4-aryl-2-hydroxy-4-oxobut-2-enoic acids N-(2-pyridyl)amides in reactions with diazo compounds

Article abstract of DOI:10.1134/S1070428008050138

Reactions of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids N-(2-pyridyl)amides with diazomethane, diazoethane, diaryldiazomethanes, and diazofluorene lead to the formation of 2-alkoxy-4-aryl-4-oxobut-2-enoic acids N-(2-pyridyl)amides, 3-aroyl-5-methylpyrazole-4-carboxylic acids N-(2-pyridyl)amides, and 3-alkoxy-3-(2-aryl-2-oxoethyl)-2,3-dihydro-2-oxoimidazo[1,2-a]pyridines. The composition and structure of compounds obtained depend on the nucleophilic nature of the diazo compound and on the character of substituents in the aryl and pyridine parts of the substrate.

Full text of DOI:10.1134/S1070428008050138

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 5, pp. 709−714. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.E. Gavrilova, V.V. Zalesov, N.A. Pulina, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 5, pp. 718−723.
4-Aryl-2-hydroxy-4-oxobut-2-enoic Acids N-(2-Pyridyl)amides
in Reactions with Diazo Compounds
N. E. Gavrilovaa, V. V. Zalesova, and N. A. Pulinab
aPerm State University, Perm, 614900 Russia
bPerm State Pharmaceutical Academy, Perm, 614900 Russia
e-mail: pulina_jane@mail.ru
Received October 16, 2007
Abstract—Reactions of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids N-(2-pyridyl)amides with diazomethane,
diazoethane, diaryldiazomethanes, and diazofluorene lead to the formation of 2-alkoxy-4-aryl-4-oxobut-2-enoic
acids N-(2-pyridyl)amides, 3-aroyl-5-methylpyrazole-4-carboxylic acids N-(2-pyridyl)amides, and 3-alkoxy-3-
(2-aryl-2-oxoethyl)-2,3-dihydro-2-oxoimidazo[1,2-a]pyridines. The composition and structure of compounds
obtained depend on the nucleophilic nature of the diazo compound and on the character of substituents in the aryl
and pyridine parts of the substrate.
DOI: 10.1134/S1070428008050138
methyl-3-methoxy-2-oxo-2,3-dihydroimidazo[1,2-
a]pyridines IIa and IIb, in 11–15% yield (Scheme 1).
Spectral characteristics of compounds IIa and IIb are
consistent with the corresponding data of the previously
obtained imidazo[1,2-a]pyridines [2]. Besides from the
reaction products of amide Ie alongside the compound IIa
3-benzoyl-4-hydroxy-4,5-dihydropyrazole-4-carboxylic
acid N-(6-methyl-2-pyridyl)amide (III) was isolated.
The formation of pyrazole III occurred by 1,3-dipolar
cycloaddition of diazomethane across the multiple C2=C3
bond of the initial pyridylamide Ie. From the reaction
products of amide Ii 4-(2,4-dimethylphenyl)-2-methoxy-
4-oxobut-2-enoic acid N-(6-methyl-2-pyridyl)amide
(IVa) was isolated in a good yield (Scheme 1).
We formerly reported on cyclization of 4-aryl-2-
hydroxy-4-oxobut-2-enoic acids N-(2-thiazolyl)amides
and N-(2-pyridyl)amides effected by diazoalkanes giving
derivatives of imidazo[2,1-b]thiazoles and imidazo-
[1,2-a]pyridines respectively. Therewith a simultaneous
process was observed of O-alkylation of the initial amides
[1–3]. In extension of the research on the intramolecular
cyclization of heterylamides under the action of diazo
nucleophiles we aimed in this study to investigate the
reaction of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids
N-(2-pyridyl)amides having substituents in aryl and
pyridine fragments with diazomethane, diazoethane,
diaryldiazomethanes, and diazofluorene.
Firstly by analogy with the cyclization of 4-aryl-2-
hydroxy-4-oxobut-2-enoic acids N-(2-pyridyl)amides
Ia–Id into imidazo[1,2-a]pyridines [2] we investigated
the reaction of amides Ie–Im with diazomethane at
a ratio 1:4. The reaction of N-(6-methyl-2-pyridyl)amides
Ie–Ii with diazomethane took several routes to produce
a complex mixture of compounds (from 4 to 9 according
to TLC). In all events save in reaction of amide Ii
derivatives of imidazo[1,2-a]pyridine were detected in
the reaction mixture owing to their blue fluorescence
under UV irradiation. This property permits the reliable
detection of their formation in the course of reaction
and checking their presence or absence during isolation
[4]. However we succeeded in isolation of only two
compounds of this series, 3-(2-aryl-2-oxoethyl)-5-
In going in the reaction with diazomethane from
amides Ie–Ii to N-(5-bromo-2-pyridyl)amides Ij–Im its
main direction became the α-O-methylation providing
compounds IVb–IVe.
