Synthesis of 4-Alkynyl-substituted 3,4-Dihydropyrimidin-2(1 H)-ones

Article abstract of DOI:10.1080/00397911.2011.556298

4-Alkynyl-3,4-dihydropyrimidin-2-(1H)-ones were synthesized by a one-pot reaction of propynals, ethyl acetoacetate, and urea. The yields of acetylenic dihydropyrimidinones depend significantly upon the propynal structure and catalyst type. A comparative s

Full text of DOI:10.1080/00397911.2011.556298

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Synthesis of 4-Alkynyl-substituted 3,4-
Dihydropyrimidin-2(1H)-ones
Vladimir V. Novokshonov a , Irina A. Novokshonova a , Hien T. T.
Nguyen a & Alevtina S. Medvedeva a
a A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the
Russian Academy of Sciences, Irkutsk, Russia
Available online: 28 Nov 2011
To cite this article: Vladimir V. Novokshonov, Irina A. Novokshonova, Hien T. T. Nguyen & Alevtina
S. Medvedeva (2012): Synthesis of 4-Alkynyl-substituted 3,4-Dihydropyrimidin-2(1H)-ones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
42:16, 2346-2354
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Synthetic Communications1, 42: 2346–2354, 2012
Copyright # A. E. Favorsky Irkutsk Institute of Chemistry
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.556298
SYNTHESIS OF 4-ALKYNYL-SUBSTITUTED
3,4-DIHYDROPYRIMIDIN-2(1H)-ONES
Vladimir V. Novokshonov, Irina A. Novokshonova,
Hien T. T. Nguyen, and Alevtina S. Medvedeva
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the
Russian Academy of Sciences, Irkutsk, Russia
GRAPHICAL ABSTRACT
Abstract 4-Alkynyl-3,4-dihydropyrimidin-2-(1H)-ones were synthesized by a one-pot
reaction of propynals, ethyl acetoacetate, and urea. The yields of acetylenic dihydropyrimi-
dinones depend significantly upon the propynal structure and catalyst type. A comparative
study of the catalysts revealed an important advantage of polyphosphate ester in tetra-
hydrofuran in comparison with hydrochloric acid in methanol or trimethylchlorosilane in
dimethylformamide, allowing the preparation of target compounds in good or moderate
yields.
Keywords Biginelli reaction; 3,4-dihydropyrimidin-2-ones; multicomponent reactions;
propynals
INTRODUCTION
The Biginelli reaction,[1] one of the most useful multicomponent reactions,
offers an efficient route to multifunctionalized 3,4-dihydropyrimidin-2-(1H)-ones.
They have been found to exhibit a wide spectrum of biological activities such as
antiviral, antitumor, antibacterial, and anti-inflammatory activities. Furthermore,
appropriately functionalized 3,4-dihydropyrimidin-2-(1H)-ones have emerged as
Received December 13, 2010.
Address correspondence to Alevtina S. Medvedeva, A.E. Favorsky Irkutsk Institute of Chemistry,
1 Favorsky Street. 664033, Irkutsk, Russia. E-mail: amedved@irioch.irk.ru
2346

SYNTHESIS OF 4-ALKYNYL-3,4-DIHYDROPYRIMIDIN-2-ONES
2347
potent calcium channel modulators, antihypertensive agents, a 1a-adrenergic antago-
nists, and neuropeptide Y antagonists.[2]
The Biginelli condensation is a well-known, simple, atom-economical, and
direct method for the synthesis of dihydropyrimidinones by the three-component
reaction of aldehyde, 1,3-dicarbonyl compound, and urea under acidic conditions.[3]
Recently, it has been investigated extensively by the variation of all three building
blocks, which allows a great number of multifunctionalized dihydropyrimidinones
to be synthesized.[4] The Biginelli cyclocondensation has been widely applied to aro-
matic, unsaturated, and aliphatic aldehydes.[5] However, the use of propynals for the
synthesis of acetylenic 3,4-dihydropyrimidin-2(1H)-ones is very limited. It is note-
worthy that the 4-ethynyl-containing dihydropyridine derivatives show potent and
characteristic activities. Thus, the structure–activity studies of 3,4-dihydroquinazo-
lin-2(1H)-one derivatives containing acetylene as a small lipophilic group at the
4-position are among the best in terms of both potency and oral bioavailability
against HIV-RT.[6a,b] 4-(Phenylethynyl)-substituted 1,4-dihydropyridines are potent
and selective A3 adenosine receptor antagonists.[6c,d]
Herein, we report the multicomponent synthesis of new 4-alkynyl substituted
3,4-dihydropyrimidin-2(1H)-ones 4a–h via the reaction of propynals substituted at
the triple bond by silicon or germanium heteroatoms 1a,b and c-hydroxyalkylpropy-
nals 1d–h with ethyl acetoacetate 2 and urea 3. An efficient and convenient procedure
for the preparation of substituted propynals by oxidation of propargylic alcohols
and diols by iodoxybenzoic acid (IBX) has been reported by us recently.[7]
The introduction of an acetylenic moiety in 3,4-dihydropyrimidin-2-(1H)-ones
paves the way for new polyfunctional biologically interesting analogs. The steric
availability of the aldehyde group in propynals and the presence of two conjugated
electrophilic centers favor the formation and reaction of N-acyliminium ion
þ
=
RCꢀCCH N HCONH2 according to mechanism of the Biginelli condensation
suggested by Kappe.[8] This opens new horizons for the application of acetylenic
aldehydes as the building blocks for synthesis of new multifunctional dihydropyrimi-
dinone scaffolds.
