Reaktion #2461982

Reaktionsgleichung

TBTU

HCl

β-alanine methyl ester

DIPEA

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

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

→

title compound

Ausbeute 10.3%

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

Ausbeute 10.3%

Lösungsmittel

DMF CH2Cl2

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionextracted with CH2Cl2
2. 2
   Waschenwashed with saturated aqueous NaHCO3
3. 3
   TrocknenThe combined organic phase was dried (Na2SO4)
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated
6. 6
   workup.DISSOLUTIONThe resultant residue was re-dissolved in 2N NH3—CH3OH (10 mL)
7. 7
   SonstigeThe volatiles were removed
8. 8
   Sonstigethe residue was purified by silica gel chromatography

Vorschrift

TBTU (0.15 g), (S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (Example 14) (0.20 g), β-alanine methyl ester (0.067 g) and DIPEA (0.14 mL) were combined in 1% DMF-CH2Cl2 (10.1 mL) at room temperature and the solution was stirred for 1 h. The reaction was diluted with CH2Cl2, poured into 1N HCl, and extracted with CH2Cl2. The organic layers were combined and washed with saturated aqueous NaHCO3 followed by H2O. The combined organic phase was dried (Na2SO4), filtered and concentrated. The resultant residue was re-dissolved in 2N NH3—CH3OH (10 mL) and heated to 40-60° C. for 48 h. The volatiles were removed and the residue was purified by silica gel chromatography to afford the title compound (0.021 g) as a foam (697.2, M+1).

Quelle