For O-methyl derivative IVb a presence in the solution
of its ring form, 1-(5-bromo-2-pyridyl)-5-hydroxy-2,5-
dihydro-3-methoxy-5-phenylpyrrol-2-one A, was proved,
but we failed to isolate and characterize the pyrrolone.
The existence of arylamides of 4-aryl-2-hydroxy-4-
oxobut-2-enoic acids with a substituent in the position 3
in both ring and open-chain forms was reported earlier
[5] (Scheme 2).
709

GAVRILOVA et al.
710
Ar
Scheme 1.
R1
R1
Ph
O
Ph
OH
O
O
O
Ar
N
H
N
H
N
N
N
Ph
O
O
O
O
N
_
H
Ia Io
R2R3CN2
H3C
IIl
_
_
N
2
N2
H
N
CH3
N
R3
R1
H
N
R2
O
H
N
O
N
Ar
O
O
Ar
OH
H
N
N
H
R2
N
O
Ph
O
N
N
Ar
O
O
N
O
O
1
N
R
CH3
R3
Va, Vb
_
_
IIa IIi, IIm, IIn
IVa IVg
III
CH
3
I, R1 = H, Ar = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c), 4-BrC6H4 (d); R1 = 6-Me, Ar = Ph (e), 4-MeC6H4 (f), 4-EtOC6H4
(g), 4-ClC6H4 (h), 2,4-Me2C6H3 (i); R1 = 5-Br, Ar = Ph (j), 4-MeOC6H4 (k), 4-ClC6H4 (l), 4-BrC6H4 (m); II, R1 = Me, R2
= R3 = H, Ar = Ph (a), 4-ClC6H4 (b); R1 = H, R2 = R3 = Ph, Ar = Ph (c), 4-MeC6H4 (d), 4-BrC6H4 (e); R1 = Me, R2 = R3 =
Ph, Ar = 4-MeC6H4 (f); R1 = H, R2 = Ph, R3 = 4-BrC6H4, Ar = Ph (g), 4-MeC6H4 (h), R1 = Me, R2 = Ph, R3 = 4-BrC6H4,
Ar = 4-MeC6H4 (i); R1 = H, R2, R3 = 9-fluorenyl, Ar = Ph (k), 4-MeOC6H4 (l); IV, R1 = 6-Me, R2 = R3 = H, Ar = 2,4-
Me2C6H3 (a); R1 = 5-Br, R2 = R3 = H, Ar = Ph (b), 4-MeOC6H4 (c), 4-ClC6H4 (d), 4-BrC6H4 (e); R2 = H, R3 = Me, Ar =
Ph (f), 4-MeOC6H4 (g); V, Ar = Ph (a), 4-EtOC6H4 (b).
We established that in reactions of heterylamides
Ie, Ig, Ij, and Ik with diazoethane in ratios 1:4 and 1:6
the type of the resulting product depended primarily
on the substituent in the pyridine ring. For instance,
the main reaction products obtained from amides Ie
and Ig were 3-aroyl-5-methylpyrazole-4-carboxylic
acids N-(6-methyl-2-pyridyl)amides Va and Vb, and
from N-(5-bromo-2-pyridyl)amides Ij and Ik, O-ethyl
derivatives IVf and IVg. Therewith we did not isolate
from the reaction mixture compounds arising from the
attack of the second diazoethane molecule on the ketone
carbonyl C4=O in the already alkylated 2-pyridylamide
as was reported in [2].
The IR spectra of compounds Va and Vb contained
a broadened absorption band of the stretching vibrations
of amide and keto carbonyl groups in the region
1675–1678 cm–1 and also two absorption bands of NH
groups in the region 3175–3179 and 3534–3565 cm–1.
In the 1H NMR spectrum of compound Va alongside the
singlet of the methyl group protons and multiplets of the
protons of aromatic and pyridine rings and also of the
substituent attached thereto appeared a singlet of NH
group proton at 11.31 ppm and a singlet from the proton
of the NH group of the heterocycle at 13.72 ppm.
Scheme 2.
O CH3
Thus the chemical behavior of N-(2-pyridyl)amides
Ia–Im in reactions with diazomethane and diazoethane
is essentially affected by the substituents in the pyridine
ring, and the yield of the final products depends also on
the substituent in the aroyl residue.
