Synthesis of novel annelated systems based on the interaction and reactivity estimation of amino-1,5-benzodiazepin-2-ones with dimethyl-2-oxoglutaconate

Article abstract of DOI:10.1002/jhet.226

(Chemical Equation Presented) A number of substituted tetracyclic 4H-[1,4]diazepino[3,2,1-hi]pyrido[4,3,2-cd]indole and tricyclic 1H-[1,4]diazepino[2,3-g] or [2,3-h]quinoline derivatives were prepared from 7- (or 8, or 9)amino-1,5-benzodiazepin-2-ones by

Full text of DOI:10.1002/jhet.226

November 2009
Synthesis of Novel Annelated Systems Based on the Interaction
and Reactivity Estimation of Amino-1,5-benzodiazepin-2-ones
with Dimethyl-2-oxoglutaconate
1339
Regina Janciene,a* Zita Stumbreviciute,a Ausra Vektariene,b
Lidija Kosychova,a Algirdas Klimavicius,a Algirdas Palaima,a
and Benedikta Puodziunaitea
aDepartment of Bioorganic Compounds Chemistry, Institute of Biochemistry, Mokslininku 12,
LT-08662 Vilnius, Lithuania
bVU Institute of Theoretical Physics and Astronomy, A. Gostauto 12, LT-01108 Vilnius, Lithuania
*E-mail: apalaima@bchi.lt
Received March 4, 2009
DOI 10.1002/jhet.226
Published online 11 November 2009 in Wiley InterScience (www.interscience.wiley.com).
A number of substituted tetracyclic 4H-[1,4]diazepino[3,2,1-hi]pyrido[4,3,2-cd]indole and tricyclic 1H-
[1,4]diazepino[2,3-g] or [2,3-h]quinoline derivatives were prepared from 7- (or 8, or 9)amino-1,5-benzodia-
zepin-2-ones by the Doebner–von Miller quinoline synthesis. The structure of the cyclized products
depends on the position of the primary amino group and on the substituents of the diazepine ring of the
starting compounds. The regiochemical outcome of the reaction was estimated by calculating average local
ionization energies on the molecular surface at the Density Functional Theory (DFT) level of theory.
J. Heterocyclic Chem., 46, 1339 (2009).
INTRODUCTION
where the pyridine ring is annelated to the aromatic ring
of bicyclic benzodiazepine.
Benzodiazepines and their polycyclic derivatives are
known as medically active synthetic substances [1].
Quinoline ring system derivatives are important as anti-
malarial agents. In addition, quinolines are present as
structural subunits of naturally occurring products, such
as quinonoid alcohol dehydrogenase coenzyme [2,3].
Numerous papers have described the synthesis of poly-
cyclic 1,5-benzodiazepine derivatives with a pyridine
ring annelated to the heptatomic diazepine nucleus [4].
It is known that some of such derivatives exhibit wide-
spread biological activities. As a continuation of our
interest in polycyclic 1,5-benzodiazepines we investi-
gated the combination of the diazepine and quinoline
heterocycles in the common polyheterocyclic system
The classical Skraup-Doebner-von Miller synthesis is
among the most general approaches to the quinoline
ring system [2,3]. The key substrates for this condensa-
tion reaction are aromatic amines and a,b-unsaturated
ketones [2]. In this article, we report our results on the
preparation of tetracyclic diazepinopyridoindoles and tri-
cyclic diazepinoquinolines.
RESULTS AND DISCUSSION
In this study, 7-(or 8, or 9)amino-1,3,4,5-tetrahydro-
2H-1,5-benzodiazepin-2-ones 1a–g were used as starting
amine components to prepare annelated derivatives
C
V
2009 HeteroCorporation

1340
R. Janciene, Z. Stumbreviciute, A. Vektariene, L. Kosychova, A. Klimavicius,
A. Palaima, and B. Puodziunaite
Vol 46
Scheme 1
(Scheme 1). Cyclocondensation was accomplished by
the reaction of amines with dimethyl-2-oxoglutaconate
[5] (modified Doebner-von Miller sequence) in a single
step. Thus, the treatment of amines 1a–g with 1.5 equiv
of dimethyl-2-oxoglutaconate in dichloromethane at
room temperature for 24 h and then for additional 24 h
after the addition of 3M hydrogen chloride solution in
glacial acetic acid gave cyclic derivatives 2a–c, 3d,e, 4f,
and 5g. The yields of compounds ranged from poor to
moderate (16–51%).
For the application of this cyclization methodology,
first we employed amines 1a–c, which did not possess
an alkyl group on the N5 atom of the heterocyclic diaze-
pine ring. The reaction of 1a–c with dimethyl-2-oxoglu-
taconate afforded tetracyclic tetrahydro-4H-[1,4]diaze-
pino[3,2,1-hi]pyrido[4,3,2-cd]indole derivatives 2a–c.
During the first stage of this reaction, the amino group
added to the carbon atom of unsaturated ketone at b-
position with respect to the ketonic function and cycliza-
tion occurred to give the cyclized piperidinol [3]. The
addition of the acid catalyst effected the dehydration
and aromatization of the latter together with intramolec-
ular acylation of the diazepine ring N5 atom by the
cyclic ester group and an indole ring was formed [6].
The pyridine ring closure in 7-aminoderivatives 1a–c
took place at the 6-position of the benzodiazepine
moiety.
When 7-amino-5-alkylsubstituted benzodiazepinones
1d,e were treated with oxoglutaconate, the cycloconden-
sation proceeded at the 8-position of the bicyclic hetero-
cycle and linear tricyclic diazepinoquinolines 3d,e
were obtained. The TLC analysis did not indicate the
formation of isomeric products. On the other hand, the
reaction of amine 6 with oxoglutaconate under parallel
reaction conditions did not take place, and about 30%
of the starting N5-acetylsubstituted amine
recovered.
6 was
Analogically, the cyclocondensation of 8-amino 1f
and 9-aminoderivative 1g with oxoglutaconate under the
same conditions gave linear [1,4]diazepino[2,3-g]quino-
line 4f and angular [1,4]diazepino[2,3-h]quinoline 5g,
respectively (in low yields). The isolation of the reaction
products was rather complicated because the formation
of polymeric products of unknown structure was
observed. The attempts to prepare a new tricyclic deriv-
ative from 9-amino-2,3-dihydro-1,5-benzodiazepin-2-one
7 were not straightforward. In the reaction of 7 with
oxoglutaconate, the isolated product was not identified.
