Reacción #8622

Ecuación de reacción

3-[1-[2-amino-3-(4-fluorophenyl)proponyl]-4-(2-naphthalen-2-ylethyl)-5-oxo-piperazin-2-yl]propionitrile

N-acetyl-L-tyrosine

1-hydroxybenzotriazole

N-methylmorpholine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

→

crude product

2-acetylamino-N-[2-[2-(2-cyanoethyl)-4-(2-naphthalen-2-ylethyl)-5-oxo-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethyl]-3-(4-hydroxyphenyl)-propionamide

Disolventes

DMF

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm
2. 2
   workup.STIRRINGstir at room temperature another 2 hours
3. 3
   Filtraciónthe resulting solid is collected by filtration
4. 4
   workup.DISSOLUTIONre-dissolved in EtOAc
5. 5
   Extracciónextracted with water
6. 6
   Otrodried
7. 7
   Concentraciónconcentrated in vacuo

Procedimiento

To a solution of 3-[1-[2-amino-3-(4-fluorophenyl)proponyl]-4-(2-naphthalen-2-ylethyl)-5-oxo-piperazin-2-yl]propionitrile, 33, (47.2 g, 100 mmol), N-acetyl-L-tyrosine (22.3 g, 120 mmol), 1-hydroxybenzotriazole (16.2 g, 120 mmol), and N-methylmorpholine (132 mL, 120 mmol) in DMF (150 mL) is cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (24.9 g, 130 mmol) is slowly added. The resulting mixture is stirred for 2 hours at 0° C. then allowed to warm and stir at room temperature another 2 hours. The reaction solution is diluted with water and the resulting solid is collected by filtration, re-dissolved in EtOAc and extracted with water, dried and concentrated in vacuo to afford the crude product which is purified over silica gel.

Fuente