New approach to the synthesis of 4-amino-2-pyridone and 1-phenyl-1,6-naphthyridinone derivatives based on substituted 3-and 5-formyl-2-pyridones

Article abstract of DOI:10.1007/s11172-006-0442-5

The reactions of 3-cyano-3(5)-formyl-2-oxo-4-(phenylamino)-1,2- dihydropyridines with CH acids were studied. The previously unknown fused 2-pyridone derivatives containing the 4-aminopyridine fragment were synthesized by the Knoevenagel reaction.

Full text of DOI:10.1007/s11172-006-0442-5

Russian Chemical Bulletin, International Edition, Vol. 55, No. 8, pp. 1470—1474, August, 2006
1470
New approach to the synthesis of 4ꢀaminoꢀ2ꢀpyridone and
1ꢀphenylꢀ1,6ꢀnaphthyridinone derivatives based on
substituted 3ꢀ and 5ꢀformylꢀ2ꢀpyridones
N. Z. Tugusheva,a L. M. Alekseeva,a A. S. Shashkov,b and V. G. Granikaꢀ
aState Research Center of Antibiotics,
3a ul. Nagatinskaya, 117105 Moscow, Russian Federation.
Fax: +7 (495) 231 4284. Eꢀmail: vggranik@mail.ru
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 5328
The reactions of 3ꢀcyanoꢀ3(5)ꢀformylꢀ2ꢀoxoꢀ4ꢀ(phenylamino)ꢀ1,2ꢀdihydropyridines with
CH acids were studied. The previously unknown fused 2ꢀpyridone derivatives containing the
4ꢀaminopyridine fragment were synthesized by the Knoevenagel reaction.
Key words: 3ꢀcyanoꢀ3(5)ꢀformylꢀ2ꢀoxoꢀ4ꢀ(phenylamino)ꢀ1,2ꢀdihydropyridines, 2,7ꢀdioxoꢀ
1ꢀphenylꢀ1,2,6,7ꢀtetrahydroꢀ1,6ꢀnaphthyridines, 2ꢀiminoꢀ5(7)ꢀoxoꢀ1ꢀphenylꢀ1,6ꢀnaphthyridiꢀ
nes, Knoevenagel reaction, NMR spectroscopy.
Scheme 1
Compounds containing the 4ꢀaminopyridine or
4ꢀaminopyridone fragment are of interest because of their
potential biological (including psychotropic, nootropic,
or antiepileptic) activity.1—3 A large number of substiꢀ
tuted naphthyridines having different biological activities
(diuretics, herbicide components, etc.) were synthesized
by condensation of orthoꢀaminopyridinecarbaldehydes
with CH acids in the presence of bases (Knoevenagelꢀ
type reaction).4,5 Earlier,6,7 we have developed a proceꢀ
dure for the synthesis of 3ꢀ and 5ꢀformylꢀsubstituted
4ꢀarylaminoꢀ2ꢀpyridones and examined the possibilities
of performing their modifications and functionalization
primarily by the reactions with various amines. In the
present study, we investigated the reactions of these aldeꢀ
hydes with compounds containing activated methylene
groups (Knoevenagel reaction). We prepared compound 2
in 96% yield by the reactions of 5ꢀformylꢀ2ꢀpyridone 1
with cyanoacetic ester in pyridine in the presence of triꢀ
ethylamine at 20 °C. Presumably, the Knoevenagel reacꢀ
tion affords a bicyclic product A (Scheme 1). The electroꢀ
spray (ES) mass spectrum of compound 2 has peaks at
m/z 335 [M + H]+• and 669 [2 M + H]+• corresponding
to the molecular weights of 2 or A but not of the form B.
The 1H NMR spectroscopic data are also consistent with
the structures 2 or A. These spectra show signals of the
COOEt group: a triplet at δ 1.35 (COOCH2CH3) and a
quartet at δ 4.35 (COOCH2CH3).
of low solubility of 2 in DMSO. To solve this problem,
compound 2 was subjected to alkylation (Me2SO4, NaH,
20 °C) to prepare compound 3 (Scheme 2). The mass
spectrum of the latter has peaks at m/z 302 [M + H]+•
and 325 [M + Na]+•. The 13C NMR spectrum shows two
It was impossible to measure the 13C NMR spectrum
of compound 2, which could allow us to unambiguously
assign its structure to the open or bicyclic form, because
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1416—1420, August, 2006.
