反应详情

A solution of 456 mg (0.088 mmol) of 71 in CH2Cl2 (20 ml) was treated with anhydrous TFA (5 mL) then stirred at room temperature under N2 for 1 hour and evaporated to dryness. The residue was repeatedly concentrated from CH2Cl2 (3×) then dried under vacuum. The resulting residue was dissolved in CH2Cl2 (20 ml), cooled to 0° C., then treated with DIEA (1.3 ml, 8 eq, 2.46 mmol) followed by 4-amino-3-chloro-benzoic acid (202 mg, 1.17 mmol), HOBT (1833 mg, 1.35 mmol), and EDC (279 mg, 1.45 mmol). The resulting mixture was allowed to warm to room temperature and stir for 18 hours. The solvent was removed in vacuo and the residue dissolved in EtOAc then washed with distilled water (3×), 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give a residue that was purified by flash chromatography, eluting with CH2Cl2/MeOH (99/1 to 97/3%), affording 285 mg (57% yield) of the title compound (72) as a yellow solid.

1. customevaporated to dryness
2. concentrationThe residue was repeatedly concentrated from CH2Cl2 (3×)
3. customthen dried under vacuum
4. dissolutionThe resulting residue was dissolved in CH2Cl2 (20 ml)
5. temperaturecooled to 0° C.
6. temperatureto warm to room temperature
7. stirringstir for 18 hours
8. customThe solvent was removed in vacuo
9. dissolutionthe residue dissolved in EtOAc
10. washthen washed with distilled water (3×), 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine
11. dry with materialThe organic layer was dried over Na2SO4
12. filtrationfiltered
13. customevaporated
14. customto give a residue that
15. customwas purified by flash chromatography
16. washeluting with CH2Cl2/MeOH (99/1 to 97/3%)