Heterocyclizations of functionalized heterocumulenes with C,N-, C,O-, and C,S-binucleophiles: XIII. Synthesis of dialkyl 2-oxo-3-allyl-1,2,3,6- tetrahydropyrimidine-4,5-dicarboxylates and their reaction with arylhydroxymoyl chlorides

Article abstract of DOI:10.1134/S1070428011110133

Dialkyl 2-oxo-3-allyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylates obtained by condensation of 1-chlorobenzyl isocyanates with N-allylfumarates reacted regioselectively with arylhydroxymoyl chlorides with the formation of dialkyl 6-aryl-3-[(3-aryl-4,5-

Full text of DOI:10.1134/S1070428011110133

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 11, pp. 1727−1732. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © O.V. Kushnir, N.V. Mel’nichenko, M.V. Vovk, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 11, pp. 1691−1695.
Heterocyclizations of Functionalized Heterocumulenes
with C,N-, C,O-, and C,S-Binucleophiles: XIІI.*
Synthesis of Dialkyl 2-Oxo-3-allyl-1,2,3,6-tetrahydropyrimidine-
4,5-dicarboxylates and Their Reaction
with Arylhydroxymoyl Chlorides
O. V. Kushnira, N. V. Mel’nichenkob, and M. V. Vovkb
a Fed’kovich Chernovtsy National University, Chernovtsy, Ukraine
b Institute of Organic Chemistry, National Academy of Sciences of Ukraine
Kiev, 02094 Ukraine
e-mail: mvovk@i.com.ua
Received January 26, 2011
Abstract—Dialkyl 2-oxo-3-allyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylates obtained by condensation of
1-chlorobenzyl isocyanates with N-allylfumarates reacted regioselectively with arylhydroxymoyl chlorides with
the formation of dialkyl 6-aryl-3-[(3-aryl-4,5-dihydro-5-isoxazolyl)methyl]-2-oxo-1,2,3,6-tetrahydropyrimidine-
4,5-dicarboxylates.
DOI: 10.1134/S1070428011110133
3,4-Dihydropyrimidine ring is the structural frag-
ment governing the biological activity of many organic
compounds [2–4]. Therewith the useful properties of
3,4-dihydropyrimidine derivatives are essentially affected
by the character of substituents at the carbon atoms of the
ring. Yet the effect of the substituents at nitrogen atoms
remains practically nonstudied to a certain extent because
of the lack of methods of the selective functionalization of
the nitrogen atoms with biophore moieties. To the latter
the isoxazoline heterocycle certainly belongs for among
its derivatives substances are found with a wide range of
the biologic action [5–8].
It was established that 1-chlorobenzyl isocyanates
Іа–Ie reacted with previously unknown dialkyl N-allyl-
aminofumarates ІІа, IIb in toluene solution at room
temperature giving dialkyl 2-oxo-3-allyl-6-aryl-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylates ІІІа–IIIh in
45–83% yields. The structure of the latter is confirmed
by 1Н and 13С NMR spectra containing typical doublets
of protons Н6 in the range 5.23–5.42 ppm and signals of
atoms С6 in the range 51.86–53.02 ppm. The presence
of the asymmetric carbon center in the position 6 of the
heterocycle results in the diastereotopic character of the
methylene group of the allyl substituent leading to the
complex multiplicity of the signal of allyl protons in the
1Н NMR spectrum.
Among the versatile procedures for the preparation
of isoxazoline derivatives the version should be spe-
cially indicated of 1,3-dipolar addition of nitrile oxides
to alkenes, in particular, to functionalized ones, which
is characterized by high regioselectivity [13, 14]. We
demonstrated that 3-allylpyrimidin-2-ones ІІІb, IIId,
IIIe–IIIh also reacted regioselectively with hydroxymoyl
chlorides IVа–IVb in the presence of triethylamine, i.e.,
The analysis of publications [9–11] reveals a lim-
ited number of isoxazoline derivatives linked to
the other heterocycles by a methylene bridge. It
was therefore feasible to extend our method [12] of
3-arylpyrimidinedicarboxylates synthesis on their 3-allyl
analogs and to use the latter for building up an isoxazoline
ring.
___________________
* For Communication XII, see [1].
