Pyrano[4,3-d]pyrimidinium salts 5. Synthesis of 7-aryl-1,3-dimethyl-2,4- dioxo-1H,3H-pyrano[4,3-d]pyrimidinium salts and their reactions with nucleophiles

Article abstract of DOI:10.1007/s11172-012-0090-x

7-Arylpyrano[4,3-d]pyrimidinium salts were synthesized starting from 1,3,6-trimethyluracil. In the reactions with N-nucleophiles, these salts were found to undergo recyclization of the pyrylium ring, whereas the addition of C- and O-nucleophiles occurs at

Full text of DOI:10.1007/s11172-012-0090-x

Russian Chemical Bulletin, International Edition, Vol. 61, No. 3, pp. 623—630, March, 2012
623
Pyrano[4,3ꢀd]pyrimidinium salts
5.* Synthesis of 7ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,3Hꢀpyrano[4,3ꢀd]pyrimidinium salts
and their reactions with nucleophiles
I. A. Gavrilenko, V. V. Kostrub, and E. B. Tsupak
Department of Chemistry, Southern Federal University,
7 ul. Zorge, 344090 RostovꢀonꢀDon, Russian Federation.
Eꢀmail: gavanja@yandex.ru
7ꢀArylpyrano[4,3ꢀd]pyrimidinium salts were synthesized starting from 1,3,6ꢀtrimethylurꢀ
acil. In the reactions with Nꢀnucleophiles, these salts were found to undergo recyclization of
the pyrylium ring, whereas the addition of Cꢀ and Oꢀnucleophiles occurs at free position 5 of
the system.
Key words: 6ꢀ(2ꢀarylethenyl)ꢀ1,3ꢀdimethylpyrimidineꢀ2,4(1H,3H)ꢀdione, 6ꢀ(2ꢀarylꢀ
ethenyl)ꢀ5ꢀformylꢀ1,3ꢀdimethylpyrimidineꢀ2,4(1H,3H)ꢀdione, 7ꢀarylpyrano[4,3ꢀd]pyrimidꢀ
inium salts, recyclization, pyrido[4,3ꢀd]pyrimidineꢀ2,4(1H,3H)ꢀdione, pyrido[4,3ꢀd]pyrꢀ
imidinium salts, pyrano[4,3ꢀd]pyrimidine.
Previously, we have reported on the synthesis of
5,7ꢀdiarylꢀ and 5ꢀarylpyrano[4,3ꢀd]pyrimidinium salts2
(1 and 2, respectively) and their reactions with nucleoꢀ
philes.1—5 It was found1,4 that, in spite of the presence of
a substituent, the nucleophilic attack occurs predominantly
at position 5. Hence, it was of interest to develop methods
for the synthesis of pyrano[4,3ꢀd]pyrimidinium salts conꢀ
taining free position 5 and investigate their reactivity,
because it would be expected that nucleophilic recyclizaꢀ
tion reactions are not the only type of transformations of
these salts.
ents at position 7 seemed to be more suitable objects. The
purpose of the present study was to synthesize these comꢀ
pounds and investigate their reactions with Nꢀ, Cꢀ, and
Oꢀnucleophiles.
According to the results of the previous studies,2,3 it is
convenient to synthesize 7ꢀarylpyrano[4,3ꢀd]pyrimidinium
salts 4 using 6ꢀ(2ꢀarylethenyl)ꢀ5ꢀformylꢀ1,3ꢀdimethylꢀ
pyrimidineꢀ2,4(1H,3H)ꢀdiones (5) as the starting comꢀ
pounds. However, a known method7 for their synthesis
is laborious and not suited for the preparation of these
compounds in amounts sufficient for their further inꢀ
vestigations. We failed to functionalize the 6ꢀmethyl
group in 5ꢀformylꢀ1,3,6ꢀtrimethyluracil (6) using methꢀ
ods developed2,3 for 5ꢀaroylꢀ1,3,6ꢀtrimethyluracils 7
(Scheme 1).
Hence, we applied another synthetic approach involvꢀ
ing the condensation of 1,3,6ꢀtrimethyluracil 8 with
aromatic aldehydes8 followed by the formylation of the
condensation products. 6ꢀ(2ꢀArylethenyl)ꢀ1,3ꢀdimethylꢀ
pyrimidineꢀ2,4(1H,3H)ꢀdiones 9 and 6ꢀ(2ꢀarylꢀ2ꢀhydrꢀ
oxyethyl)ꢀ1,3ꢀdimethylpyrimidineꢀ2,4(1H,3H)ꢀdiones 10
(Scheme 2) were synthesized in satisfactory yields from
a mixture of the corresponding benzaldehyde and 1,3,6ꢀtriꢀ
In attempting to synthesize the 1,3ꢀdimethylꢀ2,4ꢀdiꢀ
oxoꢀ1H,3Hꢀpyrano[4,3ꢀd]pyrimidinium cation (3) conꢀ
taining the unsubstituted pyrylium ring, it appeared that
this cation is stable only in solution in the presence of
a large excess of an acid.6 We failed to isolate this comꢀ
pound in the crystalline state. These obstacles substantialꢀ
ly narrowed the range of nucleophiles used for investigatꢀ
ing the reactivity of the cation and the direction of the
nucleophilic attack.
7ꢀArylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,2H,3H,4Hꢀpyrꢀ
ano[4,3ꢀd]pyrimidinium salts (4) stabilized by substituꢀ
* For Part 4, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 620—627, March, 2012.
1066ꢀ5285/12/6103ꢀ623 © 2012 Springer Science+Business Media, Inc.

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Gavrilenko et al.
Scheme 1
methyluracil 8 after longꢀterm stirring in a 10% aqueous
solution of KOH at ~20 C.8
The structures of compounds 9 and 10 were suggested
based on 1H NMR and IR spectroscopic data. The NMR
spectra of styrenes 9 show doublets of CH protons of the
ethenyl group at  6.7—7.1 (the coupling constant is
15.8 Hz), whereas the spectra of compounds 10 have sigꢀ
nals of methylene groups as two doublets of doublets of
the AB type ( 2.7—3.1), multiplets of CH protons
( 4.7—5.0), and doublets of protons of the hydroxy groups
( 5.60—5.96, the coupling constant is 4.2—4.6 Hz), which
disappear after deuteration. The presence of the hydroxy
group in pyrimidines 10 is confirmed also by IR spectroꢀ
scopy (an absorption band at 3270—3400 cm–1).
It appeared that the reaction of 1,3,6ꢀtrimethyluracil 8
with pꢀbromoꢀ and pꢀnitrobenzaldehydes stops in the step
of the addition of the carbanion to the carbonyl group
without elimination of a water molecule, whereas the adꢀ
dition products generated in the reactions with benzꢀ
aldehyde and pꢀmethoxybenzaldehyde loose a water molꢀ
ecule and are transformed into unsaturated compounds 9.
