反应详情

温度

-10 °C

A solution of 2-(2-(4-(2-bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-6-methyl-1,4-dihydropyrimidin-2-yl)thiazol-4-yl)acetic acid (3 g, 6.2 mmol), EDC.HCl (1.55 g, 8.06 mmol), HOAt (0.84 g, 6.2 mmol) and DIPEA (1.6 g, 12.4 mmol) in DMF (60 mL) was cooled to 10° C. and then stirred at −10° C. for 30 minutes. Then methanamine hydrochloride (0.63 g, 9.3 mmol) was added and the mixture was stirred for another 1 hour. The mixture was warmed to 50° C. and stirred for 4 hours. The reaction solution was diluted with EtOAc (150 mL), and washed with brine (100 mL×6). The organic layer was dried over Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=3/1) to give the title compound as a yellow solid (1.2 g, 39%). The compound was characterized by the following spectroscopic data:

1. stirringthe mixture was stirred for another 1 hour
2. temperatureThe mixture was warmed to 50° C.
3. stirringstirred for 4 hours
4. washwashed with brine (100 mL×6)
5. dry with materialThe organic layer was dried over Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=3/1)