1727

KUSHNIR et al.
1728
Scheme.
AlkO(O)C
Ar1
C(O)OAlk
C(O)OAlk
Ar1
Cl
AlkO(O)C
+
N
H
N C O
Iа_Ie
N
HN
IIа, IIb
O
IIIа_IIIh
Ar2
Cl
Et3N
N OH
IVа_IVc
AlkO(O)C
Ar1
C(O)OAlk
N
O
N
O
Ar2
HN
Vа_Vg
І, Ar1 = Ph (a), 3-BrC6H4 (b), 3-NO2C6H4 (c), 4-NO2C6H4 (d), 3,4-Cl2C6H3 (e); ІІ, Alk = Me (a), Et (b); ІІІ, Alk = Me,
Ar1 = Ph (a), 3-BrC6H4 (b), 3-NO2C6H4 (c), 4-NO2C6H4 (d), 3,4-Cl2C6H3 (e);Alk = Et, Ar = 3-BrC6H4 (f), 4-NO2C6H4 (g),
3,4-Cl2C6H3 (h); IV, Ar2 = Ph (a), 4-FC6H4 (b), 4-MeOC6H4 (c); V, Alk = Me: Ar1 = 3-BrC6H4, Ar2 = Ph (a), 4-MeOC6H4
(b); Ar1 = 4-NO2C6H4, Ar2 = 4-FC6H4 (c); Ar1 = 3,4-Cl2C6H3, Ar2 = Ph (d); Alk = Et: Ar1 = 3-BrC6H4, Ar2 = 4-MeOC6H4
(e); Ar1 = 4-NO2C6H4, Ar2 = 4-MeOC6H4 (f); Ar1 = 3,4-Cl2C6H3, Ar2 = 4-FC6H4 (g).
under the conditions of generation of the corresponding
nitrile oxides leading to the formation of 3-isoxazolinyl
methylpyrimidinones Vа–Vg (see the scheme)
125.75 MHz respectively), internal reference TMS.
GC-MS measurements were performed on an instru-
ment Agilent 1100/DAD/HSD/VLG 119562. Dialkyl
N-allylaminofumarates ІІа, IIb were synthesized as
described in [15].
The analysis of crude reaction products by the meth-
ods of 1Н NMR spectroscopy and GC-MS showed that
the content there of the target products reached 79–88%.
Therewith compounds Vc, Ve–Vg formed as single
diastereomers, and compounds Va, Vb, Vd, as mixtures
of two diastereomers in the ~2:1 ratio. The fractional
crystallization of the latter compounds from ethanol
made it possible to isolate th major diastereomers in
29–36% yields.
Dimethyl N-allylaminofumarate (ІІа). Yield 88%,
bp 72°С (0.02 mm Hg). IR spectrum , ν, cm–1: 3240 (NH),
1745 (C=O), 1680, 1645 (С=С). 1Н NMR spectrum, δ,
ppm: 3.66 s (3Н, СН3О), 3.83 s (3Н, СН3О), 3.96 m
(2Н, CH2N), 5.12 s (1H, HC=), 5.12–5.20 m (2Н, H2C=),
5.85 m (1H, НС=), 8.13 s (1Н, NН). Found, %: С 54.46;
Н 6.51; N 7.10. C9H13NO4. Calculated, %: С 54.26;
Н 6.58; N 7.03.
The presence of an isoxazoline ring in the structure
1
of compounds Vа–Vg was proved by the Н NMR
Diethyl N-allylaminofumarate (ІІb). Yield 72%,
bp 92°С (0.04 mm Hg). IR spectrum , ν, cm–1: 3235
spectra that contained the multiplet signals of methylene
(3.07–3.24 ppm) and methine (4.76–4.85 ppm) protons,
and also by 13С NMR spectra where the atoms С4' and C5'
gave rise to signals at 37.31–37.59 and 77.68–78.55 ppm
respectively.