The target 6ꢀethenylꢀ5ꢀformylꢀ1,3ꢀdimethyluracils 5
were synthesized in good yields by the Vilsmeyer—Haack
formylation of alkenes 9 (Scheme 3). A similar result was
obtained also in the Vilsmeyer—Haack reaction of carbinol
compounds 10, which readily undergo dehydration under
acidic conditions of the formylation reaction.
i. Morpholine.
Scheme 3
Scheme 2
5: R = H (a), OMe (b), Br (c), NO2 (d)
1
The H NMR spectroscopic data provide unambiguꢀ
ous evidence that the formyl group is introduced at posiꢀ
tion 5 of the uracil ring, because we observe the disappearꢀ
ance of the signal of the proton H(5) ( 5.60—5.94) and
the appearance of the signal of the aldehyde proton
( 10.09—10.20). In addition, a third absorption band
belonging to the carbonyl group (1711—1720 cm–1) apꢀ
pears in the IR spectra.
The treatment of 6ꢀethenylꢀ5ꢀformylꢀ1,3ꢀdimethylꢀ
uracils 5 with bromine in acetic acid affords the target
7ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,2H,3H,4Hꢀpyranoꢀ
[4,3ꢀd]pyrimidinium bromides 4 (Scheme 4).
We believe that the mechanism of the closure of the
pyrylium ring in the reaction of bromine with compounds
5 involves the formation of the cyclic bromonium cation.
9: R = H (a), OMe (b); 10: R = Br (a), NO2 (b)

7ꢀArylpyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
625
Scheme 4
erties of pyrylium salts. Thus, they undergo recyclization
to form pyrido[4,3ꢀd]pyrimidines 11 and pyrido[4,3ꢀd]ꢀ
pyrimidinium salts 12, respectively (Scheme 6).
The structures of compounds 11 and 12 were conꢀ
firmed by 1H NMR and IR spectroscopy.
Previously,3 we have reported that in the reactions with
hydrazine, 5,7ꢀdiarylpyrano[4,3ꢀd]pyrimidinium bromides 1
can be transformed into either diazepine derivatives 13 or
pyridinium salts 14 depending on the duration of the heatꢀ
ing and the amount of the nucleophile used (Scheme 7).
The reaction of 7ꢀarylpyrano[4,3ꢀd]pyrimidinium
bromides 4 with hydrazine, as opposed to 5,7ꢀdiarylꢀ
pyrimidopyrylium salts 1, resulted in the formation of
Nꢀaminopyrimidopyridinium salts 15 regardless of the reꢀ
action conditions (Scheme 8).
R = H (a), OMe (b), Br (c), NO2 (d)
The subsequent transfer of an electron pair from the aldeꢀ
hyde group to the C atom of the bromonium cation leads
to the ring opening with the resulting formation of the
pyran ring, which undergoes aromatization to the pyrꢀ
ylium ring through the elimination of the HBr molecule
(Scheme 5).
In the 1H NMR spectra of compounds 15a—c, the
Nꢀamino group appears as a singlet at  7.6—7.7, which
disappears after deuteration. The IR spectra show characꢀ
teristic absorption maxima of the amino group in the reꢀ
1
The H NMR spectra of bromides 4 show signals of
protons of the aryl substituents ( 7.14—8.50), singlets of
methyl protons of the uracil ring ( 3.50—3.93), and sinꢀ
glets of the H atoms of the C(5)H ( 9.50—9.72) and
C(8)H ( 7.90—8.28) groups. The IR spectra have abꢀ
sorption maxima of the carbonyl groups in the region of
1629—1698 cm–1. The mass spectrum of compound 4a
contains a molecular ion peak and fragment peaks at
m/z 212 [M – NMe – CO]+, 105 [PhCO]+, and 77 [Ph]+.
When studying the reactions of 7ꢀarylpyrano[4,3ꢀd]ꢀ
pyrimidinium salts 4 with ammonium acetate and aroꢀ
matic amines, we found that these salts exhibit usual propꢀ
gion of 3240—3480 cm–1
.
Therefore, we found that the formation of diazepines 13
observed previously3 occurs exclusively in the presence of
two bulky substituents simultaneously at positions 5 and 7
of the pyrano[4,3ꢀd]pyrimidinium system, i.e., this is asꢀ
sociated with steric factors. In monosubstituted pyrylium
salts 2 and 4, the steric hindrance is less significant and,
consequently, only thermodynamically more stable pyridꢀ
inium salts are formed, which is consistent with the literaꢀ
ture data9—11 for benzo[c]ꢀ and hetero[c]pyrylium salts.
Scheme 5
Scheme 6
11: R = H (a), OMe (b), Br (c), NO2 (d)
12: R = H (a, b), OMe (c, d), Br (e, f); Ar = Ph (a, c, e), 4ꢀBrC6H4 (b, d, f)

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Gavrilenko et al.
212 [M – CH2NO2 – CO – NMe]+, 105 [PhCO]+, and
77 [Ph]+.
Scheme 7
In the reactions with Oꢀnucleophiles (water and alcoꢀ
hols), salts 1 and 2 undergo the opening of the pyrylium
ring to form 1,5ꢀdicarbonyl derivatives12 17, whereas
7ꢀarylꢀsubstituted salts 4 are transformed into pyranoꢀ
pyrimidines 18 and 19 as a result of the addition of the
nucleophile at the C(5) atom (Scheme 10). This property
of system 4 compared to pyrylium and benzo[c]pyrylium
salts is quite unusual, because in the chemistry of pyrꢀ
ylium salts, the reactions are often performed in alcohols
as the solvents;13,14 however, data on such transformaꢀ
tions are scarce and random.15,16
Scheme 10
i. NH2H2, 1 min; ii. NH2NH2, 30 min.
Scheme 8
R = H (a), OMe (b), Br (c)
The reaction of pyrimidopyrylium bromide 4a with
nitromethane in the presence of triethylamine proceeds
similarly to the reactions of 5,7ꢀdisubstituted salts4 1 and
gives pyrano[4,3ꢀd]pyrimidine 16 (Scheme 9).
Scheme 9
17: R = Ar, H
19: R´ = Me (a), Et (b), Pr (c)
The 1H NMR spectra of pyrans 18 and 19 show signals
of protons of the phenyl substituent ( 7.38—7.84) and the
methyl groups of the uracil ring ( 3.2—3.5), as well as
signals of protons of the C(5)H ( 6.33—6.75) and C(8)H
1
( 6.30—6.45) groups. The H NMR spectrum of comꢀ
The 1H NMR spectrum of compound 16 has an
ABXꢀtype spin system formed by the C(5)H proton at
 6.4 (X part) and the protons of the methylene unit at
 4.5—4.9 (AB part), respectively. The spectrum also has
signals of the phenyl protons ( 7.4—7.8) and a singlet of
the proton of the C(8)H group ( 6.2). The mass spectrum
of pyran 16 contains a molecular ion peak and fragment
peaks at m/z 282 [M – HNO2]+, 269 [M – CH2NO2]+,
pound 18 has a signal of the OH proton ( 7.5), which
disappears after deuteration; the spectra of compounds 19
have signals of protons of the corresponding alcohol subꢀ
stituents. The mass spectrum of pyranopyrimidine 19b
contains a molecular ion peak and fragment peaks at m/z
269 [M – OEt]+, 105 [PhCO]+, and 77 [Ph]+.
