Synthesis of ethyl 6-aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido-[2′, 1′:4,5][1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates

Article abstract of DOI:10.1002/jhet.5570430614

The synthesis of ethyl 6-aryl-4-oxo-4,6-dihydro-1(12)(13)H- pyrimido[2′,1′:4,5][1,3,5]triazino[1,2-a]-benzimidazole-3- carboxylates (4a-p) was described via pyrimidine ring annulation to 4-aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole-2-amines (2a-p

Full text of DOI:10.1002/jhet.5570430614

Nov-Dec 2006
1513
Synthesis of Ethyl 6-Aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido-
[2',1':4,5][1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates [1]
Anton V. Dolzhenko, Wai-Keung Chui* and Anna V. Dolzhenko
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore
117543, Singapore. E-mail: phacwk@nus.edu.sg
Received December 29, 2005
COOEt
O
Ar
N
HN
NH
NH
NH2
2) EtO-CH=C(COOEt)2
N
N
N
1) ArCHO
N
N
H
16 examples
The synthesis of ethyl 6-aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]-
benzimidazole-3-carboxylates (4a-p) was described via pyrimidine ring annulation to 4-aryl-3,4-
dihydro[1,3,5]triazino[1,2-a]benzimidazole-2-amines (2a-p) which were obtained from 2-guanidino-
benzimidazole (1). Tautomerism in the prepared compounds was investigated using nmr spectroscopy.
Compounds 2a-p were found to be present in dimethyl sulfoxide solution predominantly as 3,4-dihydro
tautomeric form. Compounds 4a-p existed in dynamic equilibrium of 1-, 12- and 13H- forms. It was found
that methylation of 4a-d led to 13-methyl substituted derivatives 9a-d exclusively.
J. Heterocyclic Chem., 43, 1513 (2006).
Heterocyclic compounds with 1,3,5-triazino[1,2-a]-
1970 [23]. Using 1, a variety of aromatic aldehydes and
piperidine as a catalyst, we have prepared a library of
4-aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole-2-
amines (2a-p) (Scheme 1).
The formation of the dihydro-1,3,5-triazine ring with a
sp3 hybridized C-4 was confirmed by spectral data,
particularly, the signals of C-4 at 61.0-65.9 ppm in 13C
nmr spectra. The signals of the other two sp2 carbon atoms
of the formed 1,3,5-triazine ring (C-2 and C-10a),
surrounded by three nitrogen atoms each, were located at
154.9-155.5 and 153.2-153.9 ppm, respectively.
benzimidazole nucleus have been reported to possess a
variety of biological effects [2-13]. Our laboratory has
been working on the synthesis and biological evaluation
of new fused 1,3,5-triazines with a particular interest in
1,3,5-triazino[1,2-a]benzimidazoles because of their
potential antifolate activity [1-3]. In this report we
describe the synthesis of
a new fused four-ring
heterocyclic compounds bearing the 1,3,5-triazino[1,2-a]-
benzimidazole nucleus.
The reported methods for the synthesis of such fused
four-ring system can be broadly divided into 2 groups.
The first group uses benzimidazole that is substituted with
another heterocyclic ring as the starting material. [5+1]
Cyclization of the benzimidazole using a one carbon atom
inserting reagent that ring closes to give 1,3,5-triazine
which results in the formation of the four-ring nucleus
[14-19]. The formation of the fused 1,3,5-triazine ring
depends on the strategic location of the amino group in
the starting benzimidazole derivative. Only a limited
number of reports [20-22] have discussed the second
group of methods which is based on the annulation of a
fourth heterocyclic ring to an existing 1,3,5-triazino[1,2-
a]benzimidazole skeleton. The synthesis that we report
herein falls into this second group of methods and
employs 4-aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimi-
dazole-2-amines (2a-p) as amidine-type synthons.
Evidence indicating that the 4-aryl-3,4-dihydro[1,3,5]-
triazino[1,2-a]benzimidazole-2-amines (2a-p) could exist
in 3,4-dihydro, 1,4-dihydro and 4,10-dihydro tautomeric
forms was observed (Scheme 1). The prototropic
interconversion between these tautomeric forms led to the
broadening of the signals of C-2, C-4 and C-10a atoms in
the 13C nmr spectra of 2a-p. In NOESY 2D experiments
the pair of strong cross-peaks was observed for the signal
of N-H proton and the signal of H-4. The close spatial
relationship of H-4 and proton at the annular nitrogen
atom corresponded to the 3,4-dihydro tautomeric form.
The absence of cross-peaks between H-9 and NH
indicated the predominance of 3,4-dihydro tautomeric
form in dimethyl sulfoxide solution.
The reaction of the prepared 4-aryl-3,4-dihydro[1,3,5]-
triazino[1,2-a]benzimidazole-2-amines (2a-p) with
diethyl ethoxymethylenemalonate afforded the formation
of ethyl 6-aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido-
[2',1':4,5][1,3,5]triazino[1,2-a]benzimidazole-3-carboxyl-
ates (4a-p) (Scheme 2).
The synthesis of 3,4-dihydro[1,3,5]triazino[1,2-a]-
benzimidazole-2-amines through
a
base catalyzed
cyclization of 2-guanidinobenzimidazole (1) with
benzaldehyde was first reported by Nagarajan et al in

1514
A. V. Dolzhenko, W.-K. Chui and A. V. Dolzhenko
Vol 43
Scheme 1
R
N
NH2
N
N
NH
3'
4'
R
O
2'
5'
3
NH
4
H
6' 1'
5
HN
NH
R
6
NH2
NH2
N
N
7
8
2
N
1
N
H
N
10
piperidine, EtOH, reflux, 1-4 h
9
1
R
2a-p
N
NH2
N
N
N
H
The ring closure was found to be regioselective and led
to the intramolecular acylation to N-3 of the intermediates
3a-p. Structures of the compounds 4a-p were deduced
from the spectral data. The possible formation of the
compounds 5-7 (Figure) was investigated. Structure 6
might have formed from the same presumable
intermediate 3 by ring closure to N-1. Structures 5 and 7
might have been derived from 2a-p if the triazine ring
nitrogens N-3 or N-1 instead of exocyclic nitrogen were
involved in the initial adducts formation that was
followed by intramolecular acylation of the amino group.
Inasmuch as no cross peak was found for the singlets of
the triazine and pyrimidine ring protons in NOESY 2D
spectra, the structure 5 was ruled out. Only two pairs of
annular tautomeric forms with N-H proton located at
pyrimidine or triazine ring are possible for structures 6
and 7. Therefore, the broadening of some signals of
benzimidazole nucleus in 13C nmr spectra (vide infra)
made it possible to exclude the formation of the structures
6 and 7. The significant (~1 ppm) downfield shift of the
1
signal of triazine C-H proton in the H nmr spectra of
compounds 4a-p was attributed to the anisotropic effect of
the spatially close carbonyl group oxygen. This fact
proved the formation of the assigned structure 4a-p.
The tolerance of the method to the variety of
substituents was observed in the course of the reactions.
However, 18 h were required to convert compound 2e,
with 2'-methoxy group, to 4e instead of 3-5 h for the
synthesis of the other compounds in the series.
It should be noted that compounds 4a-p could exist at least
in three tautomeric forms with proton at N-1, N-12 or N-13
(Scheme 2). The prototropic interconversion between these
tautomeric forms was postulated based on the broadening of
the signals of 4,6-dihydro-1(12)(13)H-pyrimido[2',1':4,5]-
Scheme 2
R
COOEt
O
N
N
N
N
NH
EtOOC
EtO
COOEt
3'
4'
R
R
R
COOEt
3
O
EtOOC
COOEt
2'
5'
4
5
N
6
1'
6'
2
NH
N
NH
N
8
7
N
NH
1
NH
NH2
N
N
N
N
9
N
13
10
N
12
DMF, reflux, 3-18 h
R
11
COOEt
O
3a-p
2a-p
4a-p
N
N
N
N
N
H

Nov-Dec 2006
Synthesis of Ethyl 6-Aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido[2',1':4,5]-
[1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates
1515
[1,3,5]triazino[1,2-a]benzimidazole heterocyclic system in
the 13C nmr spectra of the compounds 4a-p, particularly, the
signals of C-2, C-11, C-12a, 13a and especially C-11a. These
atoms are located in close proximity with the nitrogen atoms
that are involved in the annular tautomerism. The discrete
and sharp signal of carbonyl group (C-4) in the 13C nmr
spectra indicates that the presence of theoretically possible 4-
hydroxy tautomeric form 8 (Figure) in the proton transfer
equilibrium is unlikely.
The methylation of 4a-d with methyl iodide was
attempted (Scheme 3). For elucidation of the structure of
the isolated compounds NOESY 2D experiment was used.
No cross-peaks for the introduced methyl group were
observed in the spectra that signified the structure of 13-
methyl substituted derivatives 9a-d.
Scheme 3
R
R
R
COOEt
NH
COOEt
R
O
O
COOEt
N
N
O
N
N
N
MeI, K2CO3
N
N
N
N
NH
NH
N
N
N
N
N
N
N
N
Me
DMF, rt, 12 h
COOEt
O
4a-d
9a-d
5
6
In summary, 4-aryl substituted 3,4-dihydro[1,3,5]tria-
zino[1,2-a]benzimidazole-2-amines (2a-p) were prepared.
The compounds 2a-p were found to be useful synthons
for the preparation of the hitherto unknown 4,6-dihydro-
1(12)(13)H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]benz-
imidazoles. The methylation of 4a-d was found to furnish
13-methyl substituted derivatives 9a-d exclusively. The
tautomerism of the compounds 2a-p and 3a-p was
discussed.
R
R
HO
COOEt
N
N
NH
O
N
N
N
N
N
N
N
COOEt
Figure
7
8
Table 1
4-Aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole-2-amines
Compound*
R
Yield
%
Mp
(°C)
Molecular
Formula
Analysis %, Calcd./Found
C
H
N
2b
2c
2d
2e
2f
2-Me
3-Me
4-Me
2-MeO
3-MeO
4-MeO
2-Cl
85
81
84
86
82
70
78
62
68
77
65
74
286-287
268-270
278-279
268-269
269-270
247-248
281-282
253-254
247-248
281-282
258-260
254-255
C16H15N5
69.30
69.18
69.30
69.12
69.30
69.15
65.52
65.44
65.52
65.39
65.52
65.43
60.51
60.42
60.51
60.38
60.51
60.48
52.65
52.53
52.65
52.56
52.65
52.48
5.45
5.62
5.45
5.78
5.45
5.63
5.15
5.27
5.15
5.32
5.15
5.28
4.06
4.20
4.06
4.25
4.06
4.12
3.53
3.62
3.53
3.63
3.53
3.67
25.25
25.02
25.25
24.97
25.25
25.08
23.88
23.72
23.88
23.70
23.88
23.72
23.52
23.43
23.52
23.39
23.52
23.48
20.47
20.35
20.47
20.38
20.47
20.32
C16H15N5
C16H15N5
C16H15N5O
C16H15N5O
C16H15N5O
C15H12ClN5
C15H12ClN5
C15H12ClN5
C15H12BrN5
C15H12BrN5
C15H12BrN5
2g
2k
2l
3-Cl
2m
2n
2o
2p
4-Cl
2-Br
3-Br
4-Br
*- 2a, 2h-j were described in our previous reports [2,3].

1516
A. V. Dolzhenko, W.-K. Chui and A. V. Dolzhenko
Vol 43
Table 2
Spectral Data of 4-Aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole-2-amines
Compound
1H nmr (300 MHz),
dimethyl sulfoxide-d6/TMS, ꢀ (ppm)
13C nmr (75 MHz),
dimethyl sulfoxide-d6/TMS, ꢀ (ppm)
2b
2c
2d
2.35 (s, 3H, Me), 6.32 (s, 2H, NH2), 6.41 (d, 1H, H-9, J = 7.9
Hz), 6.71 (t, 1H, H-8, J = 7.5 Hz), 6.90 (t, 1H, H-7, J = 7.7
Hz), 6.90 (s, 1H, H-4), 7.05 (d, 1H, H-6, J = 7.5 Hz), 7.15-
7.26 (m, 4H, H-3', -4', -5' and -6'), 7.97 (s, 1H, NH)
2.26 (s, 3H, Me), 6.70-6.76 (m, 4H, NH2, H-4 and -9), 6.80
(td, 1H, H-8, J = 7.5, 1.1 Hz), 6.94 (td, 1H, H-7, J = 7.5, 1.5
Hz), 7.13-7.24 (m, 4H, H-6, -2', -4' and -6'), 7.27 (t, 1H, H-5',
J = 7.5 Hz), 8.35 (br s, 1H, NH)
18.1 (Me), 64.7 (C-4), 107.9 (C-6), 115.9 (C-9), 118.7 (C-8),
120.6 (C-7), 126.4 (C-5'), 127.2 (C-6'), 129.1 (C-4'), 131.3 (C-5a),
131.3 (C-3'), 135.7 (C-2'), 137.0 (C-1'), 143.4 (C-9a), 153.9 (C-
10a), 155.2 (C-2)
20.9 (Me), 65.9 (C-4), 108.2 (C-6), 115.7 (C-9), 118.9 (C-8),
120.8 (C-7), 123.4 (C-6'), 126.6 (C-2'), 128.7 (C-5'), 129.8 (C-4'),
131.1 (C-5a), 138.1 (C-3'), 140.3 (C-1'), 142.8 (C-9a), 153.3 (C-
10a), 155.3 (C-2)
2.27 (s, 3H, Me), 6.41 (s, 2H, NH2), 6.70 (s, 1H, H-4), 6.71
(d, 1H, H-9, J = 7.9 Hz), 6.78 (td, 1H, H-8, J = 7.5, 1.1 Hz),
20.6 (Me), 65.7 (C-4), 108.2 (C-6), 115.8 (C-9), 118.9 (C-8),
120.7 (C-7), 126.1 (C-2' and -6'), 129.3 (C-3' and -5'), 131.1 (C-
6.92 (td, 1H, H-7, J = 7.5, 1.1 Hz), 7.19 (d, 2H, H-3' and -5', J 5a), 137.5* (C-1'), 138.6* (C-4'), 143.1 (C-9a), 153.5 (C-10a),
= 8.2 Hz), 7.22 (d, 1H, H-6, J = 7.9 Hz), 7.25 (d, 2H, H-2'
and -6', J = 8.2 Hz), 8.00 (s, 1H, NH)
155.4 (C-2)
2e
3.86 (s, 3H, OMe), 6.68 (s, 2H, NH2), 6.74 (d, 1H, H-9, J =
7.5 Hz), 6.75-6.82 (m, 2H, H-8 and -3'), 6.85 (t, 1H, H-5', J =
7.5 Hz), 6.94 (t, 1H, H-7, J = 7.2 Hz), 7.03 (s, 1H, H-4), 7.10
(d, 1H, H-6', J = 8.3 Hz), 7.22 (d, 1H, H-6, J = 7.9 Hz), 7.31
(t, 1H, H-4', J = 7.7 Hz), 8.08 (s, 1H, NH)
55.7 (OMe), 61.0 (C-4), 107.7 (C-6), 111.7 (C-3'), 115.8 (C-9),
118.8 (C-8), 120.5 (C-5'), 120.7 (C-7), 126.3 (C-1'), 127.4 (C-6'),
130.3 (C-4'), 131.2 (C-5a), 143.2 (C-9a), 153.8 (C-10a), 155.5 (C-
2), 156.2 (C-2')
2f
3.70 (s, 3H, OMe), 6.80 (s, 1H, H-4), 6.81-7.01 (m, 8H, NH2,
H-7, -8, -9, -2', -4' and -6'), 7.23 (d, 1H, H-6, J = 7.5 Hz),
7.29 (t, 1H, H-5', J = 7.9 Hz), 8.49 (s, 1H, NH)
55.0 (OMe), 65.5 (C-4), 108.2 (C-6), 112.2 (C-2'), 114.0 (C-4'),
115.8 (C-9), 118.0 (C-6'), 119.0 (C-8), 120.8 (C-7), 130.1 (C-5'),
131.1 (C-5a), 142.0 (C-1'), 143.0 (C-9a), 153.5 (C-10a), 155.4 (C-
2), 159.4 (C-3')
2g
3.72 (s, 3H, OMe), 6.72 (d, 1H, H-9, J = 7.5 Hz), 6.76 (s, 1H,
H-4), 6.79 (t, 1H, H-8, J = 7.5 Hz), 6.93 (t, 1H, H-7, J = 7.7
Hz), 6.93 (s, 2H, NH2), 6.94 (d, 2H, H-3' and -5', J = 8.7 Hz),
7.18 (d, 1H, H-6, J = 7.9 Hz), 7.34 (d, 2H, H-2' and -6', J =
8.7 Hz), 8.42 (s, 1H, NH)
55.1 (OMe), 65.5 (C-4), 108.3 (C-6), 114.1 (C-3' and -5'), 115.7
(C-9), 118.8 (C-8), 120.7 (C-7), 127.7 (C-2' and -6'), 131.2 (C-5a),
132.4 (C-1'), 143.1 (C-9a), 153.5 (C-10a), 155.5 (C-2), 159.7 (C-
4')
2k
6.44 (s, 2H, NH2), 6.61 (d, 1H, H-9, J = 7.5 Hz), 6.78 (t, 1H,
H-8, J = 7.5 Hz), 6.95 (t, 1H, H-7, J = 7.7 Hz), 7.08 (d, 1H,
H-6', J = 7.5 Hz), 7.09 (s, 1H, H-4), 7.25 (d, 1H, H-6, J = 7.5
Hz), 7.33 (t, 1H, H-5', J = 7.2 Hz), 7.40 (t, 1H, H-4', J = 7.2
Hz), 7.54 (d, 1H, H-3', J = 7.5 Hz), 8.10 (s, 1H, NH)
6.86 (t, 1H, H-8, J = 7.4 Hz), 6.90 (d, 1H, H-9, J = 7.6 Hz),
6.91 (s, 1H, H-4), 6.98 (td, 1H, H-7, J = 7.2, 1.9 Hz), 7.08 (br
s, 2H, NH2), 7.24-7.32 (m, 2H, H-6 and -6'), 7.37-7.45 (m,
2H, H-4' and -5'), 7.49 (s, 1H, H-2'), 8.66 (s, 1H, NH)
6.62 (s, 2H, NH2), 6.79 (d, 1H, H-9, J = 7.0 Hz), 6.82 (t, 1H,
63.4 (C-4), 107.5 (C-6), 116.0 (C-9), 118.9 (C-8), 120.9 (C-7),
128.0* (C-6'), 128.4* (C-5'), 130.1 (C-3'), 130.9 (C-4'), 131.0 (C-
2'), 131.3 (C-5a), 136.5 (C-1'), 143.3 (C-9a), 153.5 (C-10a), 155.0
(C-2)
2l
64.9 (C-4), 108.2 (C-6), 116.0 (C-9), 119.2 (C-8), 121.0 (C-7),
124.6 (C-6'), 126.1 (C-2'), 129.0 (C-5'), 131.0 (C-4'), 131.0 (C-5),
133.4 (C-3'), 142.8* (C-1'), 142.9* (C-9a), 153.3 (C-10a), 155.3
(C-2)
2m
65.0 (C-4), 108.0 (C-6), 116.0 (C-9), 118.9 (C-8), 120.8 (C-7),
H-8, J = 7.5 Hz), 6.82 (s, 1H, H-4), 6.94 (td, 1H, H-7, J = 7.2, 128.0* (C-2' and -6'), 128.9* (C-3' and -5'), 131.0 (C-5a), 133.6
2.3 Hz), 7.23 (d, 1H, H-6, J = 7.9 Hz), 7.38 (d, 2H, H-2' and -
6', J = 8.5 Hz), 7.47 (d, 2H, H-3' and -5', J = 8.5 Hz), 8.22 (s,
1H, NH)
(C-4'), 139.4 (C-1'), 143.3 (C-9a), 153.3 (C-10a), 155.2 (C-2)
2n
6.44 (s, 2H, NH2), 6.57 (d, 1H, H-9, J = 7.9 Hz), 6.78 (t, 1H,
H-8, J = 7.5 Hz), 6.95 (t, 1H, H-7, J = 7.5 Hz), 7.04 (s, 1H,
H-4), 7.07 (dd, 1H, H-6', J = 7.2, 1.5 Hz), 7.25 (d, 1H, H-6, J
= 7.9 Hz), 7.32 (td, 1H, H-4', J = 7.2, 1.5 Hz), 7.38 (td, 1H,
H-5', J = 7.2, 1.1 Hz), 7.71 (dd, 1H, H-3', J = 7.5, 1.1 Hz),
8.10 (s, 1H, NH)
65.8 (C-4), 107.6 (C-6), 116.0 (C-9), 119.0 (C-8), 120.9 (C-7),
121.1 (C-2'), 128.6* (C-6'), 128.7* (C-5'), 131.0 (C-4'), 131.2 (C-
5a), 133.3 (C-3'), 137.9 (C-1'), 143.4 (C-9a), 153.5 (C-10a), 154.9
(C-2)
2o
2p
6.82-6.91 (m, 3H, H-8, -9 and -4), 6.98 (td, 1H, H-7, J = 7.0,
2.3 Hz), 6.99 (br s, 2H, NH2), 7.26 (d, 1H, H-6, J = 7.9 Hz),
7.29-7.38 (m, 2H, H-5' and -6'), 7.55 (dt, 1H, H-4', J = 7.0,
2.0 Hz), 7.62 (s, 1H, H-2'), 8.59 (s, 1H, NH)
6.70 (s, 2H, NH2), 6.79 (d, 1H, H-9, J = 7.5 Hz), 6.82 (s, 1H,
H-4), 6.82 (t, 1H, H-8, J = 7.0 Hz), 6.95 (td, 1H, H-7, J = 7.0,
2.3 Hz), 7.23 (d, 1H, H-6, J = 7.9 Hz), 7.31 (d, 2H, H-2' and -
6', J = 8.3 Hz), 7.60 (d, 2H, H-3' and -5', J = 8.3 Hz), 8.31 (s,
1H, NH)
64.9 (C-4), 108.1 (C-6), 116.0 (C-9), 119.2 (C-8), 121.0 (C-7),
122.0 (C-3'), 125.0 (C-6'), 128.9 (C-2'), 131.0 (C-5), 131.2 (C-5'),
131.9 (C-4'), 143.0 (C-1'), 143.0 (C-9a), 153.3 (C-10a), 155.3 (C-
2)
65.0 (C-4), 108.1 (C-6), 115.9 (C-9), 119.0 (C-8), 120.8 (C-7),
122.2 (C-4'), 128.3 (C-2' and -6'), 131.0 (C-5a), 131.8 (C-3' and -
5'), 139.8 (C-1'), 143.2 (C-9a), 153.3 (C-10a), 155.2 (C-2)
* - Assignments may be reversed.

Nov-Dec 2006
Synthesis of Ethyl 6-Aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido[2',1':4,5]-
[1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates
1517
Table 3
Ethyl 6-Aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates
Compound
R
Yield
%
Mp
(°C)
Molecular
Formula
Analysis %, Calcd./Found
C
H
N
4a
4b
4c
4d
4e
4f
65.11
64.98
65.83
65.74
65.83
65.68
65.83
65.77
63.30
63.17
63.30
63.15
63.30
63.12
62.22
62.18
62.22
62.15
62.22
62.04
59.79
59.70
59.79
59.55
59.79
59.68
54.09
53.96
54.09
53.99
54.09
53.91
4.42
4.56
4.77
4.82
4.77
4.86
4.77
4.80
4.59
4.64
4.59
4.68
4.59
4.72
3.98
4.06
3.98
4.08
3.98
4.11
3.82
4.02
3.82
4.12
3.82
3.97
3.46
3.63
3.46
3.58
3.46
3.62
18.08
17.95
17.45
17.32
17.45
17.31
17.45
17.34
16.78
16.64
16.78
16.61
16.78
16.56
17.28
17.22
17.28
17.21
17.28
17.07
16.60
16.43
16.60
16.38
16.60
16.55
15.02
14.86
15.02
14.90
15.02
14.87
H
68
55
70
72
52
60
51
68
58
65
68
50
70
51
66
68
319-320
319-320
300-301
322-323
294-295
263-264
305-306
319-320
304-305
309-310
325-326
298-299
318-319
326-327
306-307
320-321
C21H17N5O3
C22H19N5O3
C22H19N5O3
C22H19N5O3
C22H19N5O4
C22H19N5O4
C22H19N5O4
C21H16FN5O3
C21H16FN5O3
C21H16FN5O3
C21H16ClN5O3
C21H16ClN5O3
C21H16ClN5O3
C21H16BrN5O3
C21H16BrN5O3
C21H16BrN5O3
2-Me
3-Me
4-Me
2-MeO
3-MeO
4-MeO
2-F
4g
4h
4i
3-F
4j
4-F
4k
4l
2-Cl
3-Cl
4-Cl
2-Br
3-Br
4-Br
4m
4n
4o
4p
Table 4
Spectral Data of Ethyl 6-Aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates
Compound
IR, potassium bromide,
ꢀ (cm-1)
1H nmr (300 MHz),
dimethyl sulfoxide-d6/TMS, ꢁ (ppm)
13C nmr (75 MHz),
dimethyl sulfoxide-d6/TMS, ꢁ (ppm)
4a
NH 3490, CH 3100-
2600, C=O 1706, 1637, CH2CH3, J = 13.9, 7.1 Hz), 4.16 (dq, 1H, CH2CH3, J =
1558, 1507, 1474,
1402, 1322, 1295,
1244, 1124, 796, 749
1.22 (dd, 3H, CH2CH3, J = 7.1, 7.1 Hz), 4.12 (dq, 1H,
14.1 (Me), 59.5 (CH2), 65.1 (C-6), 105.4 (C-
3), 110.5 (C-8), 112.8 (C-11), 122.8 (C-10),
123.8 (C-9), 126.6 (C-2' and -6'), 128.2 (C-
13.9, 7.1 Hz), 7.17 (td, 1H, H-9, J = 7.2, 1.1 Hz), 7.22
(td, 1H, H-10, J = 7.2, 1.1 Hz), 7.32-7.41 (m, 4H, H-11, 7a), 129.0 (C-3' and -5'), 129.7 (C-4'), 132.3
-3', -4' and -5'), 7.54 (dd, 2H, H-2'and -6', J = 7.9, 1.9 (C-11a), 137.3 (C-1'), 149.2 (C-13a), 154.9
Hz), 7.60 (dd, 1H, H-8, J = 7.2, 1.1 Hz), 8.05 (s, 1H, H- (C-12a), 156.8 (C-4), 160.3 (C-2), 163.3
6), 8.47 (s, 1H, H-2), 13.12 (br s, 1H, NH)
(COOEt)
4b
NH 3508, CH 3100-
2600, C=O 1706, 1636, ArMe), 4.10 (dq, 1H, CH2CH3, J = 10.6, 7.0 Hz), 4.15
1557, 1504, 1477,
1401, 1321, 1294,
1243, 1127, 799, 745
1.20 (dd, 3H, CH2CH3, J = 7.0, 7.0 Hz), 2.75 (s, 3H,
14.2 (Me), 18.7 (ArMe), 59.5 (CH2), 64.4
(C-6), 105.2 (C-3), 110.2 (C-8), 112.8 (C-
11), 122.8 (C-10), 123.7 (C-9), 127.0* (C-
5'), 127.1* (C-6'), 128.2 (C-7a), 129.5 (C-
4'), 130.9 (C-3'), 132.5 (C-11a), 136.0 (C-
2'), 138.3 (C-1'), 148.8 (C-13a), 154.9 (C-
12a), 157.1 (C-4), 160.0 (C-2), 163.2
(COOEt)
(dq, 1H, CH2CH3, J = 10.6, 7.0 Hz), 7.09-7.25 (m, 6H,
H-9, -10, -3', -4', -5' and -6'), 7.37 (d, 1H, H-11, J = 7.5
Hz), 7.40 (d, 1H, H-8, J = 7.9 Hz), 7.96 (s, 1H, H-6),
8.44 (s, 1H, H-2), 13.17 (br s, 1H, NH)
4c
NH 3455, CH 3100-
2600, C=O 1702, 1636, ArMe), 4.11 (dq, 1H, CH2CH3, J = 10.5, 7.2 Hz), 4.16
1556, 1506, 1472,
1401, 1320, 1297,
1248, 1127, 797, 746
1.22 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 2.25 (s, 3H,
14.1 (Me), 20.9 (ArMe), 59.5 (CH2), 65.1
(C-6), 105.4 (C-3), 110.5 (C-8), 112.7 (C-
11), 122.8 (C-10), 123.8 (C-9 and -6'), 127.0
(C-2'), 128.1 (C-7a), 128.8 (C-5'), 130.4 (C-
4'), 132.1 (C-11a), 137.3 (C-1'), 138.3 (C-
3'), 149.1 (C-13a), 154.8 (C-12a), 156.7 (C-
4), 160.2 (C-2), 163.3 (COOEt)
(dq, 1H, CH2CH3, J = 10.5, 7.2 Hz), 7.14 (d, 1H, H-4',
J = 7.5 Hz), 7.18 (t, 1H, H-9, J = 7.2 Hz), 7.22 (t, 1H,
H-10, J = 7.2 Hz), 7.25 (t, 1H, H-5', J = 7.3 Hz), 7.33
(d, 1H, H-6', J = 7.5 Hz), 7.36 (s, 1H, H-2'), 7.38 (dd,
1H, H-11, J = 7.7, 1.1 Hz), 7.59 (dd, 1H, H-8, J = 7.2,
1.1 Hz), 7.97 (s, 1H, H-6), 8.47 (s, 1H, H-2), 13.11 (br
s, 1H, NH)

1518
A. V. Dolzhenko, W.-K. Chui and A. V. Dolzhenko
Vol 43
Table 4 (continued)
Compound IR, potassium bromide,
1H nmr (300 MHz),
dimethyl sulfoxide-d6/TMS, ꢁ (ppm)
13C nmr (75 MHz),
dimethyl sulfoxide-d6/TMS, ꢁ (ppm)
ꢀ (cm-1)
4d
4e
4f
NH 3480, CH 3150-
2600, C=O 1706, 1638,
1557, 1507, 1476, 1439, (dq, 1H, CH2CH3, J = 10.9, 7.2 Hz), 7.16 (d, 2H, H-3'
1403, 1322, 1296, 1245, and -5', J = 8.1 Hz), 7.17 (td, 1H, H-9, J = 7.5, 1.1 Hz),
1127, 795, 750