Ph
O
Br
O
N
HO
Ph
N
H
N
O
O
We found that amides Ia, Ib, Id, and If reacted at heating
in equimolar quantities with diphenyldiazomethane, and
amides Ia, Ib, and If, with (4-bromophenyl)phenyldiazo-
methane, yielding 3-(2-aryl-2-oxoethyl)-3-diphenyl-
CH3
IVb
Br
A
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008

4-ARYL-2-HYDROXY-4-OXOBUT-2-ENOIC ACIDS N-(2-PYRIDYL)AMIDES
711
methoxy-2-oxo-2,3-dihydroimidazo-[1,2-a]-pyridines IIc–
IIf and 3-(2-aryl-2-oxoethyl)-3-[(4-bromophenyl)phenyl]-
methoxy-2-oxo-2,3-dihydroimidazo[1,2-a]pyridines
IIg–IIi respectively. The IR spectra of compounds IIc–IIi
contain absorption bands of the stretching vibrations of
lactam and keto carbonyl groups in the region 1697–
1709 and 1675–1690 cm–1, of C=C and C=N bonds at
1580–1615 cm–1, and the absorption band of the NH
N-(5-Bromo-2-pyridyl)amides Ij–Im do not enter into
reaction with diaryldiazomethanes and 9-diazofluorene
even at prolonged heating.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
1
FSM-1201 from mulls in mineral oil. H NMR spectra
1
group is absent. In the H NMR spectra of compounds
were registered on a spectrometer Bruker DRX-500
(500 MHz), internal reference HMDS. Mass spectra
were measured on a Varian MAT-311 instrument at
the ionizing electrons energy 70 eV and direct probe
admission into the ion source. UV spectra were taken
on a spectrophotometer SF-121 from ethanol solutions
of concentration 10–2 mol l−1. The reaction progress was
monitored and the purity of compounds obtained was
checked by TLC on Silufol UV-254 plates in a system
ether–benzene–acetone, 10:9:1, development in iodine
vapor.
IIc–IIi alongside the multiplet of the protons of aromatic
and heterocyclic rings appear a singlet of the methine
proton from the diarylmethyl fragment at 5.44–5.55 ppm
and a quartet at 4.08–4.25 ppm from two protons of
the methylene group at the chiral carbon atom of the
heterocycle.
The reaction of amide Ie with diphenyldiazomethane
also led to the formation of imidazopyridine, 3-(2-
hydroxy-2-phenylethenyl)-3-diphenylmethoxy-5-
methyl-2-oxo-2,3-dihydroimidazo[1,2-a]pyridine (IIj),
but unlike compounds IIa–IIi the carbonyl group of the
benzoyl substituent was completely enolized as showed
the spectral characteristics of the substance.
5-Methyl-3-methoxy-3-(2-aryl-2-oxoethyl)-2-oxo-
2,3-dihydroimidazo[1,2-a]pyridin-2(3H)-ones (IIa and
IIb). To a solution of 0.01 mol of amide Ie or Ih in
20 ml of anhydrous toluene was added a solution
of 0.17 g (0.04 mol) of diazomethane in 6 ml of ether
at 0–5°C, and the mixture was maintained for 48 h at
25°C. The mother liquor was evaporated, the residue
was dissolved in chloroform and applied on Kieselgel
G plates (10 × 12 cm) activated for 1 h at 110°C. The
chromatography was carried out by ascending method,
eluent acetonitrile. The spots were visualized by UV
irradiation resulting in a characteristic fluorescence of
the target compound. The purification was performed
by chromatography on a column packed with Kieselgel
40, eluents chloroform, acetone, ethanol; the fraction
collected had Rf 0.38 (IIa) or 0.40 (IIb). The solvents
were removed under a vacuum of a water-jet pump. We
obtained colorless oily product.
The application of diazofluorene to the reaction
with N-(2-pyridyl)amides Ia and Ic did not change its
direction, and the main products were 3-aroylmethyl-
2-oxo-3-(9-fluorenylmethoxy)-2,3-dihydroimidazo-
[1,2-a]pyridines IIk and IIl, but the process required
1
more severe conditions. IR and H NMR spectra of
compounds IIk and IIl are in agreement with those of
compounds IIa–IIi.
The formation of imidazo[1,2-a]pyridines II is
likely to commence by the protonation of the diazo
nucleophile with the hydrogen of the enol hydroxy group
and the rearrangement of the 2-pyridylamide fragment
into pyridoimide moiety forming intermediate B. The
building up of the imidazole ring involved the insertion
of the diazo carbocation into the multiple bond C2=C3,
nitrogen elimination, and hydrogen migration to the atom
C3 (Scheme 3).
5-Methyl-3-methoxy-3-(2-oxo-2-phenylethyl)-2-
oxo-2,3-dihydroimidazo[1,2-a]pyridin-2(3H)-one
Scheme 3.
O
O
R
O
Ar
Ar
N
NH
O
RCHN2
Ar
O
RH2+
_O
HN
O
O
N
_N2
H
N
C
N
O
N2
R
I
B
R
II
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008

GAVRILOVA et al.
