Synthesis and study of reactivity of pyrrolo[3,2-e][1,2,4]-triazine system1

Article abstract of DOI:10.3987/COM-07-11267

The corresponding 2-arylhydrazones 5 were obtained by coupling of diazonium salts with diethyl (3-methyl-1H-pyrrole)-2,4-dicarbamate 4. These ones were cyclized in a alkaline medium to ethyl (2-aryl-5-methyl-3-oxo-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-6-yl)carbamates 6 and tested for their stability. The starting carbamate 4 was prepared by a multistep synthesis from diethyl 3-methyl-1H-pyrrole-2,4-dicarboxylate 1.

Full text of DOI:10.3987/COM-07-11267

HETEROCYCLES, Vol. 75, No. 5, 2008
1087
HETEROCYCLES, Vol. 75, No. 5, 2008, pp. 1087 - 1095. © The Japan Institute of Heterocyclic Chemistry
Received, 15th November, 2007, Accepted, 22nd January, 2008, Published online, 25th January, 2008. COM-07-11267
SYNTHESIS AND STUDY OF REACTIVITY OF PYRROLO[3,2-e][1,2,4]-
TRIAZINE SYSTEM1
Jakub Stýskala,* Jan Slouka, and Petr Cankař
Department of Organic Chemistry, Faculty of Science, Palacky University, Tr.
Svobody 8, 771 46 Olomouc, Czech Republic. E-mail: styskala@prfnw.upol.cz
Abstract - The corresponding 2-arylhydrazones 5 were obtained by coupling of
diazonium salts with diethyl (3-methyl-1H-pyrrole)-2,4-dicarbamate 4. These
ones were cyclized in a alkaline medium to ethyl (2-aryl-5-methyl-3-
oxo-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-6-yl)carbamates 6 and tested for
their stability. The starting carbamate 4 was prepared by a multistep synthesis
from diethyl 3-methyl-1H-pyrrole-2,4-dicarboxylate 1.
INTRODUCTION
Both aza and deaza analogues of natural purine compounds are currently the object of interest mainly in
connection with the research for substances with antineoplastic and virostatic activity. The
pyrrolo-1,2,4-triazine systems also belong among substances of this kind. In some of them, the
pyrrolo[2,1-f][1,2,4]triazine derivatives, an activity connected to protein kinase inhibitors2-5 was
discovered. Also some natural antibiotics (Toyocamycin, Tubercidin) containing pyrrolo[2,3-d]-
pyrimidine (7-deazapurine) skeleton have a similar structure; they show tuberculostatic and antineoplastic
activity.6 Pyrrolo[3,2-e][1,2,4]triazine derivatives have been investigated only very little so far, which
urged us to search for synthesis leading to this heterocyclic system.
RESULTS AND DISCUSSION
The syntheses of fused 1,2,4-triazines based on the cyclization of hydrazono-carbamates are
advantageous in the cases when the starting compounds can be obtained by the azo-coupling reactions
with five membered aromatic heterocyclic compounds, e.g. the synthesis of the pyrazolo[3,4-e][1,2,4]-
triazines,7 1,2,4-triazinoindoles8,9 or 1,2,4-triazines with fused furan10,11 or thiophene ring.12
In this paper, we describe an application of this method to a pyrrole system in order to investigate an
alternative route for the synthesis of little explored pyrrolo[3,2-e][1,2,4]triazine system.13-15

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HETEROCYCLES, Vol. 75, No. 5, 2008
The starting compound for new syntheses was diethyl 3-methyl-1H-pyrrole-2,4-dicarboxylate16 1 which
was converted by hydrazinolysis to the corresponding hydrazide 2. The nitrosation in hydrochloric acid
solution was the most efficient method for the transformation of hydrazide 2 to the azide 3. The azide 3
(light sensitive compound, storage on day light causes dark colouration of product and its decomposition)
was converted by Curtius rearrangement to diethyl (3-methyl-1H-pyrrole)-2,4-dicarbamate 4 in boiling
anhydrous ethanol. This compound is highly unstable. It decomposes under wet conditions and when
exposed to oxygen, resulting dark red polymer products. Slow decomposition occurs even when it is
stored at –20 °C. The first signs of decompositions are visible within a few months.
