Reaktion #52118

Reaktionsgleichung

DIPEA

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

trifluoroacetic acid

TBTU

→

title compound

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

Lösungsmittel

EtOAc

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenwashed with water (x3), 1N HCl, and saturated NaHCO3
2. 2
   TrocknenThe organic phase was dried over Na2SO4
3. 3
   Einengenconcentrated
4. 4
   workup.DISSOLUTIONThe resulting residue was dissolved in CH2Cl2
5. 5
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 3 h
6. 6
   Waschenwashed with saturated NaHCO3 and water
7. 7
   TrocknenThe organic phase was dried over Na2SO4
8. 8
   Einengenconcentrated
9. 9
   SonstigeThe resulting residue was purified by silica gel preparative thin layer chromatography

Vorschrift

To a solution of (S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (see Example 5) (0.1 g, 0.174 mmol) in anhydrous DMF was added the above mixture of amines (0.030 g), followed by TBTU (0.084 g, 0.261 mmol) followed by DIPEA (0.075 mL, 0.435 mmol). The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was then diluted with EtOAc and washed with water (x3), 1N HCl, and saturated NaHCO3. The organic phase was dried over Na2SO4 and concentrated. The resulting residue was dissolved in CH2Cl2 and trifluoroacetic acid (1 eq) was added to the solution. The reaction mixture was stirred at room temperature for 3 h and washed with saturated NaHCO3 and water. The organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel preparative thin layer chromatography using CH2Cl2—MeOH (95:5) as an eluent to afford 0.063 g of the title compound as a white foam (M+1,671.1).

Quelle