Trifluoroacetic acid → 4'-Methyl-N-((6-methylpyridin-3-yl)methyl)-5-((3aR,6aS)-octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)biphenyl-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4′-methyl-5-((6-methylpyridin-3-yl)methylcarbamoyl)-biphenyl-3-carboxylic acid (25 mg, 0.069 mmol) in N,N-dimethylformamide (1 mL) were added (3aR,6aS)-tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (30 mg, 0.14 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (60 mg, 0.16 mmol) and N,N-diisopropylethylamine (100 μL, 0.57 mmol). The reaction mixture was stirred for 16 hours at 25° C. The reaction mixture was purified by preparative HPLC to yield Boc protected product as a white solid, which was dissolved in methylene chloride (3.0 mL) and trifluoroacetic acid (0.20 mL, 2.6 mmol) was added. The reaction mixture was stirred at rt overnight. The volatiles were removed in vacuo and the residue was purified by preparative HPLC (100×21.2 mm C18 column, 20-60% MeCN/water[10 mM Et2NH]) to afford the product as a white foam.

Provenance & Evidence