Convenient selective synthesis of substituted pyrido[2,3-d]pyrimidones and annulated derivatives

Article abstract of DOI:10.1515/znb-2007-0115

The reaction of 6-aminouracil (1) with the appropriate α,β- unsaturated ketones, gave the corresponding pyrido[2,3-d]pyrimidin-2,4-diones 3, 6, 8 and 10, respectively. Treatment of 1 with salicylaldehyde, 6-carboethoxy-3,5-diphenyl-2-cyclohexenone (13) or

Full text of DOI:10.1515/znb-2007-0115

Convenient Selective Synthesis of Substituted Pyrido[2,3-d]pyrimidones
and Annulated Derivatives
Wafaa S. Hamama, Mohamed A. Ismail, Hana’a A. Al-Saman, and Hanafi H. Zoorob
Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt
Reprint requests to Dr. W. S. Hamama. E-mail: wshamama@yahoo.com
Z. Naturforsch. 2007, 62b, 104 – 110; received April 4, 2006
The reaction of 6-aminouracil (1) with the appropriate α,β-unsaturated ketones, gave
the corresponding pyrido[2,3-d]pyrimidin-2,4-diones 3, 6, 8 and 10, respectively. Treat-
ment of 1 with salicylaldehyde, 6-carboethoxy-3,5-diphenyl-2-cyclohexenone (13) or 2,6-
bis(phenylmethylidene)cyclohexanone (15) afforded the corresponding pyrimido[4,5-d]quinoline-
2
,4-diones 12, 14 and 16, respectively. Furthermore, a pyrido[2,3-d]pyrimidine incorporating 3,2’-
bis(quinoline) derivative 18 was synthesized. Annulation of pyrido[2,3-d]pyrimidine with pyrazole
or imidazole moieties was achieved via reaction of 1 with benzylidene derivatives of pyrazolone, im-
idazolone or 3-carboethoxycoumarin (23) to give 21, 22 and 24, respectively.
Key words: Uracil, Annulation, Biselectrophilic Reagent, Cyclocondensation
Introduction
and biselectrophiles, the 5-position of the pyrimi-
dine is the most nucleophilic and attacks the most
electrophilic carbon atom of the biselectrophile, fol-
lowed by ring closure between the 6-amino group
and the second electrophilic center. This experi-
mental observation was supported by computational
studies, which revealed a direct correlation between
charge densities at the C-5 carbon atom of the 6-
aminopyrimidine and their enamine-like nucleophilic-
ity toward enones [19, 20]. However, unexpected reac-
tions have also been observed in some cases, depend-
ing on the substitution in the pyrimidine, the biselec-
trophile, and the solvent used [21].
The one-step assemblage of monocyclic as well
as polycyclic heterocycles represents a practical ap-
proach in modern organic synthesis. These reactions
are of particular interest in combinatorial chemistry [1]
because they allow the production of vast arrays of
molecules in an efficient mode. Recently, Quiroga [2]
has reported the selective preparation of a number of
condensed heterocycles as potential biologically active
compounds. Amongst these, pyrido[2,3-d]pyrimidine
derivatives known as deazalumazines [3, 4] present in-
teresting biological properties. These compounds have
been used as dihydrofolate reductase inhibitors and
antitumor agents [5 – 9]; some of them have shown a
broad spectrum of antimicrobial activity [10 – 13], di-
uretic properties [14] and activity against platelet ag-
gregation [15].
A wide variety of polycyclic molecules have been
shown to interfere with the replication of DNA through
intercalation between adjacent partially unwound base
pairs as first described by Lerman [22]. Actino-
mycin [23], ethidium bromide [24], acridines [25]
and proflavine [26] are known to bind to DNA by
this intercalative process. This type of binding to
DNA was also observed for other planar hetero-
cyclic ring systems such as ellipticine, a pyridocar-
bazole derivative with a high degree of activity against
leukemia [27– 29]. Therefore, this study provides a
convenient method for the selective synthesis of 7-
The therapeutic importance of this molecular frame-
work motivated us to develop selective procedures of
synthesis in which constituents could be arranged in
a pharmacophoric pattern to display a high degree of
pharmacological activities.