1
In the H NMR spectrum, the observed signals at 8.79
(pyridine ring), doublets at 8.73 and 7.91 (benzene
ring), and singlets at 4.09 and 4.10 ppm (COOCH3
groups) confirmed the presence of the 2,4-substituted
quinoline structure fragment (compare with 5g), but
there were no signals dependant on diazepine unit
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Synthesis of Novel Annelated Systems Based on the Interaction and Reactivity
Estimation of Amino-1,5-benzodiazepin-2-ones with Dimethyl-2-oxoglutaconate
1341
protons. Our early studies showed that in acidic medium
the split of the N5AC4 bond of dihydro-1,5-benzodiaze-
pinones or their transformation to a five-membered cycle
could occur [7].
The quinoline derivatives are highly colored com-
pounds and ethanolic solutions of 3d,e and 4f exhibit
deep colors accompanied with fluorescence.
Generally, we have described the synthesis of novel
heterocyclic systems from various N1- and N5-substi-
tuted amino-1,5-benzodiazepinones employing the Doeb-
ner-von Miller quinoline synthesis. It is confirmed that
the formation of a new pyridine ring takes place at the
adjacent position with respect to the primary amine
group of the starting compound. However, the regio-
chemical outcome of cyclization reaction for asymmetri-
cally substituted aromatic amines is unpredictable
[3,15]. To get more insight into the nature of the studied
cyclization process, the theoretical investigation of the
electronic structure of the starting compounds was car-
ried out.
The synthesis of the starting materials 1a [8] and 1d,f
[9] was described in our previous studies. Derivatives
1b,c,e,g, 6 and 7 were then easily obtained from the cor-
responding nitroderivatives 8b,c,e,g, 5-acetyl-3-methyl-
7-nitro-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one (9)
and 2,3-dihydro-4-methyl-9-nitro-1H-1,5-benzodiazepin-
2-one (10) [10] by catalytic hydrogenation. 1,4-Dimethyl-
7-nitro-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one (8b)
and 4-methyl-7-nitro-5-(2,2,2-trifluorethyl)-1,3,4,5-tetrahy-
dro-2H-1,5-benzodiazepin-2-one (8e) were prepared
according to the procedure described in our previous work
[11]. Compound 8c was synthesized by alkylation of 4-
methyl-7-nitro-1,3,4,5,-tetrahydro-2H-1,5-benzodiazepin-
2-one [12] with 1-bromopropane under phase-transfer
catalysis conditions. 4,5-Dimethyl-9-nitroderivative 8g
was prepared by reductive alkylation of dihydronitroder-
ivative 10 with sodium borohydride and formic acid.
Compound 9 was synthesized by nitration of 5-acetyl-3-
methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one
[13]. The starting aminobenzodiazepinones carrying var-
ious alkyl groups at the N1 and N5 atoms of the diaze-
pine heterocycle ring were chosen for their acute solu-
bility in organic solvents.
Considering the reaction mechanism of the Doebner-
von Miller quinoline synthesis, it was shown [2,3,15]
that cyclization reaction involves a stepwise mechanism.
The cyclocondensation step is based on the electrophilic
addition to the carbon atom of the aromatic ring [2,15].
This step determinates the regiochemical features of the
reaction. Hence, our goal was to estimate the most reac-
tive aromatic sites for electrophilic attack. One of the
best indicators of electrophilic attraction is provided by
local ionization energy map calculations based on mo-
lecular electron density surfaces [16–22].
The structures attributed to the compounds described
in this article are consistent with the results of elemental
In this study, we computed local ionization energy
maps for a series of N1- and N5-substituted amino-1,5-
benzodiazepinones 1a,b,d,f,g and 6. First, a conforma-
tional search was performed using Molecular Mechanics
Force Field to identify the lowest energy conformer for
each structure [23]. The lowest energy conformer struc-
tures were further optimized using quantum mechanics
at the DFT level of theory with B3LYP functional and
6-31G* basis set [24]. This basis set then was used to
calculate the local ionization energy map on three
dimension surfaces corresponding to the contour of con-
stant electronic density equal to 0.025 electron/bohr3
[17,23–25]. The surface of value 0.025 electron/bohr3
displays the surface that indicates electron density on
the p-electron surface of aromatic compounds. The
literature [17,25] suggests that this contour gives physi-
cally reasonable molecular dimensions and reflects mo-
lecular features such as bond formation, electron lone
pairs, etc.
We present two distinct and typical local ionization
energy maps, which are most important for the interpre-
tation of the observed regiochemistry. Figure 1 demon-
strates the optimized geometry structures of 1a and 6
heterocycles and shows the computed local ionization
energy maps onto the molecular surfaces of these het-
erocycles. The dark gray regions on the surface area
around the aromatic ring represent localizations on the
1
analysis, IR, H and 13C NMR spectral data. In this con-
1
nection, the H NMR spectra of linear and angular con-
densed regioisomeric systems are particularly significant.
