(S)-1-(1-(5-bromopyrimidin-2-yl)piperidin-4-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)pyrrolidin-2-one → (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1-(1-(5-(pyridin-2-yl)pyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

Pyridin-2-yl zinc(II) bromide (0.5M; 632 μL, 0.316 mmol) was added to a nitrogen purged flask. Pd(PPh3)4 (17.4 mg, 0.0151 mmol) was added followed by (S)-1-(1-(5-bromopyrimidin-2-yl)piperidin-4-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)pyrrolidin-2-one (Example 90; 80 mg, 0.151 mmol) dissolved in THF (1 mL). The reaction was stirred at ambient temperature for 1 hour and 55° C. for 6 hours. Additional zinc reagent and palladium were added and the reaction stirred at 55° C. overnight. The reaction was partitioned between aqueous NH4Cl and CH2Cl2, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (95% EtOAc in hexanes) to afford (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1-(1-(5-(pyridin-2-yl)pyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (44.9 mg, 0.0848 mmol, 56.3% yield) as a pale yellow solid. Mass spectrum (apci) m/z=530.2 (M+H).

Provenance & Evidence