Med Chem Res
Recently, the literature reports have revealed in vivo
anticonvulsant activities of novel heterocyclic synthons, viz.
dihydropyridines (Ulloora et al., 2013a, b), imidazo-[1,2-a]
pyridine (Ulloora et al., 2013a, b) using standard PTZ and
MES tests. As a part of our ongoing interest to find novel
psychoactive compounds, it was thought worthwhile to
evaluate the anticonvulsant activities of functionalized
pyrimidinones 3a–h synthesized by [4 ? 2] cycloaddition
reactions of differently substituted 1,3-diaza-1,3-butadienes
in CDCl
d 7.23 (m, 10H, H-aromatic);7.92 (m, 4H, H-aromatic),
NMR (75.5 MHz, CDCl ): 14.25, 44.83, 99.16, 124.38,
3
; d 1.23 (m, 6H, –CH
3
),d 3.44 (m, 4H, 2x–CH –),
2
1
3
C
3
124.39, 127.30, 128.17, 129.83, 132.75, 132.75, 134.30,
135.2, 135.09, 147.38, 154.2, 157.1, 160.12, 166.21; m/z
?
465(M ? 1) . HRMS calcd for C28
?
(M) :
H
25
N
O
3
4
465.1927, found 465.1930.
2
-(4-Dipropylamino-6-oxo-1,2-diphenyl-1,6-dihydro-pyrim
idin-5-yl)-isoindole-1,3-dione, 3b Yield 68 %; m.pt
-
1
a–h with phthalimidoketene. The phthalimidoketene was
1 1
1
54–155 °C; IR (KBr) t 1665 cm ; H NMR (300 MHz)
generated in situ from the phthaloylglycine using p-toluene
sulphonylchloride and triethylamine in dry chloroform at
room temperature.
in CDCl , d 0.74 (m, 6H, –CH ), d 1.69 (m, 4H, 2x–CH –),
3
3
2
d 3.43 (m, 4H, CH –N–CH ), d 7.19 (m, 10H, H-aromatic);
2
2
1
3
d 7.36 (2H, H-aromatic), d 7.92 (m, 2H, H-aromatic)
NMR (75.5 MHz, CDCl ) in CDCl : 11.24, 21.91, 52.05,
C
3
3
9
1
1
1.79, 123.70, 127.82, 128.16, 128.63, 129.06, 129.27,
29.70,132.28, 134.31, 134.96, 137.25, 156.09, 157.62,
Materials and methods
?
60.90, 169.46, m/z 493 (M ? 1) . HRMS calcd for
Unless otherwise noted, commercially available materials were
used without further purification. Thin-layer chromatography
?
C H N O (M ? 1) : 493.2240, found 493.2243.
0 29 4 3
3
(
TLC) was carried out using 0.2 mm Kieselgel F254 (Merck)
2-(4-Morpholin-4-yl-6-oxo-1,2-diphenyl-1,6-dihydro-pyrim
idin-5-yl)-isoindole-1,3-dione, 3c Yield 78 %; m.pt
silica plates and compounds visualized in UV. NMR spectra
were recorded on a Bruker 300 MHz spectrometer operating at
-
1 1
161–164 °C; IR (KBr) t 1671 cm ; H NMR (300 MHz)
in CDCl d 3.62 (m, 4H, –CH –N–CH –), d 3.81 (m, 4H,
CH –O–CH –), d 7.19 (m, 10H, H-aromatic); d 7.75 (m,
2H, H-aromatic), 7.93 (m, 2H, H-aromatic), C NMR
(75.5 MHz, CDCl ) in CDCl : d 49.8, 66.2, 98.21, 124.24,
1
13
3
00 MHz for H and 75 MHz for C. Chemical shifts (d) are
3
2
2
quoted in parts per million (ppm) relative to internal solvent
1
2
2
13
reference (CDCl d = 7.26 for H NMR and d = 77.0 for C
13
3
NMR). Coupling constants are given in Hz, and chemical shifts
are reported in d values in ppm. Data are reported as followed:
chemical shift, multiplicity (s = singlet, s br = broad singlet,
d = doublet, t = triplet, dd = double doublet, and
dt = double triplet, m = multiplet), coupling constants (Hz),
and integration. High-resolution mass spectra were recorded on
a Bruker-microTOF-Q II mass spectrometer. Melting points
were determined by open capillary using Veego Precision
Digital Melting Point apparatus (MP-D) and are uncorrected.
