反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- -30 °C
PROCEDURE
实验过程
To a solution of phosgene (120 μL of 20% in toluene by weight) in CH2Cl2 (1.5 mL) at −78° C. was added a solution of tert-butyl ((S)-1-(((S)-3-(4-aminophenyl)-1-((R)-3,3-dimethyl-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,3-azasilolidin-1-yl)-1-oxopropan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (Compound G of Example 1, 54 mg, 0.09 mmol) and DIEA (50 μL) in CH2Cl2 (2 mL) with stirring under N2 atm. After 30 minutes at −78° C., the mixture was concentrated in vacuo and the residue was dissolved in CH2Cl2 (2 mL), cooled to −30° C. and treated with a solution of tert-butyl ((S)-1-(((S)-1-((2S,4S)-4-amino-2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (47 mg, 0.09 mmol) and DIEA (50 μL) in CH2Cl2 (2 mL). After 10 minutes, the reaction mixture was warmed to rt, stirred for 1 h, concentrated in vacuo and the residue was purified by preparative HPLC to provide the urea product as a white solid.
WORKUP
后处理
- concentrationthe mixture was concentrated in vacuo
- dissolutionthe residue was dissolved in CH2Cl2 (2 mL)
- waitAfter 10 minutes
- temperaturethe reaction mixture was warmed to rt
- stirringstirred for 1 h
- concentrationconcentrated in vacuo
- customthe residue was purified by preparative HPLC