Synthesis of 7,8-dihydro-6H-pyrazolo[5′,1′:3,4][1,2,4]- triazino[6,5-d][1,2]diazepin-6-one, a new heterocyclic system

Full text of DOI:10.1007/s10593-009-0256-0

Chemistry of Heterocyclic Compounds, Vol. 45, No. 2, 2009
SYNTHESIS OF 7,8-DIHYDRO-
6H-PYRAZOLO[5',1':3,4][1,2,4]-
TRIAZINO[6,5-d][1,2]DIAZEPIN-6-ONE,
A NEW HETEROCYCLIC SYSTEM
V. V. Didenko1, Kh. S. Shikhaliev1*, and I. V. Ledenyova1
Keywords: hydrazine, 7,8-dihydro-6H-pyrazolo[5',1':3,4][1,2,4]triazino[6.5-d][1,2]diazepin-6-one,
3(5)-pyrazolediazonium salt, pyrazolo[5,1-c][1,2,4]triazines, azo coupling, cyclocondensation.
In a continuation of a study of the chemistry of 3(5)-pyrazolediazonium salts [1, 2], we have developed a
simple and convenient method for constructing the 1,2-diazepine ring condensed with a pyrazolo-
[5,1-c]-as-triazine fragment.
CO2R
1. OC(CH2CO2R)2 2a, b
EtOH, 0°C
H
CO2R
N
N
+
N2
N
N
–
Me
N
2. H2SO4 (45%)
Cl
N
Me
Ph
Ph
3a,b
.
N2H4 H2O
1
EtOH, ∆
O
O
H
NH2
O
N
HO
H
N
N
NH
N
NH
O
N
N
O
N
N
N
N
N
N
Me
N
N
Me
N
Me
Ph
Ph
5
Ph
4
2, 3 a R = Me, b R = Et
Azo coupling of pyrazolediazonium salt 1 with esters of acetonedicarboxylic acid 2a,b through a stage
involving cyclization of the hydrazones gave new pyrazolo[5,1-c][1,2,4]triazines 3a,b. The cyclocondensation
of triazines 3a,b with hydrazine hydrate proceeded unequivocally to give two regioisomers 4 and 5. Analysis of
1
the H NMR spectrum indicated that this transformation leads exclusively to 9-hydroxy-2-methyl-3-phenyl-
_______
* To whom correspondence should be addressed, e-mail: chocd261@chem.vsu.ru.
1Voronezh State University, Voronezh 394006, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 307-308, February, 2009. Original
article submitted December 19, 2008.
248
0009-3122/09/4502-0248©2009 Springer Science+Business Media, Inc.

7,8-dihydro-6H-pyrazolo[5',3':3,4][1,2,4]triazino[6,5-d][1,2]diazepin-6-one (4), which exists predominantly as
the enol tautomer. The spectrum of this product lacks the singlet for the amino group, corresponding to
pyrazolotriazine structure 5. In addition, broad signals are observed for the NH protons of the diazepine
fragment at δ 9.60 and 11.40 ppm.
The 1H NMR spectra were taken on a Bruker AC-300 spectrometer at 300 MHz in DMSO-d6 with TMS
as the internal standard. The mass spectra were taken on an LKB-9000 spectrometer at 70 eV ionizing electron
energy. The elemental analyses were taken on a Carlo Erba NA 1500 analyzer.
Methyl Ester of 4-(2-Methoxycarbonylmethyl)-7-methyl-8-phenylpyrazolo[5,1-c][1,2,4]triazine-
3-carboxylic Acid (3a). A solution of 5-amino-3-methyl-4-phenylpyrazole [3] (1.7 g, 1.0 mmol) in water (20 ml)
and concentrated hydrochloric acid (3 ml) was treated with NaNO2 (0.7 g, 1.0 mmol) at 0°C. The solution obtained
was added in portions to a mixture consisting of ester 2a (1.9 g, 1.1 mmol), ethanol (20 ml), and saturated aqueous
sodium acetate (12 g). The reaction mixture was mixed for 1 h. The precipitate was filtered off and washed with
water. Then, 30-40 ml 45% sulfuric acid was added and stirred for 15-30 min. The mixture was poured into water
(300 ml). The precipitate formed was filtered off, washed with water until the wash water was neutral to give 2.8 g
(83%) compound 3a; mp 98-100°C (2-propanol). 1H NMR spectrum, δ, ppm (J, Hz): 2.71 (3H, s, CH3); 3.66 (3H, s,
OCH3); 4.00 (3H, s, OCH3); 4.75 (2H, s, CH2CO2Me); 7.50-7.92 (5H, m, C6H5). Mass spectrum, m/z (Irel, %):
340 [M]+ (100). Found, %: C 59.87; H 4.87; N 16.55. C17H16N4O4. Calculated %: C 59.99; H 4.74; N 16.46.
Ethyl
Ester
of
4-(2-Ethoxycarbonylmethyl)-7-methyl-8-phenylpyrazolo[5,1-c][1,2,4]triazine-
3-carboxylic Acid (3b) was obtained in 68% yield (2.5 g); mp 123-125°C (2-propanol). 1H NMR spectrum, δ, ppm
(J, Hz): 1.22 (3H, t, J = 6.9, CH2CH3); 1.39 (3H, t, J = 6.9, CH2CH3); 2.72 (3H, s, CH3); 4.10-4.40 (4H, m,
2CH3CH2); 4.76 (2H, s, CH2CO2Et); 7.44-7.90 (5H, m, C6H5). Mass spectrum, m/z (Irel, %): 368 [M]+ (100). Found,
%: C 61.80; H 5.59; N 15.30. C19H20N4O4. Calculated, %: 61.95; H 5.47; N 15.21.
9-Hydroxy-2-methyl-3-phenyl-7,8-dihydro-6H-pyrazolo[5',1':3,4][1,2,4]triazino[6,5-d]diazepin-
6-one (4). A mixture of compounds 3a or 3b (1.0 mmol), hydrazine hydrate (1.0 ml, 2.0 mmol), and ethanol (35 ml)
was heated at reflux for 30 min. The precipitate formed was filtered off and crystallized to give 1.2 g
(40%) compound 4, mp 210°C (dec.) (acetic acid). 1H NMR spectrum, δ, ppm (J, Hz): 2.35 (3H, s, CH3); 6.23 (1H, s,
H-10); 7.26-7.50 (5H, m, C6H5); 9.60 (1H, br. s, NH); 11.32-11.58 (1H, br. d, J = 17, NH); 14.10 (1H, br. s, OH).
Mass spectrum, m/z (Irel, %): 308 [M]+ (20), 282 (28), 210 (10), 173 (45), 157 (72), 145 (37), 131 (41), 115 (100), 89
(55), 51 (55), 39 (71). Found, %: C 58.60; H 3.78; N 27.15. C15H12N6O2. Calculated, %: C 58.44; H 3.92; N 27.20.
This work was carried out with the support of Russian Basic Research Fund Grant No. 08-03-99022 r_ofi.
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