Trifluoroacetic acid → 2-(N-(4-((4-(isopentyloxy)benzoyl)oxy)benzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetic acid

Participants

Reaction Steps

Prepared using General Procedures 2 and 8: To a stirring solution of 4-(isopentyloxy)benzoic acid (37 mg, 0.178 mmol) in DCM (0.5 mL) was added DMF (1 drop) and oxalyl chloride (0.016 mL, 0.190 mmol). The reaction mixture was stirred at room temperature for 2 h. To this mixture was added a solution of tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate INT-7 (60 mg, 0.119 mmol) and TEA (0.050 mL, 0.357 mmol) in DCM (1 mL). The reaction was stirred at room temperature for 18 h then TFA (1 mL) was added. After stirring for 2 h, the solvent was concentrated and the product was purified by preparative HPLC to afford 41.2 mg (54%) of 2-(N-(4-((4-(isopentyloxy)benzoyl)oxy)benzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetic acid 46. LCMS-ESI (m/z) calculated for C37H38N2O8: 638; found 637 [M−H]−, tR=8.44 min (Method 4). 1H NMR (400 MHz, DMSO) δ 12.75 (s, 1H), 10.24 (s, 1H), 8.13-8.02 (m, 2H), 7.69-7.62 (d, J=8.4 Hz, 2H), 7.48-7.28 (m, 4H), 7.26-7.19 (dt, J=6.7, 1.9 Hz, 4H), 7.16-7.08 (m, 2H), 6.93-6.83 (m, 2H), 4.72-4.54 (d, J=31.5 Hz, 2H), 4.16-4.08 (t, J=6.6 Hz, 2H), 4.05-3.86 (d, J=27.0 Hz, 2H), 3.71 (s, 3H), 3.57 (s, 2H), 1.88-1.75 (dp, J=13.3, 6.7 Hz, 1H), 1.72-1.62 (q, J=6.7 Hz, 2H), 0.97-0.86 (d, J=6.6 Hz, 6H).

Provenance & Evidence