1066ꢀ5285/06/5508ꢀ1470 © 2006 Springer Science+Business Media, Inc.

Synthesis of 4ꢀaminoꢀ2ꢀpyridone derivatives
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 8, August, 2006
1471
Scheme 3
signals of the CN groups at δ 111.6 (CN(C(8))) and
115.0 (CN(C(3))). The position of the CH3 group was
established by the HMBC spectrum, which shows sigꢀ
nals at δ 3.58/149.7 (Me(C(6))/C(5)) and 3.58/160.6
1
(Me(C(6))/C(7)). Analysis of the H and 13C NMR and
HMBC spectra (see the Experimental section) demonꢀ
strated that compound 3 is 3,8ꢀdicyanoꢀ6ꢀmethylꢀ7ꢀoxoꢀ
1ꢀphenylꢀ1,2,6,7ꢀtetrahydroꢀ1,6ꢀnaphthyridine, which
can be derived only from open form 2.
Scheme 2
malononitrile, leads to cyclization of the Knoevenagel
reaction product to give naphthyridinone 7 in 96% yield
(Scheme 4). This conclusion was drawn based on analysis
of the 13C NMR spectrum (see the Experimental secꢀ
tion). The cyclic structure is evidenced by the presence
of signals for the C atoms of two (rather than three)
CN groups at δ 112.3 (CN(C(8))) and 115.7 (CN(C(3))).
The assignment of the signals in the 13C NMR spectrum
was made based on correlation peaks in the 2D HMBC
spectrum presented in the Experimental section.
Storage of compound 2 in ethanol in the presence of
hydrazine hydrate at 20 °C (see Scheme 2) afforded hydrꢀ
azone 4 (its H NMR and mass spectra are completely
1
identical to those of hydrazone prepared from 5ꢀformylꢀ
pyridone 1 and hydrazine hydrate7), which is also eviꢀ
dence for the monocyclic structure of compound 2.
The ethoxycarbonyl group in substituted vinylpyridone
2 is easily hydrolyzed with bases (NaOH in aqueous
methanol or an aqueous NaHCO3 solution) at 20 °C
(Scheme 3). The 1H NMR spectrum of the resulting comꢀ
pound 5 shows two singlets (1 H each) at δ 8.73 and 8.81,
signals for the protons of the phenyl ring at δ 7.67—7.74
(m, 5 H) and the NH=C(2) fragment at δ 8.39 (strongly
br.s), and strongly broadened signals of the OH and N(6)H
groups at δ 13.44 and 13.58, respectively. The ES mass
spectrum has peaks at m/z 307 [M + H]+, 289 [M – OH]+,
and 261 [M – COOH]+. Compound 5 can have either an
open (A´) or cyclic (B´) structure, or alternatively can
exist as a tautomeric mixture.
Scheme 4
Refluxing of pyridone 2 in an alkali smoothly affords
naphthyridinedione 6 in 77% yield. The electron impact
(EI) mass spectrum of compound 6 shows peaks at
m/z 307 ([M+]) and 263 ([M – CO2]+), and the ES mass
spectrum has a peak at m/z 330 ([M + Na]+).
The reaction of 3ꢀformylpyridone 8 with malononitrile
in the presence of Et3N both in ethanol and pyridine (in
the absence of a catalyst) produces 2ꢀiminonaphthyridinꢀ
5ꢀone 9 (in 61 and 86% yields, respectively), the virtually
analytically pure product being isolated from ethanol
Under analogous conditions (Py, Et3N, 20 °C), the
reaction of compound 1 with another CH acid, viz.,

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Tugusheva et al.
Scheme 5
(Scheme 5). The structure of compound 9 was confirmed
by the HMBC spectrum (δ): 5.15/105.7 (H(8)/C(4a)),
5.15/139.7 (H(8)/C(7)), 7.36/96.1 (H(7)/C(8)),
7.36/102.3 (H(7)/C(4a)), 7.36/151.8 (H(7)/C(8a)),
7.36/159.3 (H(7)/C(5)), 8.15/96.1 (H(4)/C(8)),
8.15/102.3 (H(4)/C(3)), 8.15/116.4 (H(4)/CN(C(3))),
8.15/151.8 (H(4)/C(8a)), and 8.15/159.3 (H(4)/C(5)).