Me
CO2Et
Me
CONHNH2
ii
Me
CON3
i
EtO2C
NH2NHOC
N3OC
N
H
N
H
N
H
1
2
3
iii
Me
NHCO2Et
Me
N
CO2Et
N
iv
N
EtO2CHN
EtO2CHN
N
H
H
N
H
R
v
5
4
O
N
Me
N
a: R = H
b: R = OMe
c: R = NO2
N
EtO2CHN
R
N
H
6
vii
vi
H
O
O
N
Me
N
Me
O
N
N
N
N
H2N
R
N
H
R
N
H
7
8
Scheme 1. Reaction conditions. i) hydrazine hydrate, reflux. ii) NaNO2, aqueous, HCl, 2-5 °C. iii) EtOH,
reflux. iv) arene diazonium salt and pyridine. v) aqueous ethanolic Na2CO3, reflux; vi) aqueous NaOH,
reflux. vii) aqueous HCl, reflux.

HETEROCYCLES, Vol. 75, No. 5, 2008
1089
The corresponding 3-arylazocompounds 5A, which are tautomeric with the hydrazones 5B (Scheme 2),
were prepared by a coupling reaction of diazonium salts with carbamate 4 in pyridine under inert
conditions. The azo-hydrazone tautomerism with phenyl derivative 5a was studied by IR spectroscopy in
tetrachloromethane solution. For this purpose, compound 5a containing labelled nitrogen was prepared
from aniline-15N. It was found that unlabelled derivative shows in the region N-H stretching vibrations an
absorption maximum at 3130.4 cm-1 while the compound labelled with isotope 15N has shifted the
absorption maximum to 3123.3cm-1. This shift is in accordance with the formula ΰ = 1/2π(K/μ)1/2. In view
of these facts we have concluded that the products of coupling reaction exists in tetrachloromethane
15
solution in the hydrazono form 5B. This hydrazono form was confirmed unambiguously by N-NMR
15
15
spectroscopy as well. The signal at –239.5 ppm of N-C6H5 fragment in the N-NMR spectrum of N
selectively labelled compound shows that compound 5a exists predominantly in hydrazono form
(compared with 15N chemical shifts of model hydrazo compounds17).
H
Me
N
CO2Et
N
N
Me
CO2Et
N
N
EtO2CHN
H
N
H
EtO2CHN
N
R
N
H
R
5B
5A
Scheme 2. Azo-hydrazone tautomerism of compound 5.
Cyclization reactions of hydrazones 5a-5c leading to ethyl (2-aryl-5-methyl-3-oxo-2,3-dihydro-
7H-pyrrolo[3,2-e][1,2,4]triazin-6-yl)carbamates (6a-6c) have been carrried out by heating in the alkaline
medium of sodium carbonate. Under these conditions the cyclization reaction occurs within 5 minutes.
However, the cyclization of the derivate 5c occurred only after 30 min, due to the electron withdrawing
the nitro group. Although it was detected that the compounds 5 are in the hydrazone form, which is
favourable for the thermal cyclization (heating above the melting point), a deep decomposition occurred
(note: under acid catalysis the cyclization has not been observed).
The question of stability of the created cycle of prepared compounds 6 has been paid to its hydrolytic
cleavage. It was detected that these compounds are very stable both in the mineral acids medium and in
the basic hydroxide solutions as well. In contrast to similar derivatives of
pyrazolo[3,4-e][1,2,4]triazines,18 1,2,4-triazine[5,6-b]quinoline19 or 1,2,4-triazine[4,5-a]benzimidazole,20
where the cleavage of the 1,2,4-triazine ring occurs the compounds 6 undergo the hydrolysis of the
ethoxycarbonyl group. Under alkaline hydrolysis the derivatives 7 containing the basic amino group,
which is capable to form salts with mineral acids are produced. If acid hydrolysis is performed the

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HETEROCYCLES, Vol. 75, No. 5, 2008
6-oxoderivatives 8 are yielded.
