A radical synthetic approach to the new potentially bioactive pyrimidinones

Article abstract of DOI:10.3987/com-00-9133

2-Chloromethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one was shown to react with various nitronate or malonate anions under mild conditions to give potentially bioactive nitro-4H-pyrido[1,2-a]pyrimidin-4-ones. Extension to other anions centred on S

Full text of DOI:10.3987/com-00-9133

HETEROCYCLES, Vol. 55, No. 3, pp. 535 – 544, Received, 30th November, 2000
A RADICAL SYNTHETIC APPROACH TO THE NEW POTENTIALLY
BIOACTIVE PYRIMIDINONES§
a,b
a,b
a
b
Serge Djekou, Armand Gellis, José Maldonado, Michel P. Crozet, and
a,b
Patrice Vanelle *
a
Laboratoire de Chimie Organique, Université de la Méditerranée, Faculté de
Pharmacie, 27 boulevard Jean Moulin, 13385 Marseille Cedex 5, France
Fax: (33) 04 91 79 46 77 ; E-mail: patrice.vanelle@pharmacie.univ-mrs.fr
b
LCMO, UMR 6517, CNRS-Universités d'Aix-Marseille 1 et 3, BP 562, 13397
Marseille Cedex 20, France
Abstract - 2-Chloromethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one
was shown to react with various nitronate or malonate anions under mild
conditions to give potentially bioactive nitro-4H-pyrido[1,2-a]pyrimidin-4-ones.
Extension to other anions centred on S or O atom allows to generalize this
synthetic procedure.
Wagner1 in 1977 has described the activity of 3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one derivatives
against Trichomonas foetus and Entamoeba histolytica. Satti2 has reported a good activity of some
pyrido[1,2-a]pyrimidines against Leishmania donovani in 1993. Accumulating interest in these
heterocycles was derived from their broad range of useful pharmacological properties, e.g. antidepressant,
antihypertensive, analgetic, antiinflammatory, cytoprotective, bronchodilatory, antithrombotic,
antiallergic and antiatherosclerotic activities.3 Since then, an increasing number of pharmaceutical
companies4 have investigated the pharmacological actions of various 4H-pyrido[1,2-a]pyrimidin-4-one
compounds, probably due to their favorable properties: they have relatively low toxicities, and in general
they possess good pharmacokinetic properties.
On the other hand, our research investigations into the electron transfer reactions have started in the mid
§ This paper is dedicated to the memory of Professor Claude Ghiglione.

1980’s, when we described the preparation of new 5-nitroimidazoles bearing one or two tri- or tetra-
substituted ethylenic double bonds at the 2 position by reacting original reductive alkylating agents with
various aliphatic, cyclic or heterocyclic anions.5 This work led us to synthesize the most active of all 5-
nitroimidazole derivatives, the 1-methyl-3-(1-methyl-5-nitro-1H-imidazol-2-yl-methylene)pyrrolidin-2-
one. 6
The interest of the pyrido[1,2-a]pyrimidine ring for medicinal chemistry led us to consider that electron
transfer reactions might provide easy and versatile access to original 3-nitro-4H-pyrido[1,2-a]pyrimidin-
4-ones. By this strategy, we report here a new preparative method of potentially bioactive pyrimidinones.
As suitable alkylating agent, we selected 2-chloromethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-
one (2). This chloride was easily obtained by cyclocondensation7 of 2-amino-4-methylpyridine with ethyl
4-chloroacetoacetate and nitration with H2SO4/HNO3 at 0 °C (Scheme 1).
Scheme 1
O
O
O
NO2
Cl
HNO3
H2SO4
N
PPA
N
N
OEt
+
Cl
Cl
CH3
NH2
5 h, 110 °C
O
CH3
N
CH3
N
2
1
73%
86%
Derivative (2) was treated under nitrogen and photostimulation with various nitronate or malonate anions
(3a-k). By using 4 equivalents of anion during 20 min under phase-transfer conditions with 40%
tetrabutylammonium hydroxide in water and dichloromethane,8 we obtained the ethylenic derivatives
(4a-k) in moderate to good yields (53 to 77%) as shown in Scheme 2 and indicated in the Table. This
alkene was classically formed by electron transfer C-alkylation and base-promoted nitrous acid
elimination from the C-alkylation product. The single electron transfer mechanism was confirmed in the
reaction of 2 with 2-nitropropane anion (3a) by depression of reaction rate by addition of classical
inhibitors9 (p-dinitrobenzene as radical anion scavenger, 2,2,6,6-tetramethyl-1-piperidinyloxy or TEMPO
as radical trap, bubbling dioxygen). When the ethylenic derivative was unsymmetrical, the
stereochemistry of the double bond has been determinated by NMR (NOESY), and only the E isomer was
isolated.
Scheme 2
R1
R2
NBu4
O
O
N
O
N
NO2
(4 eq.)
NO2
NO2
NO2
Cl
N
N
N
- HNO2
3a-k
R1
R1
R2
R2
NO2
CH2Cl2 - H2O
hν, Ar, 20 min
CH3
N
CH3
CH3
NPP
4a-k
2
53-77%

Table
R1
R2
R1
O2N
O2N
Anion
Compound
4 Yield (%)
R2
NPP
CH3
CH3
NO2
CH3
CH3
NPP
NPP
NPP
3a
4a
77
3b
3c
4b
4c
70
66
NO2
NO2
NO2
3d
3e
4d
4e
57
54
NPP
NPP
O
O
CH3
CH3
O2N
CH3
CH3
O
O
3f
4f
53
77
NPP
H
CH3
CH3
NO2
H
3g
4g
NPP
CH3CH2
CH2CH3
NO2
3h
3i
4h
4i
61
54
68
65
NPP
H
CH3CH2CH2
NO2
CH2CH2CH3
NO2
NPP
CH3
COOCH2CH3
OCH2CH3
CH3
NPP
NPP
3j
4j
O
NO2
COOCH2CH3
COOCH2CH3
CH3CH2O
OCH2CH3
3k
4k
O
O
As an understanding of the relationship between the nucleophile and the substrate in single electron
transfer is useful in order to increase the selectivity and the yield of the reaction,10 we have investigated
the reactivity of 2 with other conventional nucleophiles as for example S-centred anions.11 The reaction
between the sodium salt of benzenesulfinic acid (5) or benzyl mercaptan (7) and 2 in degassed methanol
gave the required products (6) and (8) respectively in 56 and 78% yields (Scheme 3). By addition of

TEMPO in catalytic quantities or when the reaction was performed in the dark, the yields of 6 and 8
strongly decreased indicating that the single electron transfer mechanism is the most probable for the S-
alkylation of chloride (2).
Scheme 3
O
PhSO2 Na+
-
NO2
N
5
(2 eq.)
56%
78%
6
O
N
CH3
CH3
N
O
SO2
CH3OH, hν, 24 h
NO2
Cl
N
PhCH2S- Na+
NO2
CH3
N
7
(2 eq.)
8
2
S
N
CH3OH, hν, 24 h
Moreover, coumarins are a class of naturally occurring lactones, which display a wide range of biological
activities.12 Kornblum has studied alkylation of 2-carbethoxycoumaran-3-one in nitrobenzylic system via
radical chain process.13 Recently, the reaction of 4-hydroxycoumarins with a series of quinonic chlorides
under photostimulation was shown to provide an efficient approach to 3-alkylated coumarin derivatives.14
Radical reduction of 2 with lithium salt of 4-hydroxycoumarin (9) in degassed methanol under irradiation
gave the C-alkylation product (10) in 62% yield as shown in Scheme 4.
Scheme 4
O
Li+
O
O
NO2
NO2
CH3OH
N
N
O
+
O
Cl
24 h, hν
CH3
N
O
O
CH3
N
(2 eq.)
HO
62%
2
9
10
In conclusion, we have demonstrated here that this present methodology based on electron transfer
reactions is a valuable and general method for the preparation of new potentially active pyrido[1,2-a]-
pyrimidin-4-ones under mild operating conditions.
ACKNOWLEDGEMENTS
This work has been supported by the Centre National de la Recherche Scientifique and the Universities of
Aix-Marseille. We express our thanks to Professor H. El-Kashef for stimulating discussions and M.
Noailly for 1H and 13C NMR spectra recording. S. Djekou thanks the Ministry of National Education for a
student research fellowship.