712
(IIa). Yield 0.33 g (11%). IR spectrum, ν, cm–1: 1709
br (NC=O, C=O), 1625, 1605 (C=C, C=N). 1H NMR
spectrum, ppm: 2.99 g (3H, CH3), 3.73 g (3H, CH3O),
4.09 q (2H, CH2, J 8.0 Hz), 7.15–7.78 m (7H, C6H4 +
C5H3N). Found, %: C 68.97; H 5.49; N 9.30. C17H16N2O3.
Calculated , %: C 68.91; H 5.44; N 9.45.
7.90 m (18H, 2C6H5 + C6H4 + C5H4N). UV spectrum,
max, nm (lgε): 257 (4.28), 368 (3.64). Found, %: C 65.45;
H 4.18; Br 15.38; N 5.52. C28H21BrN2O3. Calculated ,
%: C 65.50; H 4.12; Br 15.56; N 5.46.
λ
3-Diphenylmethoxy-5-methyl-3-[2-(4-methyl-
phenyl)-2-oxoethyl]-2-oxo-2,3-dihydroimidazo-[1,2-a]-
pyridin-2(3H)-one (IIe).Asolution of 2.97 g (0.01 mol)
of amide If and 1.94 g (0.01 mol) of diphenyldiazomethane
in 25 ml of anhydrous toluene was maintained at room
temperature for 72 h, then the reaction mixture was
evaporated. The residue was dissolved in chloroform and
and applied on Kieselgel G plates (10×12 cm) activated
for 1 h at 110°C. The chromatography was carried out
by ascending method, eluent acetonitrile. The spots were
visualized by UV irradiation resulting in a characteristic
fluorescence of the target compound. The purification was
performed by chromatography on a column packed with
Kieselgel 40, eluents chloroform, acetone, ethanol; the
fraction collected had Rf 0.42. The solvents were removed
under a vacuum of a water-jet pump to obtain colorless
oily product. Yield 1.48 g (32%). IR spectrum, ν, cm–1:
1728 br (NC=O, C=O), 1620, 1605 (C=C, C=N). Found,
%: C 77.98; H 5.42; N 6.23. C30H26N2O3. Calculated ,
%: C 77.90; H 5.66; N 6.06.
5-Methyl-3-methoxy-3-[2-oxo-2-(4-chlorophenyl)-
ethyl]-2-oxo-2,3-dihydroimidazo[1,2-a]pyridin-2(3H)-
one (IIb). Yield 0.49 g (15%). IR spectrum, ν, cm–1:
1729 br (NC=O, C=O), 1635, 1605 (C=C, C=N). Mass
spectrum, m/z (Irel, %): 332/330 (22.6) [M]+, 317/315
(7.1), 225/223 (29.9), 219 (52.0), 191 (83.2), 141/139
(36.9), 135 (100), 113/111 (22.5), 92 (39.8). Found,
%: C 61.95; H 4.79; Cl 10.90; N 8.30. C17H15ClN2O3.
Calculated , %: C 61.73; H 4.67; Cl 10.72; N 8.48.
M 330.77.
3-Diphenylmethoxy-3-(2-aryl-2-oxoethyl)-2-oxo-
2,3-dihydroimidazo[1,2-a]pyridin-2(3H)-one (IIc–IIe).
A solution of 0.01 mol of 4-aryl-2-hydroxy-4-oxobut-
2-enoic acid N-(2-pyridyl)amide Ia, Ib, or Id and
1.94 g (0.01 mol) of diphenyldiazomethane in 20 ml of
anhydrous toluene was maintained at room temperature
for 72 h, then the reaction mixture was evaporated, and
the residue was recrystallized from benzene.
3-(4-Bromophenyl)phenylmethoxy-2,3-dihydro-
3-(2-aryl-2-oxoethyl)-2-oxoimidazo[1,2-a]pyridin-
2(3H)-ones IIg–IIi. Asolution of 0.01 mol of compound
Ia, Ib, or If and 2.73 g (0.01 mol) of (4-bromophenyl)-
phenyldiazomethane in 20 ml of anhydrous toluene was
boiled for 1 h, then it was evaporated, and the residue
was recrystallized from toluene.
3-Benzoylmethyl-3-diphenylmethoxy-2-oxo-2,3-
dihydroimidazo[1,2-a]pyridin-2(3H)-one (IIc). Yield
2.52 g (58%), t.decomp. 167–168°C. IR spectrum, ν,
cm–1: 1700 (NC=O), 1690 (C=O), 1620, 1580 (C=C,
1
C=N). H NMR spectrum (DMSO-d6), δ, ppm: 4.24 q
(2H, CH2, J 8.0 Hz), 5.44 s (1H, CH), 7.10–7.85 m (19H,
3C6H5 + C5H4N). UV spectrum, λmax, nm (log ε): 250
(4.04), 367 (3.41). Found, %: C 77.34; H 5.05; N 6.52.
