Experimental Section
General. All reagents were purchased and used as received. Melting points were measured using open glass capillaries. Infrared spectra were recorded as KBr as thin films and peaks are reported in cm-1. Only representative absorptions are given. NMR spectra were taken in DMSO-d6 on a Bruker AC-300 instrument at 20-25 ºC. Chemical shifts (.) were measured in ppm relative to solvent (.=2.50 for 1H or 39.4 for 13C) as internal standard. Coupling constants, J, are reported in hertz. DEPT experiments were used to assist with the assignation of the signals and structural determinations.
Typical procedure for the synthesis of DHPMs (8a-t)
A mixture of 3-ketoamide 5 (1 mmol), urea 6 (1.5 mmol), aldehyde 7 (1 mmol) and chloroacetic acid (10 mol %) was heated in an oil bath (90 ºC) for 7-10 h in the absence of solvents. The progress of the reaction was monitored by TLC. When the reaction was completed, the flask was removed from the oil bath and allowed to stand at room temperature. Then, the mixture was poured into water and extracted with CH2Cl2. The organic extracts were dried with Na2SO4 (anh), solvent was evaporated under reduced pressure, and the resultant residue was purified, if necessary, by column chromatography (Hexanes/EtOAc, 3/7) followed by crystallization from the appropriate solvent.
6-Methyl-2-oxo-N,4-diphenyl-1,2,3,4-tetrahydropyrimidin-5-carboxamide (8a). According to the general procedure DHPM 8a was obtained from acetoacetanilide 5a, benzaldehyde 7a and urea 6a in 92% yield as an orange pale solid: mp 236-240 ºC (hexanes, lit.13c 239-240).
4-(3-Methoxyphenyl)-6-methyl-2-oxo-N-phenyl-1,2,3,4-tetrahydropyrimidin-5- carboxamide (8b). According to the general procedure DHPM 8b was obtained from acetoacetanilide 5a, 3-methoxybenzaldehyde 7b and urea 6a in 63% yield. This material had to be purified by column chromatography (CH2Cl2/MeOH, 9/1) and triturated with hexanes to afford DHPM 8b as a yellowish pure solid: mp 180-185 ºC (hexanes); IR (film). . 3237, 1672, 1400, 1200; 1H NMR (300 MHz, DMSO-d6) 2.02 (s, 3H), 3.67 (s, 3H), 5.37 (s, 1H), 6.52-6.80 (m, 4H), 6.82-6.99 (m, 3H), 7.20-7.23 (m, 3H), 8.33 (br s, 1H), 9.54 (br s, 1H); 13C NMR (75 MHz, DMSO-d6) 17.5, 55.4, 105.8, 112.7, 112.7, 118.8, 120.0, 123.5, 129.0, 130.0, 138.9, 139.7, 149.3, 153.1, 159.8, 165.8; HRMS calcd for C19H19N3O3•H+ 338.1517, found 338.1505.
6-Methyl-2-oxo-N-phenyl-4-(2-thienyl)-1,2,3,4-tetrahydropyrimidin-5-carboxamide (8c). According to the general procedure DHPM 8c was obtained from acetoacetanilide 5a, 2- thiophenecarboxaldehyde 7c and urea 6a in 89% yield as a yellowish solid: mp 174-178 ºC (hexanes); IR (film). . 3249, 1655, 1596; 1H NMR (300 MHz, DMSO-d6) 2.04 (s, 3H), 5.70 (s, 1H), 6.91-7.02 (m, 3H), 7.22-7.37 (m, 3H), 7.55-7.57 (m, 2H), 7.79 (br s, 1H), 8.85 (br s, 1H), 9.54 (br s, 1H); 13C NMR (75 MHz, DMSO-d6) 17.6, 51.0, 106.8, 120.2, 127.2, 129.0, 123.6, 124.0, 125.4, 139.7, 140.0, 149.2, 153.0, 165.4; HRMS calcd for C16H15N3O2S•H+ 314.0997, found 314.0963.