EXPERIMENTAL
Melting points were determined on Büchi B-540 and are uncorrected. Elemental analyses were performed
by the Centre de Microanalyses of the University of Aix-Marseille 3 and of the INP-ENSCT (Toulouse,
1
13
1
France). Both H and C NMR spectra were determined on a Bruker ARX 200 spectrometer. The H
13
chemical shifts are reported as parts per million downfield from tetramethylsilane (Me4Si), and the C
chemical shifts were referenced to the solvent peak: CDCl3 (76.9 ppm). Solvents were dried by
conventional methods. The following adsorbent was used for column chromatography: silica gel 60
(Merck, particule size 0.063-0.200 mm, 70-230 mesh ASTM). TLC were performed on 5 cm x 10 cm
aluminium plates coated with silica gel 60F-254 (Merck) in an appropriate solvent.
2-Chloromethyl-8-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (1)
A mixture of polyphosphoric acid (7.5 g), 2-amino-4-methylpyridine (1.35 g, 12.5 mmol) and ethyl 4-
chloroacetoacetate (2.8 g, 17 mmol) was stirred at 110 °C for 5 h. After cooling, ice-cold solution of 10%
sodium hydroxide (50 mL) was slowly added to adjust the pH to 7. The mixture was filtered and the
precipitate was purified by chromatography on silica column eluting with dichloromethane-ether (6:4)
and recrystallization from ethanol giving 1.9 g (73%) of yellow solid. 1, mp 109 °C (mp 109-110 °C
1
lit.,7), H NMR (CDCl3) δ 2.40 (s, 3H); 4.46 (s, 2H); 6.62 (s, 1H); 6.98 (d, J = 7.3 Hz, 1H); 7.43 (br s,
1H); 8.98 (d, J = 7.3 Hz, 1H).
2-Chloromethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (2)
To a solution of 2-chloromethyl-8-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (1 g, 4.8 mmol) in
concentrated sulfuric acid (3 mL), fuming nitric acid (2 mL) was added dropwise at 0 °C. The reaction
mixture was stirred at the same temperature for 1 h and poured into cold ice (50 mL). After filtration, the
crude product was dissolved in dichloromethane (20 mL). The solvent was washed with saturated sodium
bicarbonate solution (3 x 20 mL) and dried over anhydrous magnesium sulfate. After removal of the
solvent under reduced pressure, purification by chromatography on silica gel eluting with
dichloromethane-ether (6:4) and recrystallization from ethanol gave 1.05 g (86%) of yellow solid. 2, mp
170 °C, 1H NMR (CDCl3) δ 2.62 (s, 3H); 4.76 (s, 2H); 7.30 (d, J = 7.3 Hz, 1H); 7.67 (s, 1H); 9.08 (d, J =
7.3 Hz, 1H). 13C NMR (CDCl3) δ 21.89; 43.17; 121.02; 125.64; 128.38; 134.80; 150.43; 151.67; 153.79;
157.58. Anal. Calcd for C10H8N3O3Cl: C, 47.35; H, 3.18; N, 16.57. Found: C, 47.25; H, 3.14; N, 16.48.
The nitroalkanes were commercially available or prepared from the primary or secondary amines by
oxidation with m-CPBA15,16 in refluxed 1,2-dichloroethane for 3 h. 2,2-Dimethyl-5-nitro-1,3-dioxane17
and ethyl 2-nitropropionate18 were obtained as previously described. Diethyl nitromalonate was
commercially available.
General procedure for the reactions of 2 with anions (3a-k)

