EXPERIMENTAL
The 1H NMR spectra of the synthesized compounds were recorded on a Varian Mercury VX 200 (200 MHz)
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instrument. The H NMR COSY spectrum of amide 1d was recorded on a Varian Mercury 400 (400 MHz)
spectrometer. The solvent was DMSO-d6 in all cases, internal standard was TMS. Commercial 4-methyl-
cyclohexanone from Fluka was used in the study.
5-Methyl-2-oxocyclohexanecarboxylic Acid Ethyl Ester (4). Diethyl oxalate (14.6 g, 0.1 mol) was added
to a solution of sodium ethylate [from metallic sodium (2.3 g, 0.1 mol) and absolute alcohol (50 ml)] with vigorous
stirring and then 4-methylcyclohexanone (11.2 g, 0.1 mol) was added. The stirring was stopped and the reaction
mixture was left at room temperature. After 5 h, cold water (200 ml) was added, and the mixture acidified with dilute
H2SO4 to pH 3. The precipitated β-ketooxalate 3 was extracted with CH2Cl2 (3×50 ml). The organic extracts were
combined, and the solvent distilled off. The residue was heated in a flask with a still head in a metal bath at a pressure
of ~15 mm Hg, gradually increasing the bath temperature to 170°C, and maintaining this temperature until evolution
of CO had finished. At the end of the reaction (after 2 to 2½ h) the reaction mixture was distilled in vacuum,
collecting the fraction with bp 78-80°C (8 mm Hg). Ester 4 (14.9 g, 81%) was obtained.
5-Methyl-2-propylaminocyclohex-1-enecarboxylic Acid Ethyl Ester (5). A mixture of compound 4 (18.4
g, 0.1 mol) and propylamine (12.4 ml, 0.15 mol) was stirred at 45°C for 5 h, after which it was left at room
temperature for 8-10 h. The separated water and the excess of propylamine were removed in vacuum. The residue
(crude enamine 5) was used in further synthesis without additional purification.
4-Hydroxy-6-methyl-2-oxo-1-propyl-1,2,5,6,7,8-hexahydroquinoline-3-carboxylic Acid Ethyl Ester (7).
Unpurified enamine 5, obtained from ester 4 (0.1 mol) by the method described above, was dissolved in CH2Cl2 (100
ml), triethylamine (15.4 ml, 0.11 mol) was added, and then ethoxymalonyl chloride (16.56 g, 0.11 mol) was added
dropwise with stirring and cooling. The mixture was left at room temperature for 4-5 h. The reaction mixture was
diluted with water, the organic layer separated, and dried with anhydrous CaCl2. The solvent was distilled (finally in
vacuum). A solution of sodium ethylate [from metallic sodium (3.45 g, 0.15 mol) and absolute alcohol (150 ml)] was
added to the residue (diester 6), the mixture boiled for 30 min, after which heating was stopped, and the mixture left
for 7-8 h at room temperature. The reaction mixture was diluted with water and acidified with dilute (1 : 1) HCl to pH
4.5-5.0. The separated ester 7 was extracted with CH2Cl2 (3×100 ml). The solvent was distilled off (finally in
vacuum). Ester 7 (25.2 g, 86%) was obtained as a bright yellow oily mass, used in the synthesis of amides 1a-h
without additional purification.
N-R-Amides of 4-Hydroxy-6-methyl-2-oxo-1-propyl-1,2,5,6,7,8-hexahydroquinoline-3-carboxylic Acid
1a-h (General Procedure). A mixture of ethyl ester 7 (2.93 g, 0.01 mol), the appropriate aniline or hetarylamine
(0.01 mol), and DMF (1 ml) was stirred and maintained at 160-170°C for 3 min. The mixture was cooled, diluted
with alcohol (20 ml), thoroughly mixed, and filtered. The amide 1 obtained was washed on the filter with alcohol,
dried, and crystallized from DMF.
X-Ray Structural Investigation. Crystals of amide 1d, grown from DMF, were monoclinic, at 20°C
a = 12.306(2), b = 14.516(3), c = 14.516(3) Å, β = 112.767(14)°, V = 2455.2(8) Å3, Mr = 481.64, Z = 4, space group
P21/c, dcalc = 1.303 g/cm3, µ(MoKα) = 0.166 mm-1, F(000) = 1032. The parameters of the unit cell and the intensities
of 4515 reflections (4340 independent, Rint = 0.086) were measured on a Siemens P3/PC automatic four-circle
diffractometer (MoKα, graphite mono-chromator, θ/2θ scanning, 2θmax = 50°).
The structure was solved by the direct method with the SHELX97 set of programs [7]. The positions of the
hydrogen atoms were calculated geometrically and refined with the rider model with Uiso = 1.2×Ueq of the non-
hydrogen atom linked with the given hydrogen. The disordered fragments were refined by superimposing limitations
on C-C bond length and valence angles. The total number of geometric limitations was 618. The structure was refined
on F2 by the full-matrix least squares method in an anisotropic approximation for the
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