The signals of two benzene ring protons form two dou-
blets or two singlets for compounds 2a–c, 5g and 3d,e,
4f, respectively. These assignments are unambiguously
confirmed when NOE is observed between amide group
(NAH) or methyl group (NACH3) protons and the near-
est benzene ring proton (16–25% and 11–24%, respec-
1
tively). Furthermore, we can point out that the H NMR
spectra of 2a–c confirm the structure attributed to these
tetracyclic systems because no signals for heterocyclic
amine (NAH) group and for one of OCH3 group protons
were detected. Moreover, the diazepine CH proton sig-
nals were shifted downfield by about 0.9 ppm with
respect to those of the starting compounds 1a–c. It is
interesting to note that the vicinal spin-spin coupling
constants of seven-membered ring protons for 2a–c
were very low (2.1–2.4 and 5.3–5.4 Hz) in comparison
with those of precursors 1b,c (7.5–7.7 and 5.2 Hz) or 5-
acetyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiaze-
pin-2-one (13.0 Hz) [14]. This observation suggests
that the conformation of the seven-membered ring in
tetracyclic derivatives 2a–c is exchanged. 13C NMR
spectral data agree with the proposed structures.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1342
R. Janciene, Z. Stumbreviciute, A. Vektariene, L. Kosychova, A. Klimavicius,
A. Palaima, and B. Puodziunaite
Vol 46
amount of energy is required to remove the electron
from the surface and show the most reactive sites to-
ward electrophiles. The lowest average local ionization
energy localizations (Fig. 1) for 7-amino substituted 1a
are found on the molecular surface over the aromatic C6
and C8 atoms. Furthermore, as shown in Table 1, the
Imin values for 1a,b are lower for C6 position than for
C8. This suggests a higher electrophilic affinity and pro-
pensity of ring cyclization at C6 position. In the experi-
ments with 7-aminoderivatives 1a–c, the pyridine ring
closure is observed at C6 position. The lowest Imin val-
ues for 7-amino-5-methylsubstituted 1d located above
the C8 atom show the C8-directing ring closure tend-
ency. Accordingly, the experimental cyclocondensation
of compound 1d proceeds at C8 position. In the case of
7-amino-5-acetylsubstituted derivative 6, Imin values are
higher than those for compounds 1a,b,d,f,g. The calcu-
lated Imin values for 8-aminosubstituted 1f show that the
lowest value is located above the C7 carbon atom and is
consistent with the tendency of the ring closure at the
C7 position. The same consequence of calculated and
experimental results is in accordance with 9-aminoderi-
vative 1g where Imin values are located at C8 position of
the aromatic ring. Thus, in general, the obtained results
are in agreement with experimental data.
Figure 1. Optimized geometry structures and local ionization energy
surface maps on the molecular surfaces defined by the contour of con-
stant electron density equal 0.025 electron/bohr3 for compounds 1a
and 6. Color ranges in kcal/mol: from dark gray 259.43 to bright gray
593.62.
molecular surface where electron removal occurs easily
(with minimal energy). For 1a the lowest average local-
ization of local ionization energies are found at adjacent
positions with respect to the aromatic primary amino
group. The results indicate the affinity to electrophiles
at the adjacent positions of the aromatic carbon atoms.
Analogical tendencies in localization of the lowest aver-
age local ionization energies are observed for hetero-
cycles 1b,d,f,g (not shown in Fig. 1). Otherwise, the
pictured evenly gray molecular surface above the aro-
matic ring area for 6 shows that the aromatic ring is
deactivated toward the electrophilic attack. Experimen-
tally, the reaction of amine 6 with oxoglutaconate does
not lead to the cyclized product. These findings reveal
the deactivating tendency of the acetyl group in 6 for
the pending reaction. In Table 1, the smallest local ioni-
zation energy values (Imin) and total energy values for
optimized geometry structures 1a,b,d,f,g and 6 are pre-
sented. Imin values are the points at which the smallest
In conclusion, quantum-chemical calculations show
that cyclization reaction behavior is governed by the easi-
ness of electron removal (ionization) from definite p-elec-
tron density surface regions of molecules. Local ioniza-
tion energy maps and Imin values are indicative tools for
the calculation of the relative activating and deactivating
tendencies of the aromatic ring in the studied compounds.
EXPERIMENTAL
Melting points were determined in open capillaries method
on a MEL-TEMP 1202D apparatus and are uncorrected. The
IR spectra (potassium bromide) were taken on a Perkin Elmer
Spectrum GX FTIR spectrometer. The electronic absorption
spectra were obtained on Nicolet evoliution 300
Table 1
Calculated total energies (a.u.) of optimized geometries and smallest local ionization energy values Imin (kcal/mol) on the molecular
surfaces defined by the contour of constant electron density equal 0.025 electron/bohr3 on carbon atoms of the aromatic
ring and the nitrogen atom of the primary amino group for compounds 1a,b,d,f,g and 6.
Compounds
1a
1b
1d
1f
1g
6
Total energy, a.u.
min, kcal/mol
ꢀ628.5704
358.58(N7)
358.28(C6)
399.40(C7)
380.49(C8)
381.64(C9)
ꢀ667.6857
287.79(N7)
301.39(C6)
353.28(C7)
320.30(C8)
328.61(C9)
ꢀ667.6856
368.50(N7)
379.90(C6)
399.40(C7)
368.96(C8)
375.88(C9)
ꢀ667.6741
287.79(N8)
329.76(C6)
313.62(C7)
352.82(C8)
320.30(C9)
ꢀ667.6892
293.09(N9)
315.23(C6)
328.84(C7)
314.77(C8)
360.89(C9)
ꢀ781.0432
436.99(N7)
431.22(C6)
441.37(C7)
436.61(C8)
439.52(C9)
I
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Synthesis of Novel Annelated Systems Based on the Interaction and Reactivity
Estimation of Amino-1,5-benzodiazepin-2-ones with Dimethyl-2-oxoglutaconate
1343
spectrophotometer, and the fluorescence emission spectra were
recorded on Hitachi MPF-4 Fluorescence spectrophotometer in
Methyl 6-methyl-4,8-dioxo-9-propyl-6,7,8,9-tetrahydro-
4H-[1,4]diazepino[3,2,1-hi]pyrido[4,3,2-cd]indole-2-carboxy-
late (2c). Orange crystals (mixture of diethyl ether and ethyl
acetate, yield 25%), mp 163–165ꢂC; IR: 1725, 1702, 1660
1
ethanol. Except where noted otherwise, H (300 MHz) and 13C
(75 MHz) NMR spectra were recorded in deuteriochloroform
on a Varian Unity Inova 300 spectrometer at 302 K. The chem-
ical shifts are referenced to tetramethylsilane (d (1H) ¼ 0) and
the solvent signal deuteriochloroform (d (13C) ¼ 77.0 ppm),
deuteriodimethylsulfoxide (d (13C) ¼ 49.5 ppm). The values of
chemical shifts are expressed in ppm and coupling constants
(J) in Hz. The CH3, CH2, CH and Cquart groups in 13C NMR
were differentiated by means of the APT method. The reactions
were controlled by the TLC method and performed on a Merck
precoated silica gel aluminum roll (60F254) with chloroform-
ethyl acetate-methanol (m/m, 14:7:1) as the eluent and was
visualized with UV light. Dry column vacuum chromatography
[26] was performed with silica gel Chemapol L 5/40 mesh.