1
(NH), 1750 (C=O), 1675, 1645 (С=С). Н NMR spec-
trum, δ, ppm: 1.28 t (3Н, СН3, J 7.0 Hz), 1.34 t (3Н,
СН3, J 7.0 Hz), 3.99 m (2Н, CH2N), 4.15 q (2Н, СН2О,
J 7.0 Hz), 4.29 q (2Н, СН2О, J 7.0 Hz), 5.14 s (1H, HC=),
5.16–5.24 m (2Н, H2C=), 5.88 m (1H, НС=), 8.17 s (1Н,
NН). Found, %: С 58.31; Н 7.57; N 6.18. C11H17NO4.
Calculated, %: С 58.14; Н 7.54; N 6.16.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Dialkyl 3-allyl-6-aryl-2-oxo-1,2,3,6-tetrahydro-
pyrimidine-4,5-dicarboxylates ІІІа–IIIh. To a solu-
tion of 6 mmol of dialkyl N-allylaminofumarate IIa,
IIb in 25 ml of anhydrous toluene was added 6 mmol
of isocyanate Іа–Ie, and the mixture was left standing
UR-20 in thin film (for compounds IIa, IIb) or in
pellets with KBr. Н NMR spectra [of compounds
IIa, IIb in CDCl3, of the other in (СD3)2SO] and
13С NMR spectra [in (СD3)2SO] were registered on
a spectrometer Bruker Advance DRX-500 (500.13 and
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

HETEROCYCLIZATIONS OF FUNCTIONALIZED HETEROCUMULENES...: XIІI.
1729
at room temperature for 24 h. The solvent was decanted
from the oily precipitate, the precipitate was treated
with hexane and left standing for 24 h. The formed solid
reaction product was filtered off, dried, and crystallized
from ethanol .
162.53 (C=O), 163.63 (C=O). Found, %: С 54.71;
Н 4.52; N 11.39. [M + 1]+ 376. C17H17N3O7. Calculated,
%: С 54.40; Н 4.57; N 11.20. M 375.3.
Dimethyl 3-allyl-6-(4-nitrophenyl)-2-oxo-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (ІІІd). Yield
63%, mp 170–171°С. IR spectrum , ν, cm–1: 3260, 3150
Dimethyl 3-allyl-2-oxo-6-phenyl-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (ІІІа). Yield
45%, mp 108–109°С. IR spectrum , ν, cm–1: 3250, 3110
1
(NH), 1750, 1710 (C=O). Н NMR spectrum, δ, ppm:
3.58 s (3Н, СН3О), 3.80 s (3Н, СН3О), 3.92 d.d, 4.28 d.d
(2H, СH2, J 17.0, J 6.7 Hz), 5.06 d (1H, НС=, J 15.8 Hz),
5.13 d (1H, НС=, J 8.5 Hz), 5.38 d (1Н, Н6, J 3.3 Hz),
5.74 m (1H, HС=), 7.53 d (2Нarom, J 8.0 Hz), 8.27 d
(2Нarom, J 8.0 Hz), 8.40 d (1Н, NH, J 3.0 Hz). 13С NMR
spectrum, δ, ppm: 46.00 (CH2), 51.98 (CH3O), 52.22
(CH3O), 52.91 (C6), 101.53 (C5), 117.18 (H2C=), 124.02,
127.52, 133.21, 143.38 (CAr), 147.09 (HC=), 149.66 (C4),
150.71 (C2), 162.47 (C=O), 163.58 (C=O). Found, %:
С 54.19; Н 4.63; N 11.39. [M + 1]+ 375. C17H17N3O7.
Calculated, %: С 54.40; Н 4.57; N 11.20. M 375.3.
1
(NH), 1740, 1695 (C=O). Н NMR spectrum, δ, ppm:
3.58 s (3Н, СН3О), 3.86 s (3Н, СН3О), 3.99 d.d, 4.30 d.d
(2H, СH2, J 16.5, J 5.5 Hz), 5.05 d (1H, HС=, J 17.0 Hz),
5.10 d (1H, НС=, J 10.0 Hz), 5.23 d (1Н, Н6, J 3.5 Hz),
5.73 m (1H, HС=), 7.27–7.41 m (5Нarom), 8.27 d (1Н,
NH, J 3.5 Hz). 13С NMR spectrum, δ, ppm: 45.89 (CH2),
51.97 (CH3O), 52.53 (CH3O), 52.88 (C6), 102.52 (C5),
117.32 (H2C=), 126.10, 127.90, 128.71, 133.36 (CAr),
142.69 (HC=), 142.88 (C4), 151.12 (C2), 162.82 (C=O),
163.90 (C=O). Found, %: С 61.54; Н 5.55; N 8.55. [M +
1]+ 331. C17H18N2O5. Calculated, %: С 61.81; Н 5.49;
N 8.48. M 330.3.