Under nitrogen atmosphere, an aqueous solution of 40% tetrabutylammonium hydroxide in water (2.6 g,
4 mmol) reacted with nitroalkane (4 mmol) or 2,2-dimethyl-5-nitro-1,3-dioxane (0.64 g, 4 mmol) or ethyl
2-nitropropionate (0.58 g, 4 mmol) or diethyl nitromalonate (0.81 g, 4 mmol) for 1 h. A solution of 2
(0.25 g, 1 mmol) in dichloromethane (10 mL) was added and the mixture was stirred at rt during 20 min
under nitrogen and irradiation with two 60 W tungsten lamps from a distance of 10 cm. The organic layer
was separated and the aqueous layer was extracted with dichloromethane (3 x 10 mL). The combinated
organic layers were dried over magnesium sulfate and evaporated under reduced pressure. Purification by
chromatography on silica column eluting with pentane-ether (8:2) (purification A) or dichloromethane-
ethyl acetate (6:4) (purification B) and recrystallization from ethanol gave the required products (4a-k).
8-Methyl-2-(2-methylpropenyl)-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (4a)
Yellow solid, 77% yield (purification A), mp 210 °C, 1H NMR (CDCl3) δ 2.07 (s, 3H); 2.23 (s, 3H); 2.56
(s, 3H); 6.31 (s, 1H); 7.12 (d, J = 7.3 Hz, 1H); 7.52 (s, 1H); 8.98 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3)
δ 21.08; 21.74; 28.49; 117.58; 119.37; 125.00; 127.77; 133.83; 149.46; 151.51; 152.29; 155.81; 159.19.
Anal. Calcd for C13H13N3O3: C, 60.22; H, 5.05; N, 16.21. Found: C, 60.14; H, 5.05; N, 16.18.
2-Cyclopentylidenemethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (4b)
1
Yellow solid, 70% yield (purification B), mp 209 °C, H NMR (CDCl3) δ 1.66-1.83 (m, 4H); 2.52-2.68
(m, 2H); 2.62 (s, 3H); 2.98-3.01 (m, 2H); 6.50 (s, 1H); 7.07 (d, J = 7.2 Hz, 1H); 7.67 (s, 1H); 8.96 (d, J =
7.2 Hz, 1H). 13C NMR (CDCl3) δ 21.60; 25.31; 26.84; 33.82; 37.64; 112.70; 118.93; 124.85; 127.58;
149.25; 151.06; 155.20; 167.71. Anal. Calcd for C15H15N3O3: C, 63.15; H, 5.30; N, 14.73. Found: C,
63.23; H, 5.32; N, 14.71.
2-Cyclohexylidenemethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (4c)
1
Yellow solid, 66% yield (purification B), mp 212 °C, H NMR (CDCl3) δ 1.56-1.63 (m, 6H); 2.31-2.34
(m, 2H); 2.54 (s, 3H); 2.75-2.78 (m, 2H); 6.25 (s, 1H); 7.09 (d, J = 7.3 Hz, 1H); 7.50 (s, 1H); 9.01 (d, J =
7.3 Hz, 1H). 13C NMR (CDCl3) δ 21.69; 26.26; 27.89; 28.64; 30.79; 38.73; 114.83; 119.33; 125.00;
127.73; 149.29; 151.43; 155.31; 158.74. Anal. Calcd for C16H17N3O3: C, 64.20; H, 5.72; N, 14.04. Found:
C, 64.06; H, 5.69; N, 14.09.
2-Cycloheptylidenemethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (4d)
1
Yellow solid, 57% yield (purification B), mp 239 °C, H NMR (CDCl3) δ 1.60-1.80 (m, 8H); 2.52-2.55
(m, 2H); 2.59 (s, 3H); 2.94-2.97 (m, 2H); 6.30 (s, 1H); 7.11 (d, J = 7.2 Hz, 1H); 7.48 (s, 1H); 8.99 (d, J =
7.2 Hz, 1H). 13C NMR (CDCl3) δ 21.63; 26.79; 28.17; 28.91; 29.52; 32.67; 40.09; 117.12; 119.18;
125.00; 127.63; 149.20; 151.22; 152.73; 155.72; 162.41. Anal. Calcd for C17H19N3O3: C, 65.16; H, 6.11;
N,13.41. Found: C, 65.31; H, 6.09; N, 13.43.
2-Cyclooctylidenemethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (4e)

Yellow solid, 54% yield (purification B), mp 223 °C, 1H NMR (CDCl3) δ 1.49-1.81 (m, 10H); 2.43-2.46
(m, 2H); 2.54 (s, 3H); 2.98-3.02 (m, 2H); 6.32 (s, 1H); 7.09 (d, J = 7.2 Hz, 1H); 7.45 (s, 1H); 8.98 (d, J =
7.2 Hz, 1H).13C NMR (CDCl3) δ 21.61; 25.57; 26.13; 26.60; 27.31; 27.65; 31.22; 39.80; 116.83; 119.08;
124.89; 127.57; 128.51; 149.16; 151.15; 151.56; 155.22; 164.86. Anal. Calcd for C18H21N3O3: C, 66.04;
H, 6.47; N, 12.84. Found: C, 65.89; H, 6.44; N, 12.89.
2-[(2,2-Dimethyl-1,3-dioxan-5-ylidene)methyl]-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one
(4f)
Yellow solid, 53% yield (purification A), mp 141 °C, 1H NMR (CDCl3) δ 1.24 (s, 3H); 1.39 (s, 3H); 2.54
(s, 3H); 4.07 (s, 2H); 4.38 (s, 2H); 5.52 (s, 1H); 7.31 (d, J = 6.9 Hz, 1H); 7.70 (s, 1H); 8.91 (d, J = 6.9
Hz, 1H).13C NMR (CDCl3) δ 21.78; 22.97; 23.49; 61.33; 63.53; 64.97; 86.74; 99.57; 119.84; 124.73;
127.95; 149.79; 152.46; 160.56. Anal. Calcd for C16H17N3O5: C, 58.00; H, 5.17; N, 12.68. Found: C,
58.12; H, 5.16; N, 12.63.
8-Methyl-3-nitro-2-propenyl-4H-pyrido[1,2-a]pyrimidin-4-one (4g)
Yellow solid, 77% yield (purification B), mp 210 °C, E isomer, 1H NMR (CDCl3) δ 2.04 (q, J = 1.5 Hz,
3H); 2.53 (s, 3H); 6.66 (d, J = 13.4 Hz, 1H); 7.08 (d, J = 7.1 Hz, 1H); 7.40-7.57 (m, 1H); 7.66 (s, 1H);
8.95 (d, J = 7.1 Hz, 1H). 13C NMR (CDCl3) δ 20.95; 21.64; 119.02; 121.25; 124.80; 127.57; 127.72;
148.86; 149.52; 151.47; 151.71; 153.54. Anal. Calcd for C12H11N3O3: C, 58.77; H, 4.52; N, 17.13. Found:
C, 58.69; H, 4.57; N, 17.15.
2-But-1-enyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (4h)
1
Yellow solid, 61% yield (purification B), mp 187 °C, E isomer, H NMR (CDCl3) δ 1.13 (t, J = 7.4 Hz,
3H); 2.28-2.44 (m, 2H); 2.53 (s, 3H); 6.62 (d, J = 15 Hz, 1H); 7.08 (d, J = 7.1 Hz, 1H); 7.36-7.50 (dd, J =
15 Hz and 6.6 Hz, 1H); 7.47 (s, 1H); 8.95 (d, J = 7.1 Hz, 1H). 13C NMR (CDCl3) δ 12.49; 21.63; 26.29;
119.01; 121.26; 124.78; 127.56; 127.70; 148.89; 149.51; 151.44; 151.70; 153.54. Anal. Calcd for
C13H13N3O3: C, 60.22; H, 5.05; N, 16.21. Found: C, 60.13; H, 5.01; N, 16.29.
8-Methyl-3-nitro-2-pent-1-enyl-4H-pyrido[1,2-a]pyrimidin-4-one (4i)
Yellow solid, 54% yield (purification B), mp 162 °C, E isomer, 1H NMR (CDCl3) δ 1.01 (t, J = 7.3 Hz,
3H); 1.47-1.62 (m, 2H); 2.26-2.37 (m, 2H); 2.53 (s, 3H); 6.64 (d, J = 15 Hz, 1H), 7.08 (d, J = 7.1 Hz,
1H), 7.32-7.43 (dd, J = 15 Hz and 6.5 Hz, 1H), 7.48 (s, 1H), 9.03 (d, J = 7.1 Hz, 1H). 13C NMR (CDCl3)
δ 13.79; 21.64; 22.34; 26.29; 119.01; 121.26; 124.78; 127.56; 127.70; 148.89; 149.51; 151.44; 151.70;
153.54. Anal. Calcd for C14H15N3O3: C, 61.53; H, 5.53; N, 15.38. Found: C, 61.61; H, 5.58; N, 15.30.
Ethyl 2-methyl-3-(8-methyl-3-nitro-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)acrylate (4j)
1
Yellow solid, 68% yield (purification A), mp 145 °C, E isomer, H NMR (CDCl3) δ 1.35 (t, J = 7.1 Hz,
3H); 2.25 (s, 3H); 2.60 (s, 3H); 4.28 (q, J = 7.1 Hz, 2H); 7.18 (d, J = 7.2 Hz, 1H); 7.58 (s, 1H); 7.61 (s,