Results and Discussion
From early studies [16 – 18], an empirical rule has styrylpyrido[2,3-d]pyrimidine 3 by reactions of 6-
emerged which specifies that in annulation reactions aminouracil 1 with 1,5-diphenyl-1,4-pentadien-3-one
involving substituted 6-aminopyrimidines, which have (2) in acetic acid in good yield via cyclocondensation
multiple competing sites for possible ring-annulation reaction (Scheme 1). We have found that this reaction
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W. S. Hamama et al. · Synthesis of Substituted Pyrido[2,3-d]pyrimidones and Annulated Derivatives
105
Scheme 1.
Scheme 2.
Scheme 3.
was regioselective and no other compound was formed adduct from a Hantzsch synthesis in this case afforded
TLC control). It is analogous to reactions of other the fully oxidized (aromatic) pyridine derivative pre-
aminopyrimidines and biselectrophiles [16, 30]. sumably due to the highly conjugated system formed
The constitution of 3 is supported by elemental anal- (Scheme 2). The constitution of 6 was affirmed through
(
1
1
1
ysis, IR, H NMR and MS spectra. The H NMR spec- its H NMR and MS spectra. The mass spectrum gave
+
trum of 3 displayed signals corresponding to a methy- a molecular ion peak at m/z = 369 (M , 66 %), 368
+
lene group (a doublet at δ = 2.13), and a methine pro- (M -1, 35 %) and a base peak at m/z = 292.
ton (triplet at δ = 4.01). Its MS fragmentation pattern
showed good agreement with the proposed structure.
In view of the interesting biological implica-
tion of nitrogen-containing heterocycles we aimed
The pyrimidine-2,4-dionering is frequently encoun- to synthesize novel bicyclic compounds which in-
tered in drugs used for the treatment of hypothy- clude an acetyl group at the pyridine ring. The syn-
roidy, hypertension, cancer and HIV infections [31]. thesis of 6-acetyl-substituted pyrido[2,3-d]pyrimidine-
Also, highly conjugated pyrimidine-2,4-dione deriva- 2,4(1H,3H)-dione 8 was achieved by condensation
tives have antiparasitic activities [32]. According to of the 6-aminouracil derivative 1 with m-nitrobenzyl-
1
the interest toward pyrido[2,3-d]pyrimidines, consid- idene-acetylacetone (7) (Scheme 3). Its H NMR spec-
erable attention has been focused on the synthesis of trum shows a singlet at δ = 2.14 for the methyl group,
highly conjugated pyrido[2,3-d]pyrimidines for bio- a singlet at δ = 3.09 for three protons (COCH ), a sin-
3
logical evaluation.
glet at δ = 5.1 for HC-Ar, a multiplet at δ = 7.5 – 8.06
Accordingly, it seemed interesting to explore for four aromatic protons and a singlet at δ = 8.83
the Michael addition of 6-amino-1,3-dimethyl-2,4- for HC-CO. Additionally, the mass spectrometric frag-
pyrimidinedione (1) to the highly conjugated α,β-un- mentation pattern of 8 coincides with the proposed
saturated ketone 4 to afford 6. The dihydropyridine structure.
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1
06
W. S. Hamama et al. · Synthesis of Substituted Pyrido[2,3-d]pyrimidones and Annulated Derivatives
Scheme 4.
Scheme 5.
Furthermore, the condensation of 1 with cin-
namaldehyde in glacial acetic acid furnished com-
pound 10 in low yield (Scheme 4). Compatible ana-
lytical and spectroscopic evidence was gained for the
structure of compound 10. The mass spectra gave a
+
molecular ion peak at m/z = 267 (M ) and a base peak
+
at m/z = 266 (M -1).
In a similar manner, 2-hydroxy-benzaldehyde
was used to assure this finding. Thus, 5-hydroxy-
1
,3-dimethylpyrimido[4,5-b]quinoline-2,4-(1H,3H)-
dione (12) was synthesized by reaction of 1 with
salicylaldehyde in acidic medium (Scheme 5). Its
1
structure was confirmed by IR, H NMR and MS
spectra.
Scheme 6.
It has been reported in the literature [33] that com-
pound 1 reacted with an excess of ethyl acetoacetate
to give 5-oxopyrido[2,3-d]pyrimidine in 2 % yield in a
basic medium or by thermal condensation [34].
In the present investigation it was also found that
condensation of 1 with 6-carboethoxy-3,5-diphenyl-
anone in the presence of Triton B as a base in mod-
erate yields. The conformation of such skeletons was
reported earlier [39].
