Chemistry of Heterocyclic Compounds, Vol. 43, No. 4, 2007
SYNTHESIS OF 4-AMINO-7-PHENYLPYRIDO[4,3-d]PYRIMIDINE 6-OXIDES
N. Cikotiene, R. Buksnaitiene, and A. Brukstus
Keywords: arylethynylpyrimidines, pyrido[4,3-d]pyrimidines, cyclization
Recently some alkylderivatives were synthesized in our laboratory and their use for obtaining
pyrrole[3,2-d]pyrimidine 7-oxides [1,2] and pyrido[4,3-d]pyrimidines [3] respectively was demonstrated. In a
continuation of investigations in this direction, we have discovered a previously unknown simple synthesis for 4-
amino-7-phenylpyrido[4,3-d]pyrimidine 6-oxides. These compounds may serve as excellent synthons for
polysubstituted pyrido[4,3-d]pyrimidines which are exciting interest because of their biological activity [4-6].
Boiling 6-(phenylethynyl)pyrimidine-5-carbaldehydes 1a,b with hydroxylamine hydrochloride in the
presence of potassium carbonate in an ethanol–water mixture led to the formation of 4-amino-
7-phenylpyrido[4,3-d]pyrimidine 6-oxides 2a,b in yields of 90 and 82% respectively.
NH2
NH2
–
+
N
CHO
O
.
NH2OH HCl
N
N
K2CO3
R
N
Ph
R
N
Ph
2a,b
1a,b
1, 2 a R = SCH3, b R = NH2
1
13
IR spectra were recorded on a Perkin-Elmer FT-IR Spectrum BX II, while H and C NMR spectra of
DMSO-d6 solutions with TMS as internal standard were recorded with a Varian Unity Inova spectrometer (300
and 75 MHz, respectively).
The 4-amino-6-(phenylethynyl)pyrimidine-5-carbaldehydes starting materials 1a,b were synthesized as reported
in [3].
4-Amino-2-methylthio-7-phenylpyrido[4,3-d]pyrimidine 6-oxide (2a). A solution of 4-amino-
2-methylthio-6-(phenylethynyl)pyrimidine-5-carbaldehyde 1a (0.2 g, 0.74 mmol), hydroxylamine hydrochloride
(0.06 g, 0.86 mmol), and potassium carbonate (0.057 g, 0.37 mmol) in 50% ethanol (10 ml) was boiled for 10 h,
cooled, and the precipitate was filtered and recrystallized from an ethanol–water mixture to give compound 2a
1
(0.21 g, 90%), mp 260°C. IR spectrum (nujol), ν, cm-1: 3324, 3305 (NH2), 1242 (NO). H NMR spectrum, δ,
ppm: 2.50 (3H, s, SCH3); 7.46-7.48 (3H, m, ArH); 7.52 (1H, s, CH); 7.79-7.83 (2H, m, ArH); 8.05 (2H, br. s,
NH2 ); 9.34 (1H, s, CH). 13C NMR spectrum, δ, ppm: 13.2, 109.5, 122.6, 127.4, 129.1, 129.2, 132.2, 134.4,
146.0, 151.8, 157.6, 170.3. Found, %: C 58.99; H 4.15; N 19.79. C14H12N4OS. Calculated, %: C 59.14; H 4.25;
N 19.70.
__________________________________________________________________________________________
Department of Organic Chemistry, Vilnius University, Vilnius LT-03225, Lithuania; e-mail:
inga.cikotiene@chf.vu.lt. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 619-620, April,
2007. Original article submitted November 3, 2006
0009-3122/07/4304-0515©2007 Springer Science+Business Media, Inc.
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