The IR spectrum of compound 9 shows signals at
This reaction in pyridine as the solvent affords a mixꢀ
ture consisting primarily of two products (in a ratio
of 1 : 1). One of these products, naphthyridinone 12, is
generated through intramolecular cyclization involving
the phenylamino and ethoxycarbonyl groups. Another
product contains the ethyl group but it is not comꢀ
1
pound 10. The H NMR spectrum of the mixture shows
two doublets (1 H each) at δ 5.28 and 5.38 and two sinꢀ
glets (1 H each) at δ 8.82 and 8.91, as well as a triplet
(3 H) and a quartet (2 H) corresponding to one ethyl
group. The ES mass spectrum has ion peaks at m/z 264
[M1 + H]+ (12), 310 [M2 + H]+, and 281 [M2 – C2H4]+.
These data suggest that the reaction of 3ꢀformylpyridine 8
with cyanoacetic ester in pyridine produces a mixture of
naphthyridinones 12 and 14. The formation of the latter is
apparently attributed to the transformation of intermediꢀ
ate 13 into compound 10 and then into 14 through
Dimroth recyclization. We failed to isolate naphthyridiꢀ
none 14 from the reaction mixture in individual form.
We also used diethyl malonate and ethyl nitroacetate
as compounds containing activated methylene groups in
condensation with 3ꢀformylpyridone 8. In the former case,
3319 (NH=) and 2200 (CN) cm–1
.
The reaction of 3ꢀformylpyridone 8 with cyanoacetic
ester in the presence of Et3N in ethanol requires proꢀ
longed refluxing (24 h). In this case, we prepared comꢀ
pound 10 in 54% yield (it should be noted that traces of
tricyclic compound 11, which we have prepared earlier,7
were detected in the mother liquor by chromatography).
The IR spectrum of compound 10 shows signals at
3302 (NH=), 1734 (COOEt), and 1693 (CO) cm–1 but
the signal of the CN group is absent. The above facts and
1
the H NMR spectroscopic data (see the Experimental
section) provide evidence that compound 10 has a biꢀ
cyclic structure, i.e., it is 3ꢀethoxycarbonylꢀ2ꢀiminoꢀ1ꢀ
phenylnaphthyridinꢀ5ꢀone.

Synthesis of 4ꢀaminoꢀ2ꢀpyridone derivatives
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 8, August, 2006
1473
1.8 mmol) was added portionwise to a solution of compound 2
(0.2 g, 0.6 mmol) in DMSO (4 mL) at 19 °C for 1 h so that the
temperature of the reaction mixture did not rise above 24 °C,
after which the solution turned darkꢀred. Then Me2SO4 (0.26 g,
2.1 mmol) was added to the resulting salt, and the reaction
mixture was stirred at 20 °C for 1 h and poured into cold water.
The precipitate that formed was filtered off and washed with
isopropyl alcohol and petroleum ether. Compound 3 was obꢀ
tained in a yield of 0.074 g (41%), m.p. 184 °C (sublim.).
Found (%): C, 65.04; H, 4.03; N, 17.62; H2O, 2.90.
C18H14N4O3•0.5H2O. Calculated (%): C, 65.18; H, 4.15;
refluxing in isopropyl alcohol in the presence of a cataꢀ
lytic amount of piperidine afforded a mixture containing
(1H NMR spectroscopic data) tricyclic compound 11 as
the major product (signals of this compound are comꢀ
1
pletely identical to those observed in the H NMR specꢀ
trum of tricyclic compound 11, which we have prepared
1
earlier7). The H NMR spectrum of the minor compoꢀ
nent shows the following signals (δ): 1.25 (t, 3 H, CH3),
4.21 (q, 2 H, CH2CH3), 5.28 (d, 1 H, H(8)), 7.32 (d, 2 H,
Ph), 8.62 (s, 1 H, H(4)). Based on these data, it can be
suggested that the minor product has the structure of
3ꢀethoxycarbonylꢀ1ꢀphenylnaphthyridineꢀ2,5ꢀdione 15.