The structural formula of 16 was deduced from
1
spectral data. The H NMR spectrum showed signals
at δ = 1.66, 2.09 and 2.57– 2.75 (three CH groups),
2
2
-cyclohexenone (13) [35– 37] as a β-ketoester (not
3
.14 and 3.54 (two N-CH groups), 4.53 and 6.49
3
as an α,β-unsaturated ketone, because its β-position
is blocked) furnished pyrimido[4,5-b]quinoline-2,4,5-
(two CH protons) and also 7.20– 7.35 (2 Ph and
Ph–CH=) protons. In addition, the mass spectrum of
(1H,3H,5aH)trione 14 (Scheme 6). Its structure was
compound 16 indicated a molecular ion peak at m/z =
confirmed by elemental analysis and MS spectrum (see
Experimental Section).
In addition, the reaction of 1 and dibenzylidenecy-
clohexanone (15) [38] in acidic medium afforded
+
4
11 (M , 6 %) corresponding to the molecular formula
C H N O .
2
6
25
3
2
In addition, the interesting pharmacological ac-
pyrimido[4,5-b]quinoline-2,4(1H,3H)-dione 16 as a tivity of quinoline in different areas of chemother-
sole product in high yield (Scheme 6). In contrast, apy [40] prompted us to prepare the 7-(quinolin-3-yl)-
Diaz [39] separated three adducts (one of them as a pyrido[2,3-d] pyrimidine-2,4-(1H,3H)-dione deriva-
monoadduct and two isomeric bisadducts) from the tive 18 through the cyclocondensation of 1 with 3-
reaction of compound 1 with dibenzylidencyclohex- cinnamoyl-1-phenyl-2,4(1H,3H)-quinolinedione (17)
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W. S. Hamama et al. · Synthesis of Substituted Pyrido[2,3-d]pyrimidones and Annulated Derivatives
107
Scheme 7.
nal standard. Chemical shifts are reported in ppm (δ) down-
field from internal TMS. Mass spectra recorded on a GC-MS
(Shimadzu QP-1000 EX). Reactions were monitored by thin
layer chromatography (TLC) using silica gel (EM science)
coated plates.
Pyrido[2,3-d]pyrimidines 3, 6 and 10; general procedure
A mixture of 6-amino-1,3-dimethyl-uracil (1 g, 6.5 mmol)
and the appropriate α,β-unsaturated compounds, namely,
1
,5-diphenyl-1,4-pentadien-3-one (2), 1,5-diphenyl-1,3-pen-
tadien-5-one (4) or cinnamaldehyde (6.5 mmol), in glacial
acetic acid (20 mL) was refluxed for 1 h on a steam bath, kept
overnight at r. t., diluted with water, then basified by ammo-
Scheme 8.
[
41] (Scheme 7). Its structure was confirmed by the nia. The precipitate formed was collected by filtration, then
H NMR spectrum which showed a singlet at δ = purified by crystallization from an appropriate solvent to give
.08 (CH ), two singlet signals at δ = 3.36 and 3.9 compounds 3, 6 and 10, respectively.
1
2
2
(
7
2 NCH ), a singlet at 3.78 (PhCH), multiplet at δ =
3
.18– 7.63 for 14 aromatic protons, and finally a sin- 5,6-Dihydro-1,3-dimethyl-5-phenyl-7-styrylpyrido[2,3-d]-
pyrimidine-2,4(1H,3H)-dione (3)
glet at δ = 17.76 ppm for enolic OH. In addition, the
mass spectrum of compound 18 indicated a molecu-
lar ion peak at m/z = 504 (M , 8 %) and a base peak
at 427 (M –Ph).
◦
M. p. 129 – 130 C (acetic acid). – R = 0.58 (pet. ether
f
+
◦
4
0 – 60 C / ethyl acetate, (1 : 1)). – Yield: 94 % (yellow
+
crystals). – IR (KBr): ν = 3060, 2975 (CH), 1637 (CO),
−
1
1
No attention has been paid to the similar reaction 1620 cm (C=N). – H NMR (200 MHz, [D6]-DMSO):
with the benzylidenepyrazolone derivative 19 or the δ = 2.13 (d, J = 6.4 Hz, 2H), 2.80 (s, 3H), 3.09 (s, 3H), 4.01
(
(
(
t, J = 6.4 Hz, 1H), 6.26 (d, J = 16.5 Hz, 1H), 6.93 – 7.28
benzylidenehydantoin derivative 20 which can be used
as key intermediates for the construction of a pyridopy-
rimidine moiety fused with pyrazole or with imida-
zole rings, respectively. The reaction of 1 with 19 [42]
or 20 [43] in the presence of glacial acetic acid gave 21
and 22, respectively (Scheme 8). Formulation of struc-
tures 21 and 22 is based on elemental analysis, IR and
mass spectra fragmentation.