Dimethyl 3-allyl-2-oxo-6-(3,4-dichlorophenyl)-
1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (ІІІe).
Yield 58%, mp 143–144°С. IR spectrum , ν, cm–1: 3255,
Dimethyl 3-allyl-6-(3-bromophenyl)-2-oxo-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (ІІІb). Yield
83%, mp 142–143°С. IR spectrum , ν, cm–1: 3245, 3125
1
3140 (NH), 1740, 1705 (C=O). Н NMR spectrum, δ,
ppm: 3.60 s (3Н, СН3О), 3.88 s (3Н, СН3О), 3.97 d.d,
4.30 d.d (2H, СH2, J 16.0, J 5.3 Hz), 5.05 d (1H, НС=,
J 16.5 Hz), 5.12 d (1H, НС=, J 10.5 Hz), 5.28 d (1Н, Н6,
J 3.0 Hz), 5.74 m (1H, HС=), 7.24 d (1Нarom, J 8.5 Hz),
7.48 с (1Нarom), 7.70 d (1Нarom, J 8.5 Hz), 8.34 d (1Н,
NH, J 3.0 Hz). 13С NMR spectrum, δ, ppm: 45.97 (CH2),
51.69 (CH3O), 52.04 (CH3O), 53.00 (C6), 101.55 (C5),
117.17 (H2C=), 126.40, 128.34, 130.9, 131.13, 131.28,
133.20 (CAr), 143.39 (HC=), 143.55 (C4), 150.78 (C2),
162.55 (C=O), 163.63 (C=O). Found, %: С 51.31; Н 4.18;
N 6.79. [M + 1]+ 400. C17H16Cl2N2O5. Calculated, %:
С 51.14; Н 4.04; N 7.02. M 399.2.
1
(NH), 1740, 1700 (C=O). Н NMR spectrum, δ, ppm:
3.59 s (3Н, СН3О), 3.80 s (3Н, СН3О), 3.86 d.d, 4.31 d.d
(2H, СH2, J 16.5, J 5.5 Hz), 5.06 d (1H, НС=, J 17.0 Hz),
5.11 d (1H, НС=, J 10.5 Hz), 5.23 d (1Н, Н6, J 3.3 Hz),
5.74 m (1H, HС=), 7.24–7.54 m (4Нarom), 8.30 d (1Н,
NH, J 3.3 Hz). 13С NMR spectrum, δ, ppm: 45.95 (CH2),
52.04 (CH3O), 52.06 (CH3O), 53.02 (C6), 101.94 (C5),
117.16 (H2C=), 121.92, 125.15, 129.08, 130.85, 131.07,
133.22 (CAr), 143.27 (HC=), 145.21 (C4), 150.95 (C2),
162.68 (C=O), 163.74 (C=O). Found, %: С 50.11;
Н 4.08; N 6.69. [M + 1]+ 410. C17H17N2O5. Calculated,
%: С 49.89; Н 4.19; N 6.85. M 409.2.
