Reaktion #628712

Reaktionsgleichung

isobutyl alcohol

HCl

1,4-dioxane

5-Oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic acid

HCTU

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

DIPEA

DMF

→

title compound

Ausbeute 1.4%

(R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)hydrazino]-2-hydroxypropionic Acid Isobutyl Ester

Ausbeute 1.4%

Lösungsmittel

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe resulting mixture was stirred overnight
2. 2
   Waschenwashed with water (3.0 mL), saturated aqueous NaHCO3 (2×3.0 mL), and saturated aqueous NaCl (3.0 mL)
3. 3
   Trocknendried over Na2SO4
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated
6. 6
   Sonstigeto give a yellowish solid
7. 7
   EinengenThe mixture was concentrated
8. 8
   workup.DISSOLUTIONthe residue was dissolved in AcOH (1.5 mL)
9. 9
   Filtrationfiltered
10. 10
    Sonstigepurified by reverse phase preparative HPLC

Vorschrift

5-Oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carboxylic acid (89.5 mg, 436 μmol) was combined with HCTU (244 mg, 589 μmol) in DMF (1.0 mL, 13 mmol) and stirred for 10 minutes. (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester (80.0 mg, 0.2 mmol) and DIPEA (0.1 mL, 0.7 mmol) were added, and the resulting mixture was stirred overnight. The mixture was diluted with EtOAc (10.0 mL) and washed with water (3.0 mL), saturated aqueous NaHCO3 (2×3.0 mL), and saturated aqueous NaCl (3.0 mL), then dried over Na2SO4, filtered and concentrated to give a yellowish solid. A portion (20 mg) of the solid was treated with isobutyl alcohol (170 μL, 1.8 mmol) and 4.0 M HCl in 1,4-dioxane (36.0 μL, 144 μmol) at room temperature overnight. The mixture was concentrated, and the residue was dissolved in AcOH (1.5 mL), filtered, and purified by reverse phase preparative HPLC to yield the title compound (1.6 mg, purity 100%). MS m/z [M+H]+ calc'd for C29H29ClFN3O3, 582.18. found 582.4.

Quelle