The ES mass spectrum of the mixture has signals at m/z 197
[M1 + H]+, 311 [M2 + H]+, 333 [M2 + Na]+, and 643
[2 M2 + Na]+, where M1 corresponds to the molecular
ion of tricyclic compound 11 and M2 corresponds to
naphthyridinone 15.
It should be noted that 3ꢀformylpyridone 8 readily
undergoes cyclization7 to give tricyclic compound 11 upon
refluxing in isopropyl alcohol in the presence of piperidine.
The reaction of 3ꢀformylpyridine 8 with nitroacetic
ester in isopropyl alcohol (refluxing, 4.5 h) in the presꢀ
ence of piperidine produced 3ꢀnitroꢀ1ꢀphenylnaphthyrꢀ
idinedione 16 in 72% yield.
1
N, 17.89; H2O, 2.87. H NMR (DMSOꢀd6), δ: 3.58 (s, 3 H,
Me); 7.41—7.57 (m, 5 H, Ph); 8.62, (s, 1 H, H(4)); 8.88 (s, 1 H,
H(5)). 13C NMR (DMSOꢀd6), δ: 39.2 (Me(C(6))); 83.6 (C(8));
100.7 (C(3)); 103.9 (C(4a)); 111.6 (CN(C(8))); 115.0
(CN(C(3))); 129.0, 130.0, 130.5, 135.4 (Ph); 148.6 (C(4)); 149.7
(C(5)); 150.9 (C(8a)); 158.8 (C(2)); 160.6 (C(7)). HMBC
(DMSOꢀd6), δ: 3.58/149.7 (Me(C(6))/C(5)); 3.58/160.6
(Me(C(6))/C(7)); 8.62/149.7 (H(4)/C(5)); 8.62/150.9
(H(4)/C(8a)); 8.62/158.8 (H(4)/C(2)); 8.62/100.7 (H(4)/C(3));
8.62/103.9 (H(4)/C(4a)); 8.62/115.0 (H(4)/C(C(3)N));
8.88/103.9 (H(5)/C(4a)); 8.88/148.6 (H(5)/C(4)); 8.88/150.9
(H(5)/C(8a)); 8.88/160.6 (H(5)/C(7)). IR, ν/cm–1: 2230 (CN),
1696 (CO), 1628 (CO). ES MS, m/z: 302 [M + H]+•, 325
[M + Na]+•, 627 [2 M + Na]+•, 275 [M – CO]+•
.
3ꢀCyanoꢀ5ꢀ(hydrazonomethyl)ꢀ2ꢀoxoꢀ4ꢀphenylaminoꢀ1,2ꢀ
dihydropyridine (4). A mixture of compound 2 (0.005 g,
0.015 mmol) and hydrazine hydrate (0.2 mL) in anhydrous EtOH
(1 mL) was kept at 20 °C for 1 h. The precipitate that formed
was filtered off and washed with EtOH. Hydrazone 4 was obꢀ
tained in a yield of 0.036 g (95%), m.p. 293—294 °C (DMF).
1H NMR (DMSOꢀd6), δ: 6.66 (br.s, 2 H, NH2); 7.25 and 7.39
(both m, 3 H and 2 H, Ph); 7.62 (s, 1 H, Hα); 7.75 (s, 1 H,
H(6)); 11.39 (br.s, 1 H, C(4)NH); 11.63 (br.s, 1 H, N(1)H). IR,
ν/cm–1: 3400, 3200 (NH), 2200 (CN), 1690 (CO), 1620, 1570
Experimental
The IR spectra were recorded on a FSMꢀ1201 instrument in
1
Nujol mulls. The H NMR spectra were measured on Bruker
ACꢀ300 and Bruker DRXꢀ500 spectrometers in DMSOꢀd6 and
DMSOꢀd6—CCl4. The HMBC spectra were recorded on a
Bruker DRXꢀ500 spectrometer in DMSOꢀd6. The EI mass specꢀ
tra (70 eV) were obtained on a Finnigan SSQꢀ710 mass specꢀ
trometer using a direct inlet system. The ES mass spectra were
recorded on a Waters ZQꢀ2000 mass spectrometer using a direct
inlet system without the use of a chromatographic column. The
course of the reactions was monitored and the purity of the
compounds was checked by TLC on Merсk 60 F254 plates. The
melting points were determined on an Electrotermal 9100 inꢀ
strument (UK).
