反应详情

A suspension of 30 mg (0.10 mmol) of (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]4-(2,5-difluorophenyl)butanoic acid, 34 mg (0.12 mmol) of amine from Step B, 25 mg (0.12 mmol) of ethyl dimethylaminopropylcarbodiimide (EDC), and 18 mg (0.12 mmol) of hydroxybenzotriazole (HOBt) in 1.0 mL of dichloromethane was treated with 0.050 mL of diisopropylethylamine. The reaction mixture was sonicated for 5 min, then shaken for 3 days at ambient temperature. The mixture was diluted with 1 mL of dichloromethane, treated with 2 mL of trifluoroacetic acid (TFA), and concentrated in vacuo. Purification by HPLC (YMC C18 Pro column, gradient elution, 10–90% MeCN:H2O containing 0.1% TFA) gave 40 mg of a viscous gum which was converted to free base on a 1-g SCX column to provide 25 mg of a white solid. The solid was triturated with ether, collected and dried under vacuo to give 21.2 mg of the title compound as a white powder. LC-MS 417.1 (M+1).

1. customThe reaction mixture was sonicated for 5 min
2. concentrationconcentrated in vacuo
3. customPurification
4. washby HPLC (YMC C18 Pro column, gradient elution, 10–90% MeCN:H2O containing 0.1% TFA)