Cesium carbonate → (S)-1'-(5-ethylpyrimidin-2-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)-1,4'-bipiperidin-2-one

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Reaction Conditions

Reaction Steps

(S)-3-amino-1′-(5-ethylpyrimidin-2-yl)-1,4′-bipiperidin-2-one (220 mg, 0.725 mmol) was dissolved in toluene (7 mL) and BINAP (45.2 mg, 0.0725 mmol), 1-bromo-2-fluoro-5-methyl-4-(methylsulfonyl)benzene (Preparation B; 291 mg, 1.09 mmol) and Cs2CO3 (284 mg, 0.870 mmol) were added. The reaction was bubbled through with nitrogen for 5 minutes. Pd2 dba3 (33.2 mg, 0.0363 mmol) was added and the reaction heated to 90° C. overnight. The reaction was cooled to ambient temperature, filtered and concentrated. The residue was purified over silica gel (90% EtOAc in hexanes) to afford a mixture. The mixture was then purified on reverse phase chromatography (15 to 95% ACN in water) to afford (S)-1′-(5-ethylpyrimidin-2-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)-1,4′-bipiperidin-2-one (178 mg, 0.364 mmol, 50.1% yield) as a white solid. Mass spectrum (apci) m/z=490.3 (M+H).

Provenance & Evidence