General Procedure for the Synthesis of 2a–c, 3d,e, 4f and
5g. To a stirred solution of the appropriate aminobenzodiazepi-
none 1a–g (5.0 mmol) in 100–300 mL of dry dichloromethane,
1.28 g (7.5 mmol) of dimethyl-2-oxoglutaconate was added.
The mixture was stirred at room temperature for 24 h. Then 4
mL (12.0 mmol) of 3M hydrogen chloride solution in glacial
acetic acid was added and the intensively colored mixture was
stirred at room temperature for additional 24 h. In some occa-
sions, the precipitate was formed. The mixture was treated
with a saturated aqueous sodium hydrogencarbonate solution
until the aqueous phase became alkaline (pH 7–8), then the or-
ganic phase was washed with water. After drying over magne-
sium sulfate and the removal of the solvent in vacuum, the
dark semisolid residue was subjected to purification. Recrystal-
lization from a proper solvent gave pure compounds 3d and
3e. Dark oily residues were subjected to dry column vacuum
chromatography (silicagel) using the dichloroethane-ethyl ace-
tate system for gradient elution. Organic fractions with Rf
ꢁ 0.35 were collected and after removal of the solvent gave
compounds 2a–c and fractions collected with Rf ꢁ 0.50 gave
compounds 4f and 5g. Pure compounds were obtained by
recrystallization from a proper solvent.
1
cmꢀ1; H NMR: d 1.00 (t, J ¼ 7.4 Hz, 3H, CH3), 1.49 (d, J ¼
6.7 Hz, 3H, CH3), 1.65–1.89 (m, 2H, CH2), 2.99 (dd, J ¼ 2.4,
14.0 Hz, 1H, CH2), 3.13 (dd, J ¼ 5.4, 13.9 Hz, 1H, CH2),
3.96–4.12 (m, 2H, CH2), 4.13 (s, 3H, OCH3), 4.89 (m, 1H,
CH), 7.64 (d, J ¼ 9.4 Hz, 1H, 10-H), 8.00 (d, J ¼ 9.4 Hz, 1H,
11-H), 8.72 (s, 1H, 3-H); 13C NMR: d 11.29 (9-CH3), 19.26
(6-CH3), 21.72 (9’’-CH2), 42.60 (7-C), 46.56 (6-C), 48.34 (9’-
CH2), 53.56 (OCH3), 119.22 (3-C), 121.90, 123.75, 124.91
(11-C), 127.28 (10-C), 127.38, 134.21, 142.37, 150.04, 164.67
(CO), 165.23 (CO), 169.65 ppm (8-CO). Anal. Calcd. for
C19H19N3O4: C, 64.58; H, 5.42; N, 11.89. Found: C, 64.30; H,
5.31; N, 11.64.
Dimethyl 4,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-[1,4]
diazepino[2,3-g]quinoline-8,10-dicarboxylate
(3d). Yellow
crystals (ethyl acetate, 46% yield), mp 203–205ꢂC; IR: 3319,
3196, 1723, 1670 cmꢀ1; UV-vis: kmax (e ꢃ 10ꢀ3) 245 (30.5),
1
290 (21.2), 355 (6.2) nm (Mꢀ1cmꢀ1); H NMR: d 1.31 (d, J ¼
6.1 Hz, 3H, CH3), 2.44 (dd, J ¼ 8.9, 13.4 Hz, 1H, CH2), 2.72
(dd, J ¼ 4.8, 13.4 Hz, 1H, CH2), 3.02 (s, 3H, CH3), 3.94 (m,
1H, CH), 4.06 (s, 3H, OCH3), 4.11 (s, 3H, OCH3), 7.83 (s, 1H,
6-H), 8.49 (s, 1H, 11-H), 8.59 (s, 1H, 9-H), 8.67 (br s, 1H,
NH); 13C NMR: d 17.26 (4-CH3), 39.33 (5-CH3), 40.89 (3-C),
52.84 (OCH3), 53.32 (OCH3), 60.62 (4-C), 116.04 (d, J ¼
165.2 Hz, 11-C), 120.01 (d, J ¼ 162.3 Hz, 6-C), 121.06 (d, J ¼
171.2 Hz, 9-C), 122.48, 133.99, 136.70, 145.02, 146.59,
147.87, 165.35 (CO), 165.97 (CO), 172.41 ppm (2-CO). Anal.
Calcd. for C18H19N3O5: C, 60.50; H, 5.36; N, 11.76. Found: C,
60.64; H, 5.30; N, 11.90.
Dimethyl
4-methyl-2-oxo-5-(2,2,2-trifluorethyl)-2,3,4,5-
tetrahydro-1H-[1,4]diazepino[2,3-g]quinoline-8,10-dicarbox-
ylate (3e). Yellow crystals (ethyl acetate, 51% yield), mp
236–238ꢂC; IR: 3320, 1745, 1727, 1693 cmꢀ1; UV-vis: kmax
(e ꢃ 10ꢀ3) 245 (18.2), 284 (12.5), 365 (4.7) nm (Mꢀ1cmꢀ1);
1H NMR: d 1.21 (d, J ¼ 6.1 Hz, 3H, CH3), 2.36 (dd, J ¼
11.3, 13.4 Hz, 1H, CH2), 2.61 (ddd, J ¼ 1.4, 5.4, 13.4 Hz, 1H,
CH2), 3.78 (m, 1H, CH), 4.06 (s, 3H, OCH3), 4.06–4.20 (m,
2H, 5-CH2), 4.10 (s, 3H, OCH3), 8.06 (s, 1H, 6-H), 8.44 (br s,
1H, NH), 8.60 (s, 1H, 11-H), 8.67 (s, 1H, 9-H); 13C NMR: d
16.45 (4-CH3), 41.05 (3-C), 52.50 (q, J ¼ 32.9 Hz, 5-CH2),
52.98 (OCH3), 53.41 (OCH3), 60.12 (4-C), 116.89 (11-C),
122.27 (9-C), 124.08, 124.47 (q, J ¼ 280.2 Hz, CF3), 125.11
(6-C), 134.43, 138.63, 142.49, 147.01, 147.37, 165.09 (CO),
165.76 (CO), 172.15 ppm (2-CO). Anal. Calcd. for
C19H18F3N3O5: C, 53.65; H, 4.27; N, 9.88. Found: C, 53.48;
H, 4.36; N, 10.01.
