Pyridine → tert-butyl (S)-1-((S)-1-((S)-2-(2-fluoro-6-(trifluoromethyl)phenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Participants

Reaction Steps

In a 50 mL round-bottomed flask, DMF (12.2 mg, 12.9 μL, 167 μmol Eq: 1.5) was combined with DCM (1 mL) to give a colorless solution. The reaction mixture was cooled in an ice bath and oxalyl chloride (21.2 mg, 14.6 μL, 167 μmol, Eq: 1.5) was added. Pyridine (13.2 mg, 13.5 μL, 167 μmol, Eq: 1.5) was then added followed by (S)-1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (Intermediate 8) (50 mg, 111 μmol Eq: 1.00) and the reaction was stirred at rt for 1 h. 2-Fluoro-6-(trifluoromethyl)aniline (30.0 mg, 167 μmol, Eq: 1.5) and N-methylmorpholine (18 μL, 167 μmol, Eq: 1.5) were added and the reaction mixture was stirred at rt over the weekend. The reaction mixture was diluted with DCM and washed with water and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 4 g, 0% to 40% EtOAc in hexanes) to give tert-butyl (S)-1-((S)-1-((S)-2-(2-fluoro-6-(trifluoromethyl)phenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(methyl)carbamate as a colorless oil (20 mg).

Provenance & Evidence