+
m, 11H). – MS (EI, 70 eV): m/z (%) = 371 (94) [M ], 370
+
+
51) [M -1], 369 (4) [M -2], 294 (100), 244 (48), 217 (2),
05 (6), 191 (2), 155 (43), 153 (9). – C H N O (371.42):
2
2
3
21
3 2
calcd. C 74.37, H 5.69; found C 74.46, H 5.80.
1
,3-Dimethyl-7-phenyl-5-styrylpyrido[2,3-d]pyrimidine-2,4
(1H,3H)-dione (6)
◦
M. p. 185 C (ethanol). – Rf = 0.65 (pet. ether 40 –
◦
6
0 C / ethyl acetate (4 : 1)). – Yield: 92 % (yellow crys-
Experimental Section
tals). – IR (KBr): ν = 2946 (CH), 1708, 1660 (CO), 1625
−1
1
All melting points (uncorrected) were determined on a (C=N), 1589 cm (C=C). – H NMR (200 MHz, CDCl ):
3
Gallenkamp electric melting point apparatus. Elemental mi- δ = 3.26 (s, 3H), 3.62 (s, 3H), 7.41 – 7.70 (m, 9H), 8.07 (s,
croanalyses were carried out at the Microanalytical Unit, 1H), 8.27 – 8.30 (m, 21H), 8.51 – 8.59 (m, 1H). – MS (EI,
+
+
Faculty of Science, Cairo University. Infrared spectra mea- 70 eV): m/z (%) = 369 (66) [M ], 368(35) [M -1], 292
sured using KBr discs on a Mattson 5000 FTIR spectrometer. (100), 242 (3), 215 (7), 192 (4), 186 (2), 155 (5), 153 (7).
1
H NMR data were obtained in CDCl or DMSO solution – C H N O (369.42): calcd. C 74.78, H 5.18; found
3
23 19 3 2
on a Varian XL 200 MHz instrument using TMS as inter- C 74.75, H 5.17.
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08
W. S. Hamama et al. · Synthesis of Substituted Pyrido[2,3-d]pyrimidones and Annulated Derivatives
1
,3-Dimethyl-5-phenylpyrido[2,3-d]pyrimidine-2,4(1H,3H)- 9-Benzylidene-5,5a,6,7,8,9-hexahydro-1,3-dimethyl-5-
dione (10)
phenylpyrimido[4,5-b]quinoline-2,4(1H,3H)-dione (16)
◦
◦
M. p. 170 C (methanol). – Rf = 0.7 (pet. ether 40 –
M. p. 258 C (acetic acid). – R = 0.57 (pet. ether (40 –
f
◦
◦
0 C / ethyl acetate (1 : 2)). – Yield: 37 % (yellow crystals). 60 C) / ethyl acetate (1 : 1)). – Yield: 93 % (yellow crystals).
6
–
(
2
(
−1
−1
IR (KBr): ν = 1709, 1680 (CO), 1584 cm (C=C). – MS – IR (KBr): ν = 3134 (CH), 1695, 1665 (CO), 1604 cm
+
1
EI, 70 eV): m/z (%) = 267 (54) [M ], 266 (100), 238 (2), (C=C). – H NMR (200 MHz, CDCl ): δ = 1.66 (t, J =
3
00 (2), 181 (3), 155 (30), 127 (16), 81 (8). – C H N O
2
8.0 Hz, 2H), 2.09 (t, J = 8.0 Hz, 2H), 2.57 – 2.75 (m, 2H),
3.14 (s, 3H), 3.54 (s, 3H), 4.53 (s, 1H), 6.49 (s, 1H), 7.20 –
.35 (m, 11H). – MS (EI, 70 eV): m/z (%) = 411 (6) [M ],
10 (4) [M -1], 409 (5), 334 (100), 320 (5), 256 (1), 91
11), 77 (3). – C H N O (411.50): calcd C 75.89, H 6.12;
found C 75.78, H 6.21.
15
13
3
267.27): calcd. C 67.40, H 4.90; found C 67.49, H 5.04.
+
7
4
(
+
6
-Acetyl-5,6-dihydro-1,3,7-trimethyl-5-(3-nitrophenyl)pyr-
ido[2,3-d]pyrimidine-2,4(1H,3H)-dione (8)
26 25
3 2
A mixture of 6-amino-1,3-dimethyl-uracil (1) (1 g,
.5 mmol) and m-nitrobenzylidene-acetylacetone
6.5 mmol) in ethanol (30 mL) containing 3 drops of acetic
acid was heated at reflux for 2 h. The reaction mixture was
6
(
7
6
,7-Dihydro-1,3-dimethyl-6,8-diphenylpyrimido[4,5-b]quin-
oline-2,4,5(1H,3H,5aH)-trione (14)
kept at r. t., diluted with H O whereby the precipitate formed
2
A mixture of 6-amino-1,3-dimethyl-uracil (1) (0.34 g,
was filtered off and crystallized from ethanol to furnish
2
.16
mmol),
6-carboethoxy-3,5-diphenyl-2-cyclohex-
◦
compound 8. – M. p. 236 C (ethanol). – R = 0.63 (pet.
f
enone 13 (2.16 mmol) in diphenyl ether (10 mL) was
refluxed until disappearance of the starting materials as
evidenced by TLC. After the reaction was over, removal of
the solvent under vacuum followed by crystallization of the
◦
ether 40 – 60 C / ethyl acetate (1 : 1)). – Yield: 48 % (yellow
crystals). – IR (KBr): ν = 3138 (CH), 1693, 1668 (CO),
−
1
1
592 cm (C=C). – 1H NMR (200 MHz, [D ]-DMSO):
6
δ = 2.14 (s, 3H), 3.09 (s, 3H), 3.32 (s, 3H), 3.43 (s, 3H), 5.1
s, 1H), 7.5 – 8.06 (m, 4H), 8.83 (s, 1H). – MS (EI, 70 eV):
◦
residue from ethanol afforded 14. – M. p. 306 C (ethanol).
(
◦
–
–
2
7
R = 0.66 (pet. ether (40 – 60 C) / ethyl acetate (3 : 2)).
f
+
+
m/z (%) = 370 (10) [M ], 368 (6) [M -2], 359 (3), 353
Yield: 51 % (brown crystals). – IR (KBr): ν = 3134,
(
(
21), 327 (47), 313 (7) 248 (100), 205 (28), 191 (15), 123
5). – C H N O (370.35) calcd. C 58.37, H 4.89; found
−1
875 (CH), 1708, 1658, 1641, 1612 cm (CO). – MS (EI,
+
+
1
8
18
4
5
0 eV): m/z (%) = 411 (77) [M ], 410 (23) [M -1], 409 (3)
M -2], 334 (100), 333 (7), 256 (8), 227 (7), 226 (6), 178
C 58.46, H 4.98.
+
[
(
4). – C H N O (411.44): calcd. C 72.98, H 5.15; found
2
5
21
3
3
C 72.29, H 5.05.
Pyrimido[4,5-b]quinolines 12 and 16; general procedure
A mixture of 6-amino-1,3-dimethyl-uracil (1) (1 g,
5
,6-Dihydro-7-(1,2-dihydro-4-hydroxy-2-oxo-1-phenylquin-
6
.5 mmol) and salicylaldehyde or 2,6-dibenzylidenecyclo-
olin-3-yl)-1,3-dimethyl-5-phenylpyrido[2,3-d]pyrimidine-
hexanone 15 (6.5 mmol) in glacial acetic acid (20 mL) was
heated for 1 h on a steam bath, kept overnight at r. t., di-
luted with water, then basified with ammonia. The precipitate
formed was collected by filtration, and then purified by crys-
tallization from an appropriate solvent to give compound 12
and 16, respectively.