Methyl
6-methyl-4,8-dioxo-6,7,8,9-tetrahydro-4H-[1,4]
diazepino[3,2,1-hi]pyrido[4,3,2-cd]indole-2-carboxylate
(2a). Brightly yellow crystals (chloroform, 30% yield), mp
299–302ꢂC [6]; 1H NMR: d 1.52 (d, J ¼ 6.6 Hz, 3H, CH3),
3.07 (dd, J ¼ 2.3, 14.8 Hz, 1H, CH2), 3.18 (ddd, J ¼ 1.3, 5.3,
14.8 Hz, 1H, CH2), 4.13 (s, 3H, OCH3), 4.99 (m, 1H, CH),
7.33 (d, J ¼ 9.1 Hz, 1H, 10-H), 7.97 (d, J ¼ 9.1 Hz, 1H, 11-
H), 8.47 (br s, 1H, NH), 8.74 (s, 1H, 3-H); 13C NMR (dime-
thylsulfoxide-d6): d 19.12 (6-CH3), 42.53 (7-C), 44.06 (6-C),
52.81 (OCH3), 117.82 (3-C), 120.72, 120.98, 123.17, 123.81
(11-C), 127.79 (10-C), 133.31, 141.47, 148.49, 163.08 (CO),
164.92 (CO), 171.04 ppm (8-CO).
Methyl 6,9-dimethyl-4,8-dioxo-6,7,8,9-tetrahydro-4H-[1,4]-
diazepino[3,2,1-hi]pyrido[4,3,2-cd]indole-2-carboxylate
(2b). Orange crystals (chloroform, 29% yield), mp 231–233ꢂC
Dimethyl 1,2-dimethyl-4-oxo-2,3,4,5-tetrahydro-1H-[1,4]
diazepino[2,3-g]quinoline-8,10-dicarboxylate
(4f). Yellow
crystals (isopropanol, 16% yield), mp 255–258ꢂC; IR: 3198,
3122, 1715, 1683 cmꢀ1; UV-vis: kmax (e ꢃ 10ꢀ3) 245 (31.1),
295 (14.7), 410 (9.0) nm (Mꢀ1cmꢀ1); fluorescence: kex 300
and 410, kem 550 nm; 1H NMR: d 1.37 (d, J ¼ 6.2 Hz, 3H,
CH3), 2.47 (dd, J ¼ 8.3, 13.5 Hz, 1H, CH2), 2.75 (dd, J ¼
4.4, 13.4 Hz, 1H, CH2), 3.09 (s, 3H, CH3), 3.94 (m, 1H, CH),
4.07 (s, 3H, OCH3), 4.10 (s, 3H, OCH3), 7.85 (s, 1H, 6-H),
8.30 (br s, 1H, NH), 8.45 (s, 1H, 11-H), 8.66 (s, 1H, 9-H); 13C
NMR: d 17.90 (2-CH3), 39.47 (1-CH3), 40.74 (3-C), 52.70
(OCH3), 53.19 (OCH3), 60.66 (2-C), 113.58 (11-C), 121.31 (6-
1
[6]; H NMR: d 1.49 (d, J ¼ 6.7 Hz, 3H, CH3), 3.00 (dd, J ¼
2.1, 14.2 Hz, 1H, CH2), 3.18 (dd, J ¼ 5.4, 14.3 Hz, 1H, CH2),
3.59 (s, 3H, 9-OCH3), 4.13 (s, 3H, OCH3), 4.90 (m, 1H, CH),
7.65 (d, J ¼ 9.3 Hz, 1H, 10-H), 8.01 (d, J ¼ 9.3 Hz, 1H, 11-
H), 8.72 (s, 1H, 3-H); 13C NMR: d 19.29 (6-CH3), 34.31 (9-
CH3), 42.60 (C-7), 46.30 (C-6), 53.52 (OCH3), 119.29 (d, J ¼
173.0 Hz, 3-C), 121.57, 124.44, 124.87 (d, J ¼ 166.7 Hz, 11-
C), 126.83, 127.17 (d, J ¼ 160.6 Hz, 10-C), 134.31, 142.31,
150.19, 164.48 (CO), 165.19 (CO), 169.92 ppm (8-CO).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1344
R. Janciene, Z. Stumbreviciute, A. Vektariene, L. Kosychova, A. Klimavicius,
A. Palaima, and B. Puodziunaite
Vol 46
C), 122.47 (9-C), 125.65, 132.23, 136.38, 145.13, 145.20 (2-
C), 165.44 (CO), 166.19 (CO), 172.21 ppm (4-CO). Anal.
Calcd. for C18H19N3O5: C, 60.50; H, 5.36; N, 11.76. Found:
C, 60.63; H, 5.29; N, 11.65.
(m, 1H, CH), 6.42–6.46 (m, 2H, 6-H, 8-H), 6.81 (m, 1H, 9-H),
7.83 (br s, 1H, NH); 13C NMR: d 17.05 (4-CH3), 41.07 (3-C),
52.80 (q, J ¼ 32.4 Hz, 5-CH2), 61.37 (4-C), 111.82, 112.00,
123.68, 124.49, 126.69, 140.05, 144.93, 173.44 ppm (CO).
Anal. Calcd. for C12H14F3N3O: C, 52.75; H, 5.16; N, 15.38.
Found: C, 52.87; H, 5.24; N, 15.30.
Dimethyl 4,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-[1,4]
diazepino[2,3-h]quinoline-8,10-dicarboxylate (5g). Dark red
crystals (tert-butylmetyl ether, 20% yield), mp 161–163ꢂC; IR:
9-Amino-4,5-dimethyl-1,3,4,5-tetrahydro-2H-1,5-benzo-
diazepin-2-one (1g). Synthesized from 8g. Cream crystals
(methanol, 70% yield), mp 213–215ꢂC; IR: 3453, 3367, 3198,
3273, 1730, 1708, 1672 cmꢀ1
;
1H NMR: d 1.38 (d, J ¼ 6.4
Hz, 3H, CH3), 2.56 (ddd, J ¼ 1.0, 7.6, 13.8 Hz, 1H, CH2),
2.84 (dd, J ¼ 4.4, 13.9 Hz, 1H, CH2), 3.07 (s, 3H, CH3), 4.02
(m, 1H, CH), 4.05 (s, 3H, OCH3), 4.06 (s, 3H, OCH3), 7.54
(d, J ¼ 9.4 Hz, 1H, 6-H), 8.52 (s, 1H, 9-H), 8.53 (d, J ¼ 9.4
Hz, 1H, 7-H), 9.24 (br s, 1H, NH); 13C NMR: d 18.37 (4-
CH3), 39.39 (5-CH3), 42.04 (3-C), 52.88 (OCH3), 53.06
(OCH3), 61.07 (4-C), 120.32 (d, J ¼ 171.6 Hz, 9-C), 120.99
(d, J ¼ 168.5 Hz, 7-C), 121.06, 124.35, 124.98 (d, J ¼ 159.6
Hz, 6-C), 135.61, 139.74, 140.55, 146.31, 165.27 (CO), 166.01
(CO), 171.72 ppm (2-CO). Anal. Calcd. for C18H19N3O5: C,
60.50; H, 5.36; N, 11.76. Found: C, 60.79; H, 5.40; N, 11.93.