3
3
128.59, 128.75, 128.91, 128.97, 129.01, 129.10, 129.78,
132.14, 134.87, 134.9, 137.8, 157.1, 160.1, 168.2; m/z 493
?
(M ? 1) , HRMS calcd for C28
?
(M ? 1) :
H
23
N
O
4
4
479.1719, found 479.1721.
2
-(6-Oxo-1,2-diphenyl-4-pyrrolidin-1-yl-1,6-dihydro-pyrim
idin-5-yl)-isoindole-1,3-dione, 3d Yield 80 %; m.pt
-
1
1
2
55–256 °C; IR (KBr) t 1720, 1655 cm
;
H NMR
(
300 MHz) in CDCl d 1.89 (m, 4H, 2x–CH –), d 3.52 (m,
3
2
IR spectra were recorded on
spectrophotometer.
a Shimadzu D-8001
4
H, (–CH –N–CH –), d 7.27 (m, 10H, H-aromatic), 7.74
2
2
1
m, 2H, H-aromatic), 7.93 (2H, H-aromatic); C NMR
3
(
General procedure for the preparation of 5-isoindole-1,3-
dione pyrimidinones pyrimidinones, (3a–h) To a solution
of 1,3-diazabutadiene 1a–h (5 g, 1 eq.), phthaloylglycine 2
(75.5 MHz, CDCl ) in CDCl : d 25.29, 48.29, 124.06,
128.40, 128.87, 129.37, 129.54, 129.96, 132.72, 134.46,
?
135.26, 137.50, 156.94, 160.85, 169.63; m/z 463 (M ? 1)
3
3
?
(M ? 1) : 463.1770, found
(
(
(
1.5 eq.), and triethylamine (4 eq.) in dry chloroform
100 mL) at 0 °C was added dropwise a solution of p-TsCl
2.0 eq.) in dry chloroform. The progress of the reaction
HRMS calcd for C28
463.1772.
H
23
N
4
O
3
2
-(6-Oxo-1,2-diphenyl-4-piperidin-1-yl-1,6-dihydro-pyrim
was monitored with the help of TLC. After completion of
reaction, a usual workup was performed using chloroform
and brine solution. The organic layers were collected, dried
over sodium sulfate, and evaporated to get crude product.
The crude product was recrystallized using 10 % chloro-
form in diethyl ether to get pure 5-isoindole-1,3-dione
pyrimidinones (3a–h) in good yields.
idin-5-yl)-isoindole-1,3-dione 3e Yield 83 %; m.pt
-
1 1
1
95–197 °C; IR (KBr) t 1658 cm ; H NMR (300 MHz)
in CDCl ; d 1.29 (m, 6H, –CH –CH –CH ), d 3.69 (m, 4H,
3
2
2
2
CH –N–CH ), 7.26 (m, 10H, H-aromatic); 7.71 (m, 2H,
2
2
1
3
H-aromatic), 7.98 (m, 2H, H-aromatic),
C NMR
(
75.5 MHz, CDCl ) in CDCl : d 26.11, 47.56, 92.69,
3
3
123.74, 127.6, 128.2, 128.5, 128.6, 129.03, 129.27, 129.75,
2
-(4-Diethylamino-6-oxo-1,2-diphenyl-1,6-dihydro-pyrim
132.33, 134.28, 134.83, 137.19, 156.5, 158.0, 160.9,
?
168.59; m/z 477 (M ? 1) HRMS calcd for C29
idin-5-yl)-isoindole-1,3-dione, 3a Yield 75 %; m.pt
-
H
25
N
O
4
3
1
1
?
(M ? 1) : 477.1927, found 477.1930.
1
85–187 °C; IR (KBr) t 1662 cm ; H NMR (300 MHz)
1
23