反应详情

温度

0 °C

To a stirring solution of triphosgene (14.87 mg, 0.05 mmol) in 8 mL of CH2Cl2 at 0° C. was added dropwise a mixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (32.58 mg, 0.15 mmol) and N,N-diisopropylethylamine (0.07841 mL, 0.45 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at 0° C. for 30 minutes. Then to the mixture at 0° C. was added a solution of the (R)-4-(4-chlorobenzyl)-3-ethyl-5-(pyrrolidin-2-yl)-4H-1,2,4-triazole HCl salt (54.57 mg, 0.15 mmol) and N,N-diisopropylethylamine (0.07841 mL, 0.45 mmol) in dichloromethane (2 mL) slowly. The resulting mixture was stirred 0° C. for 30 minutes, then at room temperature overnight. The reaction mixture was treated with sat. aqueous NaHCO3 (10 mL) and brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography purification (Hex/EtOAc gradient, 10-100% EtOAc with 10% MeOH) afforded the desired product as a white solid (73.7 mg, 92.0%).

1. stirringThe resulting mixture was stirred 0° C. for 30 minutes
2. customat room temperature
3. customovernight
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. customFlash chromatography purification (Hex/EtOAc gradient, 10-100% EtOAc with 10% MeOH)