تفاعل #657343

معادلة التفاعل

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

المردود 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

المردود 47.0%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   أخرىat RT
2. 2
   workup.ADDITIONwas added
3. 3
   تركيزbefore being concentrated under reduced pressure
4. 4
   استخلاصextracted with DCM
5. 5
   تجفيفThe organic layer was dried over Na2SO4
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىThe crude solid was purified by chromatography on SiO2 (DCM/MeOH 95/5)
9. 9
   أخرىthe resulting solid recrystallised in MeCN
10. 10
    workup.DISSOLUTIONThe solid was then dissolved in DCM
11. 11
    أخرىprecipitated with i-Pr2O

الإجراء التجريبي

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.

المصدر