反应详情

Prepared using General Procedures 6 then 8: To a stirred solution of 2-methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid INT-23 (107 mg, 0.278 mmol), TEA (77 μl, 0.556 mmol) and 4-(((2-(tert-butoxy)-2-oxoethyl)amino)methyl)-3-methoxyphenyl 4-(heptyloxy)benzoate INT-26 (135 mg, 0.278 mmol) in DMF (3 mL) was added HATU (111 mg, 0.292 mmol) and left at room temperature for 2 h. The reaction mixture was diluted with EA (50 mL). The organic phase was washed with brine (2×100 mL) then pre-absorbed onto silica gel and purified by chromatography (EA/isohexanes. The isolated material was taken up into DCM (3 mL) and TFA (2 mL) and stirred at room temperature for 2 h. After stirring for 2 h, the solvent was concentrated and the product was purified by preparative HPLC to afford 21 mg (9.4%) of 2-(N-(4-((4-(heptyloxy)benzoyl)oxy)-2-methoxybenzyl)-2-methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetic acid 316 as a white powder. LCMS-ESI (m/z) calculated for C42H45F3N2O10: 794; found 795 [M+H]+, tR=10.02 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.75-12.57 (br s, 1H), 10.33 (s, 0.5H), 10.30 (s, 0.5H), 8.12-8.00 (m, 2H), 7.52-7.41 (m, 2H), 7.32 (d, J=8.3 Hz, 0.5H), 7.26-7.03 (m, 6.5H), 6.97 (d, J=2.2 Hz, 0.5H), 6.92-6.85 (m, 1H), 6.81 (dd, J=8.2, 2.1 Hz, 0.5H), 5.00-4.70 (br s, 1H), 4.35 (s, 1H), 4.09 (td, J=6.6, 2.5 Hz, 2H), 3.88-3.83 (m, 5H), 3.82 (s, 2H), 3.77 (s, 3H), 3.70 (s, 1.5H), 3.64 (s, 1.5H), 1.80-1.70 (m, 2H), 1.48-1.24 (m, 8H), 0.93-0.84 (m, 3H).

1. customPrepared
2. washThe organic phase was washed with brine (2×100 mL)
3. customthen pre-absorbed onto silica gel
4. custompurified by chromatography (EA/isohexanes
5. stirringAfter stirring for 2 h
6. concentrationthe solvent was concentrated
7. customthe product was purified by preparative HPLC