Réaction #70196

Équation de réaction

1-(2-{2-Cyclohexyl-2-[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carboxylic acid

N-methyl-morpholine

N-methyl-morpholine

amine

3-amino-2-hydroxy-hexanoic Acid Ethyl Ester Hydrochloride

PyBOP

→

32

Rendement 82.0%

3-{[1-(2-{2-Cyclohexyl-2-[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carbonyl]-amino}-2-hydroxy-hexanoic Acid Ethyl Ester

Rendement 82.0%

Solvants

water

dichloromethane dimethylformamide

dichloromethane dimethylformamide

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONIn a 100 mL addition funnel
2. 2
   Températurewhile maintaining the temperature at 0° C
3. 3
   Températureto warm to ambient temperature as it
4. 4
   Autrethe reaction
5. 5
   workup.STIRRINGAfter stirring the precipitate
6. 6
   Filtrationwas filtered
7. 7
   Autredried

Mode opératoire

In a dry flask charged with a 1:1 mixture of dichloromethane-dimethylformamide (100 ml) was placed 1-(2-{2-Cyclohexyl-2-[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carboxylic acid 32a (2.0 g, 4.28 mmols), PyBOP (2.5 g, 4.7 mmol), and N-methyl-morpholine (2.4 ml, 21.4 mmol) and the reaction placed under an atmosphere of nitrogen. In a 100 mL addition funnel was placed a solution of the amine 14(1.0 g, 4.7 mmols) and N-methyl-morpholine (0.60 ml, 5.35 mmol) in a 1:1 mixture of dichloromethane-dimethylformamide (10 ml). The reaction was cooled to 0° C., and the amine was added while maintaining the temperature at 0° C. The reaction was allowed to warm to ambient temperature as it was stirred over night. HPLC analysis showed the reaction to be complete, and then the reaction was diluted with water to 500 mL. After stirring the precipitate was filtered and dried to give 2.4 g (82% yield) of 32 as a beige solid. This material was used as is in the next step without further purification. HPLC: RT=5.66 min, (10-90% acetonitrile-water over 7 minutes); LC/MS: retention time 3.94 min (10-90% acetonitrile-water over 5 minutes); M+H+=685.5.

Source