Synthesis of a new heterocyclic system - Pyrido[3',2':4,5]thieno- [2,3-e][1,2,3]triazolo[1,5-a]pyrimidine

Full text of DOI:10.1007/s10593-009-0338-z

Chemistry of Heterocyclic Compounds, Vol. 45, No. 7, 2009
SYNTHESIS OF A NEW HETEROCYCLIC
SYSTEM – PYRIDO[3',2':4,5]THIENO-
[2,3-e][1,2,3]TRIAZOLO[1,5-a]PYRIMIDINE
N. T. Pokhodylo1, V. S. Matiychuk1, and N. D. Obushak1*
Keywords: azides, pyrido[3',2':4,5]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine, thieno[2,3-b]pyridine,
[1,2,3]triazolo[1,5-a]pyrimidine, domino reactions.
There has been considerable recent interest in polycyclic systems with a 1,2,3-triazole ring, in particular,
[1,2,3]triazolo[1,5-a]pyrimidines, in light of the useful properties of these compounds [1]. The
[1,2,3]triazolo[1,5-a]pyrimidine fragment fused with various heterocycles is conveniently constructed by the
anionic domino reaction of ortho-substituted aryl and hetaryl azides. Such reactions have been described for
compounds containing an azido group in pyrrole [2, 3], indole [4], pyrazole [5], imidazole [6], 1,2,3-triazole
[7, 8], and thiophene rings [9]. Biological activity is noted for most of these compounds. In the present work, we
propose a convenient method to synthesize a new polycyclic system, namely, pyrido[3',2':4,5]thieno-
O
Me
Me
NH2
Me
O
1.
NaNO2 ,
H2SO4
N
N
Br
OEt
O
CH(OEt)3
AcOH
OEt
NaOMe,
O
+
H2N
S
2. NaN3
Me
N
Me
N
H
S
Me
S
MeOH
2
1
N
R
N
Me
N
N3
R
Me
OEt
N
4a–c
NH
O
NaOMe,
MeOH
S
O
Me
N
S
Me
N
3
5a–c
N
S
N
Ph
, c R =
4, 5 a R = CN, b R =
S
_______
* To whom correspondence should be addressed, e-mail: obushak@in.lviv.ua.
1Ivan Franko Lvov National University, Lvov 79005, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1100-1103, July, 2009. Original
article submitted April 29, 2009.
0009-3122/09/4507-0881©2009 Springer Science+Business Media, Inc.
881

[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine. 3-Cyanopyridine 1 [10] was used as the starting reagent and was
converted to thienopyridine 2 [11] with the aim of subsequent transformation of the amino group into an azido
group. We should note that, in many cases of such transformations, low basicity of the heterocyclic amine with
an electron-withdrawing group in the position adjacent to the ring sharply diminishes the capacity of such
compounds to react with a nitrosylating agent, thereby, hindering the synthesis of azides from available
hetarylamines through diazonium salts. In our case, amine 2 undergoes diazotization by nitrososulfuric acid
obtained by the reaction of NaNO2 with concentrated sulfuric acid [11]. Subsequent treatment of the solution of
the diazonium salt with sodium azide gives azide 3, which readily undergoes an anionic domino reaction with
nitriles 4a-c possessing an active methylene group to give a new polycyclic system, namely, pyrimidines 5a-c.
The reaction takes only a few minutes and products 5a-c are obtained in high yields after crystallization
from the reaction mixture without further purification.
This approach opens possibilities for the synthesis of representatives of this new heterocyclic system,
namely, derivatives of pyrido[3',2':4,5]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine. We also note that the
synthesis of starting pyridine 1 [10] permits the introduction of a broad range of substituents in the ring [12] and,
thus, in products 5.
1
The H NMR spectra were taken on a Varian Unity +400 spectrometer at 400 MHz in DMSO-d6 with
TMS as the internal standard. The mass spectra were taken on an Agilent 1100 LC/MSD with chemical
ionization.
Ethyl Ester of 3-Azido-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylic acid (3). Amine 2 (2.5 g,
0.01 mol) was dissolved in a mixture of concentrated sulfuric acid (2.5 ml) and water (7 ml) and cooled to 0°C.
Then, a saturated solution of NaNO2 (0.83 g, 0.012 mol) was added, maintaining the temperature below 5°C.
The reaction mixture was maintained for 5 min. Then, a solution of NaN3 (0.65 g, 0.01 mol) in water (5 ml) was
added. The reaction mixture was maintained for 10 min at room temperature. The precipitate was filtered off to
give azide 3 in 73% yield. This product was used without further purification, dec. 125-126°C. Mass spectrum,
m/z: 277 [M+H]+. Found, %: C 52.35; H 4.47; N 20.02. C12H12N4O2S. Calculated, %: C 52.16; H 4.38; N 20.28.
8,10-Dimethyl-5-oxo-4,5-dihydropyrido[3',2':4,5]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine-
3-carbonitrile (5a). Malononitrile 4a (0.66 g, 0.01 mol) and azide 3 (2.76 g, 0.01 mol) were added with
vigorous stirring to a solution of sodium methylate prepared from 0.3 g sodium and 20 ml methanol. The
mixture was stirred at room temperature until a precipitate formed. The precipitate was filtered off to give
1
compound 5a in 87% yield; mp >300°C. H NMR spectrum, δ, ppm (J, Hz): 2.58 (3H, s, CH3); 3.00 (3H, s,
CH3); 7.07 (1H, s, H Py). Mass spectrum, m/z: 297 [M+H]+. Found, %: C 52.78; H 2.54; N 28.28; S 10.98.
C13H8N6OS. Calculated, %: C 52.69; H 2.72; N 28.36; S 10.82.
Pyrimidones 5b and 5c were synthesized analogously.
8,10-Dimethyl-3-(4-phenyl-1,3-thiazol-2-yl)pyrido[3',2':4,5]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimi-
1
din-5(4H)-one (5b) was obtained in 94% yield; mp >300°C. H NMR spectrum, δ, ppm (J, Hz): 2.57 (3H, s,
3
3
CH3); 3.18 (3H, s, CH3); 7.09 (1H, s, H Py); 7.31 (1H, t, J = 7.6, H-4 Ph); 7.44 (2H, t, J = 7.6, H-3, H-5 Ph)
7.77 (1H, s, H thiazole); 8.09 (2H, d, J = 7.6, H-2, H-6 Ph). Mass spectrum, m/z: 431 [M+H]+. Found, %:
3
C 58.45; H 3.46; N 19.60; S 14.72. C21H14N6OS2. Calculated, %: C 58.59; H 3.28; N 19.52; S 14.90.
3-(1,3-Benzothiazol-2-yl)-8,10-dimethylpyrido[3',2':4,5]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimi-
1
din-5(4H)-one (5c) was obtained in 97% yield; mp >300°C. H NMR spectrum, δ, ppm (J, Hz): 2.59 (3H, s,
3
3
CH3); 3.18 (2H, s, CH3); 7.12 (1H, s, H Py); 7.33 (1H, t, J = 7.8, H-6 Ar); 7.45 (1H, t, J = 7.8, H-5 Ar);
7.97-8.00 (2H, m, H-4, H-7 Ar). Mass spectrum, m/z: 405 [M+H]+. Found, %: C 56.38; H 2.81; N 20.62;
S 15.98. C19H12N6OS2. Calculated, %: C 56.42; H 2.99; N 20.78; S 15.86.
882

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