1.22 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 2.21 (s, 3H,
ArMe), 4.12 (dq, 1H, CH2CH3, J = 10.9, 7.2 Hz), 4.16
14.1 (Me), 20.6 (ArMe), 59.5 (CH2), 64.9
(C-6), 105.5 (C-3), 110.5 (C-8), 112.7 (C-
11), 122.7 (C-10), 123.7 (C-9), 126.5 (C-2'
and -6'), 128.2 (C-7a), 129.4 (C-3' and -5'),
7.22 (td, 1H, H-10, J = 7.5, 1.1 Hz), 7.37 (d, 1H, H-11, J 132.4 (C-11a), 134.4 (C-1'), 139.4 (C-4'),
= 7.9 Hz), 7.40 (d, 2H, H-2' and -6', J = 8.1 Hz), 7.57 149.2 (C-13a), 154.8 (C-12a), 156.7 (C-4),
(dd, 1H, H-8, J = 7.5, 1.1 Hz), 7.99 (s, 1H, H-6), 8.45 (s, 160.1 (C-2), 163.4 (COOEt)
1H, H-2), 13.07 (br s, 1H, NH)
1.20 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 3.68 (s, 3H,
OMe), 4.10 (dq, 1H, CH2CH3, J = 10.2, 7.2 Hz), 4.14
NH 3450, CH 3090-
2580, C=O 1738, C=O
1707, 1637, 1557, 1505, (dq, 1H, CH2CH3, J = 10.2, 7.2 Hz), 6.97 (d, 1H, H-3', J
1475, 1440, 1321, 1299, = 7.9 Hz), 7.00 (t, 1H, H-5', J = 7.4 Hz), 7.11 (td, 1H,
1252, 1131, 799, 749
14.2 (Me), 55.5 (OMe), 59.4 (CH2), 64.9
(C-6), 105.2 (C-3), 110.0 (C-8), 112.1 (C-
3'), 112.9 (C-11), 120.1 (C-5'), 122.3 (C-
10), 123.3 (C-9), 124.2 (C-1'), 128.5 (C-7a),
131.1 (C-4' and -6'), 132.6 (C-11a), 148.7
(C-13a), 154.9 (C-12a), 156.8 (C-4), 157.0
(C-2'), 160.2 (C-2), 163.4 (COOEt)
H-9, J = 7.5, 1.1 Hz), 7.17 (td, 1H, H-10, J = 7.5, 1.1
Hz), 7.25-7.36 (m, 3H, H-11, -4' and -6'), 7.78 (dd, 1H,
H-8, J = 7.7, 1.3 Hz), 7.93 (s, 1H, H-6), 8.44 (s, 1H, H-
2), 12.98 (br s, 1H, NH)
1.23 (dd, 3H, CH2CH3, J = 7.5, 7.5 Hz), 3.71 (s, 3H,
OMe), 4.13 (dq, 1H, CH2CH3, J = 14.5, 7.5 Hz), 4.17
NH 3380, CH 3090-
2600, C=O 1736, C=O
1701, 1636, 1604, 1559, (dq, 1H, CH2CH3, J = 14.5, 7.5 Hz), 6.90 (dd, 1H, H-4',
1495, 1468, 1440, 1320, J = 8.3, 2.6 Hz), 6.99 (d, 1H, H-2', J = 7.5 Hz), 7.11-
1287, 1256, 1128, 800,
745
14.2 (Me), 55.1 (OMe), 59.4 (CH2), 64.7
(C-6), 104.7 (C-3), 110.4 (C-8), 113.3 (C-
2'), 113.3 (C-11), 114.2 (C-4'), 118.0 (C-6'),
122.4 (C-10), 123.4 (C-9), 128.6 (C-7a),
130.3 (C-5'), 134.1 (C-11a), 138.9 (C-1'),
149.8 (C-13a), 155.0 (C-12a), 156.9 (C-4),
7.22 (m, 3H, H-9, -10 and -6'), 7.26 (t, 1H, H-5', J = 7.9
Hz), 7.40 (d, 1H, H-11, J = 7.2 Hz), 7.63 (d, 1H, H-8, J
= 7.2 Hz), 8.01 (s, 1H, H-6), 8.48 (s, 1H, H-2), 12.90 (br 159.2 (C-3'), 160.3 (C-2), 163.5 (COOEt)
s, 1H, NH)
4g
4h
NH 3450, CH 3080-
2580, C=O 1705, 1636,
1613, 1557, 1508, 1475, (dq, 1H, CH2CH3, J = 10.9, 7.2 Hz), 6.90 (d, 2H, H-3'
1440, 1404, 1321, 1296, and -5', J = 8.6 Hz), 7.18 (t, 1H, H-9, J = 7.5 Hz), 7.23
1244, 1175, 1125, 797,
750
1.23 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 3.69 (s, 3H,
OMe), 4.13 (dq, 1H, CH2CH3, J = 10.9, 7.2 Hz), 4.18
14.1 (Me), 55.1 (OMe), 59.5 (CH2), 64.7
(C-6), 105.4 (C-3), 110.5 (C-8), 112.7 (C-
11), 114.2 (C-3' and -5'), 122.7 (C-10),
123.7 (C-9), 128.1 (C-2' and -6'), 128.2 (C-
7a), 129.4 (C-1'), 132.3 (C-11a), 149.2 (C-
13a), 154.8 (C-12a), 156.7 (C-4), 160.0 (C-
4'), 160.2 (C-2), 163.4 (COOEt)
(t, 1H, H-10, J = 7.2 Hz), 7.39 (d, 1H, H-11, J = 7.5
Hz), 7.47 (d, 2H, H-2' and -6', J = 8.6 Hz), 7.58 (d, 1H,
H-8, J = 7.5 Hz), 8.00 (s, 1H, H-6), 8.47 (s, 1H, H-2),
12.84 (br s, 1H, NH)
1.21 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 4.11 (dq, 1H,
CH2CH3, J = 10.9, 7.2 Hz), 4.14 (dq, 1H, CH2CH3, J =
NH 3445, CH 3080-
2550, C=O 1705, 1636,
1557, 1508, 1475, 1398, 10.9, 7.2 Hz), 7.14-7.46 (m, 7H, H-8, -9, -10, -11, -3', -
1366, 1321, 1298, 1248, 4' and -6'), 7.85 (td, 1H, H-5', J = 7.5, 1.5 Hz), 8.03 (s,
14.1 (Me), 59.5 (CH2), 62.9 (C-6), 105.2
(C-3), 109.6 (C-8), 113.0 (C-11), 116.1 (d,
C-3', J = 20.6 Hz), 122.7 (C-10), 123.7 (C-
9), 123.9 (d, C-1', J = 12.4 Hz), 124.8 (d, C-
5', J = 2.9 Hz), 128.1 (C-7a), 130.6 (d, C-6',
J = 2.9 Hz), 132.0 (d, C-4', J = 8.2 Hz),
132.5 (C-11a), 148.6 (C-13a), 154.5 (C-
12a), 156.8 (C-4), 159.7 (d, C-2', J = 248.1
Hz), 160.2 (C-2), 163.3 (COOEt)
1128, 767, 750
1H, H-6), 8.47 (s, 1H, H-2), 13.14 (br s, 1H, NH)
4i
NH 3440, CH 3080-
2600, C=O 1728, C=O
1706, 1638, 1556, 1505, 10.5, 7.2 Hz), 7.15-7.27 (m, 3H, H-9, -10 and -4'), 7.30
1475, 1320, 1295, 1244, (d, 1H, H-2', J = 7.5 Hz), 7.36-7.47 (m, 2H, H-11 and -
1.23 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 4.12 (dq, 1H,
CH2CH3, J = 10.5, 7.2 Hz), 4.17 (dq, 1H, CH2CH3, J =
14.1 (Me), 59.5 (CH2), 64.5 (C-6), 105.4
(C-3), 110.5 (C-8), 112.9 (C-11), 114.3 (d,
C-2', J = 22.9 Hz), 116.7 (d, C-4', J = 20.6
Hz), 122.3 (d, C-6', J = 2.9 Hz), 122.8 (C-
10), 123.8 (C-9), 128.1 (C-7a), 131.4 (d, C-