The prepared compounds were tested for biological activity. Human breast adenocarcinoma cell line
MCF7 was used for cytotoxicity determination by the MTT assay.20,21 The tested compounds showed
poor cytostatic activity (IC50 = 50–180 μmol/l), with the exception of the moderately active hydrazones
5a (IC50 = 10.3 μmol/l), 5b (IC50 = 14.6 μmol/l) and amino compounds 7a (IC50 = 20.6 μmol/l), 7b (IC50
= 26.8 μmol/l).
EXPERIMENTAL
Melting points were determined on a Boetius stage and are uncorrected. The IR spectra were recorded in
KBr wafers on an ATI Unicam Genesis FTIR instrument. The NMR spectra were registered on a Bruker
Avance 300 MHz DRX spectrometer; chemical shifts are reported in ppm, the coupling constants J in Hz.
Elemental analyses were performed with an EA 1108 Elemental Analyser (Fison Instruments). Mass
spectrometric experiments were performed using an LCQ ion trap mass spectrometer (Finnigan MAT,
San Jose, CA, USA).
3-Methyl-1H-pyrrole-2,4-dicarbohydrazide (2): A mixture of ester 116 (23.0 g, 0.102 mol) in 99%
hydrazine monohydrate (80 mL) was refluxed under good stirring on oil bath for 3 h. During this time,
from firstly formed solution start to precipitate white solid. To this suspension was added water (100 mL),
hydrazide 2 was filtered off and washed with water. The sample for analysis was prepared by
crystallization from EtOH. Yield: 19.4 g (96%), mp 285-290 °C (decomp). IR (cm-1): 3304, 1632, 1598,
1
1501, 1388, 1295. H-NMR, (DMSO-d6): 2.41 (s, 3H, CH3), 4.19-4.35 (bs, 4H, 2x NH2), 7.29 (s, 1H,
5-H), 8.68 (s, 1H, NH), 8.93 (s, 1H, NH), 11.30 (s, 1H, NH). 13C-NMR, (DMSO-d6): 11.5, 117.5, 121.7,
122.7, 125.6, 162.3, 165.5. MS (APCI, m/z): 198.1 [M+H]+. Anal. Calcd for C7H11N5O2 (197.2): C,
42.64; H, 5.62; N, 35.51. Found: C, 42.54; H, 5.39; N, 35.67.
3-Methyl-1H-pyrrole-2,4-dicarbonyl diazide (3): A stirred solution of hydrazide 2 (18.12 g, 91.88
mmol) in water (1200 mL) and 35% hydrochloric acid (36.2 mL) was nitrosated with a solution of
sodium nitrite (12.68 g, 183.9 mmol) in water (75 mL) at 0-5 °C. The reaction mixture was stirred for
next 3 h and allowed to stand overnight at 2-5 °C. Precipitated azide was collected on a filter, washed
thoroughly with water and dried over phosphorus pentoxide in dark place. Yield: 19.3 g (96%), mp
145-150 ° (decomp). IR (cm-1): 2145, 2140, 1670, 1663, 1478, 1234. 1H-NMR, (DMSO-d6): 2.53 (s, 3H,
13
CH3), 7.60 (s, 1H, 5-H), 11.00 (bs, 1H, NH). C-NMR, (DMSO-d6): 11.7, 117.4, 123.1, 131.3, 132.2,
164.3, 168.2. MS (APCI, m/z): 220.1 [M+H]+. Anal. Calcd for C7H5N7O2 (219.2): C, 38.36; H, 2.30; N,
