Diethyl Ether → (S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

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Reaction Conditions

Reaction Steps

To a solution of (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Table 2, compound 1; 1.5 g, 4.02 mmol) and DIEA (3.50 mL, 20.1 mmol) in DMF (15 mL) was added 2,5-dichloropyrazine (1.20 g, 8.03 mmol). This mixture was heated to 100° C. for 3 hours under nitrogen. The mixture was poured into brine (150 mL) and extracted into ethyl acetate (3×500 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an oil. Ether (100 mL) was added and a precipitate formed overnight. The ether was decanted and the solid was triturated using ethanol (100 mL) at reflux with stirring for 5 minutes. The material was purified by column chromatography using 50% to 100% ethyl acetate/hexane. The resulting solid was dried over the weekend under high vacuum to provide the title compound (0.83 g, 39% yield). Mass spectrum (apci) m/z=486.1 (M+H).

Provenance & Evidence