Reacción #52121

Ecuación de reacción

TBTU

HCl

β-alanine methyl ester

DIPEA

(S)-1-[(R)-7-(3,5-dichlorophenyl)-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

→

title compound

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

Rendimiento 10.3%

Disolventes

DMF CH2Cl2

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   Extraccióna nd extracted with CH2Cl2
2. 2
   Lavadowashed with saturated aqueous NaHCO3
3. 3
   SecadoThe combined organic phase was dried (Na2SO4)
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated
6. 6
   workup.DISSOLUTIONThe resultant residue was re-dissolved in 2N NH3—CH3OH (10 mL)
7. 7
   OtroThe volatiles were removed
8. 8
   Otrothe residue was purified by silica gel chromatography

Procedimiento

TBTU (0.15 g), (S)-1-[(R)-7-(3,5-dichlorophenyl)-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) (0.20 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, a nd 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).

Fuente