Reaktion #603626

Reaktionsgleichung

LiOH

water

1-Hydroxy-1H-1,2,3-benzotriazole-6-carboxylic acid

3-chlorophenylboronic acid

K2CO3

EtOH

water

HCTU

DIPEA

(2R,4R)-4-amino-5-(4-bromophenyl)-2-hydroxypentanoic acid ethyl ester

→

title compound

Ausbeute 21.0%

(2R,4R)-5-(3′-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid

Ausbeute 21.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe resulting mixture was stirred for 10 minutes
2. 2
   SonstigeThe mixture was evaporated under reduced pressure
3. 3
   Sonstigepurified (C18 column. 20-70% MeCN in water with 5% TFA)
4. 4
   Sonstigethe resulting mixture was microwaved at 100° C. for 10 minutes
5. 5
   FiltrationThe mixture was filtered
6. 6
   workup.STIRRINGThe mixture was stirred for 30 minutes
7. 7
   Sonstigeevaporated under reduced pressure
8. 8
   Sonstigepurified by preparative HPLC

Vorschrift

1-Hydroxy-1H-1,2,3-benzotriazole-6-carboxylic acid (56.6 mg, 316 μmol) and HCTU (131 mg, 316 μmol) were combined in DMF, and stirred for 5 minutes at room temperature. DIPEA (83 μL, 474 μmol) and (2R,4R)-4-amino-5-(4-bromophenyl)-2-hydroxypentanoic acid ethyl ester (50 mg, 0.2 mmol) were added, and the resulting mixture was stirred for 10 minutes. The mixture was evaporated under reduced pressure and purified (C18 column. 20-70% MeCN in water with 5% TFA). The clean fractions were lyophilized (40 mg). These solids were then combined with 3-chlorophenylboronic acid (44.5 mg, 285 μmol), K2CO3 (66 mg, 474 μmol), EtOH (0.8 mL, 10 mmol), and water (0.2 mL, 10 mmol). SilicaCat®DPP-Pd (0.28 mmol/g loading; 57 mg, 16 μmol) was added, and the resulting mixture was microwaved at 100° C. for 10 minutes. The mixture was filtered and 1 M LiOH in water (1.3 mL, 1.3 mmol) was added. The mixture was stirred for 30 minutes, evaporated under reduced pressure, and purified by preparative HPLC to yield the title compound (20.2 mg, purity 95%). MS m/z [M+H]+ calc'd for C24H21ClN4O5, 481.12. found 481.2.

Quelle