反应详情

Prepared using General Procedures 2 then 8: To a stirring solution of 4′-methyl-[1,1′-biphenyl]-4-carboxylic acid (334 mg, 1.57 mmol) in DCM (10 mL) were added DMF (5 drops) and oxalyl chloride (0.14 mL, 1.68 mmol). The reaction mixture was stirred at room temperature for 1 h. To this mixture was added a solution of tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate INT-9 (750 mg, 1.31 mmol) and TEA (0.37 mL, 2.62 mmol) in DCM (10 mL). The reaction mixture was stirred at room temperature for 1 h then DMAP (30 mg, 0.33 mmol) was added. After a further 2 h at room temperature, the reaction was diluted with DCM (50 mL) and washed with NaHCO3 (50 mL). The organics were pre-absorbed onto silica gel and purified by chromatography (EA/isohexanes). The isolated material was taken up into DCM (10 mL) and TFA (5 mL) was added. After 2 h the solvent was removed under vacuum and solid was evaporated from diethyl ether (5 mL) and isohexanes (20 mL) to give a fine powdery solid. Trituration from DCM/isohexanes and isolation by filtration gave a fine powder that was slurried in water (20 mL) and isolated by filtration. The solid was washed with DCM and isohexanes (9:1, 50 mL) followed by isohexanes (50 mL) to afford 15.3 mg (19%) of 2-(4-(2-(4-methoxyphenyl)acetamido)-N-(4-((4-octylbenzoyl)oxy)benzyl)benzamido)acetic acid 192. LCMS-ESI (m/z) calculated for C40H33F3N2O7: 710; found 711 [M+H]+, tR=8.81 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.96-12.60 (br s, 1H), 10.36 (s, 1H), 8.25-8.16 (m, 2H), 7.94-7.84 (m, 2H), 7.75-7.62 (m, 4H), 7.55-7.27 (m, 9H), 7.25-7.15 (m, 2H), 4.70 (s, 1H), 4.61 (s, 1H), 4.03 (s, 1H), 3.95 (s, 1H), 3.8-3.78 (m, 5H), 2.37 (s, 3H).

1. customPrepared
2. stirringThe reaction mixture was stirred at room temperature for 1 h
3. waitAfter a further 2 h at room temperature
4. washwashed with NaHCO3 (50 mL)
5. customThe organics were pre-absorbed onto silica gel
6. custompurified by chromatography (EA/isohexanes)
7. additionwas added
8. customAfter 2 h the solvent was removed under vacuum and solid
9. customwas evaporated from diethyl ether (5 mL) and isohexanes (20 mL)
10. customto give a fine powdery solid
11. filtrationTrituration from DCM/isohexanes and isolation by filtration
12. customgave a fine powder that
13. customisolated by filtration
14. washThe solid was washed with DCM and isohexanes (9:1, 50 mL)