New efficient approach for the synthesis of 2-alkyl(aryl) substituted 4H-pyrido[1,2-a]pyrimidin-4-ones

Article abstract of DOI:10.1002/jhet.5570430136

A new, efficient and easy route for the preparation of a series of 2-alkyl(aryl) substituted 4-oxo-4H-pyrido[l,2-a]pyrimidines, where alkyl = CH₃; aryl = C₆H₅, 4-FC₆H ₄,4-ClC₆H₄,

Full text of DOI:10.1002/jhet.5570430136

Jan-Feb 2006
229
New Efficient Approach for the Synthesis of 2-Alkyl(aryl) Substituted
4H-Pyrido[1,2-a]pyrimidin-4-ones
Helio G. Bonacorso*, Fernando J. Righi, Isadora R. Rodrigues, Cleber A. Cechinel,
Michelle B. Costa, Arci D. Wastowski, Marcos A. P. Martins and Nilo Zanatta
Núcleo de Química de Heterociclos – NUQUIMHE, Departamento de Química, Universidade Federal de Santa
Maria – 97105-900 – Santa Maria, RS - Brazil.
Received June 20, 2005
A new, efficient and easy route for the preparation of a series of 2-alkyl(aryl) substituted 4-oxo-4H-pyrido-
[1,2-a]pyrimidines, where alkyl = CH ; aryl = C H , 4-FC H , 4-ClC H , 4-BrC H , 4-CH C H , 4-OCH -
3
6
5
6
4
6
4
6
4
3
6
4
3
C H , 4-NO C H in 45 – 80 % yield from the reaction of β-alkoxyvinyl trichloromethyl ketones with
6
4
2 6 4
2-aminopyridine under mild conditions, is then reported.
J. Heterocyclic Chem., 43, 229 (2006).
In the last years, the introduction of a trifluoro- or
trichloromethyl group into an acyclic or cyclic compound
have widely been studied and reviewed [1,2].
Consequently, these new organic structures can bring
about remarkable changes in their physical, chemical and
biological properties.
Recently, we have also reported an addition/elimination
sequence leading to trifluoroacetyl and trichloroacetyl
acyclic enamines from the reaction of o-phenylenediamine
[3], o-aminophenol [4], 1-naphthylamine [5] and S,S-
dimethylsulfoximide [6] with 4-alkyl(aryl)-1,1,1-trihalo-
4-alkoxyalken-2-ones. The acyclic enaminones, derived
from o-phenylenediamine and o-aminophenol, were sub-
mitted to in vitro anti-tumor screens. It was observed that
the trichloromethylated compounds exhibited a superior
activity if compared to trifluoromethylated analog com-
pounds. The best activity was obtained when the structure
was derived from o-aminophenol and it presents a
trichloroacetyl- and a p-bromophenyl substituent bound at
the carbon-2 and -1, respectively [4].
β-Alkoxyvinyl trichloromethyl ketones 1 proved also to
be useful building blocks for the synthesis of five-, six-,
and seven-, member trichloromethylated heterocycles [2]
due to the fact that one of the best methods to introduce a
trichloromethyl group into heterocycles is based on the
trichloromethylated building block approach. This
approach relies on the trichloroacetylation of enol ethers or
acetals to give, in one step and good yields, the above cited
ketones 1. On the other hand, the classical haloform reac-
tion in which the trichloromethyl substituent is a leaving
group is well developed [7] and systematic studies, involv-
ing the usefulness of the leaving group ability of the
trichloromethyl in many synthetic transformations, were
reported [2,8-14]. However, just a few references from the
literature report the use of the trichloromethyl substituent
as a good leaving group in heterocyclic synthesis [15].
Furthermore, the synthetic strategy involving the ketones 1
and 2-aminopyridine was never applied in attempt to
obtain regiospecificaly 2-alkyl(aryl)substituted 4H-
pyrido[1,2-a]pyrimidin-4-ones under relative mild condi-
tions.
