反应详情

温度

150 °C

To a stirred solution of thiazole-2-carboxamidine hydrochloride (0.13 g, 1.0 mmol), methyl acetoacetate (0.12 g, 1.0 mmol) and 2-chloro-5-fluorobenzaldehyde (0.16 g, 1.0 mmol) in CF3CH2OH (8 mL) was added potassium acetate (0.20 g, 2.0 mmol). The reaction mixture was either refluxed for 16 hrs or heated at 150° C. in microwave oven for 2 hours. After it was cooled to room temperature, the reaction mixture was concentrated and the residue was dissolved in ethyl acetate and washed with brine. The organic layer was dried over sodium sulfate and concentrated, and the residue was purified by column chromatography (ethyl acetate/petroleum ether is from ¼ to ½) to afford 4-(2-chloro-4-fluoro-phenyl)-6-methyl-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (Compound B) as a yellow solid. MS: calc'd (MH+) 366, measured (MH+) 366. 1H NMR (DMSO-d6, 400 MHz): 6 ppm 9.98 (s, 1H), 7.97 (d, J=4.0 Hz, 1H), 7.90 (d, J=4.0 Hz, 1H), 7.41 (dd, J=8.0, 4.0 Hz, 1H), 7.35 (dd, J=8.0, 8.0 Hz, 1H), 7.18 (td, J=8.0, 4.0 Hz, 1H), 5.98 (s, 1H), 3.53 (s, 3H), 2.47 (s, 3H).

1. temperatureThe reaction mixture was either refluxed for 16 hrs
2. temperatureAfter it was cooled to room temperature
3. concentrationthe reaction mixture was concentrated
4. dissolutionthe residue was dissolved in ethyl acetate
5. washwashed with brine
6. dry with materialThe organic layer was dried over sodium sulfate
7. concentrationconcentrated
8. customthe residue was purified by column chromatography (ethyl acetate/petroleum ether is from ¼ to ½)