13
1H); 9.09 (d, J = 7.2 Hz, 1H). C NMR (CDCl3) δ 14.14; 14.75; 21.77; 61.50; 120.44; 125.43; 128.06;
129.86; 138.29; 141.26; 149.74; 151.10; 152.95; 155.54; 167.05. Anal. Calcd for C15H15N3O5: C, 56.78;
H, 4.76; N, 13.24. Found: C, 56.81; H, 4.75; N, 13.20.
Diethyl 2-[(8-methyl-3-nitro-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)methylene]malonate (4k)
1
Yellow solid, 65% yield (purification A), mp 152 °C, H NMR (CDCl3) δ 1.31 (t, J = 7.1 Hz, 3H); 1.35
(t, J = 6.9 Hz, 3H); 2.59 (s, 3H); 4.34 (q, J = 7.1 Hz, 2H); 4.37 (q, J = 6.9 Hz, 2H); 7.21 (d, J = 7.2 Hz,
13
1H); 7.46 (br s, 1H); 7.79 (s, 1H); 9.08 (d, J = 7.2 Hz, 1H). C NMR (CDCl3) δ 14.02; 14.09; 21.86;
61.50; 62.40; 120.65; 125.30; 128.32; 132.89; 134.77; 142.01; 149.45; 151.10; 152.59; 153.35; 162.77;
164.93. Anal. Calcd for C17H17N3O7: C, 54.40; H, 4.57; N, 11.20. Found: C, 54.21; H, 4.63; N, 11.28.
Sodium salt of benzenesulfinic acid was commercially available.
Preparation of the sodium salt of benzyl mercaptan (7) and the lithium salt of 4-hydroxycoumarine (9)
A sodium or lithium methoxide was prepared by careful addition of sodium (0.58 g, 0.025 at.g) or lithium
(0.17 g, 0.025 at.g) to methanol (15 mL). After the solution had become clear, benzyl mercaptan (3.10 g,
0.025 mol) or 4-hydroxycoumarine (4.05 g, 0.025 mol) was added, the solution was stirred at rt for 2 h
and concentrated under vacuum. When the solution became viscous, about 300 mL of ether was added to
cause precipitation. The sodium salt (7) or lithium salt (9) was filtered, washed by ether and kept under
oil-pump vacuum for 24 h.
General procedure for the reaction of 2 with anions (5) or (7) or (9)
To a solution of 2 (0.25 g, 1 mmol) in dry methanol (5 mL), sodium salt of benzenesulfinic acid (0.32 g, 2
mmol) or sodium salt of benzyl mercaptan (0.29 g, 2 mmol) or lithium salt of 4-hydroxycoumarine (0.33
g, 2 mmol) was added under dry nitrogen. The reaction mixture was then irradiated with fluorescent
lamps. After stirring at rt for 24 h, methanol was evaporated under reduced pressure. Purification by
chromatography on silica column eluting with pentane-ether (8:2) and recrystallization from ethanol gave
the required products.
2-Benzenesulfonylmethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (6)
Yellow solid, 56% yield, mp 177 °C, 1H NMR (CDCl3) δ 2.59 (s, 3H); 4.93 (s, 2H); 7.28 (d, J = 7.3 Hz,
1H); 7.49-7.89 (m, 5H); 7.87 (s, 1H); 9.07 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 21.86; 58.13;
121.07; 125.46; 128.30; 129.34; 134.29; 138.93; 149.60; 150.50; 150.92; 153.91. Anal. Calcd for
C16H13N3O5S: C, 53.48; H, 3.65; N, 11.69. Found: C, 53.39; H, 3.72; N 11.70.
2-Benzylsulfanylmethyl-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one (8)
Yellow solid, 78% yield, mp 111 °C, 1H NMR (CDCl3) δ 2.55 (s, 3H); 3.58 (s, 2H); 5.66 (s, 2H); 7.33 (d,
J = 7.25 Hz, 1H); 7.42 (s, 1H); 7.67-7.70 (m, 5H); 9.01 (d, J = 7.25 Hz, 1H). 13C NMR (CDCl3) δ 21.64;
29.68; 43.22; 127.40; 128.47; 129.28; 129.39; 130.19; 133.80; 137.32; 138.90; 151.49; 153.11; 155.14;
172.28. Anal. Calcd for C17H15N3O3S: C, 59.81; H, 4.43; N, 12.31. Found: C, 59.65; H, 4.39; N, 12.27.

2-[(4-Hydroxy-2-oxo-2H-chromen-3-yl)methyl]-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-4-one
(10)
Yellow solid, 62% yield, mp 214 °C, 1H NMR (CDCl3) δ 2.54 (s, 3H); 5.48 (s, 2H); 5.61 (s, 1H); 7.18-7.28
13
(m, 4H); 7.48 (br s, 1H); 7.75 (d, J = 9.7 Hz, 1H); 9.01 (d, J = 7.2 Hz, 1H). C NMR (CDCl3) δ 21.86;
66.22; 91.62; 115.21; 116.71; 120.85; 121.18; 123.19; 123.96; 124.28; 125.83; 128.52; 132.74; 150.10;
153.25; 154.12; 156.30; 162.74; 165.11. Anal. Calcd for C19H13N3O6: C, 60.16; H, 3.45; N, 11.08. Found:
C, 60.06; H, 3.57; N, 11.19.
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