Although some researches, up to 1951, considered that
the heterocycle obtained from the reaction of 2-aminopyri-
dine with ethyl acetoacetate was 4-methyl-2H-pyrido[1,2-
a]pyrimidin-2-one, Antaki and Petrow [16] showed (in
1951), that the product was, in fact, the 2-methyl-4-keto
isomer. To prove this hypothesis, 2-methyl-4H-pyrido[1,2-
a]pyrimidin-4-one was obtained from the reaction of 2-
bromopyridine with ethyl β-aminocrotonate at 180 – 200
ºC for 5 – 6 hours in the presence of copper bronze and
anhydrous potassium carbonate or when 2-aminopyridine
and ethyl β-aminocrotonate were heated together at 160 –
180 ºC for 6 – 8 hours. In 1968, Shur and Israelstam [17]
showed that pyrido[1,2-a]pyrimidin-4-ones can be
obtained in a one-stage process by condensing methyl- or
halo-substituted 2-aminopyridines with β-keto esters in the
presence of PPA. Optimum yields (> 80%) were obtained
by heating the 2-aminopyridines with β-keto esters at 100
ºC for about 1 hour together with four- to sixfold quantity
of PPA. Four years before, Kato et al. [18] synthesized 2-
methyl-4H-pyrido[1,2-a]pyrimidin-4-one by treating 2-
aminopyridine with diketene in only 28 % yield.
In 1972, Mendel [19] synthesized, by a new method but
in low yields, 2-methyl- (35 %) and 2-phenyl-4H-

230
H. G. Bonacorso, F. J. Righi, I. R. Rodrigues, C. A. Cechinel, M. B. Costa,
A. D. Wastowski, M. A. P. Martins and N. Zanatta
Vol. 43
pyrido[1,2-a]pyrimidin-4-one (20 %) from the reaction of
2-aminonicotinic acid with ethyl acetoacetate or ethyl ben-
zoylacetate, respectively.
In 1977, Hermecz et al. [20] reported that 3-, 6- and 8-
substituted 4H-pyrido[1,2-a]pyrimidin-4-ones can be
obtained from the ring closure reactions of 2-substituted
3-(2-pyridylamino)acrylates in a mixture of phosphoryl
chloride and PPA at 130 ºC in 40 -96 % yields.
In 2002, a series of 6(8)-methyl-, 7(9)-halo-, 8(9)ethyl-
and 8-nitro-substituted 4H-pyrido[1,2-a]pyrimidin-4-ones
[21] were obtained in 21 - 74 % yields, when the pyridy-
laminomethylene malonates synthesized from the reac-
tions of ethoxymethyleneisopropylidene malonate with 2-
aminopyridines were heated to their melting points.
Previously, 7-alkyl substituted pyridopyrimidines analogs
[22] were isolated from the 2-pyridylamino- or 5-methyl-
2-pyridylaminomethyleneisopropylidene malonates by
also melting them.
Since 1983, the interesting and non-substituted 4H-
pyrido[1,2-a]pyrimidin-4-one has only been synthesized
by laborious procedures involving a mixture of Meldrum’s
acid, trimethyl orthoformate and 2-aminopyridine [23] or
from the reaction of ethyl N-(2-pyridyl) formimidate with
ketene in 58 % yield [24].
Parallel to the growing interest in the synthesis of
pyrido[1,2-a]pyrimidin-4-ones to provide biologically
active molecules, a large number of publications showed
that several derivatives of them appeared as tranquilizer
[25], antiallergic [26], antiulcerative [27], antiasthmatic
[28] and bronchodilator agents [29] or showing analgesic
activity [30] and human platelet aggregation inhibitory
properties [31].
