Diphenylphosphinic chloride → tert-butyl (S)-1-((S)-2-((S)-2-(2-fluoro-6-methylphenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylamino)-1-oxopropan-2-yl(methyl)carbamate

Participants

Reaction Steps

To a solution of (S)-1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (60 mg, 122 pilot, Eq: 1.00) and diisopropylethylamine (64 μL, 367 μmol, Eq: 3) in DCM (1.8 mL) was added diphenylphosphinic chloride (63.7 mg, 51 μL, 269 μmol, Eq: 2.2). After stirring for 5 min, 2-fluoro-6-methylaniline (18.4 mg, 147 μmol, Eq: 1.2) was added and the resulting solution stirred at rt for 2 d. The reaction mixture was poured into aqueous 0.1 M KHSO4 (20 mL) and the resulting mixture was extracted with EtOAc. The combined organic layers were concentrated in vacuo and the crude material was purified by flash chromatography (silica gel, 4 g, 10% to 50% EtOAc in hexanes) to give tert-butyl (S)-1-((S)-2-((S)-2-(2-fluoro-6-methylphenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylamino)-1-oxopropan-2-yl(methyl)carbamate (30 mg), m/z=598 (M+H).

Provenance & Evidence