Reaktion #628687

Reaktionsgleichung

2-Hydroxy-5-thiazolecarboxylic acid

HCTU

DMF

EtOH

(R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester

DIPEA

LiOH

water

→

title compound

Ausbeute 15.7%

(R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(2-hydroxythiazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid

Ausbeute 15.7%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeresulting mixture
2. 2
   SonstigeThe mixture was then evaporated under reduced pressure
3. 3
   workup.STIRRINGthe resulting mixture was stirred at 40° C. for 3 hours
4. 4
   SonstigeThe solvent was removed in vacuo
5. 5
   Sonstigethe residue was purified by preparative HPLC

Vorschrift

2-Hydroxy-5-thiazolecarboxylic acid (43.5 mg, 0.3 mmol) and HCTU (124 mg, 0.3 mmol) were stirred in DMF (1.3 mL, 16.4 mmol) for 15 minutes at room temperature. (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester (100 mg, 0.3 mmol) and DIPEA (142 μL, 818 μmol) were added, and resulting mixture was stirred at room temperature for 30 minutes. The mixture was then evaporated under reduced pressure. The residue was dissolved in EtOH (955 μL, 16.4 mmol). A solution of 1.0 M LiOH in water (1.4 mL, 1.4 mmol) was added and the resulting mixture was stirred at 40° C. for 3 hours. LC/MS showed completion. The solvent was removed in vacuo and the residue was purified by preparative HPLC to yield the title compound (22 mg) as a TFA salt. MS m/z [M+H]+ calc'd for C20H17ClFN3O5S, 466.06. found 466.0.

Quelle