44.74. Found: C, 38.29; H, 2.44; N, 44.62.

HETEROCYCLES, Vol. 75, No. 5, 2008
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Diethyl (3-methyl-1H-pyrrole)-2,4-dicarbamate (4): A solution of azide 3 (9.5 g, 43.3 mmol) in
anhydrous EtOH (300 mL) was refluxed under nitrogen for 2.5 h. The formed dark red solution was
concentrated in vacuo to oily product. This one was dissolved in hot mixture of EtOH (50 mL) and water
(100 mL) and left to stand at 5 °C for 2 h. The precipitated dark-red gummy product was discarded, clear
solution was diluted with water (100 mL) and allow to stand for 24 h at 2-5 °C. The solid product was
filtered off and immediately dried in vacuo over phosphorus pentoxide. Yield: 5.32 g (48%), mp 68-72 °C.
1
IR (cm-1): 3323, 3313, 1750, 1745, 1264, 1207. H-NMR, (DMSO-d6): 1.18-1.28 (m, 6H, 2x CH3), 1.77
(s, 3H, CH3), 4.04-4.18 (m, 4H, 2x CH2), 6.47 (s, 1H, 5-H), 8.41 (s, 1H, NH), 8.73 (s, 1H, NH), 10.26 (s,
13
1H, NH). C-NMR, (DMSO-d6): 10.5, 14.2, 14.8, 62.3, 62.9, 110.4, 116.3, 135.3, 140.1, 164.3, 168.2.
MS (APCI, m/z): 256.2 [M+H]+. Anal. Calcd for C11H17N3O4 (255.3): C, 51.76; H, 6.71; N, 16.46. Found:
C, 51.86; H, 6.59; N, 16.40.
General procedure for ethyl (5-arylhydrazono-4-ethoxycarbonylimino-3-methyl-4,5-dihydro-1H-
pyrrol-2-yl)carbamates (5a-5c): A solution of corresponding aromatic amine (2.0 mmol) in a mixture of
ice water (8 mL) and 35% hydrochloric acid (1.2 mL) was diazotized with a solution of sodium nitrite
(2.0 mmol) in ice water (4 mL). The mixture was stirred in ice bath for 15 min and then added
portionwise to a solution of carbamate 4 in pyridine (16 mL) which was pre-cooled to 0–5 °C and stirred
with gentle stream of nitrogen. After 1 h the reaction mixture was left to stand for 12 h at 0-5 °C and
evaporated to dryness. The semi-solid product was mixed with water (20 mL) and this mixture was
extracted with CHCl3 (3 x 10 mL). The CHCl3 extract was washed with water, dried (MgSO4), evaporated
to dryness and residue crystallized from aq. EtOH.
Ethyl
[4-ethoxycarbonylimino-3-methyl-5-(phenylhydrazono)-4,5-dihydro-1H-pyrrol-2-yl]carba-
mate (5a): Yield: 60%, mp 97-99 °C. IR (cm-1): labelled with 15N (CCl4): 3299, 3123, 2983, 1753, 1598,
1
1518, 1256, 1053, unlabelled (CCl4): 3299, 3130, 2983, 1753, 1598, 1518, 1256, 1053. H-NMR,
(DMSO-d6): 1.27-1.31 (m, 6H, 2x CH3), 1.87 (s, 3H, CH3), 4.16-4.21 (m, 4H, 2x CH2), 6.88-6.95 (m, 1H,
13
arom.), 7.25-7.33 (m, 4H, arom.), 9.46 (s, 1H, NH), 10.79 (s, 1H, NH), 10.92 (s, 1H, NH). C-NMR,
(DMSO-d6): 9.6, 14.3, 14.5, 60.7, 61.0, 112.9, 120.4, 120.7, 129.0, 132.2, 136.4, 152.9, 162.3, 163.0,
163.2. 15N-NMR, (DMSO-d6): -239.5 (chemical shift referred to CH3NO2). MS (APCI, m/z): 360.2
[M+H]+. Anal. Calcd for C17H21N5O4 (359.4): C, 56.82; H, 5.89; N, 19.49. Found: C, 56.86; H, 5.71; N,
19.30.