Element-substituted propynals play a special role in the chemistry of a,b-
acetylenic aldehydes. The presence of silicon and germanium heteroatoms at the
triple bond of a propynal enhances the electrophilicity of the carbonyl center[9]
and stabilizes the molecule of the aldehyde and the target products, while subsequent
demetallation under mild conditions can result in analogs with the terminal triple
bond. Wide synthetic possibilities of element-substituted propynals in the directed
synthesis of polyfunctional acetylene derivatives and construction of heterocyclic
compounds have been reviewed by us recently.[10] Propynals containing a hydroxyl
moiety at the c-position to the carbonyl group represent polyfunctional substrates
to design new heterocyclic compounds.[11,12]
RESULTS AND DISCUSSION
We have briefly reported that the Biginelli reaction of 3-trimethylsilyl-,
(triethylgermyl)-2-propyn-1-als 1a,b, ethyl acetoacetate, and urea in classical
reaction conditions (MeOH, 5 mol% of hydrochloric acid, reflux, 24 h) leads to dihy-
dropyrimidinones 4a,b in good yields.[13] However, in the presence of LiClO4

2348
V. V. NOVOKSHONOV ET AL.
(20 mol%), one of the efficient catalysts of the Biginelli condensation,[14] the
=
=
Knoevenagel adducts, [viz., Z,E-enynes RCꢀCCH C(COMe)COOEt (R Me3Si,
Et3Ge)] are the only products of the reaction.
The application of c-hydroxyalkylpropynals 1d–h in the Biginelli reaction
with ethyl acetoacetate 2 and urea 3 under classical conditions (method A)
affords new 3,4-dihydropyrimidin-2(1H)-ones 4d–h in moderate yields (35–46%)
(Scheme 1).
To develop a selective and efficient method of 4-alkynyl substituted 3,4-
dihydropyrimidin-2(1H)-ones 4a–h synthesis suitable for the series of propynals
1a–h, we also examined trimethylchlorosilane (TMSCl) in dimethylformamide
(DMF) and polyphosphate ester (PPE) in tetrahydrofuran (THF) as the catalysts
in comparison with classical conditions. Among the various acidic reagents, TMSCl
has received considerable attention as an inexpensive and readily available promoter
of the Biginelli condensation.[15–17] The amount of TMSCl in DMF or DMF-MeCN
in this reaction varies from 1–2 equiv[16,18] to 4–6 equiv.[19]
The Biginelli reaction of aldehydes 1a–c with acetoacetic ester and urea is car-
ried out successfully in the presence of 1.2 equiv Me3SiCl in dry DMF (method B,
25 ꢁC, 3 days) to give 3,4-dihydropyrimidin-2(1H)-ones 4a–c in 72–89% yield. The
presence of 6.0 equiv Me3SiCl in DMF does not allow increasing the yields of pyr-
imidinones 4a,b. Furthermore, in the case of 4-hydroxy-4-methyl-2-pentyn-1-al 1d,
the reaction catalyzed by TMSCl (1.2 equiv) furnishes dihydropyrimidinone 4d in
poor yield (18%). The attempt to synthesize the corresponding Biginelli adducts from
c-hydroxyalkylpropynals 1e–h failed because of high resinification.