As an extension of our research we wish to report the
discovery of a new and easy route for the preparation of a
series of 2-alkyl(aryl)substituted 4-oxo-4H-pyrido[1,2-
a]pyrimidines 3 from the reaction employing β-
alkoxyvinyl trichloromethyl ketones 1 and 2-aminopyri-
dine (Scheme 1), when mild conditions were used to
obtain the respective trichloroacetyl enamines 2.
The 4-alkyl(aryl)-1,1,1-trichloro-4-alkoxy-alk-3-en-2-
ones (1) are readily available CCC synthetic blocks and
were prepared from trihaloacetylation of enol ethers (1a-b)
[32] or from enol ethers generated in situ from the respec-
tive acetophenone acetals (1c-i) [33,34] with
trichloroacetyl chloride. The most satisfactory results of
these reactions, selected physical and elemental analyses
are recorded in Table 1 and spectral data are presented in
the experimental part.
We have attempted to obtain the enamino ketone inter-
mediate N-[1-alkyl(aryl)-3-oxo-4,4,4-trichloroalk-1-en-1-
yl]-2-aminopyridines (2) by the reaction of β-alkoxyvinyl
trichloromethyl ketones 1 with 2-aminopyridine. When
these reactions were carried out in dichloromethane as sol-
vent, the respective enamino ketones were isolated in a
very low yield (> 10%). Surprisingly, when the same reac-
tions were carried out in a molar ratio of 1:1 respectively,
in anhydrous ethanol as solvent under reflux for 5 hours,
2-substituted 4-oxo-4H-pyrido[1,2-a]pyrimidines (3b-i)
were easily isolated in 45 – 81% yields. Except for reaction
involving 1a, the above described conditions allowed us to
obtain regiospecificaly pyrido[1,2-a]pyrimidin-4-ones
(Scheme 1, path b) instead 5-trichloromethyl-1,8-naph-
thyridines (Scheme 1, path a) or their 4-substitued 2-keto-
pyridopyrimidine isomer. Although, similar conditions
were employed to synthesize 5H-thiazolo[3,2-a]pyrim-
idin-5-ones previously [18c], we have found in this case an
unexpected reactivity of the endocyclic nitrogen atom of
the π-deficient pyridine ring towards the carbonyl group
of the β-alkoxyvinyl trichloromethyl ketones. Although,
the 4H-pyrido[1,2-a]pyrimidin-4-one was synthesized pre-
viously [23,24], unfortunately reactions of N-[3-oxo-
4,4,4-trichlorobut-1-en-1-yl]-2-aminopyridine (2a) in
refluxing ethanol, n-butanol or acidic media as sulfuric
acid or PPA at reflux or using TiCl as catalysts at different
4
temperatures in an attempt to obtain the respective cyclic
structure, resulted always in the recovery of precursor (2a)
Scheme I

Jan-Feb 2006
Synthesis of 2-Alkyl(aryl) Substituted 4H-Pyrido[1,2-a]pyrimidin-4-ones
231
CHN elemental analyses were performed on a Perkin Elmer 2400
CHN elemental analyzer (São Paulo University – USP / Brazil).
1
or complex mixtures of non identified products by H- and
13
C-NMR spectroscopy are produced. However, the isola-
General Procedure for the Preparation of N-[3-Oxo-4,4,4-tri-
chlorobut-1-en-1-yl]-2-aminopyridine (2a).
tion of the trichloroacetyl enamine 2a demonstrates also
that the pyrido[1,2-a]pyrimidinone system (3b-i) must be
the 4-keto isomer.
To a stirred solution of 4-ethoxy-1,1,1-trichloro-3-buten-2-one
Table 1
Selected physical and elemental analyses data of N-[1-alkyl(aryl)-3-oxo-4,4,4-trichlorobut-1-en-1-yl]-2-aminopyridine(2a)
and 2-Alkyl(aryl)-4H-pyrido[1,2-a]pyrimidin-4-ones (3b-i).
Compds.
(R Substituent)
Yield
(%)
Mp
(°C)
Molecular
Formula (g/mol)
Elemental Analyses (%)
Calcd. / Found
a
b
C
H
N
2a
(H)
3b
62
66
[96]
81
110 – 111
C H Cl N O
40.71
40.86
67.49
-
75.66
-
70.00
69.88
65.51
65.27
55.84
55.55
76.25
75.96
71.42
71.25
62.92
63.03
2.66
2.70
5.03
-
4.54
-
3.78
3.90
3.53
3.67
3.01
3.14
5.12
4.99
4.79
4.91
3.39
3.55
10.55
10.73
17.49
-
12.60
-
11.66
11.49
10.91
10.85
9.30
9
7
3 2
265.53
C H N O
118 – 119
[123 – 124]
144 – 145
[147 – 148]
201 – 202
9
8 2
c
c
c
(CH )
160.18
N O
3
3c
C
H
14 10
2
c
(C H )
[20]
222.25
H FN O
6
5
3d
65
68
71
70
45
55
C
14
9
2
(4-FC H )
240.24
C H ClN O
14
6
4
3e
(4-ClC H )
203 – 204
200 – 201
161 – 163
157 – 158
217 – 218
9
2
256.69
C H BrN O
14
6
4
3f
(4-BrC H )
9
2
301.14
N O
9.06
6
4
3g
C
H
11.86
11.63
11.10
10.98
15.72
15.83
15 12
2
(4-CH C H )
236.27
C H N O
15 12
3
6 4
3h
2 2
(4-CH OC H )
252.27
C H N O
14
3
6 4
3i
(4-NO C H )
9 3 3
267.24
2
6 4
[a] Yields of isolated compounds; [b] Melting points are uncorrected; [c] Known compounds (3b, ref. 17; 3c, ref. 24).
In summary, it was observed that the reactions of β-
alkoxyvinyl trichloromethyl ketones (1) with 2-aminopyri-
dine carried out in anhydrous ethanol under reflux give the
intermediates N-[1-alkyl(aryl)-3-oxo-4,4,4-trichloroalk-1-
en-1-yl]-2-aminopyridines 2, which were not isolated,
except for 2a. Thus, the intermediates 2 act as N-hetero-
cyclic acylating agent enabling to present a new, simple,
and convenient method to obtain substituted 4-oxo-4H-
pyrido[1,2-a]pyrimidines (3) in good yields.
1a (5 mmoles) in 15 ml of anhydrous ethanol, 2-aminopyridine (5
mmoles) was added at 20 – 25 °C. The mixture was stirred for 5
hours at 80 – 85 °C (oil bath). After the reaction time, the solvent
was evaporated under reduced pressure and the crude products 2a
purified by recrystallization from ethyl acetate.
This compound was obtained as yellow solid, yield 62 %, Mp.
1
110 - 111 ºC. H NMR (CDCl ) δ= 11.27 (bs, 1H, NH), 8.44 (dd,
3
J= 12.4, J= 8.3, 1H, H-1’), 8.33 (d, J= 3.6, 1H, PyH-6), 7.66 (m,
1H, PyH-4), 7.04 (m,1H, PyH-5), 6.85 (d, J= 8.0, 1H, PyH-3),
13
6.04 (d, J=8.3, 1H, H-2’). C NMR (CDCl ) δ = 183.4 (C=O),
3
150.5 (PyC-2), 148.7 (C-1’), 147.3 (PyC-6), 138.7 (PyC-4),
119.7 (PyC-3), 111.9(PyC-5), 96.3 (CCl ), 89.6 (C-2’). GC/MS
(EI, 70 eV): m/z (%) = 264 (M , 10), 165 (24), 201 (17), 147
3
EXPERIMENTAL
+
(100), 119 (80), 78 (93), 51 (25).
Unless otherwise indicated all common reagents and solvents
were used as obtained from commercial suppliers without further
purification. All melting points were determined on an
General Procedure for the Preparation of 2-Alkyl(aryl)-4H-
pyrido[1,2-a]pyrimidin-4-ones (3b-i).
