4-Methylmorpholine → HCID 178490477, compound

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 (216 mg, 0.360 mmol) in dioxane (4 mL) were added N-methylmorpholine (79.0 μl, 0.719 mmol) and isobutyl chloroformate (49.0 μl, 0.378 mmol). After stirring at room temperature for 1 h, the reaction mixture was added drop wise through a frit to a stirred solution of 4′-methyl-[1,1′-biphenyl]-4-carbohydrazonamide INT-39 (89.0 mg, 0.396 mmol) in DMF (2 mL). After 30 min, the reaction mixture was heated to 120° C. for 1 h. The reaction mixture was allowed to cool to room temperature then poured onto water (50 mL) and extracted with DCM (3×20 mL). The combined organic extracts were washed successively with citric acid (10 mL, 0.1 M aqueous solution) and NaHCO3 (10 mL) then dried over MgSO4 and evaporated. The crude material was purified by column chromatography (EA/isohexanes). The isolated material was dissolved in DCM (2 mL) and treated with TFA (2 mL). The reaction mixture was allowed to stir at room temperature for 2 h then concentrated and purified by preparative HPLC to afford 24 mg (9%) of tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1H-1,2,4-triazol-3-yl)benzyl)benzamido)acetic acid 361. LCMS-ESI (m/z) calculated for C41H34F3N5O5: 733; found 734 [M+H]+, tR=7.72 min (Method 9). 1H NMR (400 MHz, DMSO) δ 14.54 (s, 1H), 12.84 (s, 1H), 10.34 (s, 1H), 8.25-8.13 (m, 2H), 8.08 (d, J=7.9 Hz, 2H), 7.94-7.73 (m, 2H), 7.70-7.59 (m, 4H), 7.57-7.35 (m, 5H), 7.32 (d, J=7.9 Hz, 2H), 7.25-7.14 (m, 2H), 4.73 (s, 1H), 4.65 (s, 1H), 4.03 (s, 1H), 3.93 (s, 1H), 3.90-3.76 (m, 5H), 2.37 (s, 3H).

Provenance & Evidence