反応 #159140

反応方程式

DIEA

HCl

4-Phenyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester

HATU

DIEA

{1-[2-(4-{6-[4-(2-tert-Butoxycarbonylamino-acetyl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

→

crude material

収率 174.4%

2-{2-[4-(6-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-2-oxo-ethylcarbamoyl}-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester

収率 174.4%

溶媒

dioxane

EtOAc

DMF

DCM

反応条件

後処理

1. 1
   その他all volatiles were removed in vacuo
2. 2
   その他The crude material was used in the next step without further purification
3. 3
   workup.DISSOLUTIONThe crude material was dissolved in DMF (1.0 mL)
4. 4
   workup.STIRRINGThe reaction was stirred at room temperature
5. 5
   workup.WAITAfter 20 minutes
6. 6
   洗浄was washed with brine, saturated sodium bicarbonate solution, brine
7. 7
   乾燥was dried over sodium sulfate
8. 8
   ろ過Filtration and removal of solvents in vacuo

実験手順

{1-[2-(4-{6-[4-(2-tert-Butoxycarbonylamino-acetyl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (61.0 mg, 0.095 mmol) was dissolved in DCM (1 mL) and HCl in dioxane (4M, 1 mL) was added and stirring at room temperature was continued. After 90 minutes, all volatiles were removed in vacuo. The crude material was used in the next step without further purification. The crude material was dissolved in DMF (1.0 mL) and DIEA (23.7 mg, 0.183 mmol) was added. A solution of 4-Phenyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (17.8 mg, 0.061 mmol), HATU (23.3 mg, 0.061 mmol) and DIEA (7.9 mg, 0.061 mmol) in DMF (0.5 mL) was added. The reaction was stirred at room temperature. After 20 minutes, the reaction was diluted with EtOAc and was washed with brine, saturated sodium bicarbonate solution, brine, and was dried over sodium sulfate. Filtration and removal of solvents in vacuo gave the crude material (88 mg), which was used in the next step without further purification.

出典