تفاعل #60274

معادلة التفاعل

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

المردود 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

المردود 67.0%

المذيبات

EtOAc

water

DMF

ظروف التفاعل

المعالجة

1. 1
   غسيلwashed with sat'd aqueous NH4Cl, brine
2. 2
   تجفيفThe organic layer is dried over MgSO4
3. 3
   ترشيحfiltered
4. 4
   تركيزconcentrated in vacuo
5. 5
   أخرىto give a crude material which
6. 6
   أخرىis purified by flash chromatography (3% MeOH in CH2Cl2)

الإجراء التجريبي

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.

المصدر