反应详情

温度

35 °C

To a solution of (3R)-1,3-dimethylpiperazine dihydrochloride (Example 63) (5.88 g, 31.4 mmol) in dichloromethane (126 mL) was added N,N-diisopropylethylamine (18.11 mL, 104 mmol), and 4,6-dichloro-5-fluoro-2-methylpyrimidine (5.69 g, 31.4 mmol). The solution was heated at 35° C. and stirred for 3 days. The solution was cooled to room temperature, diluted with DCM (100 mL), and washed with sat. aq. NaHCO3 (100 mL). The aqueous phase was extracted with a fresh portion of DCM (50 mL), and the combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give crude 4-chloro-6-[(2R)-2,4-dimethyl-1-piperazinyl]-5-fluoro-2-methylpyrimidine (9.60 g, >100% yield) as a brown oil that was used without further purification. LCMS: (M+H)+: 258.9.

1. temperatureThe solution was cooled to room temperature
2. washwashed with sat. aq. NaHCO3 (100 mL)
3. extractionThe aqueous phase was extracted with a fresh portion of DCM (50 mL)
4. dry with materialthe combined organic phase was dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo