Phosphorus tribromide → 2-amino-4-((S)-1-(8-(5-hydroxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile

Participants

Reaction Steps

To a stirred mixture of (S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile 9 (15 mg, 0.031 mmol) in DCM (5 mL) at −78° C. under argon, PBr3 (77 mg, 0.31 mmol) was added and the resulting mixture was stirred from −78° C. to RT overnight. The reaction mixture was poured into ice-water (10 mL) and then neutralized with saturated aqueous NaHCO3 to adjust the pH value to 8-9. The mixture was extracted with a mixture of methanol in DCM (5%, 5×10 mL). The organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluting with 1-3% MeOH/DCM to afford 2-amino-4-((S)-1-(8-(5-hydroxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile 13. ESI-MS m/z: 476.0 [M+H]+.

Provenance & Evidence