Diisopropylethylamine → tert-Butyl methylcarbamate

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Reaction Steps

HATU (45 mg, 118 μmol, Eq: 1.48) was added to a solution of (S)-1-(2-amino-3-methylbutanoyl)-N-(2,6-difluorophenyl)-3,3-dimethylindoline-2-carboxamide (32 mg, 79.7 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (20 mg, 98.4 μmol, Eq: 1.23) and diisopropylethylamine (50 μl, 286 μmol, Eq: 3.59) in DMF (1 mL) and the resulting yellow solution was stirred at rt for 1 h. The reaction mixture was diluted with EtOAc (10 mL) and washed with 0.1 M aqueous NaOH, 0.1 M aqueous HCl and brine and then concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 4 g, 0% to 50% EtOAc in hexanes) to give ((S)-1-{(S)-1-[(R)-2-(2,6-difluoro-phenylcarbamoyl)-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl]-2-methyl-propylcarbamoyl})-ethyl)-methyl-carbamic acid tert-butyl ester (higher Rf, 15 mg) and ((S)-1-{(S)-1-[(S)-2-(2,6-difluoro-phenylcarbamoyl)-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl]-2-methyl-propylcarbamoyl})-ethyl)-methyl-carbamic acid tert-butyl ester (lower Rf, 15 mg) along with some mixed fractions.

Provenance & Evidence