反应详情

温度

0 °C

Step 3 2,4-Bis-(2,4-difluoro-phenoxy)-pyrimidine-5-carboxylic acid ((R)-1-methyl-2-methylsulfanyl-ethyl)-amide 2,4-Bis-(2,4-difluoro-phenoxy)-pyrimidine-5-carboxylic acid (63.40 g, 166.7 mmol) was added to a mixture of dry dichloromethane (1 L) and dry DMF (0.5 mL), and the reaction mixture was cooled to 0° C. and stirred under nitrogen for 30 minutes. Oxalyl chloride (21.8 mL, 249.8 mmol) was added dropwise over three minutes, and the reaction mixture was stirred at 0° C. for 8 hours, then stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, and dichloromethane (500 mL) was added to the residue. The mixture was cooled to 0° C. with stirring in an ice bath for 30 minutes, and (R)-1-methyl-2-methylsulfanyl-ethylamine (26.3 g, 1.837 mmol) was added, followed by triethylamine (51.5 mL, 369 mmol) dropwise over 10 minutes. THe reaction mixtuer was stirred for one hour at 0° C., then stirred at room temperature for 20 hours. The reaction mixture was washed with water, and the organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to give 82.63 g of crude 2,4-bis-(2,4-difluoro-phenoxy)-pyrimidine-5-carboxylic acid ((R)-1-methyl-2-methylsulfanyl-ethyl)-amide as a viscous oil. MS(M+H)=468. Step 4 2,4-Bis-(2,4-difluoro-phenoxy)-pyrimidine-5-carboxylic acid ((R)-2-methanesulfonyl-1-methyl-ethyl)-amide

1. stirringthe reaction mixture was stirred at 0° C. for 8 hours
2. stirringstirred at room temperature for 18 hours
3. concentrationThe reaction mixture was concentrated under reduced pressure, and dichloromethane (500 mL)
4. additionwas added to the residue
5. temperatureThe mixture was cooled to 0° C.
6. stirringwith stirring in an ice bath for 30 minutes
7. stirringTHe reaction mixtuer was stirred for one hour at 0° C.
8. stirringstirred at room temperature for 20 hours
9. washThe reaction mixture was washed with water
10. dry with materialthe organic layer was dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure