反応 #70196

反応方程式

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

収率 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

収率 82.0%

溶媒

water

dichloromethane dimethylformamide

dichloromethane dimethylformamide

反応条件

後処理

1. 1
   workup.ADDITIONIn a 100 mL addition funnel
2. 2
   温度while maintaining the temperature at 0° C
3. 3
   温度to warm to ambient temperature as it
4. 4
   その他the reaction
5. 5
   workup.STIRRINGAfter stirring the precipitate
6. 6
   ろ過was filtered
7. 7
   その他dried

実験手順

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.

出典