General procedure for the synthesis of 1b,c,e,g, 6 and
7. In a hydrogenation apparatus, equipped with a magnetic stir-
rer, the catalyst 10% palladium on carbon (10% of the weight of
the starting nitroderivative) was added to a solution of suitable
nitrobenzodiazepinone 8b,c,e,g, 9 and 10 (20.0 mmol) in 150–
200 mL of methanol and the mixture was hydrogenated at room
temperature and atmospheric pressure. After the consumption of
1.34 L (60 mmol) of hydrogen the catalyst was filtered off. The
filtrate was concentrated to dryness in vacuum and the resultant
solid residue was crystallized from a proper solvent.
1
1678 cmꢀ1; H NMR: d 1.09 (d, J ¼ 6.1 Hz, 3H, CH3), 2.24
(dd, J ¼ 10.0, 12.6 Hz, 1H, CH2), 2.42 (ddd, J ¼ 1.2, 5.4,
12.6 Hz, 1H, CH2), 2.77 (s, 3H, CH3), 3.86 (m, 1H, CH), 3.95
(br s, 2H, NH2), 6.45–6.51 (m, 2H, 6-H, 8-H), 6.98 (dd, J ¼
8.0, 8.0 Hz, 1H, 7-H), 8.34 (br s, 1H, NH); 13C NMR: d 15.78
(4-CH3), 38.65 (5-CH3), 41.52 (3-C), 62.83 (4-C), 110.53,
111.84, 119.72, 126.29, 139.59, 142.66, 174.76 ppm (CO).
Anal. Calcd. for C11H15N3O: C, 64.34; H, 7.37; N, 20.47.
Found: C, 64.47; H, 7.29; N, 20.59.
5-Acetyl-7-amino-3-methyl-1,3,4,5-tetrahydro-2H-1,5-ben-
zodiazepin-2-one (6). Synthesized from 9. Yellow crystals (ace-
tonitrile, 89% yield), mp 191–193ꢂC; IR: 3438, 3348, 3233,
1
1673, 1653 cmꢀ1; H NMR: d 1.11 (d, J ¼ 6.7 Hz, 3H, CH3),
1.86 (br s, 3H, CH3), 2.75 (m, 1H, CH), 3.46 (dd, J ¼ 6.9, 13.5
Hz, 1H, CH2), 3.83 (br s, 2H, NH2), 4.56 (dd, J ¼ 12.3, 13.1 Hz,
1H, CH2), 6.51 (d, J ¼ 2.5 Hz, 1H, 6-H), 6.67 (dd, J ¼ 2.5, 8.4
Hz, 1H, 8-H), 6.94 (d, J ¼ 8.5 Hz, 1H, 9-H), 7.90 (br s, 1H, NH);
13C NMR: d 12.51 (4-CH3), 22.66 (5-CH3), 34.88(3-C), 54.74
(4-C), 115.06, 115.39, 124.35, 126.05, 135.66, 145.29, 170.38,
175.20 ppm. Anal. Calcd. for C12H15N3O2: C, 61.79; H, 6.48; N,
18.01. Found: C, 61.62; H, 6.41; N, 18.13.
7-Amino-1,4-dimethyl-1,3,4,5-tetrahydro-2H-1,5-benzo-
diazepin-2-one (1b). Synthesized from 8b [11]. Yellowish
crystals (ethyl acetate, 77% yield), mp 149–151ꢂC; 1H NMR:
d 1.24 (d, J ¼ 6.2 Hz, 3H, CH3), 2.28 (dd, J ¼ 7.7, 12.7 Hz,
1H, 3-CH2), 2.51 (dd, J ¼ 5.2, 12.6 Hz, 1H, 3-CH2), 3.13 (br
s, 1H, NH), 3.28 (s, 3H, 1-CH3), 3.66 (br s, 2H, NH2), 4.00
(m, 1H, CH), 6.18 (d, J ¼ 2.5 Hz, 1H, 6-H), 6.36 (dd, J ¼
2.5, 8.4 Hz, 1H, 8-H), 6.91 (d, J ¼ 8.4 Hz, 1H, 9-H); 13C
NMR: d 23.19 (4-CH3), 35.45 (1-CH3), 40.24 (3-C), 56.80 (4-
C), 108.31, 109.43, 123.62, 127.90, 140.15, 144.72, 171.37
ppm (CO). Anal. Calcd. for C11H15N3O: C, 64.34; H, 7.37; N,
20.47. Found: C, 64.38; H, 7.30; N, 20.66.
9-Amino-2,3-dihydro-1H-1,5-benzodiazepin-2-one (7). Syn-
thesized from 10 [10] Yellowish crystals (methanol, 90%
1
yield), mp 170–172ꢂC; H NMR: d 2.39 (s, 3H, CH3), 3.16 (s,
2H, CH2), 3.81 (br s, 2H, NH2), 6.66 (dd, J ¼ 1.4, 7.8 Hz,
1H, 8-H or 6-H), 6.83 (dd, J ¼ 1.3, 8.1 Hz, 1H, 6-H or 8-H),
7.05 (t, J ¼ 7.9 Hz, 1H, 7-H), 8.00 (m, 1H, NH); 13C NMR: d
28.00, 43.80, 113.38, 117.81, 125.54, 138.41, 141.09, 163.09,
166.45 ppm. Anal. Calcd. for C10H11N3O: C, 63.48; H, 5.86;
N, 22.21. Found: C, 63.57; H, 5.79; N, 22.37.