Ethyl [4-ethoxycarbonylimino-3-methyl-5-(4-methoxyphenylhydrazono)-4,5-dihydro-1H-pyrrol-2-
1
yl]carbamate (5b): Yield: 55%, mp 81-83 °C. IR (cm-1): 3293, 2990, 1740, 1515, 1247. H-NMR,
(DMSO-d6): 1.25-1.32 (m, 6H, 2x CH3), 1.82 (s, 3H, CH3), 3.71 (s, 3H, CH3O), 4.15-4.22 (m, 4H, 2x
CH2), 6.88 (d, 2H, J = 9.0 Hz, arom.), 7.18 (d, 2H, J = 9.0 Hz, arom.), 9.35 (s, 1H, NH), 10.66 (s, 1H,

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HETEROCYCLES, Vol. 75, No. 5, 2008
NH), 10.85 (s, 1H, NH). MS (APCI, m/z): 390.2 [M+H]+. Anal. Calcd for C18H23N5O5 (389.4): C, 55.52;
H, 5.95; N, 17.98. Found: C, 55.47; H, 6.12; N, 17.88.
Ethyl [4-ethoxycarbonylimino-3-methyl-5-(4-nitrophenylhydrazono)-4,5-dihydro-1H-pyrrol-2-yl]-
carbamate (5c): Yield: 68%, mp 107-109 °C, IR (cm-1): 3328, 2997, 1721, 1637, 1525, 1500, 1249.
1H-NMR, (DMSO-d6): 1.28-1.32 (m, 6H, 2x CH3), 1.85 (s, 3H, CH3), 4.15-4.24 (m, 4H, 2x CH2), 7.85 (d,
2H, J = 9.0 Hz, arom.), 8.20 (d, 2H, J = 9.0 Hz, arom.), 9.46 (s, 1H, NH), 10.77 (s, 1H, NH), 10.92 (s, 1H,
NH). MS (APCI, m/z): 405.2 [M+H]+. Anal. Calcd for C17H20N6O6 (404.4): C, 50.49; H, 4.99; N, 20.78.
Found: C, 50.37; H, 4.89; N, 20.85.
General procedure for ethyl (2-aryl-5-methyl-3-oxo-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-
6-yl)carbamates (6a-6c): A mixture of compound 5 (1.0 mmol) and sodium carbonate (1.3 mmol) in
solution of EtOH (15 mL) and water (10 mL) was refluxed for 30 min. After cooling, the formed solution
was neutralized with 10% aqueous AcOH, precipitated solid filtered off and washed with water. The
sample for analysis was prepared by crystallization from EtOH.
Ethyl (5-methyl-3-oxo-2-phenyl-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-6-yl)carbamate (6a):
1
Yield: 84%, mp > 360 °C, IR (cm-1): 3283, 3005, 2863, 1699, 1610, 1262, 1260. H-NMR, (DMSO-d6):
1.27 (t, 3H, J = 6.9 Hz, CH3), 1.89 (s, 3H, CH3), 4.13 (q, 2H, J = 6.9 Hz, CH2), 7.37 (t, 1H, J = 7.4 Hz,
arom.), 7.49 (t, 2H, J = 7.4, arom.), 7.57 (d, 2H, J = 7.4 Hz, arom.), 10.96 (s, 1H, NH), 12.01 (bs, 1H,
NH). 13C-NMR, (DMSO-d6): 6.7, 14.2, 60.8, 125.6, 126.8, 128.3, 128.5. Due to low solubility other
signals were not observed. MS (APCI, m/z): 314.1 [M+H]+. Anal. Calcd for C15H15N5O3 (313.3): C,
57.50; H, 4.83; N, 22.35. Found: C, 57.48; H, 4.62; N, 22.37.
