4-Methylmorpholine → tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(2-(4'-methyl-[1,1'-biphenyl]-4-carbonyl)hydrazine carbonyl)benzyl)benzamido)acetate

Participants

Reaction Steps

To a stirring solution of 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)benzoic acid INT-37 (157 mg, 0.26 mmol) and 4-methylmorpholine (63.0 μL, 0.58 mmol) in THF (3 mL) was added isobutyl chloroformate (34.0 μL, 0.26 mmol). After 1 h, the reaction mixture was added to a stirring solution of 4′-methyl-[1,1′-biphenyl]-4-carbohydrazide INT-50 (65.0 mg, 0.29 mmol) in DMF (2 mL). After 2 h, additional 4′-methyl-[1,1′-biphenyl]-4-carbohydrazide INT-50 (12 mg, 0.05 mmol) was added. After stirring at room temperature for 18 h, the reaction mixture was diluted with DCM (4 mL), washed with NaHCO3 (10 mL) and split though a hydrophobic frit. The crude product was purified by column chromatography (EA/isohexanes) to yield 138 mg (65%) of tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(2-(4′-methyl-[1,1′-biphenyl]-4-carbonyl)hydrazine carbonyl)benzyl)benzamido)acetate INT-51. LCMS-ESI (m/z) calculated for C45H43F3N4O7: 808; found 809 [M+H]+, tR=2.75 min (Method 5).

Provenance & Evidence