Reaktion #2461972

Reaktionsgleichung

HATU

DIPEA

aniline

tetrabutylammonium fluoride

(S)-1-[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid

(R)-2-({(S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carbonyl}-amino)-propionic acid

→

title compound

Ausbeute 62.4%

(S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (4-hydroxy-phenyl)-amide

Ausbeute 62.4%

Lösungsmittel

THF

methylene chloride

Water

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   SonstigeThe solvent was evaporated
3. 3
   Sonstigethe resulting residue chromatographed over silica gel (gradient EtOAc/hexanes)
4. 4
   Sonstigeto provide a white solid
5. 5
   workup.STIRRINGthe reaction stirred for 3 h
6. 6
   Sonstigethe layers separated
7. 7
   TrocknenThe organic layer was dried over sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Sonstigeevaporated
10. 10
    SonstigeThe resulting residue was chromatographed over silica gel (25% EtOAc in methylene chloride)

Vorschrift

(S)-1-[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (see Example 5) (122 mg, 0.2 mmol) was dissolved in methylene chloride (2 mL) under a nitrogen atmosphere. HATU (121 mg, 0.3 mmol) and DIPEA (111 μL, 0.64 mmol) were added. The t-butyldimethylsilyl-(TBDMS-) protected aniline (71 mg, 0.3 mmol) was added and the reaction was stirred overnight. The solvent was evaporated and the resulting residue chromatographed over silica gel (gradient EtOAc/hexanes) to provide a white solid. The white solid was dissolved in methylene chloride (2 mL) and a 1.0 M solution in THF of tetrabutylammonium fluoride (TBAF) (1 mL) was added and the reaction stirred for 3 h. Water and a few drops of 1 N HCl were added and the layers separated. The organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting residue was chromatographed over silica gel (25% EtOAc in methylene chloride) to provide 83 mg of the title compound as a white solid (M+1, 665.2).

Quelle