Reaction #52119

Reaction equation

TBTU

HCl

(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-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid

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

2-Methoxyethylamine

DIPEA

→

title compound

Yield 44.9%

(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-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (2-methoxy-ethyl)-amide

Yield 44.9%

Solvents

DMF CH2Cl2

CH2Cl2

Conditions

Workup

1. 1
   Extractionextracted with CH2Cl2
2. 2
   ExtractionThe organic layers were subsequently extracted with CH2Cl2 from saturated aqueous NaHCO3
3. 3
   DryingThe combined organic phase was dried (MgSO4)
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   OtherThe residue was purified by silica gel chromatography

Procedure

TBTU (0.077 g), DIPEA (0.090 mL) and (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-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (Example 14) (0.10 g) were combined in 5% DMF-CH2Cl2 (4.2 mL) at room temperature. 2-Methoxyethylamine (0.036 g) was then added and the reaction solution was stirred overnight. The reaction was diluted with CH2Cl2, poured into 1N HCl, and extracted with CH2Cl2. The organic layers were subsequently extracted with CH2Cl2 from saturated aqueous NaHCO3 followed by brine. The combined organic phase was dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel chromatography to afford 0.045 g of the title compound (684.2, M+1) as a foam.

Source