The best results for the synthesis of target dihydropyrimidinones 4a–h from
aldehydes 1a–h have been reached under PPE=THF-catalyzed Biginelli cycloconden-
sation. The advantages of PPE include its solubility in organic solvents, relatively
nonhazardous nature, simple procedure for its preparation, and mild reaction
conditions.[20] It should be noted that ethyl 6-methyl-2-oxo-4-(phenylethynyl)-
1,2,3,4-tetrahydropyrimidine-5-carboxylate 4c has been prepared by the PPE=THF
method from phenylpropynal.[21]
The yields of 3,4-dihydropyrimidin-2-ones 4a–h in the case of PPE=THF
(method C, reflux, 24 h) are 57–94% compared to 35–81% in the classical conditions
(Table 1).
Scheme 1. R ¼ Me3S (a); Et3Ge (b); Ph (c); Me2C(OH) (d); MeEtC (OH) (e); MePrC (OH) (f); 1-hydro-
xyoyclohexyl (g); MePhC (OH) (h). (i) HCl=MeOH, reflux, 24 h; (ii) 1.2 eg. Me3 SiC=DMF; rt; 72 h; and
(iii) PPE=THF, reflux, 24 h.

SYNTHESIS OF 4-ALKYNYL-3,4-DIHYDROPYRIMIDIN-2-ONES
2349
Table 1. Synthesis of 3,4-dihydropirimidin-2-ones 4a–h in different conditions
Isolated yields (%)
Entry
Product
R
Aa
Bb
Cc
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
Me3Si
Et3Ge
Ph
81[13]
78[13]
54
72
86
89
18
79
94
70
75
64
68
57
71
Me2C(OH)
MeEtC(OH)
46
35
d
—
—
—
—
d
d
d
MePrC(OH)
1-hydroxycyclohexyl
MePhC(OH)
40
35
4g
4h
43
aMethod A: HCl=MeOH, reflux, 24 h.
bMethod B: 1.2 equiv Me3SiCl=DMF, rt, 72 h.
cMethod C: PPE=THF, reflux, 24 h.
dResinification.
In summary, we have developed a selective synthesis of new highly functiona-
lized acetylenic 3,4-dihydropyrimidin-2(1H)-ones, available for further modification,
from a-silicon, germanium propynals, and c-hydroxyalkylpropynals. The effect of
propynal structure and catalyst nature on the efficiency of Biginelli condensation
has been revealed. PPE=THF turns out to be an efficient catalyst for a series of
propynals, containing various substituents at the triple bond, to afford target hetero-
cycles in good to excellent yields.
EXPERIMENTAL
1H and 13C NMR spectra were recorded at 400.13 MHz and 101.62 MHz
respectively on a Bruker DPX-400 spectrometer using dimethylsulfoxide (DMSO-
d6) or CDCl3 as solvents. Chemical shifts (d) are given in parts per million (ppm)
relative to hexamethyldisiloxane (HMDS) as internal standard. Infrared (IR) spectra
were taken on a Bruker IFS-25 spectrometer in KBr pellets are reported in cen-
timetersꢂ1. Melting points were determined with a Kofler hot-stage apparatus and
were uncorrected. Polyphosphate ester (PPE) was synthesized by the method in
Ref. 20 and propynals 1a–h with the method in Ref. 7.
General Procedures for Preparation of Dihydropyrimidinones 4a–h
Method A. A mixture of the appropriate aldehyde (1.8 mmol), ethyl acetoace-
tate (0.234 g, 1.8 mmol), urea (0.216 g, 3.6 mmol), and concentrated hydrochloric
acid (5 mol%) in 10 mL of methanol was stirred under reflux for 24 h. After cooling
of the reaction mixture to room temperature and removing the solvent, 5 mL of
water and 10 mL of diethyl ether were added. The aqueous layer was extracted by
6 ꢃ 5 mL of ether. The combined organic solution was dried over MgSO4 and
evaporated to dryness. The product was purified by recrystallization from aqueous
EtOH.

2350
V. V. NOVOKSHONOV ET AL.
Method B. Trimethylchlorosilane (TMSCl) (3.6 mmol) was added dropwise
to the solution of the appropriate aldehyde (2.0 mmol), ethyl acetoacetate (0.260 g,
2.0 mmol), and urea (0.240 g, 4.0 mmol) in 5 mL of DMF and stirred at room tem-
perature for 72 h. The mixture was poured into 25 mL of cold H2O, and 15 mL of
diethyl ether was added. The aqueous layer was extracted by 4 ꢃ 5 mL of ether.