1
To a stirred solution of 4-alkoxy-4-alkyl(aryl)-1,1,1-trichloro-3-
buten-2-one 1b-i (5 mmoles) in 15 ml of anhydrous ethanol, 2-
aminopyridine (5 mmoles) was added at 20 – 25 °C. The mixture
was stirred for 5 hours at 80 – 85 °C (oil bath). After the reaction
time, the solvent was evaporated under reduced pressure and the
crude products 3b purified by recrystallization from a mixture of
ethyl acetate and n-hexane (3:1). Compounds 3c-i precipitated after
the reaction time and were isolated by filtration and purified by
recrystallization from a mixture of ethanol and n-hexane (3:1).
Electrothermal Melt-Temp 3.0 apparatus and are uncorrected. H
13
and C NMR spectra were acquired on a Bruker DPX 200 spec-
1
13
trometer ( H at 200.13 MHz and C at 50.32 MHz), 5 mm sam-
ple tubes, 298 K, digital resolution 0.01 ppm, in chloroform-d
1
using TMS as internal reference. Mass spectra were registered in
a HP 6890 GC connected to a HP 5973 MSD and interfaced by a
Pentium PC. The GC was equipped with a split-splitless injector,
autosampler, cross-linked HP-5 capillary column (30m, 0.32mm
of internal diameter), and helium was used as the carrier gas. The

232
H. G. Bonacorso, F. J. Righi, I. R. Rodrigues, C. A. Cechinel, M. B. Costa,
A. D. Wastowski, M. A. P. Martins and N. Zanatta
Vol. 43
2-Methyl-4H-pyrido[1,2-a]pyrimidin-4-ones (3b).
1
157 - 158 ºC. H NMR (CDCl ) δ = 9.04 (d, J=7.0, 1H, H-6), 8.07
3
(d, J=8.9, 2H, Ph), 7.72 (m, 2H, H-7, H-9), 7.09 (m, 1H, H-8), 7.0
(d, J=8.9, 2H, Ph), 6.84 (s, 1H, H-3), 3.87 (s, 3H, OCH ).
This compound was obtained as white solid, yield 66 %, Mp.
13
1
C
118 -119 ºC. H NMR (CDCl ) δ = 9.03 (d, J=7.1, 1H, H-6), 7.73
3
3
NMR (CDCl ) δ = 161.7 (C-2), 161.3 (C-4), 158.4 (C-9a), 150.7
(t, J=7.6, 1H, H-7), 7.59 (d, J=8.8, 1H, H-9), 7.12 (t, J=7.0, 1H,
H-8), 6.34 (s, 1H, H-3), 2.47 (s, 3H, CH ). C NMR (CDCl ) δ
= 165.0 (C-2), 157.5 (C-4), 150.5 (C-9a), 136.0 (C-7), 126.9 (C-
3
13
(Ph), 136.1 (C-7), 129.0 (Ph), 128.9 (Ph), 127.2 (C-6), 126.4 (C-
3
3
9), 114.1 (Ph), 114.9 (C-8), 98.7 (C-3), 55.3 (OCH ). GC/MS (EI,
70 eV): m/z (%) = 252 (M , 87), 223 (100), 78 (75), 51 (28).
3
+
6), 125.5 (C-9), 114.8 (C-8), 103.0 (C-3), 24.4 (CH ). GC/MS
3
(EI, 70 eV): m/z (%) = 160 (M+, 57), 131(100), 78 (75), 51 (41).
2-(4-Nitrophenyl)-4H-pyrido[1,2-a]pyrimidin-4-ones (3i).
2-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-ones (3c).
This compound was obtained as yellow solid, yield 55 %, Mp.
1
217 - 218 ºC. H NMR (CDCl ) δ = 9.01 (d, J=6.9, 1H, H-6),
This compound was obtained as yellow solid, yield 81 %, Mp.
3
1
8.22 (m, 4H, Ph), 7.74 (m, 2H, H-7, H-9), 7.15 (m, 1H, H-8), 6.87
144 - 145 ºC. H NMR (CDCl ) δ = 9.06 (d, J=7.1, 1H, H-6),
3
13
(s, 1H, H-3). C NMR (CDCl ) δ = 157.9 (C-2), 157.6 (C-4),
8.09 (m, 2H, Ph), 7.75 (m, 2H, Ph), 7.49 (m, 3H, Ph, H-7, H-9),
3
13
150.8 (C-9a), 148.5 (Ph), 142.7 (Ph), 138.1 (C-7), 128.5 (Ph),
127.1 (C-6), 126.4 (C-9), 123.8 (Ph), 116.7 (C-8), 100.1 (C-3).
GC/MS (EI, 70 eV): m/z (%) = 267 (M , 89), 239 (77), 192
7.13 (m, 1H, H-8), 6.91 (s, 1H, H-3). C NMR (CDCl ) δ =
161.7 (C-2), 158.3 (C-4), 150.8 (C-9a), 137.0 (Ph), 135.9 (C-7),
130.4 (C-6), 128.5 (Ph), 127.2 (Ph), 127.0 (Ph), 126.3 (C-9),
3
+
+
(100), 78 (96), 51 (41).
114.9 (C-8), 99.7 (C-3). GC/MS (EI, 70 eV): m/z (%) = 222 (M ,
97), 194 (100), 78 (88), 51 (43).
Acknowledgments.
2-(4-Fluorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-ones (3d).
The authors are thankful for the financial support from Conselho
Nacional de Desenvolvimento Científico e Tecnológico – CNPq
(Proc. Nr. 303636/2002-5). Fellowships from Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior - CAPES and
CNPq ( F. J. Righi, C. A. Cechinel and M. B. Costa) and CNPq /
PIBIC (I. R. Rodrigues), are also acknowledged.
This compound was obtained as white solid, yield 65 %, Mp.
1
201 - 202 ºC. H NMR (CDCl ) δ = 9.05 (d, J=7.0, 1H, H-6), 8.10
3
(t, 2H, Ph), 7.75 (d, 2H, Ph), 7.17 (t, 2H, Ph, H-7, H-9), 7.13 (m,
1H, H-8), 6.84 (s, 1H, H-3). C NMR (CDCl ) δ = 164.5 (d, J=
251.4, F-Ph), 160.7 (C-2), 158.3 (C-4), 150.9 (C-9a), 136.4 (C-7),
133.1 (d, J=2.8, F-Ph), 129.5 (d, J=9.1, F-Ph), 127.3 (C-6), 126.5
(C-9), 115.7 (d, J=21.1, F-Ph), 115.2 (C-8), 99.5 (C-3). GC/MS
(EI, 70 eV): m/z (%) = 240 (M , 47), 212 (100), 78 (65), 51 (20).
13
1
3
4
3
2
REFERENCES AND NOTES
+
2-(4-Chlorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-ones (3e).
*
Author to whom correspondence should be addressed.
(E-mail heliogb@base.ufsm.br)
[1] S. Z. Zhu, Y. L. Wang, W. M. Peng, L. P. Song, G. F. Jin, Curr.
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A. F. C. Flores, H. G. Bonacorso, N. Zanatta, Curr. Org. Chem., 1, 391
(2004).
[3] H. G. Bonacorso, S. R. T. Bittencourt, A. D. Wastowski, A. P.
Wentz, N. Zanatta, M. A. P. Martins, J. Heterocyclic Chem., 36, 45
(1999).
This compound was obtained as white solid, yield 68 %, Mp.
