The possible synthesis of (3-alkoxycarbonylmethyl-4-oxo-3,4-dihydro-2- pyrimidinylsulfanyl) acetate esters [5]

Full text of DOI:10.1007/s10593-006-0270-4

Chemistry of Heterocyclic Compounds, Vol. 42, No. 11, 2006
THE POSSIBLE SYNTHESIS OF (3-ALKOXYCARBONYL-
METHYL-4-OXO-3,4-DIHYDRO-2-PYRIMIDINYLSULFANYL)
ACETATE ESTERS
V. Yakubkene, G. Valutite, A. Lopatin, and P. Vainilavicius
Keywords: (3-alkoxycarbonylmethyl-4-oxo-3,4-dihydro-2-pyrimidinylsulfanyl)acetate esters, (2-methy-
sulfanyl-4-oxo-3,4-dihydro-3-pyrimidinyl)acetate esters
Compounds with alkoxycarbonylmethyl groups in adjacent positions in a pyrimidine ring can be used as
synthons in the preparation of polycyclic heterosystems. Our previous attempt [1] to synthesize pyrimidine
derivatives having S- and N-alkoxycarbonylmethyl groups respectively in positions 2 and 3 of the ring by
alkylation of the corresponding 4-hydroxy-2-mercaptopyrimidine or methyl 4-hydroxy-2-methoxycarbonyl-
methylsulfanylacetate with methyl bromoacetate were unsuccessful since only the S- or N-dialkylation product
was formed. Continuing our work in this area we have found that compounds 2a,b can be prepared by treating
the corresponding 2-methylsulfanyl derivatives 1a,b with methyl or ethyl mercaptoacetate in the presence
of base:
O
O
R1
CH2COOR2
SMe
R1
CH2COOR2
HSCH2COOR2
N
N
SCH2COOR2
Me
N
Me
N
1a,b
2a,b
1,2 a R1 = Br, R2 = Me; b R1 = NO2, R2 = Et
It should be noted that compound 2a was obtained by refluxing compound 1a in tert-butanol with
methyl mercaptoacetate in the presence of potassium tert-butylate whereas treatment of compound 1b with ethyl
mercaptoacetate under the same conditions gave a complex mixture of products, from which pure compounds
could not be separated. Compound 2b was prepared with the use of triethylamine as base.
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IR spectra were obtained on a Perkin-Elmer BX FT-IR spectrometer for KBr tablets. H NMR and C
NMR spectra were taken on a Varian Unity Inova instrument (300 and 75 MHz respectively) using CDCl3
relative to TMS.
Compound 1a was prepared as described before [2].
__________________________________________________________________________________________
Vilnius University, Vilnius LT-03225, Lithuania, e-mail: virginija.jakubkiene@chf.vu.lt. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1731-1733, November, 2006. Original article submitted
September 22, 2006.
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0009-3122/06/4210-1368©2006 Springer Science+Business Media, Inc.

Ethyl 6-methyl-2-methylsulfanyl-5-nitro-4-oxo-3,4-dihydro-3-pyrimidinylacetate (1b). HNO3
(d = 1.45, 0.88 g, 14 mmol) was added dropwise at room temperature to a solution of ethyl 6-methyl-2-
methylsulfanyl-4-oxo-3,4-dihydro-3-pyrimidinylacetate [3] (2.42 g, 10 mmol) in conc. H2SO4 (10 ml). The
product was stirred for 0.5 h and poured onto ice. The precipitate formed was filtered off, washed with water,
and recrystallized from methanol to give the product (1.95 g, 68%) with mp 140-141°C. IR spectrum, ν, cm-1:
1
1688, 1743 (C=O). H NMR spectrum, δ, ppm (J, Hz): 1.33 (3H, t, J = 7.1, CH2CH3); 2.48 (3H, s, CH3); 2.69
(3H, s, SCH3); 4.3 (2H, q, J = 7.1, CH2CH3); 4.87 (2H, s, NCH2). 13C NMR spectrum, δ, ppm: 14.3, 15.6, 21.7,
45.6, 62.8, 134.7, 154.4, 158.0, 164.5, 165.7. Found, %: C 41.97; H 4.48; N 14.81. C10H13N3O5S. Calculated, %:
C 41.81; H 4.56; N 14.63.
Methyl 5-bromo-3-methoxycarbonylmethyl-6-methyl-4-oxo-3,4-dihydro-2-pyrimidinylsulfanylacetate
(2a). A solution of compound 1a (1.54 g, 5 mmol) in absolute tert-butanol (15 ml) was refluxed under a nitrogen
atmosphere for 15 min. A solution prepared from methyl mercaptoacetate (0.53 g, 5 mmol), potassium (0.2 g,
5 mmol), and absolute tert-butanol (10 ml) was then added dropwise. The reaction mixture was refluxed for 2 h
with stirring, cooled to room temperature, and several drops of water were added. The precipitate formed was
filtered off, dried, and recrystallized from benzene to give the product (1.03 g, 56%) with mp 134-135oC. IR
spectrum, ν, cm-1: 1688, 1740 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.45 (3H, s, CH3); 3.81 (3H, s, OCH3);
3.83 (3H, s, OCH3); 3.99 (2H, s, SCH2); 4.88 (2H, s, NCH2). 13C NMR spectrum, δ, ppm: 24.9, 34.7, 46.2, 53.2,
53.3, 108.1, 157.7, 158.4, 161.2, 166.7, 168.4. Found, %: C 35.92; H 3.58; N 7.43. C11H13BrN2O5S. Calculated,
%: C 36.18; H 3.59; N 7.67.
Ethyl 3-ethoxycarbonylmethyl-6-methyl-5-nitro-4-oxo-3,4-dihydro-2-pyrimidinylsulfanylacetate
(2b). A solution of compound 1b (1.44 g, 5 mmol) in absolute tert-butanol (45 ml) was stirred at 70°C under a
nitrogen atmosphere for 15 min. A solution prepared from ethyl mercaptoacetate (0.6 g, 5 mmol) , triethylamine
(0.51 g, 5 mmol), and absolute tert-butanol (10 ml) was added dropwise. The reaction mixture was stirred for 4.5
h at 70°, evaporated to one third volume, cooled to room temperature, and water (3 ml) was added. A mixture of
compounds was obtained (1.26 g) and this was dissolved in a mixture of chloroform and ethyl acetate (20 : 1)
and then separated on a Kieselgel silica gel chromatographic column (Kieselgel 60, 0.063-0.200 mm) to give the
starting compound 1b (0.44 g, 31%) with Rf 0.47 and compound 2b (0.64 g, 36%) with Rf 0.4 (Alugram SIL
1
G/UV254, chloroform-ethyl acetate, 20: 1). Mp 102-104oC. IR spectrum, ν, cm-1: 1695, 1739, 1753 (C=O). H
NMR spectrum, δ, ppm (J, Hz): 1.30-1.37 (6H, m, 2 CH2CH3); 2.44 (2H, s, SCH2); 4.26-4.32 (4H, m, 2
CH2CH3); 4.88 (2H, s, NCH2). 13C NMR spectrum δ, ppm: 14.3, 14.4, 21.5, 35.0, 45.8, 62.6, 62.9, 148.0, 154.2,
157.7, 162.6, 165.4, 167.3. Found, %: C 43.38; H 4.92; N 11.65. C13H17N3O7S. Calculated, %: C 43.45; H 4.77;
N 11.69.
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