The combined organic solution was washed with 2 ꢃ 5 mL of water, dried over
MgSO4, and evaporated to dryness. The product was purified by recrystallization
from aqueous EtOH.
Method C. A mixture of the appropriate aldehyde (2.0 mmol), ethyl acetoace-
tate (0.260 g, 2.0 mmol), urea (0.240 g, 4.0 mmol), and PPE (0.300 g) in 15 mL of
THF was stirred under reflux for 24 h. After removing the solvent, 10 mL of water
and 15 mL of diethyl ether were added. The aqueous layer was extracted by 4 ꢃ 5 mL
mL of ether. The combined organic solutions was dried over MgSO4 and evaporated
to dryness. The product was purified by recrystallization from aqueous EtOH.
Selected Data
Ethyl 6-methyl-2-oxo-4-(2-trimethylsilylethynyl)-1,2,3,4-tetrahydropyri-
midine-5-carboxylate 4a. White solid; yield 81% (method A), 72% (method B),
79% (method C); mp 210–212 ꢁC (aqueous EtOH). IR: 3253, 3122 (NH), 2171
1
=
=
(CꢀC), 1712, 1226 (COO), 1662 (C O, C C), 1289, 842 (Si-C). H NMR (CDCl3):
d 0.16 [s, 9H, Si(CH3)3], 1.32 (t, 3H, CH3CH2O), 2.36 (s, 3H, ¼CCH3), 4.17 (q, 2H,
OCH2CH3), 5.13 (s, 1H, CH), 6.00 (br s, 1H, NH), 8.31 (br s, 1H, NH). 13C NMR
(CDCl3): d 0.10 [Si(CH3)3], 14.64 (CH3CH2O), 18.55 (¼ CCH3), 43.81 (CH), 60.13
(CH3CH2O), 87.29 (CꢀCSi), 98.55 (C¼CCOO), 104.85 (CCꢀC), 145.13 (CH3C¼C),
=
154.03 (C O), 164.89 (COO). Anal. calcd. for C13H20N2O3Si: C, 56.69; H, 7.18; N,
9.99; Si, 10.02. Found: C, 56.40; H, 7.01; N, 9.88; Si, 9.87.
Ethyl 6-methyl-2-oxo-4-(2-triethylgermylethynyl)-1,2,3,4-tetrahydro-
pyrimidine-5-carboxylate 4b. White solid; yield 78% (method A), 86% (method
B), 94% (method C); mp 221–222 ꢁC (aqueous EtOH). IR: 3246, 3110 (NH), 2166
1
=
=
(CꢀC), 1727, 1710, 1227 (COO), 1660 (C O, C C) H NMR (CDCl3): d 0.83 (q,
6H, GeCH2CH3), 1.06 (t, 9H, GeCH2CH3), 1.30 (t, 3H, CH3CH2O), 2.27 (s, 3H,
¼CCH3), 4.21 (q, 2H, OCH2CH3), 5.14 (s, 1H, CH), 5.81 (br s, 1H, NH), 8.50 (br
s, 1H, NH). 13C NMR (CDCl3): d 5.80 (GeCH2CH3), 9.06 (GeCH2CH3), 14.46
(CH3CH2O), 18.54 (C ¼ CCH3), 43.80 (CH), 60.28 (CH3CH2O), 85.28 (CꢀCGe),
=
99.52 (C¼CCOO), 105.21 (CCꢀC), 147.20 (CH3C¼C), 154.06 (C O), 165.22
(COO). Anal. calcd. for C16H26N2O3Ge: C, 52.36; H, 7.14; N, 7.63; Ge, 19.78.
Found: C, 52.21; H, 7.09; N, 7.57; Ge, 19.64.