Attempts to detect the products of the initial addition
of primary amines 20, similar to pyrans 18 and 19, to the

7ꢀArylpyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
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1
C, 69.41; H, 5.82. H NMR (CDCl3), : 3.36 and 3.47 (both s,
3 H each, N(1)Me, N(3)Me); 5.94 (s, 1 H, H(5)); 6.78 and 7.13
(both d, 1 H each, C(6)CH, C(6)CHCH, J = 15.8 Hz);
7.29—7.57 (m, 5 H, Ar). MS, m/z (Irel (%)): 242 [M]+ (88), 225
[M – OH]+ (65), 184 [M – NMe – CO – H]+ (55), 156
[M – 2 NMe – CO]+ (77), 155 [M – 2 NMe – CO – H]+ (100),
144 [M – NMe – 2 CO – CH]+ (29), 128 [M – 2 NMe –
– 2 CO]+ (63), 103 [PhCHCH]+ (26), 102 [PhCCH]+ (23), 77
[Ph]+ (33). IR, /cm–1: 1647, 1687 (C=O).
pyrylium ring failed. Thus, only pyridinium salts 12 were
obtained (Scheme 11) regardless of the reaction condiꢀ
tions used (the reaction temperature and time were varied).
Scheme 11
6ꢀ[2ꢀ(4ꢀMethoxyphenyl)ethenyl]ꢀ1,3ꢀdimethylpyrimidineꢀ
2,4(1H,3H)ꢀdione (9b). The stirring was performed for 112 h,
recrystallization from EtOH. The yield was 1.82 g (33%), colorꢀ
less crystals, which undergo decomposition at temperatures above
245 C (EtOH). Found (%): C, 66.01; H, 5.75. C15H16N2O3.
Calculated (%): C, 66.16; H, 5.92. 1H NMR (CDCl3), : 3.34
and 3.45 (both s, 3 H each, N(1)Me, N(3)Me); 3.82 (s, 3 H,
OMe); 5.90 (s, 1 H, H(5)); 6.62 and 7.07 (both d, 1 H each,
C(6)CH, C(6)CHCH, J = 15.8 Hz); 6.90 and 7.42 (both d, 2 H
each, ArH(3), ArH(5), ArH(2), ArH(6), J = 8.8 Hz). IR, /cm–1
:
1644, 1685 (C=O).
6ꢀ[2ꢀ(4ꢀBromophenyl)ꢀ2ꢀhydroxyethyl]ꢀ1,3ꢀdimethylpyrimidꢀ
ineꢀ2,4(1H,3H)ꢀdione (10a). The stirring was performed for 16 h.
The yield was 3.76 g (55%), colorless crystals, m.p. 148—151 C
(H2O). Found (%): C, 49.83; H, 4.27; Br, 23.72. C14H15BrN2O3.
Calculated (%): C, 49.58; H, 4.46; Br, 23.56. 1H NMR (DMSOꢀd6),
: 2.72—2.90 (m, 2 H, CH2); 3.12 and 3.35 (both s, 3 H each,
N(1)Me, N(3)Me); 4.77—4.90 (m, 1 H, CHOH); 5.60 (s, 1 H,
H(5)); 5.70 (d, 1 H, OH, J = 4.2 Hz); 7.36 and 7.52 (both d, 2 H
To summarize, we synthesized 7ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀ
dioxoꢀ1H,2H,3H,4Hꢀpyrano[4,3ꢀd]pyrimidinium salts 4.
It was shown that the reactions of these salts with amꢀ
monia, primary amines, and hydrazine result in the reꢀ
cyclization of the pyrylium ring. The reactions of pyrꢀ
ano[4,3ꢀd]pyrimidinium salts 4 with nitromethane, waꢀ
ter, and alcohols involve the regioselective addition of
nucleophiles at position 5 of the starting system, with the
pyran ring remaining intact.
each, ArH(3), ArH(5), ArH(2), ArH(6), J = 8.4 Hz). IR, /cm–1
:
1647, 1690 (C=O); 3402 br (O—H).
6ꢀ[2ꢀHydroxyꢀ2ꢀ(4ꢀnitrophenyl)ethyl]ꢀ1,3ꢀdimethylpyrimidꢀ
ineꢀ2,4(1H,3H)ꢀdione (10b). The stirring was performed for 16 h.
The yield was 3.84 g (63%), colorless crystals, m.p. 147—150 C
(H2O). Found (%): C, 55.31; H, 4.98. C14H15N3O5. Calculatꢀ
ed (%): C, 55.08; H, 4.95. 1H NMR (DMSOꢀd6), : 2.77—3.02
(m, 2 H, CH2); 3.16 and 3.40 (both s, 3 H each, N(1)Me,
N(3)Me); 4.77—5.00 (m, 1 H, CHOH); 5.66 (s, 1 H, H(5)); 5.96
(d, 1 H, OH, J = 4.6 Hz); 7.72 and 8.23 (both d, 2 H each,
Experimental
The IR spectra were measured on a Varian FTꢀIR 1000
ArH(2), ArH(6), ArH(3), ArH(5), J = 8.6 Hz). IR, /cm–1
:
1640, 1696 (C=O); 3269 br (O—H).
1
spectrophotometer. The H NMR spectra were recorded on an
Avance DPXꢀ250 instrument (Bruker) in CDCl3, DMSOꢀd6,
and CDCl3—CF3COOH using HMDS as the internal standard.
The electron impact ionization mass spectra were obtained on
a Kratos instrument using a direct inlet system (ionization enerꢀ
gy was 70 eV, controlling voltage was 1.75 kV). The melting
points were measured in glass tubes using a PTP instrument and
are uncorrected. The starting 1,3,6ꢀtrimethyluracil 8 was synꢀ
thesized according to a procedure described previously.17 The
solvents were purified according to standard procedures.18
6ꢀ(2ꢀArylethenyl)ꢀ1,3ꢀdimethylpyrimidineꢀ2,4(1H,3H)ꢀdiꢀ
ones 9a,b and 6ꢀ(2ꢀarylꢀ2ꢀhydroxyethyl)ꢀ1,3ꢀdimethylpyrimidineꢀ
2,4(1H,3H)ꢀdiones 10a,b (general procedure). A mixture of
1,3,6ꢀtrimethyluracil 8 (0.02 mol) and aromatic aldehyde
(0.022 mol) in 10% KOH (30 mL) was stirred at ~20 C. The
precipitate that formed was filtered off, washed with EtOH, and
dried at 100 C.