(C=C, C=N). ES MS, m/z: 254 [M + H]+•, 276 [M + Na]+•
,
529 [2 M + Na]+•. EI MS, m/z (Irel (%)): 253 [M]+• (50), 222
[M – NH2NH]+• (100).
5ꢀ(2ꢀCarboxyꢀ2ꢀcyanovinyl)ꢀ3ꢀcyanoꢀ2ꢀoxoꢀ4ꢀphenylaminoꢀ
1,2ꢀdihydropyridine (5). Compound 2 (0.325 g, 0.97 mmol) was
added to a solution of NaOH (1.53 g) in 30% aqueous methanol
(25 mL), and the reaction mixture was stirred at 20 °C until
complete dissolution was achieved. The resulting solution of the
sodium salt was acidified with concentrated HCl to pH 1 and
kept at 5 °C for 0.5 h. The precipitate that formed was filtered
off and washed with water. Compound 3 was obtained in a yield
of 0.25 g (84%), m.p. 328—330 °C. Found (%): C, 60.11; H, 3.56;
N, 17.39; H2O, 4.92. C16H10N4O3•0.9H2O. Calculated (%):
C, 59.63; H, 3.69; N, 17.38; H2O, 4.75. IR, ν/cm–1: 3426 (OH),
2230 (CN), 1655 (CO). ES MS, m/z: 307 [M + H]+•, 329
[M + Na]+•, 635 [2 M + Na]+•, 289 [M – OH]+•, 261
[M – HOOC]+•. EI MS, m/z (Irel (%)): 260 [M – HCOOH]+•
(100), 232 [M – HCOOH – CO]+• (13), 205 [M – HCOOH –
CO – CN]+• (10).
8ꢀCyanoꢀ2,7ꢀdioxoꢀ1ꢀphenylꢀ1,2,6,7ꢀtetrahydroꢀ1,6ꢀ
naphthyridineꢀ3ꢀcarboxylic acid (6) was prepared analogously to
compound 5 from compound 2 (0.15 g, 0.45 mmol) at 76 °C.
The reaction mixture was refluxed for 6 h. The yield was 77%,
m.p. 314—315 °C. Found (%): C, 62.34; H, 3.00; N, 13.49.
C16H9N3O4. Calculated (%): C, 62.54; H, 2.95; N, 13.68.
1H NMR (DMSOꢀd6), δ: 7.40—7.56 (m, 5 H, Ph); 8.71 and
3ꢀCyanoꢀ5ꢀ(2ꢀcyanoꢀ2ꢀethoxycarbonylvinyl)ꢀ2ꢀoxoꢀ4ꢀ(pheꢀ
nylamino)ꢀ1,2ꢀdihydropyridine (2). A mixture of formylpyridone
1 (3 g, 0.012 mol), cyanoacetic ester (2.72 g, 0.021 mol), and
triethylamine (0.5 mL) in pyridine (25 mL) was kept at 20 °C for
72 h. The reaction mixture was concentrated in vacuo, the resiꢀ
due was triturated in anhydrous EtOH (20 mL), and the precipiꢀ
tate that formed was filtered off and washed with EtOH. Comꢀ
pound 2 was obtained in a yield of 3.27 g (96%), m.p. 303—305 °C
(DMF). Found (%): C, 64.39; H, 4.52; N, 16.58. C18H14N4O3.
Calculated (%): C, 64.67; H, 4.19; N, 16.77. 1H NMR
(DMSOꢀd6), δ: 1.35 (t, 3 H, COOCH2CH3, Jo = 7.5 Hz); 4.35
(q, 2 H, COOCH2CH3, Jo = 7.5 Hz); 7.53—7.66 (m, 5 H, Ph);
8.68 and 8.75 (both s, 1 H each, H(6), H(5´)); 9.38 (br.s, 1 H,
NHPh). IR, ν/cm–1: 3147 (NH), 2208 (CN), 1697 (CO), 1665
(CO). ES MS, m/z: 335 [M + H]+•, 669 [2 M + H]+•, 691
[2 M + Na]+•, 305 [M – CHO]+•, 288 [M – EtOH]+•
.