2
,4(1H,3H)-dione (18)
A mixture of 6-amino-1,3-dimethyl-uracil (1) (1 g,
.5 mmol), 3-cinnamoyl-1-phenyl-2,4(1H,3H)-quinoline-
6
dione (2.4 g, 6.5 mmol) in glacial acetic acid (20 mL) was
heated for 1 h on a steam bath, kept overnight at r. t., diluted
with water, and then basified with ammonia. The precipitate
5
3
-Hydroxy-1,3-dimethyl pyrimido[4,5-b]quinoline-2,4(1H, formed was collected by filtration, and then purified by crys-
◦
H)-dione (12)
tallization from acetic acid to give 18. – M. p. 160 C (acetic
◦
acid). – R = 0.63 (pet. ether (40 – 60 C ) / ethyl acetate
f
◦
M. p. 240 C (acetone). – R = 0.65 (pet. ether (40 – (1 : 2)). – Yield: 97 % (yellow crystals). – IR (KBr): ν =
f
◦
6
0 C) / ethyl acetate (1 : 2)) – Yield: 38 % (yellow crys- 3454 (OH intermolecular), 3057, 2952 (CH), 1712, 1671,
−1
1
tals). – IR (KBr): ν = 3570, 3519 (OH), 2956 (CH), 1708, 1645 cm (CO). – H NMR (200 MHz, CDCl ): δ = 2.08
3
−1
(CO). – 1H NMR (200 MHz, [D ]-DMSO): (s, 2H), 3.36 (s, 3H), 3.78 (s, 1H), 3.9 (s, 3H), 7.18 – 7.63
6
1
659 cm
δ = 3.32 (m, 3H), 3.56 (m, 3H), 5.05 (br, 1H), 7.27 (m, 4H). (m, 14H), 9.05 (s, 1H), 17.76 (s, 1H). – MS (EI, 70 eV): m/z
+
+
+
–
MS (EI, 70 eV): m/z (%) = 257 (10) [M ], 230 (14), 120 (%) = 504 (8) [M ], 502 (67), [M -2], 427 (100), 367 (10),
(
22), 123 (17), 215 (11), 54 (100). – C H N O (257.24): 308 (30), 237 (30), 196 (65). – C H N O (504.52): calcd.
13
11
3
3
30 24
4
4
calcd. C 60.69, H 4.31; found C 60.61, H 4.39.
C 71, 41, H 4.79; found C 71.49, H 4.89.
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W. S. Hamama et al. · Synthesis of Substituted Pyrido[2,3-d]pyrimidones and Annulated Derivatives
Pyrido[2,3-d]pyrimidines 21 and 22, general procedure
mixture of 6-amino-1,3-dimethyl-uracil (1 g,
109
tals). – IR (KBr): ν = 3068 (CH), 1695, 1669 (CO), 1617
C=N), 1582 cm (C=C). – MS (EI, 70 eV): m/z (%) =
99 (5) [M ], 368 (5) [M –CH], 334 (5), 284 (4) 262 (36),
9 (100). – C H N O (399.44): calcd. C 69.16, H 5.30;
−1
(
3
A
+
+
6
.5 mmol), and the benzylidenepyrazolone derivative 19 [43]
8
2
3
21
5
2
or the benzylidenehydantoin derivative 20 [44] (6.5 mmol)
in glacial acetic acid (20 mL) was heated for 1 h on a
steam bath, kept overnight at room temperature, diluted with
water, then basified with ammonia. The precipitate formed
collected by filtration, and then purified by crystallization
from the appropriate solvent to give 21 and 22.
found C 69.35, H 5.39.
ꢀ
ꢀ
5
5
,5a-Dihydro-5,6,8-triphenyl-1,3-dimethyl-imidazolo[4 ,5 :
,6]pyrido[2,3-d]-pyrimidine-2,4,7(1H,3H,6H)-trione (22)
◦
◦
M. p. 112 C (ethanol). – R = 0.62 (pet. ether (40 – 60 C)
ethyl acetate (3 : 2)). – Yield: 86 % (green crystals). – IR
f
/
ꢀ
ꢀ
(KBr): ν = 2953 (CH), 1777, 1710, 1641 (CO), 1610 (C=N),
5
5
,5a-Dihydro-5,8-diphenyl-1,3,6-trimethylpyrazolo[4 ,3 :
,6]-pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione (21)
−1
1
597 cm (C=C). – MS (EI, 70 eV): m/z (%) = 477 (3)
+
[
M ], 465 (2), 439 (3), 412 (2), 353 (1), 307 (2), 267 (5),
M. p. 140 (acetic acid). – R = 0.58 (pet. ether (40 – 190 (6), 112 (15), 210 (2), 104 (100). – C28H23N5O3 (477.5):
f
◦
0 C) / ethyl acetate (1 : 1)). – Yield: 51 % (yellow crys- calcd. C 70.43, H 4.85; found C 70.32, H 4.93.
6
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