反应详情

(S)-3-Amino-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (Example 34, Steps A-D; 152 mg, 0.525 mmol) was dissolved in toluene (5 mL). 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (32.7 mg, 0.0525 mmol), 1-bromo-2-fluoro-5-methyl-4-(methylsulfonyl)benzene (Preparation B; 281 mg, 1.05 mmol) and Cs2CO3 (205 mg, 0.630 mmol) were added and nitrogen bubbled through for 5 minutes. Pd2 dba3 (24.0 mg, 0.0263 mmol) was added and the reaction plunged into a 95° C. oil bath and stirred under nitrogen overnight. The reaction was cooled, concentrated, dissolved in small amount of CH2Cl2, solids filtered away and filtrate purified over silica gel (90% EtOAc in hexanes) to afford (S)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (59.3 mg, 0.125 mmol, 24% yield) as a tan solid. Mass spectrum (apci) m/z=476.3.

1. customnitrogen bubbled through for 5 minutes
2. customplunged into a 95° C.
3. temperatureThe reaction was cooled
4. concentrationconcentrated
5. dissolutiondissolved in small amount of CH2Cl2, solids
6. filtrationfiltered away
7. customfiltrate purified over silica gel (90% EtOAc in hexanes)