Reacción #60274

Ecuación de reacción

6-(4-bromo-2-chloro-phenylamino)-3-(2-carboxy-ethyl)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester

HOBt H2O

Et3N

pyrrolidine

EDCI

→

desired product

Rendimiento 67.0%

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(3-oxo-3-pyrrolidin-1-yl-propyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

Rendimiento 67.0%

Disolventes

EtOAc

water

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with sat'd aqueous NH4Cl, brine
2. 2
   SecadoThe organic layer is dried over MgSO4
3. 3
   Filtraciónfiltered
4. 4
   Concentraciónconcentrated in vacuo
5. 5
   Otroto give a crude material which
6. 6
   Otrois purified by flash chromatography (3% MeOH in CH2Cl2)

Procedimiento

To solution of 6-(4-bromo-2-chloro-phenylamino)-3-(2-carboxy-ethyl)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester (60 mg, 0.13 mmol) in DMF (1.8 mL) is added HOBt-H2O (24 mg, 0.16 mmol), Et3N (0.043 mL, 0.31 mmol), pyrrolidine (0.011 mL, 0.13 mmol), and EDCI (34 mg, 0.18 mmol) at room temperature. The resulting yellow solution is stirred 16 hours at room temperature. The reaction mixture is diluted with EtOAc and water, washed with sat'd aqueous NH4Cl, brine, sat'd aqueous NaHCO3, and brine. The organic layer is dried over MgSO4, filtered, and concentrated in vacuo to give a crude material which is purified by flash chromatography (3% MeOH in CH2Cl2) to afford 45 mg (67%) of the desired product: MS APCI (+) m/z 523, 525 (M+, Br pattern) detected.

Fuente