Diethyl 3-allyl-6-(3-bromophenyl)-2-oxo-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (ІІІf). Yield
47%, mp 97–98°С. IR spectrum , ν, cm–1: 3245, 3125
Dimethyl 3-allyl-6-(3-nitrophenyl)-2-oxo-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (ІІІc). Yield
49%, mp 138–139°С. IR spectrum , ν, cm–1: 3250,
1
(NH), 1735, 1700 (C=O). Н NMR spectrum, δ, ppm:
1
3130 (NH), 1745, 1700 (C=O). Н NMR spectrum, δ,
1.10 t (3Н, СН3, J 7.2 Hz), 1.26 t (3Н, СН3, J 7.2 Hz),
3.81–4.58 m (6Н, СН2 + 2СН2О), 5.06 d (1H, НС=,
J 16.0 Hz), 5.14 d (1H, НС=, J 10.0 Hz), 5.24 d (1Н,
Н6, J 3.3 Hz), 5.74 m (1H, HС=), 7.25–7.53 m (4Нarom),
8.29 d (1Н, NH, J 3.3 Hz). 13С NMR spectrum, δ, ppm:
13.43 (СН3), 13.72 (СН3), 45.76 (CH2), 52.25 (C6), 60.57
(CH2O), 60.63 (CH2O), 101.96 (C5), 117.01 (H2C=),
121.73, 125.14, 129.17, 130.69, 130.96, 133.23 (CAr),
142.99 (HC=), 145.43 (C4), 150.94 (C2), 162.05 (C=O),
163.15 (C=O). Found, %: С 52.41; Н 4.58; N 6.55. [M +
ppm: 3.60 s (3Н, СН3О), 3.87 s (3Н, СН3О), 3.90 d.d,
4.35 d.d (2H, СH2, J 16.5, J 5.5 Hz), 5.07 d (1H, НС=,
J 16.5 Hz), 5.11 d (1H, НС=, J 10.0 Hz), 5.42 d (1Н,
Н6, J 3.5 Hz), 5.76 m (1H, HС=), 7.73 m (2Нarom),
8.15 s (1Нarom), 8.21 m (1Нarom), 8.42 d (1Н, NH,
J 3.5 Hz). 13С NMR spectrum, δ, ppm: 46.00 (CH2),
52.05 (CH3O), 52.10 (CH3O), 53.01 (C6), 101.65 (C5),
117.18 (H2C=), 120.95, 122.95, 130.53, 132.81, 133.18,
143.51 (CAr), 144.74 (HC=), 147.96 (C4), 150.80 (C2),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

KUSHNIR et al.
1730
1]+ 438. C19H21BrN2O5. Calculated, %: С 52.19; Н 4.84;
N 6.41. M 437.3.
(
compounds Vb–Vg).
Dimethyl 6-(3-bromophenyl)-3-[(3-phenyl-4,5-
Diethyl 3-allyl-6-(4-nitrophenyl)-2-oxo-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (ІІІg). Yield
48%, mp 113–114°С. IR spectrum , ν, cm–1: 3255, 3150
dihydro-5-isoxazolyl)methyl]-2-oxo-1,2,3,6-tetra-
hydropyrimidine-4,5-dicarboxylate (Va). Yield 29%,
mp 154–156°С. IR spectrum , ν, cm–1: 3250, 3130, (NH),
1
1
(NH), 1745, 1705 (C=O). Н NMR spectrum, δ, ppm:
1740, 1700 (C=O). Н NMR spectrum, δ, ppm: 3.15–
1.09 t (3Н, СН3, J 7.2 Hz), 1.26 t (3Н, СН3, J 7.2 Hz),
3.91–4.34 m (6Н, СН2 + 2СН2О), 5.08 d (1H, НС=,
J 17.0 Hz), 5.14 d (1H, НС=, J 10.0 Hz), 5.39 d (1Н, Н6,
J 3.0 Hz), 5.76 m (1H, HС=), 7.53 d (2Нarom, J 8.5 Hz),
8.27 d (2Нarom, J 8.5 Hz), 8.39 d (1Н, NH, J 3.0 Hz).
13С NMR spectrum, δ, ppm: 13.46 (СН3), 13.70 (СН3),
45.96 (CH2), 52.44 (C6), 60.72 (CH2O), 62.25 (CH2O),
101.56 (C5), 117.11 (H2C=), 124.03, 127.66, 133.32,
143.31 (CAr), 147.10 (HC=), 149.95 (C4), 150.89 (C2),
162.01 (C=O), 163.14 (C=O). Found, %: С 56.31; Н 5.08;
N 10.19. [M + 1]+ 404. C19H21N3O7. Calculated, %:
С 56.57; Н 5.25; N 10.42. M 403.4.
3.21 m (2Н, СН2), 3.42 m (1H, CH), 3.61 s (3H, CH3O),
3.80 s, 3.83 s (3H, CH3O), 4.11 d.d (1H, СH, J 10.5,
J 3.0 Hz), 4.83 m (1H, СH), 5.25 d (1Н, Н6, J 3.5 Hz),
7.31–7.65 m (9Нarom), 8.39 d (1Н, NH, J 3.5 Hz).