5ꢀFormylꢀ1,3ꢀdimethylꢀ6ꢀ(2ꢀphenylethenyl)pyrimidineꢀ2,4ꢀ
(1H,3H)ꢀdione (5a). Phosphorus oxychloride (0.93 mL, 1.533 g,
0.01 mol) was added dropwise to a solution of compound 9a
(2.42 g, 0.01 mol) in DMF (4 mL). The reaction mixture was
heated with stirring to 80 C, kept at this temperature for a few
minutes, cooled, and neutralized with a solution of Na2CO3
(3.75 g) in H2O (60 mL). The precipitate that formed was filꢀ
tered off, recrystallized from EtOH, and dried at 100 C. The
yield was 2.39 g (89%), paleꢀyellow crystals, m.p. 150—152 C
(EtOH). Found (%): C, 66.39; H, 5.08. C15H14N2O3. Calculatꢀ
1
ed (%): C, 66.66; H, 5.22. H NMR (CDCl3), : 3.40 and 3.55
(both s, 3 H each, N(1)Me, N(3)Me); 6.89 and 7.17 (both d, 1 H
each, C(6)CH, C(6)CHCH, J = 16.5 Hz); 7.36—7.47 (m, 3 H,
ArH(3), ArH(4), ArH(5)); 7.50—7.61 (m, 2 H, ArH(2), ArH(6));
10.11 (s, 1 H, CHO). MS, m/z (Irel (%)): 270 [M]+ (100), 241
[M – CHO]+ (48), 184 [M – 2 NMe – CO]+ (25), 156 [M –
– 2 NMe – 2 CO]+ (25), 103 [PhCHCH]+ (12), 102 [PhCCH]+
(13), 77 [Ph]+ (28). IR, /cm–1: 1640 br, 1711 (C=O).
5ꢀFormylꢀ6ꢀ[2ꢀ(4ꢀmethoxyphenyl)ethenyl]ꢀ1,3ꢀdimethylꢀ
pyrimidineꢀ2,4(1H,3H)ꢀdione (5b) was synthesized analogously
to compound 5a starting from compound 9b (2.72 g, 0.01 mol),
1,3ꢀDimethylꢀ6ꢀ(2ꢀphenylethenyl)pyrimidineꢀ2,4(1H,3H)ꢀdiꢀ
one (9a). The stirring was performed for 24 h, recrystallization
from EtOH. The yield was 2.77 g (57%), colorless crystals, which
undergo decomposition at temperatures above 195 C (EtOH).
Found (%): C, 69.54; H, 5.91. C14H14N2O2. Calculated (%):

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Gavrilenko et al.
DMF (4 mL), and POCl3 (0.93 mL, 1.533 g, 0.01 mol). The
yield was 2.74 g (91%), yellow crystals, m.p. 177—179 C (EtOH).
Found (%): C, 64.41; H, 5.51. C16H16N2O4. Calculated (%):
C, 63.99; H, 5.37. H NMR (CDCl3), : 3.42 and 3.58 (both s,
3 H each, N(1)Me, N(3)Me); 3.86 (s, 3 H, OMe), 6.84—6.99
OMe); 7.14 and 8.20 (both d, 2 H each, ArH(3), ArH(5), ArH(2),
ArH(6), J = 9.1 Hz); 7.90, 9.50 (both s, 1 H each, H(8), H(5)).
IR, /cm–1: 1635, 1687 (C=O).
1
7ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetraꢀ
hydropyrano[4,3ꢀd]pyrimidinium bromide (4c). The yield was 2.32 g
(54%), yellow crystals, m.p. 218—221 C (AcOH). Found (%):
C, 42.46; H, 2.71; Br, 37.04. C15H12Br2N2O3. Calculated (%):
C, 42.09; H, 2.83; Br, 37.33. 1H NMR (CDCl3—CF3COOH), :
3.51 and 3.89 (both s, 3 H each, N(3)Me, N(1)Me); 7.81 and
8.04 (both d, 2 H each, ArH(3), ArH(5), ArH(2), ArH(6),
J = 8.8 Hz); 8.09 and 9.61 (both s, 1 H each, H(8), H(5)). IR,
/cm–1: 1629, 1690 (C=O).
1,3ꢀDimethylꢀ7ꢀ(4ꢀnitrophenyl)ꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetraꢀ
hydropyrano[4,3ꢀd]pyrimidinium bromide (4d). The yield was 2.48 g
(63%), yellow crystals, m.p. 202—204 C (AcOH). Found (%):
C, 45.96; H, 3.01; Br, 20.57. C15H12BrN3O5. Calculated (%):
C, 45.71; H, 3.07; Br, 20.27. 1H NMR (CDCl3—CF3COOH), :
3.52 and 3.93 (both s, 3 H each, N(3)Me, N(1)Me); 8.28 (s, 1 H,
H(8)); 8.40 and 8.46 (both d, 2 H each, Ar, J = 9.3 Hz); 9.72
(s, 1 H, H(5)). IR, /cm–1: 1647, 1698 (C=O).
7ꢀArylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetrahydropyridoꢀ
[4,3ꢀd]pyrimidines 11a—d (general procedure). Ammonium acetꢀ
ate (116 mg, 1.5 mmol) was added to a mixture of bromide 4
(0.5 mmol) and AcOH (2 mL). The reaction mixture was reꢀ
fluxed for 20 min. Pyrimidopyridine hydrobromides 11 that preꢀ
cipitated upon cooling were neutralized with an aqueous Na2CO3
solution and extracted with chloroform. The chloroform layer
was concentrated, and the residue was dried at 100 C.
1,3ꢀDimethylꢀ2,4ꢀdioxoꢀ7ꢀphenylꢀ1,2,3,4ꢀtetrahydropyridoꢀ
[4,3ꢀd]pyrimidine (11a). The yield was 110 mg (82%), colorless
crystals, m.p. 247—250 C (CHCl3). Found (%): C, 67.48; H, 4.72.
C15H13N3O2. Calculated (%): C, 67.41; H, 4.90. 1H NMR
(CDCl3), : 3.47 and 3.64 (both s, 3 H each, N(3)Me, N(1)Me);
7.38 (s, 1 H, H(8)); 7.44—7.56 (m, 3 H, ArH(3), ArH(4),
ArH(5)); 7.97—8.08 (m, 2 H, ArH(2), ArH(6)); 9.33 (s, 1 H,
H(5)). IR, /cm–1: 1652, 1704 (C=O).
(d + d, 3 H, C(6)CH, ArH(3), ArH(5), JCH—CH = 16.3 Hz, JAr
=
= 8.8 Hz); 7.07 (d, 1 H, C(6)CHCH, J = 16.3 Hz); 7.53 (d, 2 H,
ArH(2), ArH(6), J = 8.8 Hz); 10.09 (s, 1 H, CHO). IR, /cm–1
:
1626, 1675, 1716 (C=O).
6ꢀ[2ꢀ(4ꢀBromophenyl)ethenyl]ꢀ5ꢀformylꢀ1,3ꢀdimethylpyrimꢀ
idineꢀ2,4(1H,3H)ꢀdione (5c). Phosphorus oxychloride (1.86 mL,
3.067 g, 0.02 mol) was added dropwise to a solution of comꢀ
pound 10a (3.39 g, 0.01 mol) in DMF (4 mL). The reaction
mixture was heated with stirring to 130—140 C, kept at this
temperature for a few minutes, cooled, and neutralized with a
solution of Na2CO3 (7.5 g) in H2O (70 mL). The precipitate that
formed was filtered off, washed with EtOH, and dried at 100 C.
The yield was 3.40 g (97%), paleꢀyellow crystals, m.p. 173—176 C
(H2O). Found (%): C, 51.18; H, 3.84; Br, 23.07. C15H13BrN2O3.
Calculated (%): C, 51.60; H, 3.75; Br, 22.88. 1H NMR (CDCl3),
: 3.40 and 3.54 (both s, 3 H each, N(1)Me, N(3)Me); 6.82 and
7.17 (both d, 1 H each, C(6)CH, C(6)CHCH, J = 16.5 Hz); 7.41
and 7.54 (both d, 2 H each, ArH(3), ArH(5), ArH(2), ArH(6),
J = 8.5 Hz); 10.12 (s, 1 H, CHO). IR, /cm–1: 1629, 1681,
1720 (C=O).
5ꢀFormylꢀ1,3ꢀdimethylꢀ6ꢀ[2ꢀ(4ꢀnitrophenyl)ethenyl]pyrimidꢀ
ineꢀ2,4(1H,3H)ꢀdione (5d) was synthesized analogously to comꢀ
pound 5c starting from compound 10b (3.05 g, 0.01 mol), DMF
(4 mL), and POCl3 (1.86 mL, 3.067 g, 0.02 mol). The yield was
3 g (95%), yellow crystals, m.p. 169—172 C (H2O). Found (%):
C, 57.28; H, 4.22. C15H13N3O5. Calculated (%): C, 57.14;
H, 4.16. 1H NMR (CDCl3), : 3.45 and 3.58 (both s, 3 H each,
N(1)Me, N(3)Me); 6.92 and 7.35 (both d, 1 H each, C(6)CH,
C(6)CHCH, J = 16.8 Hz); 7.74 and 8.30 (both d, 2 H each,
ArH(2), ArH(6), ArH(3), ArH(5), J = 8.7 Hz); 10.20 (s, 1 H,
CHO). IR, /cm–1: 1632, 1684, 1713 (C=O).
7ꢀArylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetrahydropyranoꢀ
[4,3ꢀd]pyrimidinium bromides 4a—d (general procedure). A soluꢀ
tion of Br2 (0.01 mol) in AcOH (5 mL) was added dropwise with
stirring to a solution of aldehyde 5 (0.01 mol) in AcOH (30 mL)
warmed to 40—50 C. The solution was refluxed for 1 h. The
precipitate that formed upon cooling (if the precipitation did not
occur, AcOEt (30 mL) was added) was filtered off, washed with
AcOH and AcOEt, and dried at 100 C.
7ꢀ(4ꢀMethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetraꢀ
hydropyrido[4,3ꢀd]pyrimidine (11b). The yield was 100 mg (67%),
colorless crystals, m.p. 249—251 C (CHCl3). Found (%):
C, 64.90; H, 4.98. C16H15N3O3. Calculated (%): C, 64.64; H, 5.09.
1H NMR (CDCl3), : 3.46 and 3.63 (both s, 3 H each, N(3)Me,
N(1)Me); 3.88 (s, 3 H, OMe); 7.00 and 8.01 (both d, 2 H each,
ArH(3), ArH(5), ArH(2), ArH(6), J = 8.8 Hz); 7.30 and 9.28
(both s, 1 H each, H(8), H(5)). IR, /cm–1: 1651, 1703 (C=O).
7ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetraꢀ
hydropyrido[4,3ꢀd]pyrimidine (11c). The yield was 131 mg (76%),
colorless crystals, m.p. 279—282 C (CHCl3). Found (%):
C, 52.29; H, 3.62; Br, 22.75. C15H12BrN3O2. Calculated (%):
C, 52.04; H, 3.49; Br, 23.08. 1H NMR (CDCl3), : 3.47 and 3.64
(both s, 3 H each, N(3)Me, N(1)Me); 7.36 (s, 1 H, H(8));
7.63 and 7.92 (both d, 2 H each, ArH(3), ArH(5), ArH(2),
ArH(6), J = 8.6 Hz); 9.32 (s, 1 H, H(5)). IR, /cm–1: 1658,
1706 (C=O).
1,3ꢀDimethylꢀ7ꢀ(4ꢀnitrophenyl)ꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetraꢀ
hydropyrido[4,3ꢀd]pyrimidine (11d). The yield was 148 mg (95%),
yellow crystals, m.p. 296—298 C (CHCl3). Found (%): C, 57.61;
H, 3.99. C15H12N4O4. Calculated (%): C, 57.69; H, 3.87. 1H NMR
(DMSOꢀd6), : 3.32 and 3.64 (both s, 3 H each, N(3)Me,
N(1)Me); 8.05 (s, 1 H, H(8)); 8.39 and 8.56 (both d, 2 H each,
ArH(2), ArH(6), ArH(3), ArH(5), J = 8.9 Hz); 9.18 (s, 1 H,
H(5)). IR, /cm–1: 1658, 1705 (C=O).
1,3ꢀDimethylꢀ2,4ꢀdioxoꢀ7ꢀphenylꢀ1,2,3,4ꢀtetrahydropyranoꢀ
[4,3ꢀd]pyrimidinium bromide (4a). The yield was 2.67 g (76%),
paleꢀpink crystals, m.p. 219—221 C (AcOH). Found (%):
C, 51.48; H, 3.91; Br, 22.63. C15H13BrN2O3. Calculated (%):
C, 51.60; H, 3.75; Br, 22.88. 1H NMR (CDCl3—CF3COOH), :
3.50 and 3.89 (both s, 3 H each, N(3)Me, N(1)Me); 7.61—7.72
(m, 2 H, ArH(3), ArH(5)); 7.77—7.87 (m, 1 H, ArH(4)); 8.06
(s, 1 H, H(8)); 8.13—8.22 (m, 2 H, ArH(2), ArH(6)); 9.63 (s, 1 H,
H(5)). MS, m/z (Irel (%)): 269 [M]+ (100), 212 [M – NMe –
– CO]+ (24), 105 [PhCO]+ (29), 77 [Ph]+ (29). IR, /cm–1
:
1636, 1696 (C=O).
