反应详情

Prepared using General Procedures 7 and 8: To a stirred suspension of 2-(2,6-difluoro-3-methoxyphenyl)acetic acid in DCM (1.5 mL) and DMF (10 μL) was added oxalyl chloride (9.71 μL, 0.111 mmol). After 1 h a solution of tert-butyl 2-(4-amino-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate INT-59 (50 mg, 0.074 mmol) and TEA (25.8 μL, 0.185 mmol) in DCM (1 mL) was added. After 18 h TFA (1 mL) was added and reaction stirred for 2 h. The solvent was removed from the reaction mixture and the residue purified by preparative HPLC to afford 30 mg (57%) of 2-(4-(2-(2,6-difluoro-3-methoxyphenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid 441. LCMS-ESI (m/z) calculated for C46H32F2N4O6: 702; found 703 [M+H]+, tR=8.75 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.79 (s, 1H), 10.26 (s, 1H), 8.31-8.22 (m, 2H), 8.12-8.06 (m, 2H), 8.02-7.92 (m, 2H), 7.74-7.69 (m, 2H), 7.69-7.56 (m, 2H), 7.54-7.45 (m, 1H), 7.42-7.29 (m, 4H), 7.23-7.09 (m, 2H), 6.80-6.66 (m, 1H), 4.76 (s, 1H), 4.67 (s, 1H), 4.04 (s, 1H), 3.97 (s, 1H), 2.92-2.81 (m, 5H), 2.38(s, 3H).

1. customPrepared
2. customreaction
3. customThe solvent was removed from the reaction mixture
4. customthe residue purified by preparative HPLC