Ethyl 6-methyl-2-oxo-4-(phenylethynyl)-1,2,3,4-tetrahydropyrimidine-
5-carboxylate 4c. Yellow solid; yield 54% (method A), 89% (method B), 70%
(method C); mp 225–226 ꢁC (aqueous EtOH) (lit.[22] mp 226 ꢁC). IR: 3243, 3116
1
=
=
(NH), 2235 (CꢀC), 1725, 1709, 1225 (COO), 1659 (C O, C C), 1600 (Ph). H
NMR (DMSO-d6): d 1.22 (t, 3H, CH3CH2O), 2.33 (s, 3H, ¼CCH3), 4.14 (q, 2H,
OCH2CH3), 5.12 (s, 1H, CH), 7.36 (s, 5H, Ph), 7.78 (br s, 1H, NH), 9.37 (br s,
1H, NH). 13C NMR (DMSO-d6): d 14.23 (CH3CH2O), 17.64 (C ¼ CCH3), 42.26

SYNTHESIS OF 4-ALKYNYL-3,4-DIHYDROPYRIMIDIN-2-ONES
2351
(CH), 59.41 (CH3CH2O), 80.80 (CꢀCPh), 90.20 (CCꢀC), 96.77 (C¼CCOO), 121.99,
=
128.59, 128.64, 131.28 (Ph), 149.22 (CH3C¼C), 152.26 (C O), 164.62 (COO). Anal.
calcd. for C16H16N2O3: C, 67.59; H, 5.67; N, 9.85. Found: C, 67.41; H, 5.51; N, 9.67.
Ethyl 6-methyl-2-oxo-4-(3-hydroxy-3-methyl-1-butynyl)-1,2,3,4-tetrahy-
dropyrimidine-5-carboxylate 4d. White solid; yield 46% (method A), 18%
(method B), 75% (method C); mp 179–180 ꢁC (aqueous EtOH). IR: 3380 (OH),
1
=
=
3252, 3120 (NH), 2241 (CꢀC), 1715, 1228 (COO), 1655 (C O, C C). H NMR
(DMSO-d6): d 1.25 (t, 3H, OCH2CH3), 1.32 [s, 6H, (CH3)2COH], 2.20 (s, 3H,
¼CCH3), 4.10 (q, 2H, OCH2CH3), 4.88 (s, 1H, CH), 7.51 (br s, 1H, NH), 9.16 (br
s, 1H, NH). 13C NMR (DMSO-d6): d 14.10 (CH3CH2O), 17.47 (¼ CCH3), 31.46
[(CH3)2COH], 41.62 (CH), 58.87 (CH3CH2O), 62.92 [(CH3)2COH], 80.66 (CHCꢀ),
=
86.97 (ꢀCC), 97.08 (¼CCOO), 144.62 (CH3C¼), 152.07 (C O), 164.31 (COO).
Anal. calcd. for C13H18N2O4: C, 58.63; H, 6.81; N, 10.52. Found: C, 58.48; H,
6.72; N, 10.34.
Ethyl 6-methyl-2-oxo-4-(3-hydroxy-3-methyl-1-pentynyl)-1,2,3,4-tetra-
hydropyrimidine-5-carboxylate 4e. White solid; yield 35% (method A), 64%
(method C); mp 127–128 ꢁC (aqueous EtOH). IR: 3361 (OH), 3247, 3119 (NH),
1
=
=
2232 (CꢀC), 1718, 1230 (COO), 1652 (C O, C C). H NMR (DMSO-d6): d 0.89
(t, 3H, CCH2CH3), 1.25 (t, 3H, OCH2CH3), 1.29 (s, 3H, CH3COH), 1.48 (q, 2H,
CCH2CH3), 2.19 (s, 3H, ¼CCH3), 4.07 (q, 2H, OCH2CH3), 4.88 (s, 1H, CH), 5.11
(br s, 1H, OH), 7.61 (br s, 1H, NH), 9.25 (br s, 1H, NH)13C NMR (DMSO-d6): d
9.47 (CH3CH2C), 14.74 (CH3CH2O), 18.12 (¼ CCH3), 29.88 (CH3COH), 37.01
(CH3CH2C), 42.23 (CH), 59.86 (CH3CH2O), 67.20 (CH3COH), 82.69 (CHCꢀ),
=
86.50 (ꢀCC), 97.90 (¼CCOO), 149.27 (CH3C¼), 152.82 (C O), 165.20 (COO).
Anal. calcd. for C14H20N2O4: C, 59.99; H, 7.19; N, 9.99. Found: C, 59.65; H,
7.08; N, 9.74.