4-Methyl-7-nitro-1-propyl-1,3,4,5-tetrahydro-2H-1,5-ben-
zodiazepin-2-one (8c). To a solution of 2.2 g (10.0 mmol) of
4-methyl-7-nitro-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one
[12] in 150 mL of benzene, 0.5 g (1.50 mmol) of tetrabutylam-
monium bromide, 15 mL 50% aqueous sodium hydroxide and
1.8 mL (20.0 mmol) of 1-bromopropane were added. The reac-
tion was performed according to the procedure method A pre-
viously described by us [11]. The working-up of the reaction
mixture gave 1.6 g (61%) of 8c. Yellowish crystals (ethyꢀl1 ace-
7-Amino-4-methyl-1-propyl-1,3,4,5-tetrahydro-2H-1,5-
benzodiazepin-2-one (1c). Synthesized from 8c. Beige col-
ored crystals (mixture of methanol and diethyl ether, 71% yielꢀd1),
mp 143-145ꢂC; IR: 3407, 3345, 3330, 3233, 1666–1609 cm
;
1H NMR: d 0.84 (t, J ¼ 7.4 Hz, 3H, CH3), 1.23 (d, J ¼ 6.2 Hz,
3H, CH3), 1.50 (m, 2H, CH2), 2.23 (dd, J ¼ 7.5, 12.6 Hz, 1H, 3-
CH2), 2.48 (dd, J ¼ 5.2, 12.6 Hz, 1H, 3-CH2), 3.05 (br s, 1H,
NH), 3.64 (br s, 2H, NH2), 3.73 (m, 2H, CH2), 3.98 (m, 1H, CH),
6.18 (d, J ¼ 2.5 Hz, 1H, 6-H), 6.35 (dd, J ¼ 2.5, 8.4 Hz, 1H, 8-
H), 6.93 (d, J ¼ 8.4 Hz, 1H, 9-H); 13C NMR: d 11.22 (CH3),
21.13 (CH2), 23.11 (4-CH3), 40.38 (3-C), 49.26 (CH2), 56.89 (4-
C), 108.52, 109.51, 124.08, 126.60, 141.20, 144.74, 171.20 ppm
(CO). Anal. Calcd. for C13H19N3O: C, 66.92; H, 8.21; N, 18.01.
Found: C, 67.23; H, 8.32; N, 17.89.
tate), mp 116–118ꢂC; IR: 3296, 1651, 1517, 1344 cm
;
1H
NMR: d 0.85 (t, J ¼ 7.4 Hz, 3H, CH3), 1.32 (d, J ¼ 6.3 Hz,
3H, CH3), 1.54 (m, 2H, CH2), 2.28 (dd, J ¼ 7.4, 12.9 Hz, 1H,
3-CH2), 2.57 (dd, J ¼ 5.2, 12.9 Hz, 1H, 3-CH2), 3.55 (br s,
1H, NH), 3.86 (m, 2H, CH2), 4.12 (m, 1H, CH), 7.29 (d, J ¼
8.8 Hz, 1H, 9-H), 7.76 (d, J ¼ 2.6 Hz, 1H, 6-H), 7.89 (dd, J ¼
2.5, 8.8 Hz, 1H, 8-H); 13C NMR: d 11.08 (CH3), 21.13(CH2),
23.01(4-CH3), 40.29 (3-C), 49.67 (CH2), 57.32 (4-C), 117.23,
117.84, 123.27, 140.29, 140.78, 145.10, 170.57 ppm (CO).
Anal. Calcd. for C13H17N3O3: C, 59.30; H, 6.51; N, 15.96.
Found: C, 59.61; H, 6.63; N, 16.12.
7-Amino-4-methyl-5(2,2,2-trifluoroethyl)-1,3,4,5-tetrahy-
dro-2H-1,5-benzodiazepin-2-one (1e). Synthesized from 8e
[11]. Yellowish crystals (mixture of diethyl ether and hexane,
95% yield), mp 156–158ꢂC; IR: 3454, 3371, 3174, 1677
1
cmꢀ1; H NMR: d 1.08 (d, J ¼ 6.1 Hz, 3H, CH3), 2.22–2.40
4,5-Dimethyl-9-nitro-1,3,4,5-tetrahydro-2H-1,5-benzodia-
zepin-2-one (8g). To a solution of 2.2 g (10.0 mmol) of dihy-
dro-9-nitroderivative 10 [10] in 50 mL of formic acid, 3.25 g
(m, 2H, CH2), 3.3–3.7 (br s, 2H, NH2), 3.53 (dq, J ¼ 8.9, 15.4
Hz, 1H, 5-CH2), 3.83 (dq, J ¼ 8.6, 15.4 Hz, 1H, 5-CH2), 4.02
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Synthesis of Novel Annelated Systems Based on the Interaction and Reactivity
Estimation of Amino-1,5-benzodiazepin-2-ones with Dimethyl-2-oxoglutaconate
1345
[11] Puodzhyunaite, B. A.; Yanchene, R. A.; Terent’ev, P. B.; Abdur-
akhmanov, K. A.; Dzhumakuliev, G. Chem Heterocycl Compd 1992, 28, 798.
[12] Puodzhyunaite, B. A.; Yanchene, R. A.; Stumbryavichyute,
Z. A. Chem Heterocycl Compd 1988, 24, 786.
(70.0 mmol) of sodium borohydride was added. The reaction
was performed following the procedure previously described
by us [11]. The working-up of the reaction mixture gave 1.3 g
(57%) of 8g. Yellow crystals (ethyl acetate), mp 184–186ꢂC;
IR: 3192, 3122, 1686, 1636, 1529, 1345 cmꢀ1 1H NMR: d
;
[13] Puodzhunaite, B. A.; Yanchiene, R. A.; Talaikite, Z. A.;
Zaks, A.S.; Rabotnikov, Yu. M.; Uzachev, E. A. Khim.-Farm. Zh.
1985, 19, 1195; Chem Abstr 1986, 105, 133861g.