5', J = 8.2 Hz), 132.3 (C-11a), 139.7 (d, C-
1', J = 6.5 Hz), 149.1 (C-13a), 154.6 (C-
12a), 156.8 (C-4), 160.1 (C-2), 161.8 (d, C-
3', J = 245.8 Hz), 163.3 (COOEt)
1133, 803, 750
5'), 7.51 (ddd, 1H, H-6', J = 9.4, 1.9, 1.9 Hz), 7.65 (dd,
1H, H-8, J = 7.3, 1.3 Hz), 8.05 (s, 1H, H-6), 8.47 (s, 1H,
H-2), 13.20 (br s, 1H, NH)
4j
NH 3510, CH 3070-
2550, C=O 1702, 1635,
1556, 1509, 1475, 1440, 10.9, 7.2 Hz), 7.15-7.26 (m, 4H, H-9, -10, -3' and -5'),
1402, 1321, 1296, 1245, 7.39 (d, 1H, H-11, J = 7.2 Hz), 7.56-7.65 (m, 3H, H-8, -
1.22 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 4.13 (dq, 1H,
CH2CH3, J = 10.9, 7.2 Hz), 4.16 (dq, 1H, CH2CH3, J =
14.1 (Me), 59.5 (CH2), 64.4 (C-6), 105.4
(C-3), 110.4 (C-8), 112.8 (C-11), 115.9 (d,
C-3' and -5', J = 22.3 Hz), 122.8 (C-10),
123.8 (C-9), 128.1 (C-7a), 129.1 (d, C-2'
and -6', J = 8.8 Hz), 132.4 (C-11a), 133.7
(d, C-1', J = 2.9 Hz), 149.2 (C-13a), 154.7
(C-12a), 156.8 (C-4), 160.2 (C-2), 162.4 (d,
C-4', J = 247.0 Hz), 163.3 (COOEt)
1125, 797, 749
2' and -6'), 8.06 (s, 1H, H-6), 8.47 (s, 1H, H-2), 12.56
(br s, 1H, NH)
4k
NH 3480, CH 3100-
2600, C=O 1703, 1638,
1556, 1507, 1476, 1402, 10.5, 7.2 Hz), 7.15 (t, 1H, H-9, J = 7.3 Hz), 7.16-7.28
1321, 1297, 1249, 1131, (m, 2H, H-10 and -5'), 7.34-7.50 (m, 4H, H-8, -11, -4'
1.20 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 4.10 (dq, 1H,
CH2CH3, J = 10.5, 7.2 Hz), 4.15 (dq, 1H, CH2CH3, J =
14.2 (Me), 59.5 (CH2), 65.9 (C-6), 105.1
(C-3), 109.7 (C-8), 113.0 (C-11), 122.7 (C-
10), 123.7 (C-9), 127.9 (C-5'), 128.3 (C-7a),
130.2 (C-6'), 131.2* (C-3'), 131.4* (C-4'),
131.6 (C-2'), 132.5 (C-11a), 134.3 (C-1'),
148.6 (C-13a), 154.5 (C-12a), 156.9 (C-4),
159.9 (C-2), 163.2 (COOEt)
1111, 795, 745
and -6'), 7.81 (dd, 1H, H-3', J = 7.0, 2.4 Hz), 8.00 (s,
1H, H-6), 8.45 (s, 1H, H-2), 13.16 (br s, 1H, NH)

Nov-Dec 2006
Synthesis of Ethyl 6-Aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido[2',1':4,5]-
[1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates
1519
Table 4 (continued)
Compound IR, potassium bromide,
1H nmr (300 MHz),
dimethyl sulfoxide-d6/TMS, ꢁ (ppm)
13C nmr (75 MHz),
dimethyl sulfoxide-d6/TMS, ꢁ (ppm)
ꢀ (cm-1)
4l
NH 3465, CH 3070-
2570, C=O 1704, 1635,
1557, 1501, 1475, 1440, 10.7, 7.2 Hz), 7.19 (t, 1H, H-9, J = 7.5 Hz), 7.24 (t, 1H,
1401, 1320, 1295, 1244, H-10, J = 7.2 Hz), 7.35-7.46 (m, 4H, H-11, -4', -5' and -
1127, 796, 754
1.22 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 4.13 (dq, 1H,
CH2CH3, J = 10.7, 7.2 Hz), 4.16 (dq, 1H, CH2CH3, J =
14.1 (Me), 59.5 (CH2), 64.5 (C-6), 105.4
(C-3), 110.5 (C-8), 112.9 (C-11), 122.9 (C-
10), 123.9 (C-9), 125.0 (C-6'), 127.1 (C-2'),
128.1 (C-7a), 129.8* (C-5'), 131.2* (C-4'),
132.3 (C-11a), 133.3 (C-3'), 139.4 (C-1'),
149.1 (C-13a), 154.6 (C-12a), 156.8 (C-4),
160.1 (C-2), 163.2 (COOEt)
6'), 7.64 (d, 1H, H-8, J = 7.2 Hz), 7.74 (s, 1H, H-2'),
8.04 (s, 1H, H-6), 8.47 (s, 1H, H-2), 13.19 (br s, 1H,
NH)
4m
NH 3505, CH 3080-
2600, C=O 1704, 1638,
1558, 1507, 1476, 1417, 14.2, 7.0 Hz), 7.19 (td, 1H, H-9, J = 7.5, 1.1 Hz), 7.24
1321, 1297, 1245, 1125, (td, 1H, H-10, J = 7.5, 1.1 Hz), 7.40 (dd, 1H, H-11, J =
1111, 795, 749
1.23 (dd, 3H, CH2CH3, J = 7.0, 7.0 Hz), 4.13 (dq, 1H,
CH2CH3, J = 14.2, 7.0 Hz), 4.17 (dq, 1H, CH2CH3, J =
14.2 (Me), 59.5 (CH2), 64.6 (C-6), 105.5
(C-3), 110.5 (C-8), 112.9 (C-11), 122.8 (C-
10), 123.9 (C-9), 128.1 (C-7a), 128.7 (C-2'
and -6'), 129.0 (C-3' and -5'), 132.4 (C-11a),
134.4 (C-1'), 136.2 (C-4'), 149.1 (C-13a),
154.6 (C-12a), 156.8 (C-4), 160.2 (C-2),
163.3 (COOEt)
7.2, 1.1 Hz), 7.45 (d, 2H, H-3' and -5', J = 8.3 Hz), 7.60
(d, 2H, H-2' and -6', J = 8.7 Hz), 7.60 (d, 1H, H-8, J =
7.2 Hz), 8.07 (s, 1H, H-6), 8.49 (s, 1H, H-2), 13.22 (br
s, 1H, NH)
4n
4o
4p
NH 3460, CH 3070-
2550, C=O 1702, 1638,
1556, 1505, 1476, 1441, 10.9, 7.0 Hz), 7.16 (t, 1H, H-9, J = 7.7 Hz), 7.22 (t, 1H,
1403, 1320, 1296, 1250, H-10, J = 7.2 Hz), 7.27-7.34 (m, 2H, H-5' and -6'), 7.38
1132, 1111, 795, 745
1.21 (dd, 3H, CH2CH3, J = 7.0, 7.0 Hz), 4.11 (dq, 1H,
CH2CH3, J = 10.9, 7.0 Hz), 4.14 (dq, 1H, CH2CH3, J =
14.2 (Me), 59.5 (CH2), 67.8 (C-6), 105.1
(C-3), 110.0 (C-8), 113.0 (C-11), 121.5 (C-
2'), 122.7 (C-10), 123.8 (C-9), 128.3 (C-7a),
128.6 (C-5'), 130.9 (C-6'), 131.5 (C-3'),
132.6 (C-11a), 133.4 (C-4'), 136.1 (C-1'),
148.6 (C-13a), 154.5 (C-12a), 157.0 (C-4),
159.7 (C-2), 163.2 (COOEt)
(d, 1H, H-11, J = 7.6 Hz), 7.43 (t, 1H, H-4', J = 7.9 Hz),
7.65 (d, 1H, H-8, J = 7.2 Hz), 7.73 (d, 1H, H-3', J = 7.5
Hz), 7.94 (s, 1H, H-6), 8.45 (s, 1H, H-2), 13.19 (br s,
1H, NH)
1.23 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 4.13 (dq, 1H,
CH2CH3, J = 10.7, 7.2 Hz), 4.16 (dq, 1H, CH2CH3, J =
NH 3465, CH 3080-
2600, C=O 1734, 1668,
1627, 1561, 1496, 1466, 10.7, 7.2 Hz), 7.20 (t, 1H, H-9, J = 7.2 Hz), 7.24 (t, 1H,
1440, 1389, 1272, 1254, H-10, J = 7.2 Hz), 7.32 (t, 1H, H-5', J = 8.0 Hz), 7.40
1228, 1122, 800, 753
14.1 (Me), 59.6 (CH2), 64.5 (C-6), 105.4
(C-3), 110.5 (C-8), 112.9 (C-11), 121.8 (C-
3'), 122.9 (C-10), 123.9 (C-9), 125.3 (C-6'),
128.1 (C-7a), 129.9 (C-2'), 131.4 (C-5'),
(d, 1H, H-11, J = 7.2 Hz), 7.48 (d, 1H, H-4', J = 7.9 Hz), 132.5 (C-11a), 132.7 (C-4'), 139.6 (C-1'),
7.55 (d, 1H, H-6', J = 7.9 Hz), 7.65 (d, 1H, H-8, J = 7.9
Hz), 7.88 (s, 1H, H-2'), 8.03 (s, 1H, H-6), 8.48 (s, 1H,
H-2), 13.15 (br s, 1H, NH)
1.23 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 4.13 (dq, 1H,
CH2CH3, J = 14.5, 7.2 Hz), 4.17 (dq, 1H, CH2CH3, J =
149.1 (C-13a), 154.6 (C-12a), 156.8 (C-4),
160.1 (C-2), 163.2 (COOEt)
NH 3455, CH 3070-
2560, C=O 1704, 1634,
1559, 1508, 1476, 1413, 14.5, 7.2 Hz), 7.18 (td, 1H, H-9, J = 7.5, 1.1 Hz), 7.24
1321, 1296, 1245, 1126, (td, 1H, H-10, J = 7.5, 1.1 Hz), 7.40 (d, 1H, H-11, J =
795, 750
14.2 (Me), 59.5 (CH2), 64.7 (C-6), 105.4
(C-3), 110.5 (C-8), 112.9 (C-11), 122.8 (C-
10), 123.1 (C-4'), 123.9 (C-9), 128.1 (C-7a),
128.9 (C-2' and -6'), 132.0 (C-3' and -5'),
132.4 (C-11a), 136.6 (C-1'), 149.1 (C-13a),
154.6 (C-12a), 156.8 (C-4), 160.2 (C-2),
163.3 (COOEt)
7.2 Hz), 7.52 (d, 2H, H-3' and -5', J = 8.7 Hz), 7.59 (d,
2H, H-2' and -6', J = 8.7 Hz), 7.60 (d, 1H, H-8, J = 7.2
Hz), 8.05 (s, 1H, H-6), 8.48 (s, 1H, H-2), 13.21 (br s,
1H, NH)
* - Assignments may be reversed .
Table 5
Ethyl 6-Aryl-13-methyl-4-oxo-6,13-dihydro-4H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates
Compound*
R
Yield
%
Mp
(°C)
Molecular
Formula
Analysis %, Calcd./Found
C
H
N
9a
9b
9c
9d
H
52
62
58
70
247-248
260-261
205-206
257-259
C22H19N5O3
C23H21N5O3
C23H21N5O3
C23H21N5O3
65.83
65.60
66.49
66.22
66.49
66.24
66.49
66.25
4.77
4.85
5.09
5.35
5.09
5.32
5.09
5.28
17.45
17.32
16.86
16.68
16.86
16.55
16.86
16.63
2-Me
3-Me
4-Me

1520
A. V. Dolzhenko, W.-K. Chui and A. V. Dolzhenko
Vol 43
Table 6
Spectral Data of Ethyl 6-Aryl-13-methyl-4-oxo-6,13-dihydro-4H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates
Compound
IR, potassium bromide,
ꢀ (cm-1)
1H nmr (300 MHz),
dimethyl sulfoxide-d6/TMS, ꢁ (ppm)
13C nmr (75 MHz),
dimethyl sulfoxide-d6/TMS, ꢁ (ppm)
9a
CH 2790-3090, C=O
1740, 1671, 1560, 1520,
1497, 1455, 1286, 1253,
1127, 1111, 766, 744,
699
1.24 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 3.79 (s, 3H,
NMe), 4.16 (dq, 1H, CH2CH3, J = 11.3, 7.0 Hz), 4.21
(dq, 1H, CH2CH3, J = 11.3, 7.0 Hz), 7.13 (td, 1H, H-9, 122.0 (C-10), 122.8 (C-9), 126.6 (C-2' and -
J = 7.3, 1.2 Hz), 7.18 (td, 1H, H-10, J = 7.3, 1.5 Hz),
7.31-7.39 (m, 3H, H-3', -4' and -5'), 7.48-7.57 (m, 3H,
H-11, -2' and -6'), 7.67 (dd, 1H, H-8, J = 7.2, 1.5 Hz),
8.07 (s, 1H, H-6), 8.58 (s, 1H, H-2)
14.0 (CH2Me), 31.6 (NMe), 60.1 (CH2), 64.8
(C-6), 108.4 (C-3), 110.3 (C-8), 117.9 (C-11),
6'), 129.0 (C-3' and -5'), 129.7 (C-4'), 131.3
(C-7a), 136.4 (C-1'), 141.6 (C-11a), 144.4 (C-
13a), 149.9 (C-12a), 155.6 (C-4), 159.3 (C-2),
162.9 (COOEt)
9b
CH 2790-3100, C=O
1710, 1684, 1560, 1523,
1496, 1456, 1301, 1294,
1261, 1135, 795, 739
1.22 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 2.80 (s, 3H,
ArMe), 3.83 (s, 3H, NMe), 4.15 (dq, 1H, CH2CH3, J =
10.9, 7.2 Hz), 4.20 (dq, 1H, CH2CH3, J = 10.9, 7.2
Hz), 7.08-7.25 (m, 6H, H-9, -10, -3', -4', -5' and -6'),
7.35 (d, 1H, H-11, J = 7.9 Hz), 7.54 (dd, 1H, H-8, J =
7.9, 1.1 Hz), 7.94 (s, 1H, H-6), 8.57 (s, 1H, H-2)
14.1 (CH2Me), 18.8 (ArMe), 31.6 (NMe),
60.1 (CH2), 64.1 (C-6), 108.1 (C-3), 109.5
(C-8), 117.9 (C-11), 122.1 (C-10), 122.8 (C-
9), 126.7 (C-5')*, 127.2 (C-6')*, 129.5 (C-4'),
130.9 (C-3'), 131.3 (C-7a), 135.2 (C-1'),
136.3 (C-2'), 141.5 (C-11a), 143.7 (C-13a),
149.7 (C-12a), 155.9 (C-4), 159.2 (C-2),
162.8 (COOEt)
9c
CH 2790-3120, C=O
1742, 1712, 1683, 1519,
1496, 1456, 1400, 1286,
1259, 1134, 1113, 745,
711
1.24 (dd, 3H, CH2CH3, J = 7.2, 7.2 Hz), 2.24 (s, 3H,
ArMe), 3.79 (s, 3H, NMe), 4.16 (dq, 1H, CH2CH3, J =
11.1, 7.0 Hz), 4.20 (dq, 1H, CH2CH3, J = 11.1, 7.0
Hz), 7.08-7.19 (m, 3H, H-9, -10 and -4'), 7.22 (t, 1H,
H-5', J = 7.5 Hz), 7.29 (d, 1H, H-6', J = 7.5 Hz), 7.36
(s, 1H, H-2'), 7.54 (dd, 1H, H-11, J = 6.8, 1.5 Hz),
7.64 (dd, 1H, H-8, J = 6.8, 1.5 Hz), 7.99 (s, 1H, H-6),
8.57 (s, 1H, H-2)
14.0 (CH2Me), 20.8 (ArMe), 31.6 (NMe),
60.1 (CH2), 64.9 (C-6), 108.4 (C-3), 110.3
(C-8), 117.8 (C-11), 122.0 (C-10), 122.7 (C-
9), 123.7 (C-6'), 127.1 (C-2'), 128.9 (C-5'),
130.5 (C-4'), 131.2 (C-7a), 136.4 (C-1'),
138.4 (C-3'), 141.6 (C-11a), 144.3 (C-13a),
149.9 (C-12a), 155.5 (C-4), 159.3 (C-2),
162.9 (COOEt)
9d
CH 2750-3095, C=O
1720, 1694, 1558, 1517,
1498, 1456, 1291, 1267,
1254, 1133, 796, 736
1.24 (dd, 3H, CH2CH3, J = 7.0, 7.0 Hz), 2.20 (s, 3H,
ArMe), 3.78 (s, 3H, NMe), 4.16 (dq, 1H, CH2CH3, J =
11.3, 7.0 Hz), 4.21 (dq, 1H, CH2CH3, J = 11.3, 7.0
Hz), 7.12 (td, 1H, H-9, J = 7.3, 1.2 Hz), 7.13 (d, 2H,
H-3' and -5', J = 8.0 Hz), 7.18 (td, 1H, H-10, J = 7.6,
1.5 Hz), 7.39 (d, 2H, H-2' and -6', J = 8.0 Hz), 7.54
(dd, 1H, H-11, J = 7.2, 1.5 Hz), 7.63 (dd, 1H, H-8, J =
7.2, 1.5 Hz), 8.02 (s, 1H, H-6), 8.57 (s, 1H, H-2)
14.0 (CH2Me), 20.6 (ArMe), 31.6 (NMe),
60.1 (CH2), 64.7 (C-6), 108.4 (C-3), 110.3
(C-8), 117.8 (C-11), 122.0 (C-10), 122.7 (C-
9), 126.5 (C-2' and -6'), 129.4 (C-3' and -5'),
131.2 (C-7a), 133.5 (C-1'), 139.4 (C-4'),
141.6 (C-11a), 144.4 (C-13a), 149.9 (C-12a),
155.5 (C-4), 159.3 (C-2), 162.9 (COOEt)
* - Assignments may be reversed .
EXPERIMENTAL
General Procedure for Preparation of Ethyl 6-Aryl-4-oxo-4,6-
dihydro-1(12)(13)H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]-
benzimidazole-3-carboxylates (4a-p).
Melting points (uncorrected) were determined on
Gallenkamp melting point apparatus. The infrared spectra were
performed on Jasco FT-IR-430 spectrophotometer in
a
A solution of appropriate 4-aryl-3,4-dihydro[1,3,5]triazino-
[1,2-a]benzimidazole-2-amines 2a-p (2.5 mmol) and diethyl
ethoxymethylenemalonate (0.5 mL, 2.5 mmol) in DMF (15
mL) was heated under reflux for 3-18 h. After cooling, the
product was filtered, washed with ethanol, dried and
recrystallized from DMF.
a
potassium bromide pellets. 1H and 13C nmr spectra were
recorded on a Bruker DPX-300 spectrometer in dimethyl
sulfoxide-d6 solution using TMS as an internal reference.
2-Guanidinobenzimidazole (1) was prepared from o-phenyl-
enediamine according to the reported method [24]. Synthesis
and proprieties of 4-aryl-3,4-dihydro[1,3,5]triazino[1,2-a]-
benzimidazole-2-amines (2a, 2h-j) were described in our
previous reports [2,3].
General Procedure for Preparation of Ethyl 6-Aryl-13-methyl-4-
oxo-6,13-dihydro-4H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]-
benzimidazole-3-carboxylates (9a-d).
A mixture of the appropriate ethyl 6-aryl-4-oxo-4,6-dihydro-
1(12)(13)H-pyrimido[2',1':4,5][1,3,5]triazino[1,2-a]benzimi-
dazole-3-carboxylate 4a-d (1.0 mmol) and anhydrous
potassium carbonate (0.27 g, 1.5 mmol) in 7 mL DMF was
stirred at room temperature while iodomethane (0.71 g, 5.0
mmol) was added dropwise over a period of 10 min. The
mixture was stirred for 24 h at room temperature. At the end of
this time, the reaction mixture was poured into 25 mL of ice
cold water and allowed to stand at 4° for 5-10 h. The
General Procedure for Preparation of 4-Aryl-3,4-dihydro[1,3,5]-
triazino[1,2-a]benzimidazole-2-amines (2b-g, k-p).
A solution of 2-guanidinobenzimidazole 1 (1.75 g, 10.0
mmol), appropriate benzaldehyde (10.0 mmol) and 0.5 mL
piperidine in ethanol (30-50 mL) was heated under reflux for
1-4 h. After cooling, the product was filtered, washed with
ethanol, dried and recrystallized from DMF/ethanol.

Nov-Dec 2006
Synthesis of Ethyl 6-Aryl-4-oxo-4,6-dihydro-1(12)(13)H-pyrimido[2',1':4,5]-
[1,3,5]triazino[1,2-a]benzimidazole-3-carboxylates
1521
Wolter, W. Kochmann, W. Kramer, and W. Steinke, East German
Patent, 214,054 (1984); Chem. Abstr., 102, 127347 (1985).
[11] C. Bennion and D. Robinson, European Patent, 93,515
(1983); Chem. Abstr., 100, 85727 (1984).
precipitate was collected by filtration and recrystallized from
ethanol to give pure products 9a-d.
Acknowledgement.
[12] J. F. Koerwer, Canadian Patent, 1,146,376 (1983); Chem.
Abstr., 99, 175809 (1983).
[13] C. E. Ward and R. V. Berthold, Canadian Patent, 1,159,065
(1983); Chem. Abstr., 100, 209880 (1984).
This work is supported by the Academic Research Fund from
the National University of Singapore.
[14] F. Saczewski, T. Debowski, and J. Szmigiel, Heterocycles,
48, 1879 (1998).
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