3,8ꢀDicyanoꢀ6ꢀmethylꢀ2,7ꢀdioxoꢀ1ꢀphenylꢀ1,2,6,7ꢀtetraꢀ
hydroꢀ1,6ꢀnaphthyridine (3). A 80% NaH solution (0.5 g,

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Tugusheva et al.
8.77 (both s, 1 H each, H(4), H(5)); 12.95 and 13.30 (both br.s,
1 H each, N(6)H, COOH). IR, ν/cm–1: 2217 (CN), 1731
(COOH), 1650 (CO), 1600 (C=C, C=N). ES MS, m/z: 330
[M + Na]+•, 637 [2 M + Na]+. EI MS, m/z (Irel (%)): 307 [M]+•
(30), 263 [M – CO2]+• (100), 234 [M – CO2 – CO – H]+•
(10), 206 [M – HCOOH – CO – CN]+• (15).
7.5 Hz); 4.27 (q, 2 H, COOCH2CH3, Jo = 7.5 Hz); 5.12 (d, 1 H,
H(8), Jo = 7.4 Hz); 7.34 (d, 1 H, H(7), Jo = 7.4 Hz); 7.26, 7.48,
and 7.51 (all m, 2 H each, 1 H, 2 H, Ph); 8.42 (s, 1 H, H(4));
8.77 and 11.56 (both br.s, 1 H each, N(6)H, NH=C(2)). IR,
ν/cm–1: 3302, 3087 (NH); 1734, 1693, 1651, 1620 (CO). ES MS,
m/z: 310 [M + H]+•, 332 [M + Na]+•, 641 [2 M + H] +•, 296
3,8ꢀDicyanoꢀ2ꢀiminoꢀ7ꢀoxoꢀ1ꢀphenylꢀ1,2,6,7ꢀtetrahydroꢀ
1,6ꢀnaphthyridine (7). A mixture of formylpyridone 1 (1.2 g,
5 mmol), malononitrile (0.33 g, 5 mmol), and triethylamine
(0.5 mL) in pyridine (25 mL) was kept at 20 °C for 20 h. The
reaction mixture was concentrated in vacuo, the residue was
triturated with anhydrous EtOH (20 mL), and the precipitate
that formed was filtered off and washed with EtOH. Compound 7
was obtained in a yield of 1.3 g (96%), m.p. > 315 °C (DMF).
Found (%): C, 66.59; H, 3.25; N, 24.25. C16H9N5O. Calcuꢀ
lated (%): C, 66.90; H, 3.14; N, 24.39. 1H NMR (DMSOꢀd6), δ:
7.47 and 7.57—7.66 (both m, 2 H and 3 H each, Ph); 8.23 (s,
1 H, H(4)); 8.30 (s, 1 H, H(5)); 11.00—12.00 (strongly br.s,
1 H each, N(6)H, HN=C(2)). 13C NMR (DMSOꢀd6), δ: 83.1
(C(8)); 100.0 (C(3)); 104.8 (C(4a)); 112.3 (CN(C(8))); 115.7
(CN(C(3))); 130.6, 131.6, 134.7 (Ph); 144.1 (C(4)); 145.4
(C(5)); 151.0 (C(8a)); 152.0 (C(2)); 162.3 (C(7)). HMBC NMR
(DMSOꢀd6), δ: 8.23/115.7 (H(4)/CN(C(3))); 8.23/151.0
(H(4)/C(C(8a))); 8.30/104.8 (H(5)/C(4a)); 8.30/144.1
(H(5)/C(4)); 8.30/151.0 (H(5)/C(8a)), 8.30/162.3 (H(5)/C(7)).
IR, ν/cm–1: 3304 (NH), 2218 (CN), 1654 (CO). ES MS, m/z:
[M + H – 14]+•, 264 [M + H – C2H5OH]+•
.