1.19 (d, J ¼ 6.1 Hz, 3H, CH3), 2.25 (dd, J ¼ 9.8, 13.0 Hz,
1H, CH2), 2.55 (ddd, J ¼ 1.4, 5.7, 13.0 Hz, 1H, CH2), 2.88 (s,
3H, 5-CH3), 3.95 (m, 1H, CH), 7.24 (dd, J ¼ 8.1, 8.1 Hz, 1H,
7-H), 7.37 (dd, J ¼ 1.4, 8.1 Hz, 1H, 6-H), 7.77 (dd, J ¼ 1.5,
8.2 Hz, 1H, 8-H), 8.80 (br s, 1H, NH); 13C NMR: d 15.93 (4-
CH3), 39.41 (5-CH3), 41.37 (3-C), 62.77 (4-C), 119.42,
124.36, 127.95, 130.04, 140.28, 143.11, 171.89 ppm (CO).
Anal. Calcd. for C11H13N3O3: C, 56.16; H, 5.57; N, 17.86.
Found: C, 56.35; H, 5.65; N, 17.71.
ˇ
˙
ˇ
˙
ˇ
˙
[14] Puodziu¯naite, B.; Janciene, R.; Stumbreviciu¯te, Z. Topics in
chemistry of heterocyclic compounds, 7th Symposium on Chemistry of
Heterocyclic Compounds, Bratislava, Czechoslovakia, August 31–Sep-
tember 3, 1981, 281.
[15] Yamashkin, S. A.; Yudin, L. G.; Kost, A. N. Chem Hetero-
cycl Compd 1992, 28, 845.
[16] Murray, J. S.; Sen, K. Molecular Electrostatic Potentials:
Concepts and Applications, 1st ed.; Elsevier Science: Amsterdam,
1996; pp 125–175.
5-Acetyl-3-methyl-7-nitro-1,3,4,5-tetrahydro-2H-1,5-ben-
zodiazepin-2-one (9). A solution of 2.2 g (10.0 mmol) of 5-
acetyl-3-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one
[13] in 30 mL of conc. sulfuric acid, and a solution of 2.2 g
(20.0 mmol) of potassium nitrate in 25 mL of conc. sulfuric
acid were precooled to ꢀ18ꢂC and were combined. The reac-
tion mixture was kept at ꢀ18ꢂC for 1 h, then at 4ꢂC for 5 h
and at room temperature for 24 h. After that the reaction mix-
ture was poured on ice and extracted with ethyl acetate (3 ꢃ
70 mL). The organic phase was washed successively with
water and a saturated aqueous sodium hydrogencarbonate solu-
tion (3 ꢃ 40 mL), dried over magnesium sulfate and concen-
trated in vacuum to dryness. Recrystallization of the solid resi-
due from ethyl acetate gave 1.3 g (50%) of yellowish crystals
of 9, mp 212–214ꢂC; IR: 3208, 3156, 1697, 1650, 1523, 1347
[17] (a) Ehresmann, B.; Martin, B.; Horn, A. H. C.; Clark, T. J.
Mol Model 2003, 9, 342; (b) Vektariene, A.; Vektaris, G.; Svoboda, J.
ARKIVOC, 2009, 7, 311.
[18] Sjoberg, P.; Murray, J. S.; Brinck, T.; Politzer, P. Can J
Chem 1990, 68, 1440.
[19] Politzer, P.; Murray, J. S.; Concha, M. C. Int J Quantum
Chem 2002, 88, 19.
[20] Hussein, W.; Walker, C. G.; Peralta-Inga, Z.; Murray, J. S.
Int J Quantum Chem 2001, 82, 160.
[21] Murray, J. S.; Abu-Awwad, F.; Politzer, P. J Mol Struct
(Theochem) 2000, 501, 241.
[22] Luo, J.; Xue, Q. Z.; Liu, W. M.; Wu, L. J.; Yang, Z. Q.
J Phys Chem A 2006, 110, 12005.
0
[23] Spartan 06, Shao, Y.; Molnar, L. F.; Jung, Y.; Kussmann, J.;
Ochsenfeld, C.; Brown, S. T.; Gilbert, A. T. B.; Slipchenko, L. V.; Lev-
chenko, S. V.; O’Neill, D. P.; DiStasio, R. A., Jr; Lochan, R. C.; Wang, T.;
Beran, G. J. O.; Besley, N. A.; Herbert, J. M.; Lin, C. Y.; Van Voorhis, T.;
Chien, S. H.; Sodt, A.; Steele, R. P.; Rassolov, V. A.; Maslen, P. E.; Koram-
bath, P. P.; Adamson, R. D.; Austin, B.; Baker, J.; Byrd, E. F. C.; Dachsel,
H.; Doerksen, R. J.; Dreuw, A.; Dunietz, B. D.; Dutoi, A. D.; Furlani, T. R.;
Gwaltney, S. R.; Heyden, A.; Hirata, S.; Hsu, C-P.; Kedziora, G.; Khalliu-
lin, R. Z.; Klunzinger, P.; Lee, A. M.; Lee, M. S.; Liang, W. Z.; Lotan, I.;
Nair, N.; Peters, B.; Proynov, E. I.; Pieniazek, P. A.; Rhee, Y. M.; Ritchie,
J.; Rosta, E.; Sherrill, C. D.; Simmonett, A. C.; Subotnik, J. E.; Woodcock,
H. L., III; Zhang, W.; Bell, A. T.; Chakraborty, A. K.; Chipman, D. M.;
Keil, F. J.; Warshel, A.; Hehre, W. J.; Schaefer, H. F.; Kong, J.; Krylov, A.
I.; Gill, P. M. W.; Head-Gordon, M.; Wavefunction Inc., Irvine, CA; Phys
Chem Chem Phys 2006, 8, 3172.
1
cmꢀ1; H NMR: d 1.22 (br d, 3H, CH3), 1.88 (br s, 3H, CH3),
2.82 (br m, 1H, CH), 3.63 (br m, 1H, CH2), 4.67 (br m, 1H,
CH2), 7.34 (d, J ¼ 8.7 Hz, 1H, 9-H), 8.17 (br d, 1H, 6-H),
8.29 (br dd, 1H, 9-H), 9.05 ppm (br s, 1H, NH). Anal. Calcd.
for C12H13N3O4: C, 54.75; H, 4.98; N, 15.96. Found: C,
54.93; H, 4.79; N, 16.17.
Acknowledgments. The calculations of this study was supported
by the European Commission, project BalticGrid-II (GA No.
223807), and the Lithuanian Ministry of Education and Science,
LitGrid programme (SUT-325/LNS-1100000-795).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet