反应 #657343

反应方程式

HATU

[(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid

ethylamine

DIEA

→

title compound

收率 47.0%

2-[(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide

收率 47.0%

溶剂

THF

反应条件

后处理

1. 1
   其他at RT
2. 2
   workup.ADDITIONwas added
3. 3
   浓缩before being concentrated under reduced pressure
4. 4
   萃取extracted with DCM
5. 5
   干燥The organic layer was dried over Na2SO4
6. 6
   过滤filtered
7. 7
   浓缩concentrated in vacuo
8. 8
   其他The crude solid was purified by chromatography on SiO2 (DCM/MeOH 95/5)
9. 9
   其他the resulting solid recrystallised in MeCN
10. 10
    workup.DISSOLUTIONThe solid was then dissolved in DCM
11. 11
    其他precipitated with i-Pr2O

实验过程

To a solution of [(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid (for a preparation see Intermediate 1) (16.0 g, 40 mmol) in THF at RT was added DIEA (14 mL, 80 mmol) followed by HATU (30.4 g, 80 mmol). The reaction mixture was stirred for 3 h at this temperature and ethylamine (40 mL, 2M in THF, 80 mmol) was added. The mixture was stirred for 48 h before being concentrated under reduced pressure. The crude material was suspended in water and extracted with DCM. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude solid was purified by chromatography on SiO2 (DCM/MeOH 95/5) and the resulting solid recrystallised in MeCN. The solid was then dissolved in DCM and precipitated with i-Pr2O to give the title compound (8 g, 47% yield) as a white solid.

来源