Synthesis of 1,3-dialkyl-5-(pyrrol-1-yl)-1,3-dihydro-2H-imidazo[4,5-b] pyridin-2-ones

Full text of DOI:10.1134/S1070428009050273

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 5, pp. 796−797. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © N.N. Smolyar, D.A. Lomov, Ya.S. Borodkin, S.V. Gresko, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45,
No. 5, pp. 807−808.
SHORT
COMMUNICATIONS
Synthesis of 1,3-Dialkyl-5-(pyrrol-1-yl)-1,3-dihydro-
2H-imidazo[4,5-b]pyridin-2-ones
N. N. Smolyar, D. A. Lomov, Ya. S. Borodkin, and S. V. Gresko
Litvinenko Institute of Physical Organic and Coal Chemistry, Ukrainian National Academy of Sciences
Donetsk, 83114, Ukraine
Received Julyl 9, 2008
DOI: 10.1134/S1070428009050273
imidazo[4,5-b]pyridin-2-ones Ia–Ic with 2,5-dimethoxy-
tetrahydrofuran (II) in glacial acetic acid we obtained
1,3-dialkyl-1,3-dihydro-5-(pyrrol-1-yl)-2H-imidazo[4,5-b]-
pyridin-2-ones IIIa–IIIc in 50–80% yield.
Derivatives of imidazo[4,5-b]pyridine, structural ana-
logs of purine, exhibit versatile biological action: antiviral,
cytostatic, antimicrobial, fungicidal, cardiovascular,
secretoinhibitory, and they are also antagonists of
angiotonin [1].
Obtained compounds IIIa–IIIc are well soluble in
water and organic solvents (alcohols, benzene) and are
readily purified from these solvents. The synthesized
compounds are stable and are not oxidized in air. The
composition and structure of compounds IIIa–IIIc were
confirmed by elemental analysis and 1H NMR spectra.
In extension of the research on the synthesis of tri-
cyclic imidazopyridine derivatives containing an imidazole,
triazole, and pyrrolidine fragments [2] it seemed purpose-
ful using synthetic methods to build up in the structure of
imidazo[4,5-b]pyridine a pyrrole ring.
1
In the H NMR spectra of compounds IIIa–IIIc
The pyrrole ring is known to be present in the
composition of many antibiotics [3]. This stimulates the
search for new biologically active compounds including
the fragments of imidazo[4,5-b]pyridine and pyrrole.
Applying the Clauson–Kaas reaction [4] we synthesized
imidazo[4,5-b]pyridine derivatives containing a pyrrole
fragment at the C5 atom of the pyridine ring. In the
condensation of 5-amino-1,3-dialkyl-1,3-dihydro-2H-
alongside the signals of alkyl groups of the imidazole ring,
protons H6 (7.52–7.55 ppm) and H7 (7.24–7.25 ppm) of
the pyridine ring singlet signals are present from protons
H2' – H5' of the pyrrole fragment in the region 6.25 and
7.54–7.58 ppm. The prerequisite fact of the possible
interest in compounds synthesized IIIa–IIIc for
pharmacology consists in the presence in their structure
of the N-substituted pyrroles that are important synthons
in the synthesis of biologically active substances [5], and
the fragments of pyrrole derivatives are included in the
composition of a number of drugs [3].
R
N
O
+
N
MeO
O
OMe
H2N
N
General synthetic procedure. To a dispersion of
1.21 mmol of reagent Ia–Ic in 2 – 3 ml of glacial acetic
acid was added 1.21 mmol of 2,5-dimethoxytetra-
hydrofuran (II), and the mixture was heated for 0.5 h at
130°C. Then the excess acetic acid was distilled off to
dryness, and the residue was dissolved in warm hexane.
The precipitate was filtered off and recrystallized.
R
Ià_Ic
II
R
N
AcOH
O
N
N
N
R
1,3-Dimethyl-5-(pyrrol-1-yl)-1,3-dihydro-2H-
imidazo[4,5-b]pyridin-2-one (IIIa). Yield 0.22 g (80%),
IIIà_IIIc
796

SYNTHESIS OF 1,3-DIALKYL-5-(PYRROL-1-YL)-1,3-DIHYDRO-2H-...
797
mp 101–103°C (heptane). 1H NMR spectrum (DMSO-
d6), δ, ppm: 3.32 t (3H, N1CH3), 3.46 s (3H, N3CH3),
6.25 s (2H, H3', H4'), 7.25 d (1H, H7, J 8.4 Hz), 7.52d
(1H, H6, J 8.4 Hz), 7.54 s (2H, H2', H5'). Found, %:
C 62.98; H 5.24; N 24.39. C12H12N4O. Calculated, %:
C 63.14; H 5.30; N 24.55.
compounds obtained was performed by TLC on Silufol
UV-254 plates (eluent ethanol, development in iodine
vapor and under UV irradiation). The synthesis of
compounds Ia–Ic was published in [6].
REFERENCES
5-(Pyrrol-1-yl)-1,3-diethyl-1,3-dihydro-2H-imid-
azo[4,5-b]pyridin-2-one (IIIb). Yield 0.19 g (63%), mp
88–90°C (heptane). H NMR spectrum (DMSO-d6), δ,
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1
ppm: 1.36 t (3H, N1CH2CH3), 1.42 t (3H, N3CH2CH3),
3.96 q (2H, N1CH2CH3), 4.02 q (3H, N3CH2CH3),
6.25 s (2H, H3', H4'), 7.24 d (1H, H7, J 8.4 Hz), 7.55 d
(1H, H6, J8.4 Hz), 7.58 s (2H, H2', H5'). Found, %: C 65.42;
H 6.23; N 21.71. C24H20N4O. Calculated, %: C 65.60;
H 6.29; N 21.86.
1,3-Dibenzyl-5-(pyrrol-1-yl)-1,3-dihydro-2H-
imidazo[4,5-b]pyridin-2-one (IIIc). Yield 0.23 g
(50%), mp 133–135°C (decene). H NMR spectrum
4. Clauson-Kaas, N., Tyle, Z. Chem. Scand., 1952, vol. 6,
pp. 667, p. 867.
1
5. Feng, X. Lancelot, J.C., Prunier, H., and Rault, S., J. Hetero-
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Greco, G., Cagnotto,A., Goegan, M., Cervo, L., Valle, F.D.,
Fracasso, C., Caccia, S., and Mennini, T., J. Med. Chem.,
1999, vol. 42, p. 4362;Aborina, R., Insuasty, B., Quiroga, J.,
Kolshorn, H., and Meier, H., J. Heterocycl. Chem., 2001,
vol. 38, p. 671; Kopp, M., Lancelot, J.C., Dallemagne, P., and
Rault, S., J. Heterocycl. Chem., 2001, vol. 38, p. 1045.
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and Yutilov, Yu.M., Zh. Org. Khim., 2007,vol. 43, p. 1706.
(DMSO-d6), δ, ppm: 5.12 s (2H, N1CH2C6H5), 5.17 s
(2H, N3CH2C6H5), 6.25 s (2H, H3', H4'), 7.24 d (1H, H7,
J8.4Hz), 7.42 br.s (5H, N1CH2C6H5), 7.50 br.s (5H,
N3CH2C6H5), 7.52 d (1H, H6, J8.4Hz), 7.54s (2H, H2',
H5'). Found, %: C 75.60; H 5.25; N 14.58. C24H20N4O.
Calculated,%: C75.76; H 5.30; N 14.73.
1H NMR spectra of compounds were registered on
a spectrometer Bruker Avance II 400 at operating
frequency 400 ΜHz. The purity and homogeneity of
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