C28H22N2O3. Calculated , %: C 77.40; H 5.10; N 6.45.
3-Benzoylmethyl-3-[4-bromophenyl(phenyl)meth
oxy]-2-oxo-2,3-dihydroimidazo[1,2-a]-pyridin-2(3H)-
one (IIg). Yield 3.54 g (69%), t.decomp. 181–182°C. IR
spectrum, ν, cm–1: 1701 (NC=O), 1690 (C=O), 1605,
3-Diphenylmethoxy-3-[2-oxo-2-(4-methyl-
phenyl)ethyl]-2-oxo-2,3-dihydroimidazo[1,2-a]-
pyridine (IId).Yield 2.87 g (64%), t.decomp. 179–180°C.
IR spectrum, ν, cm–1: 1709 (NC=O), 1675 (C=O), 1610,
1
1595 (C=C, C=N). H NMR spectrum (DMSO-d6), δ,
ppm: 4.25 q (2H, CH2, J 8.0 Hz), 5.50 s (1H, CH), 7.15–
7.95 m (18H, 2C6H5 + C6H4 + C5H4N). UV spectrum,
1
1590 (C=C, C=N). H NMR spectrum (DMSO-d6–CCl4,
λ
max, nm (lgε): 249 (4.24), 367 (3.60). Found, %: C 65.48;
1:3), δ, ppm: 2.42 s (3H, CH3), 4.08 q (2H, CH2,
J 8.0 Hz), 5.49 s (1H, CH), 7.15–7.90 m (18H, 2C6H5
+ C6H4 + C5H4N). UV spectrum, λmax, nm (log ε): 256
(4.49), 366 (3.82). Found, %: C 77.93; H 5.30; N 6.18.
C29H24N2O3. Calculated , %: C 77.66; H 5.39; N 6.25.
H 4.20; Br 15.50; N 5.53. C28H21BrN2O3. Calculated ,
%: C 65.50; H 4.12; Br 15.56; N 5.46.
3-[4-Bromophenyl(phenyl)methoxy]-3-[2-(4-
methylphenyl)-2-oxoethyl]-2-oxo-2,3-dihydro-
imidazo[1,2-a]pyridin-2(3H)-one (IIh). Yield 2.42 g
(46%), t.decomp. 187–188°C. IR spectrum, ν, cm–1:
1709 (NC=O), 1695 (C=O), 1610, 1580 (C=C, C=N). UV
spectrum, λmax, nm (log ε): 257 (4.48), 366 (3.80). Found,
%: C 66.15; H 4.23; Br 15.21; N 5.42. C29H23BrN2O3.
Calculated , %: C 66.04; H 4.39; Br 15.15; N 5.31.
3-Diphenylmethoxy-3-[2-oxo-2-(4-bromophenyl)-
ethyl]-2-oxo-2,3-dihydroimidazo[1,2-a]pyridin-2(3H)-
one (IId). Yield 1.85 γ (36%), t.decomp. 174–176°C. IR
spectrum, ν, cm–1: 1697 (NC=O), 1686 (C=O), 1615,
1
1600 (C=C, C=N). H NMR spectrum (DMSO-d6), δ,
ppm: 4.20 q (2H, CH2, J 8.0 Hz), 5.55 s (1H, CH), 7.10–
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4-ARYL-2-HYDROXY-4-OXOBUT-2-ENOIC ACIDS N-(2-PYRIDYL)AMIDES
713
3-[4-Bromophenyl(phenyl)methoxy]-5-methyl-3-
[2-oxo-2-(4-methylphenyl)ethyl]-2-oxo-2,3-dihydro-
imidazo[1,2-a]pyridin-2(3H)-one (IIi). Yield 1.89 g
(35%), t.decomp. 146–148°C. IR spectrum, ν, cm–1:
1705 (NC=O), 1682 (C=O), 1605, 1595 (C=C, C=N).
UV spectrum, λmax, nm (log ε): 256 (3.60), 371 (2.84).
Mass spectrum, m/z (Irel, %): 269/267 (39.0), 259/257
(60.0), 241/239 (9.8), 199 (60.0), 185/183 (100), 157/155
(48.8). Found, %: C 66.45; H 4.59; Br 14.88; N 5.21.
C30H25BrN2O3. Calculated , %: C 66.55; H 4.65; Br 14.76;
N 5.17. M 541.44.
ml of anhydrous toluene was added a solution of 0.17 g
(0.04 mol) of diazomethane in 6 ml of ether at 0–5°C,
and the reaction mixture was maintained for 48 h at 25°C,
then it was evaporated, the residue was recrystallized
from ethanol. Yield 0.68 g (21%), mp 237–239°C. IR
spectrum, ν, cm–1: 3449 (OH), 3337 br (2NH), 1685
br (NC=O, C=O), 1605, 1690 (C=C, C=N) 1H NMR
spectrum (DMSO-d6), δ, ppm: 2.41 s (3H, CH3), 4.58 s
(2H, CH2), 6.98 s (1H, OH), 7.54–8.50 m (8H, C6H5 +
C5H3N), 9.37 s (1H, NHC=O), 13.43 s (1H, NH). Found,
%: C 63.00; H 5.46; N 17.10. C17H16N4O3. Calculated ,
%: C 62.95; H 5.15; N 17.27.
