HETEROCYCLES, Vol. 83, No. 5, 2011
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2H); 13C NMR (100 MHz, CDCl3, 25 C) δ 14.2, 14.3, 60.8, 64.1, 118.8, 122.1, 137.3, 158.4, 165.7,
166.2.
Ethyl 3-(2-ethoxypyrimidin-5-yl)propionate (4)
A suspension of 3 (0.210 g, 0.945 mmol) in EtOH (2 mL) and 10% Pd/C (0.012 g), triethylamine (0.2
mL) was hydrogenated at 50 psi overnight. The catalyst was filtered off and the filtrate was evaporated.
The residue was dissolved in CH2Cl2, washed by saturated aqueous NH4Cl and brine respectively, and
dried over anhydrous Na2SO4. After evaporation of solvent, the residue was purified by flash
chromatography on silica gel (Hexanes : Et2O = 1 : 1) to give compound 4 as colorless oil (0.170 g, 0.758
mmol, 80%). 1H NMR (400 MHz, CDCl3, 25 oC) δ 1.23 (t, J = 7.2 Hz, 3H), 1.42 (t, J = 6.9 Hz, 3H), 2.60
(t, J = 6.9 Hz, 2H), 2.86 (t, J = 7.2 Hz, 2H), 4.25 (q, J = 7.2 Hz, 2H), 4.39 (q, J = 7.2 Hz, 2H), 8.35 (s,
2H); 13C NMR (100MHz, CDCl3, 25 oC) δ 14.4, 14.7, 24.8, 35.5, 60.6, 63.5, 126.7, 159.2, 164.4, 172.2.
2-(Methoxymethylene)-3-(2-ethyoxypyrimidin-5-yl)propionic acid ethyl/methyl ester (5)
To a stirring suspension of freshly made EtONa (0.118 g, 1.74 mmol) in THF (0.5 mL) was added
dropwise a solution of 4 (0.100 g, 0.446 mmol) and methyl formate (0.100 g, 0.793 mmol) in THF (0.5
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mL) at 0 C. After the mixture was stirred at rt overnight and cooled to 0 C, the dimethyl sulfate (0.1
mL) was added slowly. After 4 h the solvent was evaporated and the residue was treated with water and
extracted with EtOAc. The extracts were washed with water, dried over anhydrous Na2SO4. After
evaporation of solvent, the residue was purified by flash chromatography on silica gel (Hexanes : EtOAc
= 1 : 1) to give compound 5 as colorless oil 2-(ethoxymethylene)-3-(2-methyoxypyrimidin-5-yl)propionic
acid ethyl ester (0.030 g, 0.0945 mmol, 21%) and methyl ester (0.03 g, 0.142 mmol, 32%). 1H NMR (400
MHz, CDCl3, 25 oC) Ethyl ester: δ 1.25 (t, J = 6.9 Hz, 3H), 1.41 (t, J = 7.5 Hz, 3H), 3.44 (s, 2H), 3.88 (s,
3H), 4.15 (q, J = 7.5 Hz, 2H), 4.37 (q, J = 6.9 Hz, 2H), 7.37 (s, 1H), 8.37 (s, 2H); Methyl ester: δ 1.40 (t,
J = 7.2 Hz, 3H), 3.42 (s, 2H), 3.66 (s, 3H), 3.85 (s, 3H), 4.36 (q, J = 7.2 Hz, 2H), 7.35 (s, 1H), 8.35 (s,
2H); 13C NMR (100 MHz, CDCl3, 25 oC) δ 14.5, 23.7, 51.4, 61.7, 63.1, 109.1, 126.8, 159.0, 159.6, 163.8,
167.9.
2-(Methoxymethylene)-3-(2-ethyoxypyrimidin-5-yl)propionic acid (6)
A suspension of the ester 5 (0.23 g, 0.86 mmol) in 2 M aqueous lithium hydroxide (2 mL) was stirred at rt
overnight. The resulting clear yellow solution was acidified by 1 M HCl to pH = 3 and extracted with
CH2Cl2, and dried over anhydrous Na2SO4. White solid 6 (0.18 g, 0.756 mmol, 88%) was obtained after
evaporation of solvent. 1H NMR (400 MHz, CDCl3, 25 oC) δ 1.41 (t, J = 7.2 Hz, 3H), 3.44 (s, 2H), 3.91 (s,
3H), 4.37 (q, J = 7.2 Hz, 2H), 7.48 (s, 1H), 8.39 (s, 2H).
1-(4-Ethoxycarbonylphenyl)-5-(2-ethoxypyrimidin-5-ylmethyl)-2-thiouracil (10)
To the solution of 6 (0.086 g, 0.361 mmol) in dry CH2Cl2 (2 mL) one drop of DMF, then oxalyl chloride
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(0.28 mL) was added slowly at 0 C. After stirring at rt for 2 h, the solvent was removed and additional