(S)-3-(4-bromo-2-fluoro-5-methylphenoxy)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one → (S)-4-(1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-5-fluoro-2-methylbenzonitrile

Participants

Reaction Conditions

Reaction Steps

(S)-3-(4-bromo-2-fluoro-5-methylphenoxy)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (Example 96, Steps A-F; 200 mg, 0.419 mmol) was dissolved in NMP (1 mL) and cyanocopper (150 mg, 1.68 mmol) was added and heated to 160° C. overnight. The reaction was partitioned between dilute sodium bicarbonate and EtOAc, dried, filtered and concentrated. The residue was purified on 25M biotage (90% EtOAc/hexane) to afford (S)-4-(1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-5-fluoro-2-methylbenzonitrile (99.6 mg, 0.235 mmol, 56.1% yield) as a pale yellow solid. Mass spectrum (apci) m/z=424 (M+H).

Provenance & Evidence