(R)-(+)-1-Boc-3-aminopyrrolidine → (3R)-tert-butyl 3-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-ylamino)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 3-(6-chloropyrazin-2-yl)-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (250 mg, 0.586 mmol) and (R)-(+)-1-boc-3-aminopyrrolidine (149 μL, 0.879 mmol, CNH technologies) in p-dioxane (2.5 mL) followed by chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (BrettPhos precatalyst) (23.39 mg, 0.029 mmol), sodium tert-butoxide (143 μL, 1.171 mmol) and BrettPhos precatalyst (15.72 mg, 0.029 mmol). The reaction mixture was stirred and heated in an oil bath at 85° C. for 2 h, and then solvent was removed. The residue was purified by silica gel chromatography (eluting with 5-30% EtOAc in DCM with 1% MeOH) to give (3R)-tert-butyl 3-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-ylamino)pyrrolidine-1-carboxylate (280 mg, 83% yield). MS (ESI, pos. ion) m/z: 577 (M+1).

Provenance & Evidence