反応 #657343

反応方程式

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

収率 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

収率 47.0%

溶媒

THF

反応条件

後処理

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

実験手順

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.

出典