13С NMR spectrum, δ, ppm: 37.31 (С4' ), 46.12 (CH2N),
52.03 (C6), 52.26 (CH3O), 53.10 (CH3O), 78.02 (C5'),
102.50 (C5), 121.86, 125.20, 126.51, 128.78, 129.01,
130.09, 130.97, 142.91, 143.51 (CAr), 144.98 (C4), 151.19
(C3'), 156.34 (C2), 162.75 (C=O), 163.71 (C=O). Found,
%: С 54.81; Н 4.08; N 7.69. [M + 1]+ 529. C24H22BrN3O6.
Calculated, %: С 54.56; Н 4.20; N 7.95. M 528.3.
Dimethyl 6-(3-bromophenyl)-3-{[3-(4-methoxy-
phenyl)-4,5-dihydro-5-isoxazolyl]methyl}-2-oxo-
1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (Vb).
Yield 66%, mp 203–205°С. IR spectrum , ν, cm–1: 3240,
Diethyl 3-allyl-2-oxo-6-(3,4-dichlorophenyl)-
1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate
(ІІІh). Yield 50%, mp 99–100°С. IR spectrum , ν, cm–1:
3255, 3135 (NH), 1730, 1695 (C=O). 1Н NMR spectrum,
δ, ppm: 1.10 t (3Н, СН3, J 7.2 Hz), 1.26 t (3Н, СН3,
J 7.2 Hz), 3.82–4.35 m (6Н, СН2 + 2СН2О), 5.09 d (1H,
НС=, J 17.4 Hz), 5.14 d (1H, НС=, J 10.2 Hz), 5.26 d
1
3135 (NH), 1735, 1700 (C=O). Н NMR spectrum, δ,
ppm: 3.10–3.18 m (2Н, СН2), 3.41 m (1H, CH), 3.63 s
(3H, CH3O), 3.81 s, 3.83 s (3H, CH3O),, 4.03 d.d (1H,
СH, J 10.5, J 3.3 Hz) 4.76 m (1H, СH), 5.22 d (1Н, Н6,
J 3.0 Hz), 7.01 d (2Нarom, J 7.5 Hz), 7.36–7.62 m (6Нarom),
8.34 d (1Н, NH, J 3.0 Hz). 13С NMR spectrum, δ, ppm:
37.55 (С4'), 47.06 (CH2N), 52.05 (CH3O), 52.26 (C6),
53.11 (CH3O), 55.27 (CH3O), 77.68 (C5'), 102.50 (C5),
114.22, 121.51, 121.89, 125.27, 128.26, 129.37, 130.85,
131.01, 143.54, 155.79 (CAr), 145.01 (C4), 151.30 (C3'),
160.66 (C2), 162.74 (C=O), 163.75 (C=O). Found, %:
С 53.41; Н 4.28; N 7.79. [M + 1]+ 559. C25H24BrN3O7.
Calculated, %: С 53.77; Н 4.33; N 7.53. M 558.4.
(1Н, Н6, J 3.0 Hz), 5.74 m (1H, HС=), 7.25 d (1Нarom
,
J 8.4 Hz), 7.47 s (1Нarom), 7.70 d (1Нarom, J 8.4 Hz),
8.32 d (1Н, NH, J 3.0 Hz). 13С NMR spectrum, δ, ppm:
13.44 (СН3), 13.73 (СН3), 45.83 (CH2), 51.86 (C6), 60.64
(CH2O), 62.22 (CH2O), 101.57 (C5), 117.06 (H2C=),
126.44, 128.45, 130.48, 131.06, 131.14, 133.24 (CAr),
143.18 (HC=), 143.79 (C4), 150.81 (C2), 161.99 (C=O),
163.10 (C=O). Found, %: С 53.31; Н 4.68; N 6.49. [M +
1]+ 428. C19H20Cl2N2O5. Calculated, %: С 53.41; Н 4.72;
N 6.56. M 427.3.
Dimethyl 6-(4-nitrophenyl)-3-{[3-(4-fluorophenyl)-
4,5-dihydro-5-isoxazolyl]methyl}-2-oxo-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (Vc). Yield
36%, mp 197–199°С. IR spectrum , ν, cm–1: 3245, 3150
Dialkyl 6-aryl-3-[(3-aryl-4,5-dihydro-5-isoxazolyl)
methyl]-2-oxo-1,2,3,6-tetrahydro-pyrimidine-4,5-
dicarboxylates Vа–Vg. To a solution of 2 mmol of
dicarboxylate ІІІb, IIId, IIIe–IIIh in 10 ml of di-
chloromethane cooled to –15° was added at stirring in
succession 2 mmol of hydroxymoyl chloride IVа–IVc
and 2 mmol of triethylamine. The reaction mixture was
stirred for 1 h, warmed to room temperature, and left
standing for 12 h. Then it was treated with the saturated
ammonium chloride solution. The organic layer was
separated, dried with magnesium sulfate, and evaporated.
The residue was purified by recrystallization from the
mixture benzene–hexane, 1 : 2 (compound Va) or ethanol
1
(NH), 1730, 1695 (C=O). Н NMR spectrum, δ, ppm:
3.08–3.24 m (2Н, СН2), 3.42 m (1H, CH), 3.60 s (3H,
CH3O), 3.81 s (3H, CH3O), 4.18 d.d (2H, СH2N, J 14.8,
J 3.4 Hz), 4.82 m (1H, СH), 5.37 d (1Н, Н6, J 2.7 Hz),
7.29–7.67 m (6Нarom), 8.17 d (2Нarom, J 7.6 Hz), 8.54 d
(1Н, NH, J 2.7 Hz). 13С NMR spectrum, δ, ppm: 37.55
(С4'), 45.78 (CH2N), 51.13 (CH3O), 52.05 (C6), 53.31
(CH3O), 78.55 (C5'), 102.88 (C5), 115.72, 123.89, 125.54,
127.59, 143.32, 146.97 (CAr), 149.24 (C4), 151.37
(C3'), 155.67 (C2), 162.67 (C=O), 163.15 d (4-FC6H4,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

HETEROCYCLIZATIONS OF FUNCTIONALIZED HETEROCUMULENES...: XIІI.
1731
СН), 5.37 d (1Н, Н6, J 2.7 Hz), 7.00 d (2Нarom, J 8.7 Hz),
7.44–7.77 m (4Нarom), 8.17 d (1Нarom, J 8.0 Hz), 8.24 d
(1Нarom, J 8.0 Hz), 8.49 d (1Н, NH, J 2.7 Hz). 13С NMR
spectrum, δ, ppm: 13.39 (СН3), 13.75 (СН3), 37.39 (С4'),
46.01 (CH2N), 55.22 (C6), 55.24 (CH3O), 60.82 (CH2O),
62.53 (CH2O), 78.02 (C5'), 102.82 (C5), 114.18, 121.38,
123.88, 127.62, 128.04, 143.13, 147.00, 155.88 (CAr),
149.50 (C4), 151.38 (C3'), 160.68 (C2), 162.09 (C=O),
163.08 (C=O). Found, %: С 58.41; Н 5.22; N 10.39. [M +
1]+ 553. C27H28N4O9. Calculated, %: С 58.69; Н 5.11; N
10.14. M 552.5.
JC-F 250.6 Hz), 164.04 (C=O). 19F NMR spectrum, δ,
ppm: –109.89. Found, %: С 56.51; Н 4.18; N 11.00. [M +
1]+ 513. C24H21FN4O8. Calculated, %: С 56.25; Н 4.13;
N 10.83. M 512.4.
Dimethyl 6-(3,4-dichlorophenyl)-3-{[3-(4-phenyl)-
4,5-dihydro-5-isoxazolyl]methyl}-2-oxo-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (Vd). Yield
31%, mp 168–169°С. IR spectrum , ν, cm-1: 3245,
1
3135 (NH), 1725, 1690 (C=O). Н NMR spectrum, δ,
ppm: 3.12–3.20 m (2Н, СН2), 3.44 m (1H, CH), 3.62 s
(3H, CH3O), 3.80 s, 3.83 s (3H, CH3O), 4.16 d.d (2H,
СH2N, J 15.2, J 3.2 Hz), 4.83 m (1H, СH), 5.28 d (1Н,
Н6, J 3.5 Hz), 7.36–7.68 m (8Нarom), 8.41 d (1Н, NH,
J 3.5 Hz). 13С NMR spectrum, δ, ppm: 37.31 (С4'),
47.18 (CH2N), 51.80 (C6), 52.12 (CH3O), 53.14 (CH3O),
78.00 (C5'), 102.19 (C5), 126.45, 126.53, 128.61, 128.88,
129.09, 130.14, 130.61, 131.01, 131.36, 143.13 (CAr),
143.75 (C4), 151.16 (C3'), 156.41 (C2), 162.66 (C=O),
163.69 (C=O). Found, %: С 55.33; Н 4.24; N 8.29. [M +
1]+ 519. C24H21Cl2N3O6. Calculated, %: С 55.61; Н 4.08;
N 8.11. M 518.3.
Diethyl 6-(3,4-dichlorophenyl)-3-{[3-(4-fluoro-
phenyl)-4,5-dihydro-5-isoxazolyl]methyl}-2-oxo-
1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (Vg).
Yield 73%, mp 159–160°С. IR spectrum , ν, cm–1: 3240,
1
3145 (NH), 1725, 1695 (C=O). Н NMR spectrum,
δ, ppm: 1.12 t (3Н, СН3, J 7.0 Hz), 1.25 t (3Н, СН3,
J 7.0 Hz), 3.10–3.21 m (2Н, СН2), 3.34 m (1H, CH),
3.74–4.28 m (5Н, 2СН2O + СН2), 4.85 m (1Н, СН),
5.25 d (1Н, Н6, J 2.9 Hz), 7.31–7.74 m (7Нarom), 8.49 d
(1Н, NH, J 2.9 Hz). 13С NMR spectrum, δ, ppm: 13.40
(СН3), 13.75 (СН3), 37.38 (С4'), 46.03 (CH2N), 51.84
(C6), 60.77 (CH2O), 62.56 (CH2O), 78.52 (C5'), 102.87
(C5), 115.77, 125.60, 126.52, 128.65, 128.90, 130.50,
131.18, 142.88, 143.44 (CAr), 149.25 (C4), 151.19
(C3'), 155.57 (C2), 162.14 (C=O), 163.28 d (4-FC6H4,
JC-F 242.0 Hz), 163.56 (C=O). 19F NMR spectrum, δ,
ppm: –109.99. Found, %: С 55.57; Н 4.14; N 7.69.
[M + 1]+ 565. C26H24Cl2FN3O6. Calculated, %: С 55.33;
Н 4.29; N 7.45. M 564.4.
Diethyl 6-(3-bromophenyl)-3-{[3-(4-methoxy-
phenyl)-4,5-dihydro-5-isoxazolyl]methyl}-2-oxo-
1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (Ve).
Yield 71%, mp 174–175°С. IR spectrum , ν, cm–1: 3240,
1
3140 (NH), 1735, 1695 (C=O). Н NMR spectrum,
δ, ppm: 1.14 t (3Н, СН3, J 7.0 Hz), 1.24 t (3Н, СН3,
J 7.0 Hz), 3.16–3.24 m (2Н, СН2), 3.42 m (1H, CH),
3.80 s (3H, CH3O), 4.03–4.29 m (5Н, 2СН2О + CH2),
4.82 m (1Н, СН), 5.24 d (1Н, Н6, J 3.3 Hz), 7.02 d
(2Нarom, J 9.0 Hz), 7.38–7.78 m (6Нarom), 8.38 d (1Н,
NH, J 3.3 Hz). 13С NMR spectrum, δ, ppm: 13.36 (СН3),
13.73 (СН3), 37.59 (С4'), 46.26 (CH2N), 55.26 (C6),
60.70 (CH2O), 62.51 (CH2O), 77.90 (C5'), 103.05 (C5),
114.21, 121.44, 121.73, 125.30, 128.12, 129.36, 130.74,
130.94, 142.72, 155.75 (CAr), 145.20 (C4), 151.26 (C3'),
160.67 (C2), 162.22 (C=O), 163.12 (C=O). Found, %:
С 55.41; Н 4.89; N 7.00. [M + 1]+ 587. C27H28BrN3O7.
Calculated, %: С 55.30; Н 4.81; N 7.17. M 586.4.
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