Diisopropylethylamine → HCID 131736481, compound

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Reaction Steps

TFA (2 mL, 26.0 mmol, Eq: 76.8) was added to a solution of tert-butyl (S)-1-((S)-2-(2,6-difluorophenylcarbamoyl)indolin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (0.16 g, 338 μmol, Eq: 1.00) in DCM (2 mL) and the resulting solution was stirred at rt for 1 h. The reaction mixture was concentrated in vacuo and the residue was azeotroped with n-heptane (20 mL) to give a viscous oil (0.16 g) which was used directly without further purification. HATU (0.21 g, 552 μmol, Eq: 1.68) was added to a solution of (S)-1-((S)-2-amino-3-methylbutanoyl)-N-(2,6-difluorophenyl)indoline-2-carboxamide 2,2,2-trifluoroacetate (0.16 g, 328 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (0.1 g, 492 μmol, Eq: 1.5) and diisopropylethylamine (0.29 mL, 1.66 mmol, Eq: 5.06) in DMF (2 mL) and the reaction was stirred at rt for 30 min. The reaction mixture was diluted with EtOAc (20 mL) and washed with 0.1 M aqueous NaOH (10 mL) and 0.1 M aqueous HCl (10 mL). Hexanes (20 mL) were added to the organic layer and it was washed with water (3×10 mL) and brine. The organic layer was concentrated in vacuo and the resulting crude material was purified by flash chromatography (silica gel, 12 g, 0% to 50% EtOAc in hexanes) to give tert-butyl (S)-1-((S)-1-((S)-2-(2,6-difluorophenylcarbamoyl)indolin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(methyl)carbamate (0.15 g), m/z=559 (M+H).

Provenance & Evidence