3-(2-Hydroxy-2-phenylethenyl)-3-diphenyl-
methoxy-5-methyl-2-oxo2,3-dihydroimidazo[1,2-a]-
pyridine (IIj).Asolution of 2.83 g (0.01 mol) of compound
Ie and 1.94 g (0.01 mol) of diphenyldiazomethane in
30 ml of anhydrous toluene was boiled for 0.5 h and
then evaporated, the residue was recrystallized from
acetonitrile. Yield 2.77 g (62%), t.decomp. 161–163°C.
IR spectrum, ν, cm–1: 1725 (NC=O), 1632, 1600 (C=C,
4-(2,4-Dimethyl-phenyl)-2-methoxy-4-oxobut-2-
enoic acid N-(6-methyl-2-pyridyl)amide (IVa). To
a solution of 3.10 g (0.01 mol) of amide Ii in 20 ml of
anhydrous benzene was added a solution of 0.17 g
(0.04 mol) of diazomethane in 6 ml of ether at 0–5°C,
and the reaction mixture was maintained for 48 h at 25°C,
then it was evaporated, the residue was recrystallized from
ethanol. Yield 1.98 g (61%), mp 142–144°C. IR spectrum
cm–1: 3400 br (NH), 1740 (NC=O), 1642, 1605 (C=O,
1
C=N). H NMR spectrum (DMSO-d6), δ, ppm: 2.22 s
(3H, CH3), 5.96 s (1H, CH), 6.38 (1H, =CH), 7.05–7.85
m (18H, 3C6H5 + C5H3N). UV spectrum, λmax, nm (lgε):
219 (4.19), 287 (4.06). Found, %: C 77.95; H 5.09; N 6.34.
C29H23N2O3. Calculated , %: C 77.83; H 5.18; N 6.26.
1
C=C, C=N). H NMR spectrum (DMSO-d6), δ, ppm:
2.30 s (6H, 2CH3), 2.40 s (3H, CH3), 3.75 (3H, CH3O),
5.98 s (1H, CH), 7.15–7.65 m (6H, C6H3 + C5H3N),
11.80 br.s (1H, NH). UV spectrum, λmaqC, nm (log ε): 235
(3.95), 366 (4.30). Found, %: C 70.20; H 6.15; N 8.81.
C19H20N2O3. Calculated , %: C 70.35; H 6.22; N 8.64.
3-(2-Aryl-2-oxoethyl)-3-(9-fluorenylmethoxy)2-
oxo-2,3-dihydroimidazo[1,2-a]pyridines IIk and IIl.
A solution of 0.01 mol of compound Ia or Ic and 1.92
g (0.01 mol) of 9-diazofluorene in 30 ml of anhydrous
toluene was boiled for 72 h and then evaporated, the
residue was recrystallized from benzene.
4-Aryl-2-methoxy-4-oxobut-2-enoic acid N-(5-
bromo-2-pyridyl)amides IVb–IVd. To a dispersion of
0.01 mol of amide Ij–Il in 50 ml of anhydrous benzene
was added a solution of 0.26 g (0.06 mol) of diazomethane
in 9 ml of ether at 0–5°C, and the reaction mixture was
maintained for 48 h at 25°C, then it was evaporated,
the dry residue was dissolved in 10 ml of toluene and
subjected to chromatography on a column of internal
diameter 2 cm packed with Silicagel LS 5/40, eluent
40% solution of benzene in petroleum ether. The fraction
collected had Rf 0.90 (IVb), 0.53 (IVc), 077 (IVd), the
solvent was evaporated, the residue was recrystallized
from toluene.
2-Oxo-3-(2-oxo-2-phenylethyl)-3-(9-fluorenyl-
methoxy)-2,3-dihydroimidazo[1,2-a]pyridine (IIk).
Yield 1.47 g (34%), t.decomp. 166–168°C. IR spectrum,
ν, cm–1: 1697 (NC=O), 1685 (C=O), 1610, 1585 (C=C,
C=N). UV spectrum, λmax, nm (lgε): 279 (4.24). Found,
%: C 77.93; H 4.82; N 6.39. C28H20N2O3. Calculated ,
%: C 77.76; H 4.66; N 6.47.
3-[2-(4-Methoxyphenyl)-2-oxoethyl]-2-oxo-3-
(9-fluorenylmethoxy)-2,3-dihydroimidazo[1,2-a]-
pyridine (IIl). Yield 2.17 g (47%), t.decomp. 172–174°C.
