Synthesis of novel heterocyclic system 9-methyl-8-phenyl-1,4-dihydro-5H- pyrazolo-[5',1':2,3]pyrimido[4,5-e][1,2,4]triazepin-5-one

Full text of DOI:10.1007/s10593-011-0682-7

Chemistry of Heterocyclic Compounds, Vol. 46, No. 11, February, 2011 (Russian Original Vol. 46, No. 11, November, 2010)
SYNTHESIS OF NOVEL HETEROCYCLIC SYSTEM
9-METHYL-8-PHENYL-1,4-DIHYDRO-5H-PYRAZOLO-
[5',1':2,3]PYRIMIDO[4,5-e][1,2,4]TRIAZEPIN-5-ONE
A. S. Tchuvashlev1*, A. S. Shestakov1, D. V. Krylskiy 2, and Kh. S. Shikhaliev1
Keywords: 7-imino-2-methyl-3-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimdine-6-carbohydrazide, 9-methyl-
8-phenyl-1,4-dihydro-5H-pyrazolo[5',1':2,3]pyrimido[4,5-e][1,2,4]triazepin-5-one, ethyl 7-imino-2-methyl-
3-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carboxylate.
The reaction of ethyl 7-imino-2-methyl-3-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carboxylate
(1) [1] with hydrazine hydrate in n-butanol medium gave 7-imino-2-methyl-3-phenyl-4,7-dihydropyrazolo-
[1,5-a]pyrimidine-6-carbohydrazide (2).
Treatment of compound 2 with triethyl orthoformate gives compound 4 which can possibly exist in the
tautomeric forms A-D. Formation of the expected pyrimidine ring containing compound 3 did not occur. This
was evidence by the absence of a signal for the two protons of an exocyclic amino group along with the
observation of two broadened singlets for NH group protons at 8.35 and 9.10 ppm which corresponds to
structure 4. Moreover, compound 4 does not take part in a reaction with benzaldehyde and isothiocyanates
which points to the absence of a primary amino group in the structure discussed. The absence of a signal for a
hydroxyl group proton in the low field region points to the existence of compound 4 in a keto form. The position
1
and intensity of the signals for the remaining protons in the H NMR spectrum confirm the formation of the
pyrazolopyrimidotriazepino system but, for a precise definition of the predominant tautomeric form of
compound 4, we have used a 1H NMR 2D NOESY experiment.
Hence the absence of a cross peak for an o-proton of the phenyl substituent with one of the NH proton
signals points to the occurrence of the pyrimidine ring in an aromatic form and so excludes the structural variant
4A. The absence of a cross peak for the proton on position C-6 with other protons confirms the proposal that
compound 4 exists in a keto form. The absence of a mutual splitting of the NH protons excludes its possible
existence in form 4C. In addition, the {1H-1H} NOESY spectrum has a cross peak corresponding to the
interaction of the NH proton at 8.35 ppm with water and this points to the existence of exchange processes in the
system studied so explaining the absence of an interaction of the protons with the C-2 and N-1 atoms.
_______
* To whom correspondence should be addressed, e-mail: alextsh@yandex.ru.
1Voronezh State University, Voronezh 394006, Russia.
2Science Research Institute for Applied Acoustics, Dubna 141981, Moscow region, Russia; e-mail:
niipa@dubna.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1735-1737, November, 2010.
Original article submitted February 7, 2010.
0009-3122/11/4611-1411©2011 Springer Science+Business Media, Inc.
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Hence the reaction of 7-imino-2-methyl-3-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carbohydra-
zide 2 with triethyl orthoformate gives the novel heterocyclic system 9-methyl-8-phenyl-1,4-dihydro-5H-
pyrazolo[5',1':2,3]pyrimido[4,5-e][1,2,4]triazepin-5-one (4B).
NH2
N
N
NH
O
NH
O
HC(OEt)3
.
NH2
N2H4 H2O
N
N
O
N
N
N
N
N
OEt
H
BuOH
Me
N
Me
N
H
Me
N
H
Ph
Ph
3
Ph
2
1
HC(OEt)3
N
N
HN
NH
N
N
NH
N
N
N
O
O
Me
N
Me
4A
N
H
Ph
Ph
4B
H
H
N
N
N
N
NH
O
N
N
N
N
N
OH
N
Me
4D
N
Me
Ph
Ph
4C
1H NMR and {1H-1H} NOESY spectra were recorded on a Bruker DRX-500 (500 MHz) instrument
using DMSO-d6.
7-Imino-2-methyl-3-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carbohydrazide (2). A mixture of
ester 1 (1 g, 3.4 mmol) and hydrazine hydrate (0.67 g, 13.5 mmol) was refluxed in n-butanol (5 ml) for 3 h. The
precipitated white crystals were filtered off, washed with 2-propanol, and recrystallized from a mixture of
1
toluene and DMF. Yield 0.6 g (63%). H NMR spectrum, , ppm: 2.56 (3H, s, CH3); 4.33 (2H, br. s, NH2);
7.20-7.75 (5H, m, Ph); 8.42 (1H, s, imino-NH); 8.55 (1H, s, pyrimid. NH); 8.61 (1H, s, H-5); 9.73 (1H, s, NH).
Found, %: C 59.50; H 5.02; N 29.65. C14H14N6O. Calculated, %: C 59.56; H 5.00; N 29.77.
9-Methyl-8-phenyl-1,4-dihydro-5H-pyrazolo[5',1':2,3]pyrimido[4,5-e][1,2,4]triazepin-5-one (4B)
was prepared by refluxing hydrazide 2 (2.82 g, 0.01 mol) in triethyl orthoformate with addition of a catalytic
amount of acetic acid. It was recrystallized from acetic acid. Yield 2.2 g (75%). 1H NMR spectrum, , ppm: 2.60
(3H, s, CH3); 7.30-7.75 (5H, m, Ph); 8.35 (1H, br. s, NH); 8.65 (1H, s, H-6); 9.10 (1H, br. s, NH); 9.33 (1H, s,
H-2). Found, %: C 61.65; H 4.13; N 28.75. C15H12N6O. Calculated, %: C 61.64; H 4.14; N 28.75.
REFERENCES
1.
D. V. Krylskiy, A. S. Tchuvashlev, A. P. Arzamastsev, and A. I. Slivkin, Khim.-Farm. Zh., 43, No. 6, 74
(2009).
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