Cesium carbonate → (S)-3-(6-chloro-4-oxochroman-7-ylamino)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one

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Reaction Steps

(S)-3-Amino-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (Example 34, Steps A-D; 120 mg, 0.42 mmol) was dissolved in toluene (3 mL). 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (26 mg, 0.042 mmol), 6-chloro-4-oxochroman-7-yl trifluoromethanesulfonate (206 mg, 0.62 mmol) and Cs2CO3 (162 mg, 0.498 mmol) were added and the reaction was bubbled through with nitrogen for 5 minutes. Pd2 dba3 (19.0 mg, 0.021 mmol) was added and the reaction plunged into 95° C. oil bath overnight. The reaction was cooled to ambient temperature, partitioned between water and EtOAc, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (75 to 100% EtOAc in hexanes) to afford a mixture. The mixture was further purified by reverse phase chromatography (25 to 95% ACN in water) to afford (S)-3-(6-chloro-4-oxochroman-7-ylamino)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (10 mg, 0.022 mmol, 5% yield. Mass spectrum (apci) m/z=470.3 (M+H).

Provenance & Evidence