反应详情

2-Hydroxy-5-thiazolecarboxylic acid (9.0 mg, 62 μmol) and HATU (28.3 mg, 74 μmol) were stirred in DMA (0.5 mL, 5 mmol) for 10 minutes. (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester (22.7 mg, 62 μmol) and DIPEA (32.4 μL, 186 μmol) were added, and resulting mixture was stirred at room temperature for 2 hours. The mixture was then concentrated under reduced pressure and the residue was dissolved in 50% AcOH-water (1.5 mL), filtered, purified by reverse phase preparative HPLC, and lyophilized to yield the title compound (11.9 mg, purity 96%) as a TFA salt. MS m/z [M+H]+ calc'd for C22H21ClFN3O5S, 494.09. found 494.4.

1. customresulting mixture
2. concentrationThe mixture was then concentrated under reduced pressure
3. dissolutionthe residue was dissolved in 50% AcOH-water (1.5 mL)
4. filtrationfiltered
5. custompurified by reverse phase preparative HPLC