IR spectrum, ν, cm–1: 1713 (NC=O), 1667 (C=O), 1610,
1
1590 (C=C, C=N). H NMR spectrum (DMSO-d6), δ,
2-Methoxy-4-oxo-4-phenylbut-2-enoic acid N-(5-
bromo-2-pyridyl)amide (IVb). Yield 0.76 g (21%),
mp 176–178°C. IR spectrum, ν, cm–1: 3214 br (NH),
ppm: 3.17 s (3H, CH3O), 4.23 q (2H, CH2, J 6.0 Hz), 5.47
s (1H, CH), 7.05–7.95 m (16H, 3C6H4 + C5H4N). Found,
%: C 75.28; H 4.85; N 6.24. C29H22N2O4. Calculated ,
%: C 75.31; H 4.79; N 6.06.
1
1770 (NC=O), 1640, 1610 (C=O, C=C, C=N). H NMR
spectrum (DMSO-d6), δ, ppm: 4.03 s (3H, CH3O),
7.64 s (1H, CH), 7.20–7.71 m (8H, C6H5 + C5H3BrN),
11.78 br.s (1H, NH). UV spectrum, λmax, nm (log ε): 211
(4.36), 253 (4.12). Found, %: C 53.04; H 3.47; Br 21.95;
3-Benzoyl-4-hydroxy-4,5-dihydropyrazole-4-
carboxylic acid N-(6-methyl-2-pyridyl)amide (III).
To a solution of 2.82 g (0.01 mol) of compound Ie in 20
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GAVRILOVA et al.
714
4-Oxo-(4-methoxyphenyl)-2-ethoxybut-2-enoic
acid N-(5-bromo-2-pyridyl)amide (IVg). Yield 0.44 g
(11%), mp 126–128°C (C2H5OH). IR spectrum, ν, cm–1:
3380 br (NH), 1686 (NC=O), 1665 (C=O), 1620, 1605
(C=C, C=N). H NMR spectrum (DMSO-d6), δ, ppm:
1.27 t (3H, CH3, J 7.4 Hz), 3.82 q (2H, CH2, J 7.4 Hz),
N 7.58. C16H13BrN2O3. Calculated , %: C 53.31; H 3.63;
Br 22.12; N 7.76.
2-Methoxy-4-(4-methoxyphenyl)-4-oxobut-2-enoic
acid N-(5-bromo-2-pyridyl)amide (IVc). Yield 0.70 g
(18%), mp 134–136°C. IR spectrum, ν, cm–1: 3380 br
(NH), 1695 (NC=O), 1675 (C=O), 1615, 1605 (C=C,
C=N). UV spectrum, λmax, nm (log ε): 221 (4.54), 283
(4.50), 328 (4.36). Found, %: C 52.02; H 4.00; Br 20.60;
N 6.95. C17H15BrN2O4. Calculated , %: C 52.19; H 3.87;
Br 20.42; N 7.16.
1
3.91 s (3H, CH3O), 6.46 s (1H, CH), 7.20–7.89 m (7H,
C6H4 + C5H3BrN), 9.58 s (1H, NH). UV spectrum, λmax
,
nm (log ε): 249 (4.22), 289 (4.03). Found, %: C 53.17;
H 4.07; Br 19.91; N 7.02. C18H17BrN2O4. Calculated , %:
C 53.35; H 4.23; Br 19.72; N 6.91.
2-Methoxy-4-oxo-4-(4-chlorophenyl)but-2-enoic
acid N-(5-bromo-2-pyridyl)amide (IVd). Yield 0.51 g
(13%), mp 92–94°C. IR spectrum, ν, cm–1: 3374 br (NH),
1730 (NC=O), 1660, 1615 (C=O, C=C, C=N). Found, %:
C 48.51; H 2.90; Hlg 28.25; N 6.89. C16H12ClBrN2O3.
Calculated , %: C 48.57; H 3.06; Hlg 28.02; N 7.08.
3-Aroyl-5-methylpyrazole-4-carboxylic acid N-(6-
methyl-2-pyridyl)amides Va and Vb. To a solution of
0.01 mol of compound Ie or Ig in20mlofanhydroustoluene
was added a solution of 0.23 g (0.04 mol) of diazoethane
in 7.5 ml of ether at 0–5°C, and the reaction mixture was
maintained for 48 h at 25°C, then it was evaporated, the
residue was recrystallized from toluene.
4-(4-Bromophenyl)-2-methoxy-4-oxobut-2-enoic
acid N-(5-bromo-2-pyridyl)amide (IVe). To a dispersion
of 4.27 g (0.01 mol) of amide Im in 40 ml of anhydrous
toluene was added a solution of 0.26 g (0.06 mol) of
diazomethane in 9 ml of ether at 0–5°C, and the reaction
mixture was maintained for 48 h at 25°C, then it was
evaporated, the residue was recrystallized from a mixture
hexane–benzene, 1:1. Yield 0.97 g (22%), mp 77–79°C.
