反应详情

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.

1. customat RT
2. additionwas added
3. concentrationbefore being concentrated under reduced pressure
4. extractionextracted with DCM
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude solid was purified by chromatography on SiO2 (DCM/MeOH 95/5)
9. customthe resulting solid recrystallised in MeCN
10. dissolutionThe solid was then dissolved in DCM
11. customprecipitated with i-Pr2O