢀC per more
3
9.55 (1H, d, JNH,CH¼10.3 Hz, NH in NH–CH), 5.64 (1H, dd,
3
3
3JCH,NH¼10.3, JCH,CH¼4.5 Hz, CH–N), 4.44 (1H, d, JCH,CH¼4.5 Hz,
CH–C]O), 4–4.24 (2H, m, signals overlap with signals of analogous
protons of minor diastereomer, OCH2), 2.26 (3H, s, CH3 in Ac), 2.03
3
(3H, s, CH3 in N–Ac), 1.21 (3H, t, JCH3,CH2¼7.1 Hz, CH3 in OEt). 1H
NMR of minor diastereomer d: 10.74 (1H, s, NH in NHAc), 9.50 (1H,
3
3
d, JNH,CH¼10.3 Hz, NH in NH–CH), 5.57 (1H, dd, JCH,NH¼10.3,
3JCH,CH¼6.1 Hz, CH–N), 4.38 (1H, d, 3JCH,CH¼6.1 Hz, CH–C]O), 4.06–
4.24 (2H, m, signals overlap with signals of analogous protons of
major diastereomer, OCH2), 2.26 (3H, s, CH3 in Ac), 2.04 (3H, s, CH3
in N–Ac), 1.19 (3H, t, 3JCH3,CH2¼7.3 Hz, CH3 in OEt). 13C NMR of major
than 58 s). 1H NMR
d
: 9.74 (1H, d, 4JN(1)H,N(3)H¼1.9 Hz, N(1)H), 8.54
3
4
(1H, dd, JN(3)H,4-H¼4.8, JN(3)H,N(1)H¼1.9 Hz, N(3)H), 4.91 (1H, d,
3J4-H,N(3)H¼4.8 Hz, 4-H), 4.12 (1H, dq, 2JCH(A),CH(B)¼10.8,
3JCH(A),CH3¼7.1 Hz, A part of ABX3 spin system, CH(A) in OCH2), 4.10
2
3
diastereomer
d: 198.60 (C]O in Ac), 172.98 (C]O in NHAc), 166.58
(1H, dq, JCH(B),CH(A)¼10.8, JCH(B),CH3¼7.1 Hz, B part in ABX3 spin
(C]O in COOEt), 152.90 [N–C(O)–N], 101.31 (CCl3), 62.00 (OCH2),
system, CH(B) c OCH2), 2.23 (3H, s, 6-CH3), 1.20 (3H, t,
60.81 (CH–N), 59.23 (CH in CH–Ac), 28.83 (CH3 in Ac), 23.58 (CH3 in
3JCH3,CH(A)¼3JCH3,CH(B)¼7.1 Hz, X part of ABX3 spin system, CH3
c
NHAc),13.59 (CH3 in OEt). 13C NMR of minor diastereomer
d: 200.42
OEt). 13C NMR
d: 165.57 (C]O in COOEt), 151.76 (C(2)), 151.41 (C(6)),
(C]O in Ac),172.99 (C]O in NHAc), 166.65 (C]O in COOEt), 153.00
[N–C(O)–N], 101.05 (CCl3), 62.63 (CH–N), 62.14 (OCH2), 58.07 (CH in
CH–Ac), 30.95 (CH3 in Ac), 23.62 (CH3 in NHAc), 13.75 (CH3 in OEt).
105.70 (CCl3), 94.14 (C(5)), 65.96 (C(4)), 59.80 (OCH2), 17.75 (6-CH3),
14.15 (CH3 in OEt). IR NH), 1726 (s) (
, cmꢁ1: 3225 (s), 3108 (s) (
C]O in COOEt), 1709 (s) (amide-I), 1644 (s) ( C]C), 1229 (s),
1098 cmꢁ1 (s) (
C–O). Anal. Calcd for C9H11Cl3N2O3: C, 35.85; H,
3.68; N, 9.29%. Found: C, 35.59; H, 2.95; N, 9.24%.
n
n
n
n
IR
n
, cmꢁ1: 3258 (s), 3200 (m) (
n
NH), 1748 (s), 1727 (vs) (
n
C]O in
n
COOEt and Ac), 1673 (s) (amide-I), 1535 (s), 1501 (s) (amide-II), 1213

A.A. Fesenko et al. / Tetrahedron 66 (2010) 940–946
945
4.13. Ethyl 4-(trichloromethyl)-2-oxo-6-phenyl-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (9d)
vacuo and the residue was dried to constant weight in a desiccator
over P2O5. The resulting solid was extracted with boiling EtOH
(6ꢂ10 mL) and the combined extracts were concentrated in vacuo.
The dry residue was triturated with Et2O until crystallization, upon
cooling to 0 ꢀC, the precipitate was filtered, washed with cold Et2O,
and dried to give compound 13a (0.561 g, 72.0%). Mp 215–217 ꢀC
Compound 9d (0.918 g, 75.2%) was prepared (analogously to 9a)
from 7d (1.282 g, 3.36 mmol) and TsOH$H2O (1.920 g, 10.09 mmol)
in MeCN (10 mL) (reflux, 14 h 11 min). Mp 201.5–210 ꢀC (EtOH). 1H
NMR
d
: 9.89 (1H, unresolved d, 4JN(1)H,N(3)H¼1.2 Hz, N(1)H), 8.65 (1H,
(decomp., MeOH) (Lit.3b mp 204–205 ꢀC). 1H NMR
br s, NH), 8.83 (1H, s, 4-H), 2.50 (3H, s, 6-CH3), 2.43 (3H, s, CH3 in Ac).
13C NMR
: 194.54 (C]O in Ac),169.10 (very br, C(6)),160.79 (very br,
d: 12.36 (1H, very
dd, 3JN(3)H,4-H¼4.8, 4JN(3)H,N(1)H¼1.2 Hz, N(3)H), 7.28–7.48 (5H, m, Ph),
3
3
5.03 (1H, d, J4-H,N(3)H¼4.8 Hz, 4-H), 3.81 (2H, q, JCH2,CH3¼7.1 Hz,
d
OCH2), 0.81 (3H, t, 3JCH3,CH2¼7.1 Hz, CH3). 13C NMR
d: 165.08 (C]O in
C(4)), 154.49 (C(2)), 114.20 (C(5)), 28.37 (CH3 in Ac), 22.22 (br, 4-CH3).
COOEt), 152.08 (C(2)), 151.50 (C(6)), 134.20 (C(1) in Ph), 129.29 (C(4) in
Ph), 128.44 (C(2) and C(6) in Ph), 127.68 (C(3) and C(5) in Ph), 105.55
4.17. 5-Benzoyl-6-phenyl-1,2-dihydropyrimidin-2-one (13b)
(CCl3), 95.28 (C(5)), 66.08 (C(4)), 59.69 (OCH2),13.49 (CH3). IR
3272 (s), 3223 (s), 3112 (s) ( NH),1709 (s) ( C]O in COOEt),1674 (s)
(amide-I), 1645 (s) ( C]C), 1599 (m) ( CC in Ph), 1254 (s), 1196 (s),
1106 (s) ( CH in Ph). Anal. Calcd for
C–O), 765 (s), 705 cmꢁ1 (s) (
n :
, cmꢁ1
n
n
To a mixture of NaH (0.038 g, 1.58 mmol) and compound 9b
(0.502 g, 1.27 mmol) was added anhydrous DME (4.6 mL). The
obtained solution was stirred for 25 min and then precipitation
occurred. The reaction mixture was stirred for additional 2 h
23 min at rt. The solvent was removed in vacuo, to the dry residue
was added H2O (2 mL) and the obtained suspension was neutral-
ized with HCl (2%) to pH 7 (indicator paper). Upon cooling to 0 ꢀC,
the precipitate was filtered, washed with ice-cold water, hexane,
and dried to give compound 13b (0.310 g, 88.4%). Mp 237.5–238 ꢀC
n
n
n
d
C14H13Cl3N2O3: C, 46.24; H, 3.60; N, 7.70%. Found: C, 46.36; H, 3.55;
N, 7.82%.
4.14. 4-(Trichloromethyl)-6-methyl-1,2,3,4-tetrahydro-
pyrimidin-2-one (10)
A solution of compound 11 (0.259 g, 1.05 mmol) and TsOH$H2O
(0.033 g, 0.17 mmol) in EtOH (8 mL) was refluxed for 1 h and the
solvent was removed in vacuo. The resulting residue was triturated
until crystallization with saturated aqueous solution of NaHCO3
(1 mL). Upon cooling to 0 ꢀC, the precipitate was filtered, washed
with ice-cold water, light petrol, and dried to give compound 10
(EtOH) [Lit.5a mp 228 ꢀC (i-PrOH)]. 1H NMR
d: 12.57 (1H, br s, NH),
8.33 (1H, s, 4-H), 7.69–7.74 (2H, m, C(2)H and C(6)H in Bz), 7.49–7.56
(1H, m, C(4)H in Bz), 7.25–7.42 (7H, m, C(3)H and C(5)H in Bz, CH in 4-
Ph). 13C NMR
d: 192.37 (C]O in Bz), 171.19 (very br, C(6)), 155.62
(C(2)), 152.07 (very br, C(4)), 136.99 (C(1) in Bz), 136.40 (very br, C(1) in
6-Ph),133.17 (C(4) in Bz),130.51 (C(4) in 6-Ph),129.55 (C(2) and C(6) in
Bz), 128.64 (C(2) and C(6) in 6-Ph), 128.51 (C(3) and C(5) in 6-Ph),
128.17 (C(3) and C(5) in Bz), 115.66 (C(5)).
(0.200 g, 83.3%). Mp 201.5 ꢀC (decomp., toluene). 1H NMR
d: 8.74
4
(1H, dd, JN(1)H,N(3)H¼4JN(1)H,5-H¼1.8 Hz, N(1)H), 7.68 (1H, ddd,
4
3JN(3)H,4-H¼3.8, JN(3)H,N(1)H¼4JN(3)H,5-H¼1.8 Hz, N(3)H), 4.71 (1H,
3
4
4
dddd, J5-H,4-H¼4.6, J5-H,N(1)H¼4J5-H,N(3)H¼1.8, J5-H,6-CH3¼1.3 Hz, 5-
4.18. Ethyl 6-methyl-2-oxo-1,2-dihydropyrimidine-5-
carboxylate (13c)
H), 4.48 (1H, ddq, 3J4-H,5-H¼4.6, 3J4-H,N(3)H¼3.8, 5J4-H,6-CH3¼1.0 Hz, 4-
H), 1.78 (3H, dd, 4J6-CH3,5-H¼1.3, 5J6-CH3,4-H¼1.0 Hz, CH3). 13C NMR
d:
152.59 (C(2)), 138.97 (C(6)), 105.95 (CCl3), 83.38 (C(5)), 67.23 (C(4)),
To a mixture of NaH (0.129 g, 5.38 mmol) and compound 9c
(1.356 g, 4.50 mmol) was added anhydrous THF (8.5 mL) and the
resulted suspension was stirred for 3 min in an ice bath and for 1 h
33 min at rt. The solvent was removed in vacuo, to the dry residue
was added H2O (3 mL), and the resulting suspension was neutral-
ized with HCl (2%) to pH 7 (indicator paper). Upon cooling to 0 ꢀC,
the precipitate was filtered, washed with ice-cold H2O, light petrol,
and dried to give compound 13c (0.720 g, 87.9%). Mp 250 ꢀC
18.17 (CH3). IR
n
, cmꢁ1: 3218 (s), 3089 (s) (
C]C). Anal. Calcd for C6H7Cl3N2O: C,
n NH), 1714 (sh), 1696 (s),
1672 cmꢁ1 (sh) (amide-I and
n
31.40; H, 3.07; N, 12.21%. Found: C, 31.09; H, 2.79; N, 11.85%.
4.15. (4R*,6S*)-6-(Trichloromethyl)-4-hydroxy-4-
methylhexahydropyrimidin-2-one (11)
To a solution of KOH (0.072 g, 1.28 mmol) in H2O (3.5 mL) was
added compound 7a (0.231 g, 0.80 mmol) and the obtained suspen-
sion was stirred for 2 h at rt. Upon cooling to 0 ꢀC, the precipitate was
filtered, washed with ice-cold water, light petrol, and dried to give
compound 11 (0.144 g, 72.9%) as a single diastereomer. Mp 204.5 ꢀC
(decomp., EtOH) [Lit.3a mp 248–250 ꢀC (decomp., H2O)]. 1H NMR
d:
12.46 (1H, br s, NH), 8.74 (1H, s, 4-H), 4.22 (2H, q, 3JCH2,CH3¼7.1 Hz,
OCH2), 2.53 (3H, s, 6-CH3), 1.28 (3H, t, 3JCH3,CH2¼7.1 Hz, CH3 in OEt).
13C NMR
d: 167.10 (very br, C(6)), 163.51 (C]O in COOEt), 162.47
(very br, C(4)), 155.66 (C(2)), 106.11 (C(5)), 60.45 (OCH2), 20.70 (br, 6-
CH3), 14.11 (CH3 in OEt).
(decomp., EtOH). 1H NMR
d
: 7.34 (1H, dd, 4JN(3)H,N(1)H¼1.6, 4JN(3)H,5-He
¼
4
4
1.5 Hz, N(3)H), 6.55 (1H, ddd, JN(1)H,5-He¼1.9, JN(1)H,N(3)H¼1.6,
4JN(1)H,6-H¼1.0 Hz, N(1)H), 5.68 (1H, d, JOH,5-Ha¼0.9 Hz, OH), 4.24
4.19. Ethyl 2-oxo-6-phenyl-1,2-dihydropyrimidine-5-
carboxylate (13d)
4
3
3
4
(1H, ddd, J6-H,5-Ha¼11.3, J6-H,5-He¼4.4, J6-H,N(1)H¼1.0 Hz, 6-H),
2
3
4
2.26 (1H, dddd, J5-He,5-Ha¼12.6, J5-He,6-H¼4.4, J5-He,N(1)H¼1.9,
4J5-He,N(3)H¼1.5 Hz, 5-He), 1.67 (1H, ddd, 2J5-Ha,5-He¼12.6,
To a mixture of NaH (0.071 g, 2.96 mmol) and compound 9d
(0.895 g, 2.46 mmol) was added anhydrous THF (8.2 mL) and the
obtained suspension was stirred in an ice bath for 3 min. The
resulting solution was stirred for 1 h 57 min at rt. After the reaction
was complete the solvent was removed in vacuo, the residue was
dried to constant weight, extracted with boiling EtOH (10 mL), and
then with EtOH at rt (2ꢂ5 mL). The combined extracts were con-
centrated in vacuo, the dry residue was dissolved in CHCl3 (30 mL),
4
3J5-Ha,6-H¼11.3, J5-Ha,OH¼0.9 Hz, 5-Ha), 1.39 (3H, s, CH3). 13C
NMR
d: 154.93 (C(2)), 102.09 (CCl3), 77.24 (C(4)), 63.39 (C(6)),
37.27 (C(5)), 28.56 (CH3). IR
n
, cmꢁ1: 3274 (s), 3107 (s) (
n
OH,
n
NH), 1666 (vs) (amide-I), 1500 (s) (amide-II), 1131 cmꢁ1 (s) (
n
C–O). Anal. Calcd for C6H9Cl3N2O2: C, 29.12; H, 3.67; N, 11.32%.
Found: C, 29.25; H, 3.45; N, 10.96%.
4.16. 5-Acetyl-6-methyl-1,2-dihydropyrimidin-2-one (13a)
the solution was refluxed with silica gel (100–400 mm) for 5 min
and filtered. The CHCl3 was removed in vacuo, the resulted residue
was triturated with light petrol until crystallization, the precipitate
was filtered, washed with light petrol, and dried to give compound
13d (0.419 g, 69.6%). Mp 124.5–125.5 ꢀC (EtOAc-hexane, 7:4 v/v)
To a mixture of NaH (0.147 g, 6.13 mmol) and compound 9a
(1.389 g, 5.12 mmol) was added anhydrous THF (8.5 mL), the
resulted suspension was stirred for 9 h 12 min at rt and neutralized
with 11.6 M HCl (0.528 mL, 6.14 mmol). The solvent was removed in
(Lit.7h mp 130–132 ꢀC). 1H NMR
d: 12.60 (1H, br s, NH), 8.62 (1H, s,

946
A.A. Fesenko et al. / Tetrahedron 66 (2010) 940–946
3
6. Kappe, C. O.; Roschger, P. J. Heterocycl. Chem. 1989, 26, 55.
4-H), 7.41–7.56 (5H, m, Ph), 4.03 (2H, q, JCH2,CH3¼7.1 Hz, OCH2),
3
7. (a) Kadysh, V. P.; Stradyn’, Ya. P.; Khanina, E. L.; Dubur, G. Y.; Mutsenietse, D. Kh.
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1.00 (3H, t, JCH3,CH2¼7.1 Hz, CH3).13C NMR
d: 170.73 (very br, C(6)),
163.84 (C]O in COOEt), 155.34 (C(2)), 154.86 (very br, C(4)), 136.52
(very br, C(1) in Ph), 130.13 (C(4) in Ph), 128.25 (C(2) and C(6) in Ph),
127.79 (C(3) and C(5) in Ph), 107.36 (C(5)), 60.55 (OCH2), 13.61 (CH3).
Acknowledgements
We thank Dr. Andrei Guzaev (A.M. Chemicals LLC, Oceanside,
C.A., USA) for helpful discussions.
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