IR spectrum, ν, cm–1: 3380 br (NH), 1730 (NC=O), 1655,
1610 (C=O, C=C, C=N). UV spectrum, λmax, nm (log ε):
255 (4.42). Mass spectrum, m/z (Irel, %): 442/440 (17.0)
[M]+, 269/267 (39.1), 259/257 (60.5), 241/239 (9.8),
201/199 (60.3), 185/183 (100), 175/173 (15.0), 157/155
(49.2). Found, %: C 43.50; H 2.59; Br 36.50; N 6.22.
C16H12Br2N2O3. Calculated , %: C 43.66; H 2.75; Br 36.31;
N 6.37. M 440.09.
3-Benzoyl-5-methylpyrazole-4-carboxylic acid N-
(6-methyl-2-pyridyl)amide (Va). Yield 0.74 g (23%),
mp 230–232°C. IR spectrum, ν, cm–1: 3565 (NHHt),
3175 (NH), 1675 br (NC=O, C=O), 1605, 1595 (C=C,
1
C=N). H NMR spectrum (DMSO-d6), δ, ppm: 2.34 s
(3H, CH3), 2.51 s (3H, CH3), 7.18–7.95 m (8H, C6H5 +
C5H3N), 11.31 s (1H, NHCO), 13.72 br.s (1H, NH). UV
spectrum, λmax, nm (log ε): 248 (4.52). Mass spectrum,
m/z (Irel, %): 320 (13.0) [M]+, 215 (31.0), 213 (70.4), 108
(85.2), 105 (58.5), 77 (100). Found, %: C 67.51; H 4.88;
N 17.60. C18H16N4O2. Calculated , %: C 67.49; H 5.03;
N 17.49. M 320.35.
5-Methyl-3-(4-ethoxybenzoyl)pyrazole-4-carb-
oxylic acid N-(6-methyl-2-pyridyl)amide (Vb). Yield
0.69 g (19%), mp 181–183°C. IR spectrum, ν, cm–1: 3534
(NHHt), 3179 (NH), 1678 br (NC=O, C=O), 1610, 1600
(C=C, C=N). UV spectrum, λmax, nm (log ε): 291 (4.37).
Found, %: C 66.11; H 5.45; N 15.50. C20H20N4O3.
Calculated , %: C 65.92; H 5.53; N 15.38.
4-Aryl-4-oxo-2-ethoxybut-2-enoic acid N-(5-
bromo-2-pyridyl)amides IVf and IVg. To a dispersion
of 0.01 mol of compound Ij or Ik in 60 ml of anhydrous
benzene was added a solution of 0.34 g (0.06 mol) of
diazoethane in 11 ml of ether at 0–5°C, and the reaction
mixture was maintained for 48 h at 25°C, then it was
evaporated, the residue was recrystallized.
REFERENCES
4-Oxo-4-phenyl-2-ethoxybut-2-enoic acid N-(5-
bromo-2-pyridyl)amide (IVf). Yield 1.66 g (46%), mp
172–174°C (MeCN). IR spectrum, ν, cm–1: 3326 (NH),
1697 (NC=O), 1675 (C=O), 1615, 1605 (C=C, C=N).
1H NMR spectrum (CDCl3), δ, ppm: 1.47 t (3H, CH3,
J 7.4 Hz), 4.27 q (2H, CH2 J 7.4 Hz), 6.81 s (1H, CH),
7.21–7.85 m (8H, C6H5 + C5H3BrN), 9.53 s (1H, NH). UV
spectrum, λmax, nm (lgε): 229 (4.34), 302 (4.10). Found,
%: C 54.27; H 3.85; Br 21.49; N 7.30. C17H15BrN2O3.
Calculated , %: C 54.42; H 4.03; Br 21.30; N 7.47.
1. Gavrilova, N.E., Zalesov, V.V., and Kashin, D.N., Khim.
Geterotsikl. Soedin., 2002, p. 853.
2. Kataev, S.S., Gavrilova, N.E., and Zalesov, V.V., Khim.
Geterotsikl. Soedin., 2003, p. 1506.
3. Aliev, Z.G., Atovmyan, L.O., Kataev, S.S., and Zale-
sov, V.V., Khim. Geterotsikl. Soedin., 2007, p. 464.
4. Zalesov, V.V. and Kataev, S.S., RF Patent 213772, 1998;
RF Byull. Izobr., 1999, no. 26.
5. Maslivets, A.N., Tarasova, O.P., and Andreichikov, Yu.S.,
Zh. Org. Khim., 1992, no. 28, p. 1287.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008