Ethyl 6-methyl-2-oxo-4-(3-hydroxy-3-methyl-1-hexynyl)-1,2,3,4-tetrahy-
dropyrimidine-5-carboxylate 4f. White solid; yield 40% (method A), 68%
(method C); mp 122–125 ꢁC (dec.) (aqueous EtOH). IR: 3352 (OH), 3249, 3120
1
=
=
(NH), 2230 (CꢀC), 1717, 1229 (COO), 1654 (C O, C C). H NMR (DMSO-d6):
d 0.88 (t, 3H, CH2CH2CH3), 1.20 (m, 2H, CH2CH2CH3), 1.25 (t, 3H, OCH2CH3),
1.28 (s, 3H, CH3COH), 1.42 (t, 2H, CH2CH2CH3), 2.20 (s, 3H, ¼CCH3), 4.10 (q,
2H, OCH2CH3), 4.87 (s, 1H, CH), 7.48 (br s, 1H, NH), 9.14 (br s, 1H, NH). 13C
NMR (DMSO-d6):
d
13.50 (CH3CH2CH2), 14.01 (CH3CH2O), 16.56
(CH3CH2CH2), 17.39 (¼ CCH3), 29.67 (CH3COH), 41.61 (CH3CH2CH2), 45.89
(CH), 58.83 (CH3CH2O), 65.89 (CH3COH), 81.90 (CHCꢀ), 86.05 (ꢀCC), 97.17
=
(¼CCOO), 148.32 (CH3C¼), 152.05 (C O), 164.27 (COO). Anal. calcd. for
C15H22N2O4: C, 61.21; H, 7.53; N, 9.52. Found: C, 60.98; H, 7.32; N, 9.36.
Ethyl 6-methyl-2-oxo-4-[2-(1-hydroxycyclohexyl)ethynyl]-1,2,3,4-tetra-
hydropyrimidine-5-carboxylate 4g. White solid; yield 35% (method A), 57%
(method C); mp 165–166 ꢁC (aqueous EtOH). IR: 3378 (OH), 3248, 3116 (NH),
1
=
=
2238 (CꢀC), 1714, 1229 (COO), 1654 (C O, C C). H NMR (DMSO-d6): d 1.20
(t, 3H, OCH2CH3), 1.38 (t, 2H, c-CH2), 1.53–1.68 (m, 8H, a,b-CH2), 2.19 (s, 3H,
¼CCH3), 4.08 (q, 2H, OCH2CH3), 4.90 (s, 1H, CH), 7.57 (br s, 1H, NH), 9.21 (br
s, 1H, NH). 13C NMR (DMSO-d6): d 14.16 (CH3CH2O), 17.97 (¼ CCH3), 23.16

2352
V. V. NOVOKSHONOV ET AL.
(b-C), 25.33 (c-C), 42.13 (CH), 49.75 (a-C), 59.75 (CH3CH2O), 67.04 (COH), 84.19
=
(CHCꢀ), 86.36 (ꢀCC), 97.93 (¼CCOO), 149.16 (CH3C¼), 152.76 (C O), 165.08
(COO). Anal. calcd. for C16H22N2O4: C, 62.73; H, 7.24; N, 9.14. Found: C, 62.59;
H, 7.22; N, 9.23.
Ethyl 6-methyl-2-oxo-4-(3-hydroxy-3-phenyl-1-butynyl)-1,2,3,4-tetrahy-
dropyrimidine-5-carboxylate 4h. White solid; yield 43% (method A), 71%
(method C); mp 130–131 ꢁC (aqueous EtOH). IR: 3407 (OH), 3262, 3123 (NH),
1
=
=
2245 (CꢀC), 1704, 1230 (COO), 1650 (C O, C C). H NMR (DMSO-d6): d 1.20
(t, 3H, OCH2CH3), 1.55 [s, 3H, CH3C(OH)], 2.20 (s, 3H, ¼CCH3), 4.10 (q, 2H,
OCH2CH3), 4.98 (s, 1H, CH), 7.23–7.51 (m, 5H, Ph), 7.70 (br s, 1H, NH) 9.30 (br
s, 1H, NH). 13C NMR (DMSO-d6): d 14.19 (CH3CH2O), 17.57 (¼ CCH3), 33.99
[CH3C(OH)], 41.81 (CH), 59.38 (CH3CH2O), 67.92 [CH3C(OH)], 83.79 (CHCꢀ),
85.76 (ꢀCC), 97.02 (¼CCOO), 124.80, 126.98, 127.77, 138.79 (Ph), 148.97 (CH3C¼),
=
152.21 (C O), 164.63 (COO). Anal. calcd. for C18H20N2O4: C 65.84; H 6.14; N 8.53.
Found: C, 65.80; H, 6.11; N, 8.48.
ACKNOWLEDGMENT
The authors thank the Russian Foundation for Basic Research (10-03-01024-a)
for financial support.
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