3ꢀNitroꢀ2,5ꢀdioxoꢀ1ꢀphenylꢀ1,2,5,6ꢀtetrahydroꢀ1,6ꢀnaphꢀ
thyridine (16). A mixture of 3ꢀformylpyridone 8 (0.1 g,
0.47 mmol), nitroacetic ester (0.12 g, 0.9 mol), and piperidine
(0.086 g) in isopropyl alcohol (5 mL) was refluxed for 4 h. The
precipitate that formed was filtered off and washed with isoproꢀ
pyl alcohol. Compound 16 was obtained in a yield of 0.093 g
(72%), m.p. 335 °C (decomp., EtOH). Found (%): C, 59.36;
H, 3.23; N, 14.76. C14H9N3O4. Calculated (%): C, 59.38;
H, 3.20; N, 14.84. 1H NMR (DMSOꢀd6), δ: 5.35 (d, 1 H, H(8),
Jo = 7.4 Hz); 7.41—7.84 (m, 6 H, Ph, H(7)); 8.91 (s, 1 H, H(4));
11.56 (br.s, 1 H, N(6)H). IR, ν/cm–1: 3158 (NH); 1659,
1631 (CO); 1518 (NO2). ES MS, m/z: 284 [M + H]+•, 306
[M + Na]+•, 589 [2 M + H]+.
This study was financially supported by the Federal
Agency for Science and Innovations of the Russian Fedꢀ
eration (Contract No. 1/05).
References
288 [M + H]+•, 310 [M + Na]+•, 575 [2 M + Na]+•
.
3ꢀCyanoꢀ2ꢀiminoꢀ5ꢀoxoꢀ1ꢀphenylꢀ1,2,5,6ꢀtetrahydroꢀ1,6ꢀ
naphthyridine (9). A mixture of 3ꢀformylpyridone 8 (0.1 g,
0.47 mmol), malononitrile (0.03 g, 0.47 mmol), and triꢀ
ethylamine (0.05 mL) in EtOH (2 mL) was refluxed for 1 h.
The precipitate that formed upon refluxing was filtered off and
washed with EtOH. Compound 9 was obtained in a yield of
0.073 g (61%), m.p. 340 °C (PriOH—DMF, 1 : 1). Found (%):
C, 68.97; H, 3.94; N, 21.55. C15H10N4O. Calculated (%):
1. M. I. RodriguezꢀFranco, M. I. FernandezꢀBachiller, C. Perez,
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1
C, 68.69; H, 3.84; N, 21.36. H NMR (DMSOꢀd6), δ: 5.15 (d,
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p137285.
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1 H, H(8), Jo = 7.4 Hz); 7.34—7.41 (both m, 3 H each,
Ph, H(7)); 8.15, (s, 1 H, H(4)); 11.20—12.40 (strongly br.s,
1 H each, N(6)H, HN=C(2)). 13C NMR (DMSOꢀd6), δ: 96.1
(C(8)); 102.3 (C(3)); 105.7 (C(4a)); 116.4 (CN(C(3))); 129.0,
130.1, 131.1, 135.8 (Ph); 139.7 (C(7)); 141.1 (C(4)); 151.8
(C(8a)); 153.2 (C(2)); 159.3 (C(5)). IR, ν/cm–1: 3319, 3087
(NH); 2230 (CN); 1674, 1625 (CO). EI MS, m/z (Irel (%)):
261 [M – H]+• (100).
Ethyl 2ꢀiminoꢀ5ꢀoxoꢀ1ꢀphenylꢀ1,2,5,6ꢀtetrahydroꢀ1,6ꢀnaphꢀ
thyridineꢀ3ꢀcarboxylate (10). A mixture of 3ꢀformylpyridone 8
(0.354 g, 1.65 mmol), cyanoacetic ester (0.237 g, 2.61 mol), and
triethylamine (0.13 mL) in EtOH (18 mL) was refluxed for 24 h.
The reaction mixture was concentrated in vacuo, the residue was
triturated in anhydrous EtOH (10 mL), and the residue was
filtered off and washed with EtOH. Compound 10 was obꢀ
tained in a yield of 0.275 g (54%), m.p. 264—265 °C (EtOH).
Found (%): N, 13.57. C17H15N3O3. Calculated (%): N, 13.58.
Received May 26, 2006;
in revised form July 12, 2006
1H NMR (DMSOꢀd6), δ: 1.32 (t, 3 H, COOCH2CH3, Jo
=