Ethyl [5-methyl-3-oxo-2-(4-methoxyphenyl)-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-6-yl]carba-
1
mate (6b): Yield: 87%, mp > 360 °C. IR (cm-1): 3337, 2948, 1702, 1595, 1513, 1258. H-NMR,
(DMSO-d6): 1.25 (t, 3H, J = 6.9 Hz, CH3), 1.87 (s, 3H, CH3), 3.78 (s, 3H, CH3O), 4.08 (q, 2H, J = 6.9 Hz,
CH2), 6.98 (d, 2H, J = 9.2 Hz, arom.), 7.40 (d, 2H, J = 9.2 Hz, arom.), 10.96 (s, 1H, NH), 12.03 (bs, 1H,
NH). MS (APCI, m/z): 344.2 [M+H]+. Anal. Calcd for C16H17N5O4 (343.3): C, 55.97; H, 4.99; N, 20.40.
Found: C, 55.85; H, 5.04; N, 20.31.
Ethyl-[5-methyl-3-oxo-2-(4-nitrophenyl)-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-6-yl]carba-
1
mate (6c): Yield: 63%, mp > 360°C. IR (cm-1): 3353, 2978, 1705, 1622, 1528, 1345, 1257. H-NMR,
(DMSO-d6): 1.25 (t, 3H, J = 6.9 Hz, CH3), 1.85 (s, 3H, CH3), 4.15 (q, 2H, J = 6.9 Hz, CH2), 7.90 (d, 2H, J
= 9.0 Hz, arom.), 8.29 (d, 2H, J = 9.0 Hz, arom.), 10.97 (s, 1H, NH), 12.05 (bs, 1H, NH). MS (APCI,
m/z): 359.2 [M+H]+. Anal. Calcd for C15H14N6O5 (358.3): C, 50.28; H, 3.94; N, 23.45. Found: C, 50.30;
H, 3.99; N, 23.38.

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General procedure for 6-amino-2-aryl-5-methyl-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-3-ones
(7a-7c): A solution of 6 (0.15 mmol) in 1M NaOH (5 mL) was refluxed for 30 min. The cooled solution
was neutralized with 10% aqueous AcOH, precipitated solid filtered off, washed with water and dried at
120°C for 1.5 h.
6-Amino-5-methyl-2-phenyl-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-3-one (7a): Yield: 87%, mp
1
> 300 °C (decomp). IR (cm-1): 3395, 3068, 1667, 1554, 1427. H-NMR, (DMSO-d6): 1.82 (s, 3H, CH3),
7.33 (t, 1H, J = 7.6, arom.), 7.46 (t, 2H, J = 7.6, arom.), 7.56 (d, 2H, J = 7.6, arom.), 8.95 (bs, 2H, NH2),
13
11.67 (bs, 1H, NH). C-NMR, (DMSO-d6): 6.4, 125.5, 126.2, 128.1, 128.2. Due to low solubility other
signals were not observed. MS (APCI, m/z): 242.1 [M+H]+. Anal. Calcd for C12H11N5O (241.2): C, 59.74;
H, 4.60; N, 29.03. Found: C, 59.58; H, 4.70; N, 28.94.
6-Amino-5-methyl-2-(4-methoxyphenyl)-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-3-one
(7b):
1
Yield: 82%, mp > 300 °C (decomp). IR (cm-1): 3381, 3065, 1672, 1550, 1437. H-NMR, (DMSO-d6):
1.83 (s, 3H, CH3), 3.75 (s, 3H, CH3O), 7.01 (d, 2H, J = 9.0 Hz, arom.), 7.50 (d, 2H, J = 9.0 Hz, arom.),
8.90 (bs, 2H, NH2), 11.70 (bs, 1H, NH). MS (APCI, m/z): 272.2 [M+H]+. Anal. Calcd for C13H13N5O2
(271.3): C, 57.56; H, 4.83; N, 25.82. Found: C, 57.65; H, 4.93; N, 25.74.
6-Amino-5-methyl-2-(4-nitrophenyl)-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-3-one (7c): Yield:
92%, mp > 330 °C (decomp). IR (cm-1): 3370, 3063, 1650, 1523, 1551, 1425. 1H-NMR, (DMSO-d6): 1.89
(s, 3H, CH3), 7.86 (d, 2H, J = 9.0 Hz, arom.), 8.36 (d, 2H, J = 9.0 Hz, arom.), 8.87 (bs, 2H, NH2), 11.71
(bs, 1H, NH). MS (APCI, m/z): 286.1 [M+H]+. Anal. Calcd for C12H10N6O3 (286.2): C, 50.35; H, 3.52; N,
29.36. Found: C, 50.32; H, 3.56; N, 29.27.
General procedure for 2-aryl-5-methyl-2H-pyrrolo[3,2-e][1,2,4]triazine-3,6(4H,7H)-diones (8a-8c):
A solution of compound 6 (0.15 mmol) in 2M-HCl (7 mL) was refluxed for 1 h. Precipitated crystalline
yellow solid was collected on a filter by suction, washed with water and dried at 120 °C for 1.5 h.
5-Methyl-2-phenyl-2H-pyrrolo[3,2-e][1,2,4]triazine-3,6(4H,7H)-dione (8a): Yield: 81%, mp > 340 °C
(decomp). IR (cm-1): 3014, 2863, 1694, 1662, 1369, 1082. 1H-NMR, (DMSO-d6): 1.82 (s, 3H, CH3), 7.35
(t, 1H, J = 7.6, arom.), 7.47 (t, 2H, J = 7.6, arom.), 7.55 (d, 2H, J = 7.6, arom.), 10.66 (bs, 1H, NH), 11.85
13
(bs,1H, NH). C-NMR, (DMSO-d6): 4.6, 96.7, 123.8, 125.0, 126.7, 126.9, 130.7, 139.8, 141.7, 170.1.
MS (APCI, m/z): 243.1 [M+H]+. Anal. Calcd for C12H10N4O2 (242.2) C, 59.50; H, 4.16; N, 23.13. Found:
C, 59.54; H, 4.20; N, 23.07.
5-Methyl-2-(4-methoxyphenyl)-2H-pyrrolo[3,2-e][1,2,4]triazine-3,6(4H,7H)-dione (8b): Yield: 88%,
1
mp > 310 °C (decomp). IR (cm-1): 3020, 2870, 1697, 1651, 1368, 1080. H-NMR, (DMSO-d6): 1.82 (s,
3H, CH3), 3.79 (s, 3H, CH3O), 7.00 (d, 2H, J = 8.7 Hz, arom.), 7.49 (d, 2H, J = 8.7 Hz, arom.), 10.60 (bs,
1H, NH), 11.81 (bs, 1H, NH). MS (APCI, m/z): 273.2 [M+H]+. Anal. Calcd for C13H12N4O3 (272.3): C,

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HETEROCYCLES, Vol. 75, No. 5, 2008
57.35; H, 4.44; N, 20.58. Found: C, 57.32; H, 4.54; N, 20.47.
5-Methyl-2-(4-nitrophenyl)-2H-pyrrolo[3,2-e][1,2,4]triazine-3,6(4H,7H)-dione (8c): Yield: 84%, mp
1
> 360 °C (decomp). IR (cm-1): 3021, 2877, 1690, 1527, 1343. H-NMR, (DMSO-d6): 1.89 (s, 3H, CH3),
7.88 (d, 2H, J = 9.0 Hz, arom.), 8.40 (d, 2H, J = 9.0 Hz, arom.), 10.59 (bs, 1H, NH), 11.83 (bs, 1H, NH).
MS (APCI, m/z): 288.1 [M+H]+. Anal. Calcd for C12H9N5O4 (287.2): C, 50.18; H, 3.16; N, 24.38. Found:
C, 50.13; H, 3.25; N, 24.31.
ACKNOWLEDGEMENT
We are grateful to the Ministry of Education, Youth and Sport of the Czech Republic, for the grant MSM
6198959216.
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