Cesium carbonate → (3S)-3-cyclopropyl-1-(2-((1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of (3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (200 mg) obtained in Step E of Example 103, (1-(4-amino-1H-pyrazol-1-yl)cyclopropyl)methanol (120 mg) obtained in Step C of Example 128, cesium carbonate (500 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (71 mg) in tetrahydrofuran (10 mL) was added tris(dibenzylideneacetone)dipalladium(0) (70 mg), and the mixture was stirred at 90° C. for 10 hr under argon atmosphere. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate). The obtained crude product was subjected to HPLC (C18, mobile phase: water/acetonitrile (containing 5 mM AcONH4), to the obtained fraction was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized (ethyl acetate/diisopropyl ether) to give the title compound (71 mg).

Provenance & Evidence