反应详情

温度

100 °C

2-Amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (85 mg, 0.272 mmol), (4-chloropyrimidin-2-yl)methyl methylcarbamate (54.9 mg, 0.272 mmol), Pd2 dba3 (24.92 mg, 0.027 mmol), K2CO3 (41.4 mg, 0.299 mmol) and X-Phos (64.9 mg, 0.136 mmol) were added to a 5 mL microwave vial. Degassed tert-amyl alcohol (0.6 mL) was added and the vial evacuated and back-filled with N2 (3×). The resulting mixture was stirred at 100° C. overnight. The reaction mixture was cooled to room temperature, MeOH and silica gel were added, and the solvent was removed in vacuo. Purification of the residue twice by silica gel chromatography (0-10% MeOH-DCM) gave [4-({3-(aminocarbonyl)-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyrimidin-2-yl]methyl methylcarbamate as a beige solid after triturating in DCM.

1. customthe vial evacuated
2. additionback-filled with N2 (3×)
3. temperatureThe reaction mixture was cooled to room temperature
4. additionMeOH and silica gel were added
5. customthe solvent was removed in vacuo
6. customPurification of the residue twice by silica gel chromatography (0-10% MeOH-DCM)