3-N-acylation of 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2-one

Full text of DOI:10.1007/s10593-005-0139-y

Chemistry of Heterocyclic Compounds, Vol. 41, No. 2, 2005
3-N-ACYLATION OF 5-ETHOXYCARBONYL-
6-METHYL-4-PHENYL-3,4-DIHYDROPYRIMIDIN-2-ONE
M. A. Kolosov and V. D. Orlov
Keywords: 3-N-acylation, 5-carbethoxy-6-methyl-4-phenyl-3,4-dihydropyrimidin-2-one, anhydride,
SOCl2.
We know that acetylation of derivatives of 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-
2-one (1) at the N(3) atom occurs in good yields when compound 1 is boiled in acetic anhydride [1, 2]. However,
anhydrides of higher fatty acids are less accessible than the acids themselves, so it would be sensible to develop
a general method for acylation that proposes using the carboxylic acids directly.
We have developed a convenient preparative method for synthesis of 3-acyl derivatives of compound 1
by boiling its solution in a mixture of the corresponding carboxylic acid and thionyl chloride in 10-fold excess
relative to compound 1. Under these conditions, we could obtain 3-acyl derivatives 2a-e in 47-70% yields.
Ph
O
O
Ph
O
RCOOH/SOCl2
HN
OEt
R
N
OEt
O
N
H
Me
O
N
H
Me
1
2a–e
a R = Me, b R = Et, c R = n-Pr, d R = n-Bu, e R = n-Am
1
Elemental analysis, IR and H NMR spectra of the compounds obtained are completely consistent with
the structure of 3-acyl derivatives of 5-carbethoxy-6-methyl-4-phenyl-3,4-dihydropyrimidin-2-one.
Compounds 2a-d (General Procedure). A mixture of SOCl2 (4.8 g, 40 mmol) and 1 drop of DMF were
added to a solution of compound 1 (4 mmol) in the corresponding carboxylic acid (40 mmol) that was cooled
down to 20°C. Then the solution was boiled for 1-3 h (monitored by TLC). 4 ml water was added to the solution
obtained; this was cooled and then EtOH was added dropwise until the solution was homogenized.
Crystallization of the material was stimulated by rubbing with a rod. The material was filtered out and washed
three times with 3 ml EtOH each.
3-Acetyl-5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidinin-2-one (2a). Yield 47%;
mp 176-177°C (EtOH). 1H NMR spectrum (DMSO-d6, 300 MHz), δ, ppm (J, Hz): 10.15 (1H, s, NH); 7.13-7.37
(5H, m, Ph); 6.45 (1H, s, CH); 4.1 (2H, quartet, J = 8, OCH2); 2.42 (3H, s, CH3); 2.29 (3H, s, CH3); 1.29 (3H, t,
J = 8, CH3CH2). IR spectrum (KBr), ν, cm-1: 1649, 1702, 1715, 2970, 3196, 3236. Found, %: N 9.30.
C16H18N2O4. Calculated, %: N 9.27.
__________________________________________________________________________________________
V. N. Karazin
Kharkov
National
University,
Kharkov
61077,
Ukraine;
e-mail:
orlov@univer.kharkov.ua, k-maksim@bigmir.net, koljsov@univer.kharkov.ua. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 2, pp. 292-293, February, 2005. Original article submitted October 11,
2004.
260
0009-3122/05/4102-0260©2005 Springer Science+Business Media, Inc.

5-Ethoxycarbonyl-6-methyl-4-phenyl-3-propionyl-3,4-dihydropyrimidin-2-one (2b). Yield 70%; mp
1
185-186°C (EtOH). H NMR spectrum (DMSO-d6, 200 MHz), δ, ppm (J, Hz): 10.14 (1H, s, NH); 7.14-7.37
(5H, m, Ph); 6.48 (1H, s, CH); 4.10 (2H, quartet, J = 7, OCH2), 2.84-3.06 (1H, m, COCH2); 2.62-2.84 (1H, m,
COCH2); 2.29 (3H, s, CH3); 1.16 (3H, t, J = 7, CH3CH2O); 1.02 (3H, t, J = 7.2, CH3CH2CO). IR spectrum
(KBr), ν, cm-1: 1642, 1689, 1709, 2990, 3096, 3230, 3263. Found, %: N 9.09. C17H20N2O. Calculated, %:
N 8.86.
3-Butyroyl-5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2-one (2c). Yield 54%;
mp 138-140°C (EtOH). 1H NMR spectrum (DMSO-d6, 300 MHz), δ, ppm (J, Hz): 10.13 (1H, s, NH); 7.12-7.37
(5H, m, Ph); 6.47 (1H, s, CH); 4.10 (2H, quartet, J = 7.4, OCH2); 2.82-3.02 (1H, m, COCH2); 2.60-2.80 (1H, m,
COCH2); 2.29 (3H, s, CH3); 1.36-1.75 (2H, m, COCH2CH2); 1.16 (3H, t, J = 7.4, CH3CH2O); 0.86 (3H, t,
J = 7.4, CH3(CH2)2CO). IR spectrum (KBr), ν, cm-1: 1648, 1702, 2959, 3129, 3227. Found, %: N 8.59.
C18H22N2O4. Calculated, %: N 8.48.
5-Ethoxycarbonyl-6-methyl-4-phenyl-3-valeroyl-3,4-dihydropyrimidin-2-one (2d). Yield 67%;
mp 167-168°C (EtOH). 1H NMR spectrum (DMSO-d6, 300 MHz), δ, ppm (J, Hz): 10.15 (1H, s, NH); 7.12-7.37
(5H, m, Ph); 6.46 (1H, s, CH); 4.10 (2H, quartet, J = 7, OCH2), 2.84-3.03 (1H, m, COCH2); 2.62-2.82 (1H, m,
COCH2); 2.28 (3H, s, CH3); 1.35-1.70 (2H, m, COCH2CH2Et); 1.15-1.37 (2H, m, CO(CH2)2CH2CH3); 1.16 (3H,
t, J = 7, CH3CH2O); 0.84 (3H, t, J = 7, CH3(CH2)3CO). IR spectrum, (KBr), ν, cm-1: 1635, 1702, 2863, 2963,
3243, 3390. Found, %: N 8.20. C19H24N2O4. Calculated, %: N 8.14.
3-Caproyl-5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2-one (2e). Yield 58%;
mp 180-181°C (EtOH). 1H NMR spectrum (DMSO-d6, 300 MHz), δ, ppm (J, Hz): 10.12 (1H, s, NH); 7.12-7.37
(5H, m, Ph); 6.45 (1H, s, CH); 4.10 (2H, quartet, J = 7, OCH2); 2.82-3.02 (1H, m, COCH2Bu); 2.62-2.82 (1H, m,
COCH2Bu); 2.28 (3H, s, CH3); 1.42-1.68 (2H, m, COCH2CH2Pr); 1.17-1.30 (4H, m, CO(CH2)2CH2CH2CH3);
1.16 (3H, t, J = 7, CH3CH2O); 0.83 (3H, t, J = 6.4, CH3(CH2)4CO). IR spectrum (KBr), ν, cm-1: 1635, 1695,
1710, 2956, 2920, 3130, 3236, 3396. Found, %: N 7.93. C20H26N2O4. Calculated, %: N 7.82.
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