1
203 - 204 ºC. H NMR (CDCl ) δ = 9.07 (d, J=7.0, 1H, H-6),
3
8.03 (d, J=8.8, 2H, Ph), 7.75 (m, 2H, H-7, H-9), 7.47 (d, J=8.8,
13
2H, Ph), 7.15 (m, 1H, H-8), 6.88 (s, 1H, H-3). C NMR (CDCl )
3
δ = 160.5 (C-2), 158.3 (C-4), 150.9 (C-9a), 136.7 (Ph), 136.2 (C-
7), 135.5 (Ph), 128.9 (Ph), 128.6 (Ph), 127.2 (C-6), 126.6 (C-9),
+
115.2 (C-8), 99.7 (C-3). GC/MS (EI, 70 eV): m/z (%) = 256 (M ,
47), 228 (100), 78 (73), 51 (33).
[4] H. G. Bonacorso, A. P. Wentz, S. R. T. Bittencourt, L. M. L.
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New York, 1992; pp 632.
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(1982).
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705 (1980).
[10] H. S. Lins, F. Nome, M. C. Rezende, I. de Souza, J. Chem.
Soc. Perkin Trans. 2, 1521 (1984).
[11] M. Uieara, C. Zucco, D. Zanatte, M. C. Rezende, F. Nome, J.
Chem. Soc. Perkin Trans. 2, 463 (1987).
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Comm., 17, 1741 (1987).
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1181 (1989).
2-(4-Bromophenyl)-4H-pyrido[1,2-a]pyrimidin-4-ones (3f).
This compound was obtained as white solid, yield 71 %, Mp.
1
200 - 201 ºC. H NMR (CDCl ) δ = 9.05 (d, J=7.2, 1H, H-6),
3
7.96 (d, J=8.5, 2H, Ph), 7.75 (m, 2H, H-7, H-9), 7.62 (d, J=8.6,
13
2H, Ph), 7.14 (m, 1H, H-8), 6.86 (s, 1H, H-3). C NMR (CDCl )
3
δ = 160.6 (C-2), 158.4 (C-4), 151.0 (C-9a), 136.4 (C-7), 135.9
(Ph), 131.9 (Ph), 128.9 (Ph), 127.3 (C-6), 126.6 (C-9), 125.3
(Ph), 115.3 (C-8), 99.8 (C-3). GC/MS (EI, 70 eV): m/z (%) = 301
+
(M , 47), 272 (85), 78 (100), 51 (49).
2-(4-Toluyl)-4H-pyrido[1,2-a]pyrimidin-4-ones (3g).
This compound was obtained as yellow solid, yield 70 %, Mp.
1
161 - 163 ºC. H NMR (CDCl ) δ = 9.01 (d, J=7.0, 1H, H-6),
3
7.97 (d, J=8.2, 2H, Ph), 7.67 (m, 2H, H-7, H-9), 7.27 (d, J=8.0,
2H, Ph), 7.05 (m, 1H, H-8), 6.86 (s, 1H, H-3), 2.39 (s, 3H, CH ).
3
13
C NMR (CDCl ) δ = 161.6 (C-2), 158.3 (C-4), 150.6 (C-9a),
140.7 (C-7), 135.9 (Ph), 134.0 (Ph), 129.2 (Ph), 127.0 (Ph), 126.9
3
(C-6), 126.3 (C-9), 114.8 (C-8), 99.1 (C-3), 21.2 (CH ). GC/MS
3
[14] S. C. Hess, F. Nome, C. Zucco, M. C. Rezende, Synthetic
Comm., 19, 3037 (1989).
+
(EI,70 eV): m/z (%) = 236 (M , 66), 208 (100), 78 (32), 51 (11).
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2-(4-Methoxyphenyl)-4H-pyrido[1,2-a]pyrimidin-4-ones (3h).
This compound was obtained as white solid, yield 45 %, Mp.

Jan-Feb 2006
Synthesis of 2-Alkyl(aryl) Substituted 4H-Pyrido[1,2-a]pyrimidin-4-ones
233
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