Reactions of ethyl 4-amino-6-(ethoxycarbonylmethyl)-2-phenylpyrimidine-5- carboxylate with hydrazines

Article abstract of DOI:10.1007/s11172-008-0335-x

New substituted 4,6-diamino-7-hydroxypyrido[4,3-d]pyrimidin-5(6H)-ones were synthe-sized by treatment of ethyl 4-amino-6-(ethoxycarbonylmethyl)-2- phenylpyrimidine-5-car-boxylic acid with hydrazine hydrate and phenylhydrazine. In the case of methylhydrazine, the reaction proceeded in an unusual way and afforded a product identified, relying on NMR data, as functionally substituted 8-(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-7-ylidene)-5,6,7, 8-tetrahydropyrido[4,3-d]pyrimidine comprising two amineimide fragments. A diacetyl derivative of this compound was obtained.

Full text of DOI:10.1007/s11172-008-0335-x

Russian Chemical Bulletin, International Edition, Vol. 57, No. 11, pp. 2353—2358, November, 2008
2353
Reactions of ethyl 4ꢀaminoꢀ6ꢀ(ethoxycarbonylmethyl)ꢀ
2ꢀphenylpyrimidineꢀ5ꢀcarboxylate with hydrazines
A. V. Komkov, A. S. Shashkov, and V. A. Dorokhov
N. D. Zelinsky Institute of Organic Chemistry,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Еꢀmail: vador@ioc.ac.ru
New substituted 4,6ꢀdiaminoꢀ7ꢀhydroxypyrido[4,3ꢀd]pyrimidinꢀ5(6H)ꢀones were syntheꢀ
sized by treatment of ethyl 4ꢀaminoꢀ6ꢀ(ethoxycarbonylmethyl)ꢀ2ꢀphenylpyrimidineꢀ5ꢀcarꢀ
boxylic acid with hydrazine hydrate and phenylhydrazine. In the case of methylhydrazine, the
reaction proceeded in an unusual way and afforded a product identified, relying on NMR data,
as functionally substituted 8ꢀ(5,6,7,8ꢀtetrahydropyrido[4,3ꢀd]pyrimidinꢀ7ꢀylidene)ꢀ5,6,7,8ꢀ
tetrahydropyrido[4,3ꢀd]pyrimidine comprising two amineimide fragments. A diacetyl derivaꢀ
tive of this compound was obtained.
Key words: ethyl 4ꢀaminoꢀ6ꢀ(ethoxycarbonylmethyl)ꢀ2ꢀphenylpyrimidineꢀ5ꢀcarboxylate,
hydrazines, substituted pyrido[4,3ꢀd]pyrimidines, heterocyclization.
Substituted 4ꢀaminopyrido[4,3ꢀd]pyrimidines inhibit
tyrosine kinase,1 and pyrido[4,3ꢀd]pyrimidinꢀ5(6H)ꢀone
derivatives exhibit antihypertensive,2 antiallergic,3 and
herbicidal4 activities. Our interest was in the development
of new versions of the synthesis of pyrido[4,3ꢀd]pyrimidinꢀ
5ꢀones containing an amino group.
Scheme 1
In the previous paper,5 we reported that ethyl 4ꢀaminoꢀ
6ꢀ(ethoxycarbonylmethyl)ꢀ2ꢀphenylpyrimidineꢀ5ꢀcarbꢀ
oxylate (1), obtained from Nꢀcyanobenzamidine and
diethyl acetoneꢀ1,3ꢀdicarboxylate in the presence of
Ni(OAc)2, is converted, under the treatment by primary
amines, into amides 2, which cyclize under the treatment
by MeONa in MeOH to give pyrido[4,3ꢀd]pyrimidinꢀ
5ꢀone derivatives 3 (Scheme 1).
