反应详情

To a stirred solution of (2R)-1-(tert-butoxycarbonyl)-4-isopropylpiperazine-2-carboxylic acid (0.078 g, 0.29 mmol, 50% strength by NMR), 1-(4-fluorophenyl)-piperazine (0.031 g, 0.174 mmol), HOBT (0.024 g, 0.174 mmol) and DIPEA (0.091 ml, 0.52 mmol) in DMF (2 ml) was added EDCI (0.033 g, 0.174 mmol) and the reaction allowed to stir at room temperature over weekend. The solvents were then removed in vacuo and the residue partitioned between DCM/water, extracted twice with DCM, the organics passed through phase separating cartridge and concentrated under reduced pressure to give a colourless gum. This was then purified by prep HPLC (basic, high throughput machine) to give a white solid. This was then dissolved in DCM (2 ml), TFA (2 ml) added and reaction allowed to stir overnight at room temperature. The solvents were then removed under reduced pressure to give a brown gum. This was partitioned between DCM and 2M NaOH, extracted twice with DCM, the combined organics passed through a phase separating cartridge and concentrated in vacuo to give the title compound, as a yellow gum (12 mg, 0.036 mmol, 12% over 2 steps).

1. customThe solvents were then removed in vacuo
2. customthe residue partitioned between DCM/water
3. extractionextracted twice with DCM
4. customseparating cartridge
5. concentrationconcentrated under reduced pressure
6. customto give a colourless gum
7. customThis was then purified by prep HPLC (basic, high throughput machine)
8. customto give a white solid
9. customreaction
10. stirringto stir overnight at room temperature
11. customThe solvents were then removed under reduced pressure
12. customto give a brown gum
13. customThis was partitioned between DCM and 2M NaOH
14. extractionextracted twice with DCM
15. customseparating cartridge
16. concentrationconcentrated in vacuo