7ꢀ(4ꢀMethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetraꢀ
hydropyrano[4,3ꢀd]pyrimidinium bromide (4b). The yield was 2.85
g (75%), yellow crystals, m.p. 207—209 C (AcOH). Found (%):
C, 51.02; H, 3.79; Br, 21.35. C16H15BrN2O4. Calculated (%):
C, 50.68; H, 3.99; Br, 21.07. 1H NMR (CDCl3—CF3COOH), :
3.50 and 3.86 (both s, 3 H each, N(3)Me, N(1)Me); 3.98 (s, 3 H,

7ꢀArylpyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
629
1,3ꢀDimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetrahydropyrido[4,3ꢀd]ꢀ
pyrimidinium bromides 12a—f (general procedure). A mixture
of salt 4 (0.5 mmol), AcOH (2 mL), and aromatic amine
(0.525 mmol) was refluxed for 15 min. The resulting solution
was concentrated. The residue was triturated with diethyl ether,
filtered, washed with diethyl ether, and dried at 100 C.
1,3ꢀDimethylꢀ6,7ꢀdiphenylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetrahydroꢀ
pyrido[4,3ꢀd]pyrimidinium bromide (12a). The yield was 203 mg
(96%), colorless crystals, which undergo decomposition at temꢀ
peratures above 149 C (diethyl ether). Found (%): C, 59.38;
H, 4.35; Br, 18.97. C21H18BrN3O2. Calculated (%): C, 59.45;
H, 4.28; Br, 18.83. 1H NMR (CDCl3), : 3.43 and 3.82 (both s,
3 H each, N(3)Me, N(1)Me); 7.25—7.46 (m, 6 H, ArH(3), ArH(4),
ArH(5), Ar´H(3), Ar´H(4), Ar´H(5)); 7.56—7.67 (m, 4 H,
ArH(2), ArH(6), Ar´H(2), Ar´H(6)); 7.74 and 9.11 (both s,
1 H each, H(8), H(5)). IR, /cm–1: 1638, 1669 (C=O).
6ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ7ꢀphenylꢀ1,2,3,4ꢀ
tetrahydropyrido[4,3ꢀd]pyrimidinium bromide (12b). The yield
was 240 mg (95%), colorless crystals, which undergo decompoꢀ
sition at temperatures above 167 C (diethyl ether). Found (%):
C, 50.21; H, 3.48; Br, 32.04. C21H17Br2N3O2. Calculated (%):
C, 50.13; H, 3.41; Br, 31.76. 1H NMR (CDCl3), : 3.42 and 3.79
(both s, 3 H each, N(3)Me, N(1)Me); 7.27—7.52 (m, 5 H,
ArH(3), ArH(4), ArH(5), Ar´H(3), Ar´H(5)); 7.54—7.66 (m, 4 H,
ArH(2), ArH(6), Ar´H(2), Ar´H(6)); 7.67 and 9.09 (both s,
1 H each, H(8), H(5)). IR, /cm–1: 1637, 1673 (C=O).
7ꢀ(4ꢀMethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ6ꢀphenylꢀ
1,2,3,4ꢀtetrahydropyrido[4,3ꢀd]pyrimidinium bromide (12c). The
yield was 182 mg (80%), yellow crystals, which undergo deꢀ
composition at temperatures above 149 C (diethyl ether).
Found (%): C, 57.98; H, 4.51; Br, 17.68. C22H20BrN3O3. Calꢀ
culated (%): C, 58.16; H, 4.44; Br, 17.59. 1H NMR (CDCl3), :
3.42 and 3.74 (both s, 3 H each, N(3)Me, N(1)Me); 3.83 (s, 3 H,
OMe); 6.77 and 7.53 (both d, 2 H each, ArH(3), ArH(5), ArH(2),
ArH(6), J = 8.5 Hz); 7.32—7.48 (m, 3 H, Ar´H(3), Ar´H(4),
Ar´H(5)); 7.56—7.67 (m, 2 H, Ar´H(2), Ar´H(6)); 7.75 and 9.06
(both s, 1 H each, H(8), H(5)). IR, /cm–1: 1637, 1675 (C=O).
6ꢀ(4ꢀBromophenyl)ꢀ7ꢀ(4ꢀmethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀ
dioxoꢀ1,2,3,4ꢀtetrahydropyrido[4,3ꢀd]pyrimidinium bromide (12d).
The yield was 244 mg (91%), pale yellow crystals, which underꢀ
go decomposition at temperatures above 151 C (diethyl ether).
Found (%): C, 49.65; H, 3.63; Br, 29.78. C22H19Br2N3O3. Calꢀ
culated (%): C, 49.56; H, 3.59; Br, 29.97. 1H NMR (CDCl3), :
3.41 (s, 3 H, N(3)Me); 3.77 and 3.79 (both s, 6 H each, N(1)Me,
OMe); 6.80 and 7.60 (both d, 2 H each, ArH(3), ArH(5), ArH(2),
ArH(6), J = 8.8 Hz); 7.50 and 7.51 (both d, 2 H each, Ar´,
J = 8.7 Hz); 7.67 and 9.05 (both s, 1 H each, H(8), H(5)). IR,
/cm–1: 1636, 1675 (C=O).
was 270 mg (93%), colorless crystals, which undergo decompoꢀ
sition at temperatures above 189 C (diethyl ether). Found (%):
C, 43.49; H, 2.71; Br, 41.29. C21H16Br3N3O2. Calculated (%):
C, 43.33; H, 2.77; Br, 41.18. 1H NMR (CDCl3), : 3.45 and 3.80
(both s, 3 H each, N(3)Me, N(1)Me); 7.43—7.58 (m, 6 H,
Ar´H(3), Ar´H(5), Ar); 7.64 (d, 2 H, Ar´H(2), Ar´H(6), J = 8.5 Hz);
7.69 and 9.08 (both s, 1 H each, H(8), H(5)). IR, /cm–1: 1637,
1674 (C=O).
6ꢀAminoꢀ7ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetrahydroꢀ
pyrido[4,3ꢀd]pyrimidinium bromides 15a—c (general procedure).
A mixture of salt 4 (0.5 mmol), AcOH (2 mL), and hydrazine
hydrate (0.028 mL, 0.55 mmol) was refluxed for 5 min. The
resulting solution was concentrated. The residue was recrystalꢀ
lized from EtOH, filtered off, washed with EtOH and CHCl3,
and dried at 100 C.
6ꢀAminoꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ7ꢀphenylꢀ1,2,3,4ꢀtetrahyꢀ
dropyrido[4,3ꢀd]pyrimidinium bromide (15a). The yield was 144 mg
(79%), colorless crystals, which undergo decomposition at temꢀ
peratures above 194 C (EtOH). Found (%): C, 49.55; H, 4.23;
Br, 21.77. C15H15BrN4O2. Calculated (%): C, 49.60; H, 4.16;
Br, 22.00. 1H NMR (DMSOꢀd6), : 3.35 and 3.63 (both s,
3 H each, N(3)Me, N(1)Me); 7.58—7.73, 7.66 (m + s, 5 H,
ArH(3), ArH(4), ArH(5), NH2); 7.78—7.89 (m, 2 H, ArH(2),
ArH(6)); 7.95 and 9.46 (both s, 1 H each, H(8), H(5)). IR,
/cm–1: 1630, 1672 (C=O); 3022, 3117 br (NH2).
6ꢀAminoꢀ7ꢀ(4ꢀmethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ
1,2,3,4ꢀtetrahydropyrido[4,3ꢀd]pyrimidinium bromide (15b). The
yield was 151 mg (77%), colorless crystals, which undergo deꢀ
composition at temperatures above 194 C (EtOH). Found (%):
C, 48.72; H, 4.40; Br, 20.49. C16H17BrN4O3. Calculated (%):
C, 48.87; H, 4.36; Br, 20.32. 1H NMR (DMSOꢀd6), : 3.34 and
3.63 (both s, 3 H each, N(3)Me, N(1)Me); 3.88 (s, 3 H, OMe);
7.19 and 7.84 (both d, 2 H each, ArH(3), ArH(5), ArH(2),
ArH(6), J = 8.9 Hz); 7.64 (s, 2 H, NH2); 7.87 and 9.41 (both s,
1 H each, H(8), H(5)). IR, /cm–1: 1630, 1677 (C=O); 3009,
3075 br (NH2).
6ꢀAminoꢀ7ꢀ(4ꢀbromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀ
tetrahydropyrido[4,3ꢀd]pyrimidinium bromide (15c). The yield
was 164 mg (74%), colorless crystals, which undergo decomposiꢀ
tion at temperatures above 195 C (EtOH). Found (%): C, 40.93;
H, 3.25; Br, 36.01. C15H14Br2N4O2. Calculated (%): C, 40.75;
H, 3.19; Br, 36.15. 1H NMR (DMSOꢀd6), : 3.34 and 3.62 (both s,
3 H each, N(3)Me, N(1)Me); 7.64 (s, 2 H, NH2); 7.78 and 7.87
(both d, 2 H each, ArH(3), ArH(5), ArH(2), ArH(6), J = 8.4 Hz);
7.98 and 9.45 (both s, 1 H each, H(8), H(5)). IR, /cm–1: 1628,
1655 (C=O); 3017, 3079 br (NH2).
1,3ꢀDimethylꢀ5ꢀnitromethylꢀ7ꢀphenylꢀ1,5ꢀdihydroꢀ2Hꢀ
pyrano[4,3ꢀd]pyrimidineꢀ2,4(3H)ꢀdione (16). Triethylamine
(0.14 mL, 1 mmol) was added dropwise to a mixture of salt 4a
(175 mg, 0.5 mmol) and nitromethane (2 mL). The reaction
mixture was heated to boiling and then cooled. The precipitate
of the byꢀproduct of the reaction with water was filtered off and
discarded. The filtrate was concentrated. The residue was disꢀ
solved in chloroform, washed three times with water, and conꢀ
centrated. The precipitate was recrystallized from EtOH and
dried at 100 C. The yield was 55 mg (33%), yellow crystals, m.p.
171—173 C (EtOH). Found (%): C, 58.19; H, 4.70. C16H15N3O5.
Calculated (%): C, 58.36; H, 4.59. 1H NMR (CDCl3), : 3.36
and 3.53 (both s, 3 H each, N(1)Me, N(3)Me); 4.46—4.88
(dd + dd, 2 H, CH2, AB part of the ABX system, J = 2.6 Hz,
J = 10.0 Hz, J = 12.5 Hz); 6.17 (s, 1 H, H(8)); 6.35 (dd, 1 H,
7ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ6ꢀphenylꢀ
1,2,3,4ꢀtetrahydropyrido[4,3ꢀd]pyrimidinium bromide (12e). The
yield was 243 mg (97%), colorless crystals, which undergo
decomposition at temperatures above 151 C (diethyl ether).
Found (%): C, 50.03; H, 3.48; Br, 32.01. C21H17Br2N3O2. Calꢀ
culated (%): C, 50.13; H, 3.41; Br, 31.76. 1H NMR (CDCl3), :
3.45 and 3.83 (both s, 3 H each, N(3)Me, N(1)Me); 7.36—7.49
(m, 5 H, Ar´H(3), Ar´H(4), Ar´H(5), ArH(3), ArH(5)); 7.54
(d, 2 H, ArH(2), ArH(6), J = 8.9 Hz); 7.60—7.67 (m, 2 H,
Ar´H(2), Ar´H(6)); 7.77 and 9.11 (both s, 1 H each, H(8), H(5)).
IR, /cm–1: 1636, 1673 (C=O).
6,7ꢀBis(4ꢀbromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀ
tetrahydropyrido[4,3ꢀd]pyrimidinium bromide (12f). The yield

630
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
Gavrilenko et al.
X part of the ABX system, H(5), J = 2.6 Hz, J = 10.0 Hz);
7.36—7.54 (m, 3 H, ArH(3), ArH(4), ArH(5)); 7.60—7.71
(m, 2 H, ArH(2), ArH(6)). MS, m/z (Irel (%)): 329 [M]+ (5), 282
[M – HNO2]+ (32), 269 [M – CH2NO2]+ (100), 212 [M –
– CH2NO2 – CO – NMe]+ (13), 105 [PhCO]+ (47), 77 [Ph]+
(66). IR, /cm–1: 1649, 1690 (C=O).
OCH2CH2); 3.36 and 3.51 (both s, 3 H each, N(1)Me, N(3)Me);
3.73—3.97 (m, 2 H, OCH2); 6.28 and 6.41 (both s, 1 H each,
H(8), H(5)); 7.38—7.51 (m, 3 H, ArH(3), ArH(4), ArH(5));
7.71—7.83 (m, 2 H, ArH(2), ArH(6)). IR, /cm–1: 1651,
1702 (C=O).
5ꢀHydroxyꢀ1,3ꢀdimethylꢀ7ꢀphenylꢀ1,5ꢀdihydroꢀ2Hꢀpyranoꢀ
[4,3ꢀd]pyrimidineꢀ2,4(3H)ꢀdione (18). A mixture of salt 4a
(175 mg, 0.5 mmol), water (4 mL), Na2CO3 (106 mg, 1 mmol),
and chloroform (1 mL) was stirred at ~20 C for 1 h. The preꢀ
cipitate was filtered off, washed with water and chloroform,
and dried at 100 C. The yield was 87 mg (61%), colorless crysꢀ
tals, m.p. 159—162 C (H2O). Found (%): C, 63.09; H, 4.89.
C15H14N2O4. Calculated (%): C, 62.93; H, 4.93. 1H NMR
(DMSOꢀd6), : 3.21 and 3.49 (both s, 3 H each, N(1)Me,
N(3)Me); 6.44 and 6.74 (both s, 1 H each, H(8), H(5)); 7.39—7.65
(m, 4 H, ArH(3), ArH(4), ArH(5), OH); 7.86—8.03 (m, 2 H,
ArH(2), ArH(6)). MS, m/z (Irel (%)): 286 [M]+ (25), 285 [M – H]+
(30), 257 [M – CHO]+ (23), 229 [M – CO – NMe]+ (24), 105
[PhCO]+ (78), 77 [Ph]+ (100). IR, /cm–1: 1648, 1699 (C=O);
3183 br (O—H).
