4-Methylmorpholine → tert-butyl 2-(4-((tert-butoxycarbonyl)amino)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate

Participants

Reaction Conditions

Reaction Steps

Prepared from INT-62 and INT-40. To a stirred solution of 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-((tert-butoxycarbonyl)amino)benzamido)methyl)benzoic acid INT-62 (1.57 g, 3.24 mmol) in dioxane (40 mL) and 4-methylmorpholine (0.712 mL, 6.48 mmol) was added isobutyl carbonochloridate (0.420 mL, 3.24 mmol) dropwise. After 30 min the reaction mixture was added to a solution of (Z)—N′-hydroxy-4′-methyl-[1,1′-biphenyl]-4-carboximidamide INT-40 (0.733 g, 3.24 mmol) in DMF (4 mL). After 30 mins the reaction was heated at 110° C. for 2 h. The reaction mixture was cooled to room temperature, diluted with EA (150 mL) and washed with brine (200 mL). The organics were pre-absorbed onto silica gel and purified by chromatography (MeCN/DCM) to afford 659 mg (30%) of tert-butyl 2-(4-((tert-butoxycarbonyl)amino)-N-(4-(3-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate INT-63 as a viscous oil. LCMS-ESI (m/z) calculated for C40H42N4O6: 674; no m/z observed, tR=3.29 min (Method 10).

Provenance & Evidence