In continuation of this work, we studied the reactions
of diester 1 with hydrazines. We found that refluxing
of diester 1 with a large excess of phenylhydrazine in
pꢀxylene affords diaminopyrido[4,3ꢀd]pyrimidinꢀ5ꢀone 4
similar in structure to compounds 3 (Scheme 2). Apparently,
hydrazide 5 is formed intermediately; however, under the
reaction conditions, it is converted into bicyclic product
4 as a result of intramolecular condensation. The 1H NMR
spectrum (DMSOꢀd6) of this product shows a singlet at
5.42 ppm (H(8)) and a broad singlet centered at 12.22 ppm
for the OH group (cf. signals at 5.39 and 12.18 ppm
for compound 3a). These data do not contradict the
pyridopyrimidine structure of 4 and do not correspond to
the alternative pyrimidodiazepine structure 6. The mass
spectrum of compound 4 shows a molecular ion peak and
the IR spectrum exhibits a carbonyl absorption band
at 1680 cm–1.
R = PhCH2 (a), Bu (b)
The reaction of diester 1 with a large excess of hydrꢀ
azine hydrate in boiling butanol also yields pyrido[4,3ꢀd]ꢀ
pyrimidinꢀ5ꢀone but in this case, the process is accomꢀ
panied by replacement of the NH2 group by hydrazine.
Compound 7 thus obtained was then converted into
diacetyl derivative 8 by treatment with excess Ac2O in
boiling benzene (Scheme 3).
The structures of compounds 7 and 8 were confirmed
by spectral methods. The mass spectra of these compounds
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2307—2312, November, 2008.
1066ꢀ5285/08/5711ꢀ2353 © 2008 Springer Science+Business Media, Inc.

2354
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008
Komkov et al.
Scheme 2
Scheme 4
and 7, but contains three closely located singlets with
different intensity (3.81, 3.82, and 3.84 ppm), which
correlate with the carbon signal at 18.9 ppm in the
2D {1H—13C} HSQC NMR spectra. Analysis of the GATED
and APT6 13C NMR spectra shows that this signal is
related to the CH2 group. The integral intensity ratio
of the 1H NMR signals of CH2 protons to the rest protons
corresponds to structure 9, which is formally the product
of condensation of two pyridopyrimidine molecules
involving the CH2 group of one molecule and the carꢀ
bonyl group of the other molecule. Indeed, the {1H—13C}
HMBC 2D NMR spectrum of compound 9 recorded in a
mixture of CF3COOH and DMSOꢀd6 shows a correlation
of CH2 protons with four carbon atoms: 95.2 ppm.
(C(4а´)), 142.8, 143.6 ppm (C(7´) and C(8)) and 162.5 ppm
(C(8а´)), which confirms the presence of a double bond
between the carbon atoms (C(7´) and C(8)) connecting
two bicyclic fragments. In turn, the unusually highꢀfield
13C NMR chemical shift (18.9 ppm) for a CH2 group
connected to the electronꢀwithdrawing pyrimidine ring
(for example, for pyrimidine 1, the CH2ꢀgroup signal is
observed at 45.7 ppm), which suggests that this molecule
incorporates fragments with oppositely charged nitrogen
atoms.
1
show strong molecular ion peaks. The H NMR spectra
(DMSOꢀd6), like the spectra of compounds 3 and 4, exꢀ
hibit a singlet at 5.42—5.45 ppm (H(8)). The spectrum of
compound 7 has a broadened singlet at 10.88 ppm (NH)
and a very broad singlet in the range of 5.0—5.8 ppm from
two NH2 groups. The spectrum of heterocycle 8 exhibits
three broadened singlets at 10.78 (NH), 10.10, and
11.39 ppm (2 NHCO).
The reaction of diester 1 with methylhydrazine proꢀ
ceeds in an unusual way. Longꢀterm refluxing of comꢀ
pound 1 with a large excess of methylhydrazine in butanol
gave a yellow solid poorly soluble in organic solvents, and
its structure was obviously different from that of the above
described pyridopyrimidines 3, 4, and 7. Detailed investiꢀ
gation of the product by NMR and mass spectrometry
together with elemental analysis data point to structure 9
(Scheme 4).
1
Thus the H NMR spectrum (DMSOꢀd6) of comꢀ
pound 9 does not show the singlet at 5.33—5.45 ppm
(CH), which is present in the spectra of heterocycles 3, 4,
Scheme 3

6ꢀ(Ethoxycarbonylmethyl)pyrimidineꢀ5ꢀcarboxylate Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008 2355
In the 1H NMR spectrum of heterocycle 9, as in specꢀ
Scheme 5
tra of bicyclic compounds 3 and 4, the signals for NH2
groups are observed as two broadened singlets at 8.83 and
9.52 ppm and the chemical shifts of the Ph protons of all
of these compounds are similar. In addition, compound 9
has two OH groups (four closely located relatively narrow
singlets at 13.43, 13.50, 13.54, and 13.59 ppm with twoꢀ
proton total intensity)* and two NH groups (broad singlet
at 5.6—6.2 ppm) whose protons do not show correlation
with the carbon atoms in the HSQC 2D spectrum. The
1
signals of the NMe groups in the H NMR spectrum
overlap with the DMSO signal, which is confirmed by
correlation of these protons with the carbon at 36.3 ppm
in the HSQC 2D spectrum. The {1H—1H} COSY 2D
spectrum shows correlation only between the Ph group
protons and between the NH2 group protons, which
confirms the singlet character of the CH2ꢀgroup signals
and points to the absence of the MeNH fragment.
1
The fact that the H NMR spectrum of compound 9
exhibits three signals with 1 : 2 : 1 ratio for the CH2 group
and four signals for the OH group is explained by the
presence of two asymmetric centers (tetrahedral positively
charged nitrogen atoms) in the molecule, resulting in the
possible formation of four stereoisomers (RR, SR and
RS, SS).
The EI mass spectrum of heterocycle 9 does not show
a molecular ion peak (fragmentation is presented in the
Experimental); however, the MALDI mass spectrum
contains an intensive ion peak at 567 [М + H]+. The
IR spectrum of compound 9 in KBr exhibits only one
carbonyl absorption band (1656 cm–1), which is also in
line with the assumed structure.
1,1ꢀDimethylhydrazine is known7 to react with
epoxides by more nucleophilic nitrogen to give amineꢀ
imides 10. In addition, the reaction of 1,3ꢀdimethylꢀ
6ꢀdimethylaminovinylꢀ5ꢀformyluracils with hydrazines
affords the corresponding products 11 (Scheme 5)8.
All this suggests that the reaction of diester 1 with
methylhydrazine occurs according to Scheme 6.
Apparently, methylhydrazine first reacts with diester 1
by more nucleophilic MeNH fragment to give hydrazide
12, which cyclizes to give not pyrimidodiazepine 13 but
pyridopyrimidine 14. The subsequent proton transfer from
the NH2 group to the negatively charged oxygen atom and
elimination of EtOH affords pyridopyrimidine 16 where
the electrophilicity of carbonyl groups is enhanced due to the
presence of positive charge on the endocyclic nitrogen
atom. This promotes condensation of two molecules of
this bicyclic compound to give compound 17. The subsequent
hydration of this intermediate leads to heterocycle 9.
R´ = H, Me, Ac
It is known7 that amineimides are readily acylated at
the imide nitrogen; therefore, we studied the reactions of
compound 9 with acid anhydrides. Refluxing of heteroꢀ
cycle 9 with excess Ac2O in toluene gave a yellow precipiꢀ
tate of compound 18 (Scheme 7). Treatment of more
bulky isobutyric anhydride does not give acylated product
for steric reasons, the initial heterocycle being recovered
unchanged.
The structure of compound 18 is confirmed by specꢀ
tral data. The MALDI mass spectrum of this heterocycle
exhibits an intense ion peak at 651 [М + H]+, while the
IR spectrum (KBr), like that of the initial compound 9,
exhibits only one absorption band for carbonyl groups at
1668 cm–1, while absorption below 1600 cm–1 is typical of
carbonyl groups of acylhydrazinium compounds.7
In comparison with the 1H NMR spectrum (DMSOꢀd6)
of the starting compound 9, the spectrum of the diacetyl
derivative 18 does not exhibit signals at 4.0—7.0 ppm,
while three singlets at ~3.8 ppm (CH2) are retained, broad
singlets for two acetyl groups appear (1.65 and 1.91 ppm),
and the signal of NMe groups (2.97 ppm) is broadened. In
addition, as opposed to the spectrum of the initial comꢀ
pound 9, this spectrum exhibits a double set of signals for
NH2 groups (8.82 and 9.38 ppm, 8.98 and 9.38 ppm),
which is confirmed by correlation of these proton couples
with each other in the COSY 2D spectrum. Also it should
be noted that the signal of the OH group at 13.1 ppm
becomes very broad (now its intensity corresponds to one
* Lowꢀfield chemical shifts correspond to hydrogen bond beꢀ
tween the hydroxyl protons and negatively charged nitrogen
atoms and are thus indicative of the Zꢀconfiguration of comꢀ
pound 9.

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008
Komkov et al.
Scheme 6
Scheme 7
proton) and the other OH group is manifested as a broadꢀ
ened singlet at 10.2 ppm. In the H NMR spectrum
1
(DMSOꢀd6) recorded at 100 °C, the COMe and NMe
group signals narrow down and the OH signal at 13.1 ppm
narrows down to a greater extent, which indicates the
hindrance of rotation around the C—N bond of the amide
fragment. The 13C NMR spectrum of heterocycle 18 shows
signals for two COМе groups (19.3 and 20.2 ppm), a
signal for the NMe group (33.5 ppm), and a broad signal
at 18.9 ppm, which corresponds to the CH2 group accordꢀ
ing to the AРТ 13C NMR spectrum.
Thus, the results presented in this work demonstrate
that in reactions with hydrazine and its monosubstituted
derivatives, diester 1 tends to form a pyridine rather than
a diazepine ring. Note in this connection that the
compounds synthesized from homophthalic anhydride
or methyl 1ꢀmethylꢀ2ꢀ(methoxycarbonylmethyl)indoleꢀ
3ꢀcarboxylate and hydrazine hydrate were initially believed
to be fused diazepines.9,10 However, the subsequent studies11,12
showed that in these cases, too, it is the pyridine ring that
is annulated.

6ꢀ(Ethoxycarbonylmethyl)pyrimidineꢀ5ꢀcarboxylate Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008 2357
22.58. C17H16N6O4. Calculated (%): C, 55.43; H, 4.38; N, 22.82.
MS, m/z (Irel (%)): 368 [M]+ (30), 326 [M – COCH2]+ (52),
284 [M – 2 COCH2]+ (100), 269 [M – COCH2 – МеCON]+
(95), 254 [M – COCH2 – МеCONHN]+ (53), 253 [M – COCH2
– МеCONHNH]+ (52), 226 [M – COCH2 – МеCONHNCO]+
(35), 104 [PhC=NH]+ (62). IR, ν/cm–1: 3230 (NH), 1688 (CO),
1664 (CO), 1624, 1560, 1524. 1H NMR, δ: 2.00 (s, 3 H, COMe);
2.05 (s, 3 H, COMe); 5.42 (s, 1 H, H(8)); 7.62 (m, 3 H, Ph);
8.20 (m, 2 H, Ph); 10.10 (br.s, 1 H, NHCO); 10.78 (br.s, 1 H,
NH); 11.39 (br.s, 1 H, NHCO); 12.49 (br.s, 1 H, OH).
Experimental
1H NMR spectra were recorded on Bruker AMꢀ300 and
Bruker DRXꢀ500 instruments and 13C NMR and {1H—1H}
COSY and {1H—13C} HSQC and HMBC 2D NMR spectra
were measured on a Bruker DRXꢀ500 spectrometer in DMSOꢀd6.
IR spectra (KBr pellets) were measured on a SpecordꢀM82
instrument and mass spectra were run on a Kratos MSꢀ30
mass spectrometer (EI, 70 eV, ionization chamber at 250 °C,
direct sample injection) and REFLEX III Bruker Daltonics
mass spectrometer (MALDI TOF MS, positive ion mode,
2,5ꢀdihydroxybenzoic acid or 2ꢀaminoꢀ4ꢀmethylꢀ5ꢀnitropyridine
as the matrix).
Diester 1 was synthesized by a known procedure.5 13C NMR
(CDCl3), δ: 14.1 (Ме); 14.2 (Ме); 45.7 (CH2); 60.8 (CH2O);
61.4 (CH2O); 102.9 (C(5)); 128.3 (mꢀCH, Ph); 128.7 (oꢀCH,
Ph); 131.1 (pꢀCH, Ph); 136.9 (ipsoꢀC, Ph); 164.1 (C(4)); 164.5
(C(2)); 165.1 (C(6)); 167.0 (CO); 170.1 (CH2CO) (the signals
were assigned using HSQC and HMBC 2D spectra).
4ꢀAminoꢀ8ꢀ(4ꢀaminoꢀ6ꢀimidoꢀ6ꢀmethylꢀ5ꢀoxoꢀ2ꢀphenylꢀ
5,6,7,8ꢀtetrahydropyrido[4,3ꢀd]pyrimidinꢀ7ꢀylidene)ꢀ7,7ꢀdihydroxyꢀ
6ꢀmethylꢀ5ꢀoxoꢀ2ꢀphenylꢀ5,6,7,8ꢀtetrahydropyrido[4,3ꢀd]ꢀ
pyrimidine 6ꢀimide (9). A mixture of diester 1 (0.24 g, 0.73 mmol)
and methylhydrazine (1.6 mL, 30 mmol) in BuOH (4 mL) was
refluxed for 12 h and cooled to 20 °C, and the precipitate was
filtered off and washed with MeOH (5 mL) to give 0.10 g (48%)
of compound 9, m.p. > 350 °C. Found (%): C, 58.92; H, 4.66;
N, 24.39. C28H26N10O4. Calculated (%): C, 59.36; H, 4.63; N,
24.72. MS MALDI, m/z: 567 [M + H]+. MS EI, m/z (Irel (%)):
281 [A – H2O]+ (41), 269 [A – MeNH]+ (52), 267 [B]+ (16),
266 [B – H]+ (29), 254 [A – MeNNH2]+ (40), 238 [B – MeN]+ (87),
211 [A – MeNHNCO – H2O + H2]+ (35), 195 [B – MeNHNCO]+
(21), 104 [PhC=NH]+ (100), where A and B are fragments
obtained upon cleavage of the bond connecting the bicyclic
moieties, their weights are 299 and 267, respectively. IR,
ν/cm–1: 3276, 3132, 1656 (CO), 1624, 1568, 1540, 1520.
1H NMR, δ: 2.50 (s, 6 H, 2 NMe); 3.81, 3.82, 3.84 (all s, 2 H,
CH2); 5.60—6.20 (br.s, 2 H, 2 NH); 7.70 (m, 6 H, mꢀH, pꢀH,
2 Ph); 8.41 (m, 4 H, оꢀH, 2 Ph); 8.83, 9.52 (both br.s, 4 H,
2 NH2); 13.43, 13.50, 13.54, 13.59 (all s, 2 H, 2 OH). 13C NMR,
δ: 18.9 (t, CH2, 1J = 127.0 Hz); 36.3 (q, 2 NMe, 1J = 136.0 Hz);
86.1, 92.4 (C(4а), C(4а´), C(7)); 128.4 (d, оꢀCH, 2 Ph, mꢀCH,
All of the prepared compounds were poorly soluble in organic
solvents and were isolated in analytically pure form without
recrystallization.
4ꢀAminoꢀ7ꢀhydroxyꢀ2ꢀphenylꢀ6ꢀphenylaminopyrido[4,3ꢀd]ꢀ
pyrimidineꢀ5(6H)ꢀone (4). A mixture of diester 1 (0.165 g,
0.5 mmol) and phenylhydrazine (0.50 mL, 5 mmol) in pꢀxylene
(4 mL) was refluxed for 12 h and cooled to 20 °C, and the
precipitate was filtered off and washed with petroleum ether to
give 0.047 g (27%) of compound 4, m.p. > 350 °C. Found (%):
C, 65.75; H, 4.23; N, 20.03. C19H15N5O2. Calculated (%):
C, 66.08; H, 4.38; N, 20.28. MS, m/z (Irel (%)): 345 [M]+ (45),
254 [M – PhN]+ (83), 238 [M – PhNHNH]+ (29), 211
[M – PhNHNCO]+ (41), 104 [PhC=NH]+ (50), 93 (100). IR,
ν/cm–1: 3312 (NH), 3200—3000 (NH, CH), 1680 (CO), 1604,
1588, 1512. 1H NMR, δ: 5.42 (s, 1 H, H(8)); 6.57 (d, 2 H, оꢀH,
PhN, J = 7.5 Hz); 6.71 (t, 1 H, pꢀH, PhN, J = 7.5 Hz); 7.12 (t,
2 H, mꢀH, PhN, J = 7.5 Hz); 7.65 (m, 3 H, Ph); 8.11 (m, 2 H,
Ph); 8.13 (br.s, 1 H, NH); 8.63, 9.30 (both br.s, 1 H each,
NH2); 12.22 (br.s, 1 H, OH).
6ꢀAminoꢀ4ꢀhydrazinoꢀ7ꢀhydroxyꢀ2ꢀphenylpyrido[4,3ꢀd]ꢀ
pyrimidinꢀ5(6H)ꢀone (7). A mixture of diester 1 (0.197 g,
0.6 mmol) and hydrazine hydrate (1.1 mL, 21 mmol) in BuOH
(4 mL) was refluxed for 3 h, butanol and excess hydrazine were
removed in vacuo, MeOH (10 mL) was added to the residue, the
mixture was heated to boiling, and the insoluble precipitate was
filtered off to give 0.11 g (67%) of compound 7, m.p. > 350 °C.
Found (%): C, 54.72; H, 3.90; N, 29.14. C13H12N6O2. Calculꢀ
ated (%): C, 54.92; H, 4.25; N, 29.56. MS, m/z (Irel (%)): 284
[M]+ (100), 269 [M – NH]+ (75), 254 [M – NH2N]+ (89), 253
[M – NH2NH]+ (94), 238 [M – NH2N – NH2]+ (56), 104
[PhC=NH]+ (89). IR, ν/cm–1: 3324 (NH), 3232 (NH), 1666
(CO), 1624, 1608, 1560, 1540. 1H NMR, δ: 5.00—5.80 (br.s,
4 H, 2 NH2); 5.45 (s, 1 H, H(8)); 7.62 (m, 3 H, Ph); 8.26 (m,
2 H, Ph); 10.88 (br.s, 1 H, NH).
1
2 Ph, J = 162.8 Hz); 131.3 (ipsoꢀC, 2 Ph); 132.6 (d, pꢀCH,
1
2 Ph, J = 164.6 Hz); 140.5, 142.3 (C(7´), C(8)); 157.2, 157.9,
159.4, 161.3, 161.7 (C(2), C(2´), C(4), C(4´), C(8а), C(8а´));
182.5 (C(5), C(5´)).
4ꢀAminoꢀ8ꢀ(6ꢀacetylimidoꢀ4ꢀaminoꢀ6ꢀmethylꢀ5ꢀoxoꢀ2ꢀphenylꢀ
5,6,7,8ꢀtetrahydropyrido[4,3ꢀd]pyrimidinꢀ7ꢀylidene)ꢀ7,7ꢀdihydroxyꢀ6ꢀ
methylꢀ5ꢀoxoꢀ2ꢀphenylꢀ5,6,7,8ꢀtetrahydropyrido[4,3ꢀd]ꢀ
pyrimidine 6ꢀacetylimide (18). A mixture of compound 9
(0.142 g, 0.5 mmol) and acetic anhydride (1.6 mL, 17 mmol) in
toluene (10 mL) was refluxed for 4 h and cooled to 20 °C, and
the precipitate was filtered off and washed with petroleum ether
to give 0.14 g (87%) of compound 18, m.p. > 350 °C. Found
(%): C, 58.66; H, 4.35; N, 21.24. C32H30N10O6. Calculated
(%): C, 59.07; H, 4.65; N, 21.53. MS MALDI, m/z: 651
[M + H]+. IR, ν/cm–1: 3356, 3288, 3212, 1668 (CO), 1628,
1568, 1560, 1516. 1H NMR, δ: 1.65, 1.91 (both br.s, 6 H,
2 COМе); 2.97 (br.s, 6 H, 2 NMe); 3.77, 3.80, 3.82 (all s, 2 H,
CH2); 7.70 (m, 6 H, mꢀH, pꢀH, 2 Ph); 8.35 (m, 4 H, оꢀH, 2 Ph);
8.82, 8.98, 9.38 (all br.s, 4 H, 2 NH2); 10.21, 13.10 (both
br.s, 2 H, 2 OH). 13C NMR, δ: 18.9 (CH2); 19.3 (q, COМе,
1
1J = 130 Hz); 20.2 (q, COМе, J = 129 Hz); 33.5 (q, 2 NMe,
6ꢀAcetylaminoꢀ4ꢀ(2ꢀacetylhydrazino)ꢀ7ꢀhydroxyꢀ2ꢀphenylꢀ
pyrido[4,3ꢀd]pyrimidinꢀ5(6H)ꢀone (8). A mixture of pyridoꢀ
pyrimidinone 7 (0.142 g, 0.5 mmol) and acetic anhydride
(0.20 mL, 2.1 mmol) in anhydrous benzene (5 mL) was refluxed
for 2 h and cooled to 20 °C, the precipitate was filtered off and
washed with petroleum ether to give 0.14 g (77%) of compound
8, m.p. 336—340 °C (dec.). Found (%): C, 55.12; H, 4.21; N,
1J = 146.5 Hz); 86.3, 86.7, 92.0, 92.3, 92.7 (C(4а), C(4а´),
C(7)); 128.5 (d, оꢀCH, 2 Ph, mꢀCH, 2 Ph, 1J = 162.5 Hz); 131.4
1
(ipsoꢀC, 2 Ph); 132.9 (d, pꢀCH, 2 Ph, J = 166.6 Hz); 145.7,
146.5 (C(7´), C(8)); 158.6, 158.9, 160.2, 160.7, 161.8, 163.7,
164.2, 167.8, 170.9 (C(2), C(2´), C(4), C(4´), C(5), C(5´),
C(8а), C(8а´), 2 COМе).

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008
Komkov et al.
5. A. V. Komkov, V. A. Dorokhov, Izv. Akad. Nauk. Ser. Khim.,
2007, 2212 [Russ. Chem. Bull., Int. Ed., 2007, 56, 2290].
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1998, 47, 871.
The authors are grateful to A. A. Stomakhin (V. A.
Engelgardt Institute of Molecular Biology of the RAS)
for recording the MALDI mass spectra.
This work was supported by the Russian Academy
of Sciences (Fundamental Research Program of the
Presidium of the RAS “Development of the Strategy
of Organic Synthesis and Design of Compounds with
Valuable Applied Properties”).
9. W. F. Whitmore, R. C. Cooney, J. Am. Chem. Soc., 1944, 66,
1237.
10. A. Monge, J. A. Palop, T. Goni, A. Martinez, E. Fernandezꢀ
Alvares, J. Heterocycl. Chem., 1984, 21, 381.
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Received April 4, 2008;
in revised form June 10, 2008