5ꢀAlkoxyꢀ1,3ꢀdimethylꢀ7ꢀphenylꢀ1,5ꢀdihydroꢀ2Hꢀpyranoꢀ
[4,3ꢀd]pyrimidineꢀ2,4(3H)ꢀdiones 19a—c (general procedure).
A mixture of salt 4a (175 mg, 0.5 mmol) and the appropriate
alcohol (4 mL) was refluxed for a few minutes. The precipitate
that formed after cooling of the reaction mixture was filtered off,
washed with the corresponding alcohol, and dried at 100 C
(except for pyran 19c, which was dried in air).
5ꢀMethoxyꢀ1,3ꢀdimethylꢀ7ꢀphenylꢀ1,5ꢀdihydroꢀ2Hꢀpyranoꢀ
[4,3ꢀd]pyrimidineꢀ2,4(3H)ꢀdione (19a). The yield was 138 mg
(92%), colorless crystals, which undergo decomposition at temꢀ
peratures above 168 C (MeOH). Found (%): C, 63.82; H, 5.45.
C16H16N2O4. Calculated (%): C, 63.99; H, 5.37. 1H NMR
(CDCl3), : 3.36 and 3.51 (both s, 3 H each, N(1)Me, N(3)Me);
3.63 (s, 3 H, OMe); 6.30 and 6.33 (both s, 1 H each, H(8),
H(5)); 7.38—7.51 (m, 3 H, ArH(3), ArH(4), ArH(5)), 7.73—7.84
(m, 2 H, ArH(2), ArH(6)). IR, /cm–1: 1665, 1705 (C=O).
5ꢀEthoxyꢀ1,3ꢀdimethylꢀ7ꢀphenylꢀ1,5ꢀdihydroꢀ2Hꢀpyranoꢀ
[4,3ꢀd]pyrimidineꢀ2,4(3H)ꢀdione (19b). The yield was 138 mg
(88%), colorless crystals, which undergo decomposition at temꢀ
peratures above 171 C (EtOH). Found (%): C, 65.14; H, 5.70.
C17H18N2O4. Calculated (%): C, 64.96; H, 5.77. 1H NMR
(CDCl3), : 1.23 (t, 3 H, CH2CH3, J = 7.1 Hz); 3.37 and 3.51
(both s, 3 H each, N(1)Me, N(3)Me); 3.78—4.11 (m, 2 H,
CH2CH3); 6.29 and 6.43 (both s, 1 H each, H(8), H(5)); 7.38—7.51
(m, 3 H, ArH(3), ArH(4), ArH(5)); 7.71—7.82 (m, 2 H, ArH(2),
ArH(6)). MS, m/z (Irel (%)): 314 [M]+ (7), 269 [M – OEt]+
(100), 105 [PhCO]+ (15), 77 [Ph]+ (14). IR, /cm–1: 1668,
1705 (C=O).
References
1. V. V. Kostrub, E. B. Tsupak, A. F. Smol´yakov, Izv. Akad.
Nauk, Ser. Khim., 2009, 1426 [Russ. Chem. Bull., Int. Ed.,
2009, 58, 1469].
2. E. B. Tsupak, M. A. Shevchenko, V. V. Kostrub, Yu. N.
Tkachenko, Izv. Akad. Nauk, Ser. Khim., 2007, 2251 [Russ.
Chem. Bull., Int. Ed., 2007, 56, 2330].
3. V. V. Kostrub, E. B. Tsupak, Yu. N. Tkachenko, M. A.
Shevchenko, Izv. Akad. Nauk, Ser. Khim., 2008, 1720 [Russ.
Chem. Bull., Int. Ed., 2008, 57, 1754].
4. V. V. Kostrub, E. B. Tsupak, Y. V. Nelyubina, Mendeleev
Commun., 2009, 19, 220.
5. V. V. Kostrub, E. B. Tsupak, Izv. Akad. Nauk, Ser. Khim.,
2009, 1422 [Russ. Chem. Bull., Int. Ed., 2009, 58, 1465].
6. E. B. Tsupak, I. A. Gavrilenko, V. V. Kostrub, Mendeleev
Commun., 2009, 19, 157.
7. K. Hirota, T. Asao, I. Sugiyama, S. Senda, Heterocycles,
1981, 15, 289.
8. A. I. Rakhimov, I. E. Kryukov, Zh. Org. Khim., 2000, 792
[Russ. J. Org. Chem. (Engl. Transl.), 2000, 36, 763].
9. G. N. Dorofeenko, E. I. Sadekova, V. M. Goncharova, Khim.
Geterotsikl. Soedin., 1970, 1308 [Chem. Heterocycl. Compd.
(Engl. Transl.), 1970, 6, 1218].
10. J. Körösi, T. Láng, Chem. Ber., 1974, 107, 3883.
11. S. V. Tolkunov, S. Yu. Suikov, M. Yu. Zubritskii, V. I. Duꢀ
lenko, Khim. Geterotsikl. Soedin., 1998, 1137 [Chem. Heteroꢀ
cycl. Compd. (Engl. Transl.), 1998, 8, 1137].
12. V. V. Kostrub, Ph. D. (Chem.) Thesis, Southern Federal
University, RostovꢀonꢀDon, 2009, 126 pp. (in Russian).
13. E. V. Kuznetsov, I. V. Shcherbakova, A. T. Balaban, Adv.
Heterocycl. Chem., 1990, 50, 157.
14. A. T. Balaban, A. Dinculescu, G. N. Dorofeenko, G. W.
Fischer, A. V. Koblic, V. V. Mezheritskii, W. Schroth, Adv.
Heterocycl. Chem., Suppl. 2, Academic Press, New York,
USA, 1982, 434 pp.
15. Z.ꢀL. Hu, W.ꢀJ. Qian, Z.ꢀJ. Yao, S. Wang, S. Wang, Org.
Lett., 2009, 11, 4676.
16. R. Aveta, G. Doddi, N. Insam, F. Stegel, J. Org. Chem.,
1980, 45, 5160.
17. S. Senda, K. Hirota, K. Banno, J. Med. Chem., 1972, 15, 471.
18. A. J. Gordon, R. A. Ford, Chemist´s Companion: A Handbook
of Practical Data, Techniques, and References, Wiley, New
York, 1973, 560 pp.
1,3ꢀDimethylꢀ7ꢀphenylꢀ5ꢀpropoxyꢀ1,5ꢀdihydroꢀ2Hꢀpyranoꢀ
[4,3ꢀd]pyrimidineꢀ2,4(3H)ꢀdione (19c). The yield was 128 mg
(78%), colorless crystals, which undergo decomposition at temꢀ
peratures above 150 C (PrOH). Found (%): C, 65.96; H, 6.07.
C18H20N2O4. Calculated (%): C, 65.84; H, 6.14. 1H NMR
(CDCl3), : 0.87 (t, 3 H, CH2CH3, J = 7.4 Hz); 1.51—1.71 (m, 2 H,
Received April 4, 2011;
in revised form November 13, 2011