Reaction #657343

Reaction equation

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

Yield 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

Yield 47.0%

Solvents

THF

Conditions

Workup

1. 1
   Otherat RT
2. 2
   workup.ADDITIONwas added
3. 3
   Concentrationbefore being concentrated under reduced pressure
4. 4
   Extractionextracted with DCM
5. 5
   DryingThe organic layer was dried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   OtherThe crude solid was purified by chromatography on SiO2 (DCM/MeOH 95/5)
9. 9
   Otherthe resulting solid recrystallised in MeCN
10. 10
    workup.DISSOLUTIONThe solid was then dissolved in DCM
11. 11
    Otherprecipitated with i-Pr2O

Procedure

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.

Source