Reacción #657343

Ecuación de reacción

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

Rendimiento 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

Rendimiento 47.0%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroat RT
2. 2
   workup.ADDITIONwas added
3. 3
   Concentraciónbefore being concentrated under reduced pressure
4. 4
   Extracciónextracted with DCM
5. 5
   SecadoThe organic layer was dried over Na2SO4
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated in vacuo
8. 8
   OtroThe crude solid was purified by chromatography on SiO2 (DCM/MeOH 95/5)
9. 9
   Otrothe resulting solid recrystallised in MeCN
10. 10
    workup.DISSOLUTIONThe solid was then dissolved in DCM
11. 11
    Otroprecipitated with i-Pr2O

Procedimiento

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.

Fuente