反应详情

To a stirring solution of tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(2-(4′-methyl-[1,1′-biphenyl]-4-carbonyl)hydrazine carbonyl)benzyl)benzamido)acetate INT-51 (138 mg, 0.17 mmol) and triethylamine (37 μL, 0.26 mmol) in DCM (4 mL) was added 2-chloro-1,3-dimethylimidazolinium chloride (32.0 mg, 0.19 mmol). After stirring at room temperature for 16 h, the reaction mixture was warmed to 40° C. After 1 h, additional triethylamine (37.0 μL, 0.26 mmol) was added. After a further 2 h, the reaction mixture was allowed to cool to room temperature then washed with NaHCO3 (10 mL), split through a hydrophobic frit and evaporated. The crude material was purified by column chromatography (EA/isohexanes). The isolated material was diluted with DCM (2 mL), treated with TFA (2 mL) and allowed to stir for 1 h at room temperature. The solvents were concentrated and the residue purified by preparative HPLC to afford 10 mg (8%) of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,3,4-oxadiazol-2-yl)benzyl)benzamido)acetic acid 367 as a white solid. LCMS-ESI (m/z) calculated for C41H33F3N4O6: 734; found 735 [M+H]+, tR=8.40 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.96 (s, 1H), 10.36 (s, 1H), 8.26-8.09 (m, 4H), 7.99-7.87 (m, 2H), 7.77-7.50 (m, 6H), 7.47-7.31 (m, 5H), 7.26-7.14 (m, 2H), 4.76 (s, 1H), 4.69 (s, 1H), 4.04 (s, 1H), 3.96 (m, 1H), 3.88-3.77 (m, 5H), 2.38 (s, 3H).

1. temperaturethe reaction mixture was warmed to 40° C
2. waitAfter 1 h
3. waitAfter a further 2 h
4. temperatureto cool to room temperature
5. washthen washed with NaHCO3 (10 mL)
6. customsplit through a hydrophobic frit
7. customevaporated
8. customThe crude material was purified by column chromatography (EA/isohexanes)
9. additionThe isolated material was diluted with DCM (2 mL)
10. additiontreated with TFA (2 mL)
11. stirringto stir for 1 h at room temperature
12. concentrationThe solvents were concentrated
13. customthe residue purified by preparative HPLC